Blackwell's Five-Minute Veterinary Consult: Canine and Feline [7 ed.] 1119513170, 9781119513179

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Blackwell’s Five-Minute Veterinary Consult: Canine and Feline Seventh Edition

Blackwell’s Five-Minute Veterinary Consult

Canine and Feline Seventh Edition Edited by

Larry P. Tilley, DVM

Diplomate, American College of Veterinary Internal Medicine (Small Animal Internal Medicine) President, VetMed Consultants, Inc. Santa Fe, New Mexico USA

Francis W.K. Smith, Jr., DVM

Diplomate, American College of Veterinary Internal Medicine (Small Animal Internal Medicine and Cardiology) Vice-President, VetMed Consultant, Inc. Lexington, Massachusetts USA

Meg M. Sleeper, VMD

Diplomate, American College of Veterinary Internal Medicine (Cardiology) Professor of Clinical Cardiology College of Veterinary Medicine University of Florida, Florida USA

Benjamin M. Brainard, VMD

Diplomate, American College of Veterinary Anesthesia and Analgesia and American College of Veterinary Emergency and Critical Care Edward H. Gunst Professor of Small Animal Critical Care College of Veterinary Medicine University of Georgia Athens, Georgia USA

  

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This edition first published 2021 © 2021 by John Wiley & Sons, Inc. Edition History First Edition 1997 © Lippincott Williams & Wilkins Second Edition 2000 © Lippincott Williams & Wilkins Third edition 2004 © Lippincott Williams & Wilkins Fourth Edition 2007 © Blackwell Publishing Professional Fifth edition 2011 © John Wiley & Sons, Inc. Sixth Edition 2016 © John Wiley & Sons, Inc. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, except as permitted by law. Advice on how to obtain permission to reuse material from this title is available at http://www.wiley. com/go/permissions. Blackwell Publishing was acquired by John Wiley & Sons in February 2007. Blackwell’s publishing program has been merged with Wiley’s global Scientific, Technical and Medical business to form Wiley-Blackwell. The right of Larry P Tilley, Francis W Smith, Meg Sleeper, and Benjamin Brainard to be identified as the authors of the editorial material in this work has been asserted in accordance with law. Registered Office John Wiley & Sons, Inc., 111 River Street, Hoboken, NJ 07030, USA Editorial Office 111 River Street, Hoboken, NJ 07030, USA For details of our global editorial offices, customer services, and more information about Wiley products visit us at www.wiley.com. Wiley also publishes its books in a variety of electronic formats and by print-on-demand. Some content that appears in standard print versions of this book may not be available in other formats. Limit of Liability/Disclaimer of Warranty The contents of this work are intended to further general scientific research, understanding, and discussion only and are not intended and should not be relied upon as recommending or promoting scientific method, diagnosis, or treatment by physicians for any particular patient. In view of ongoing research, equipment modifications, changes in governmental regulations, and the constant flow of information relating to the use of medicines, equipment, and devices, the reader is urged to review and evaluate the information provided in the package insert or instructions for each medicine, equipment, or device for, among other things, any changes in the instructions or indication of usage and for added warnings and precautions. While the publisher and authors have used their best efforts in preparing this work, they make no representations or warranties with respect to the accuracy or completeness of the contents of this work and specifically disclaim all warranties, including without limitation any implied warranties of merchantability or fitness for a particular purpose. No warranty may be created or extended by sales representatives, written sales materials or promotional statements for this work. The fact that an organization, website, or product is referred to in this work as a citation and/or potential source of further information does not mean that the publisher and authors endorse the information or services the organization, website, or product may provide or recommendations it may make. This work is sold with the understanding that the publisher is not engaged in rendering professional services. The advice and strategies contained herein may not be suitable for your situation. You should consult with a specialist where appropriate. Further, readers should be aware that websites listed in this work may have changed or disappeared between when this work was written and when it is read. Neither the publisher nor authors shall be liable for any loss of profit or any other commercial damages, including but not limited to special, incidental, consequential, or other damages. Library of Congress Cataloging-in-Publication Data Names: Tilley, Lawrence P., editor. | Smith, Francis W. K., Jr., editor. |   Sleeper, Meg M., editor. | Brainard, Benjamin, editor. Title: Blackwell’s five-minute veterinary consult. Canine and feline /   edited by Larry P. Tilley, Francis W.K. Smith, Jr., Margaret M. Sleeper,   Benjamin Brainard. Other titles: Five-minute veterinary consult. Canine and feline Description: Seventh edition. | Hoboken, NJ : Wiley-Blackwell, 2021. |   Includes bibliographical references and index. Identifiers: LCCN 2020025494 (print) | LCCN 2020025495 (ebook) | ISBN   9781119513179 (hardback) | ISBN 9781119513155 (adobe pdf ) | ISBN   9781119513162 (epub) Subjects: MESH: Dog Diseases–diagnosis | Cat Diseases–diagnosis | Dog   Diseases–therapy | Cat Diseases–therapy | Veterinary Medicine–methods   | Handbook Classification: LCC SF991 (print) | LCC SF991 (ebook) | NLM SF 991 | DDC  636.7/0896–dc23 LC record available at https://lccn.loc.gov/2020025494 LC ebook record available at https://lccn.loc.gov/2020025495 Cover Design: Wiley Cover Image: School children (8-9) at lunch break © Tetra Images - Jamie Grill / Getty Images, Playing Together at School © FatCamera / Getty Images, Multi-ethnic children at autumn festival © kali9 / Getty Images, WMM - Teenagers hanging out, eating popcorn in urban park © Hero Images / Getty Images Set in 9/10pt AdobeGarmondPro by SPi Global, Pondicherry, India 10 9 8 7 6 5 4 3 2 1

To my love and joy in life, Ellen Lefkowitz, my son Kyle, and grandson Tucker. To my late mother Dorothy, who instilled values that have helped me throughout life. To family and animals who represent the purity of life. Larry P. Tilley To my wife, May, my son, Ben, and my daughter, Jade, who are a constant source of inspiration, love, and joy. To my late father, Frank, who was my perfect role model. To Kaylee (dog) and Centie (cat) who remind me each day to make time for play. Francis W.K. Smith, Jr. To my parents and sister for their stalwart support and to the many animals who have touched my life and made me a better person. Meg M. Sleeper To my family, my mentors, my colleagues; to colleagues and friends who are no longer with us. “Keep cool, but care”—Thomas Pynchon. Benjamin M. Brainard

Contents Topic 5-Fluorouracil (5-FU) Toxicosis 1 Abortion, Spontaneous (Early Pregnancy Loss)—Cats 2 Abortion, Spontaneous (Early Pregnancy Loss)—Dogs 4 Abortion, Termination of Pregnancy 6 Abscessation8 Acetaminophen (APAP) Toxicosis 10 Acidosis, Metabolic 12 Acne—Cats14 Acne—Dogs15 Acral Lick Dermatitis 16 Actinomycosis and Nocardia 17 Acute Abdomen 18 Acute Diarrhea 21 Acute Kidney Injury 23 Acute Respiratory Distress Syndrome 25 Acute Vomiting 27 Adenocarcinoma, Anal Sac 29 Adenocarcinoma, Lung 31 Adenocarcinoma, Nasal 32 Adenocarcinoma, Pancreas 34 Adenocarcinoma, Prostate 35 Adenocarcinoma, Renal 36 Adenocarcinoma, Salivary Gland 37 Adenocarcinoma, Skin (Sweat Gland, Sebaceous) 38 Adenocarcinoma, Stomach, Small and Large Intestine, Rectal 39 Adenocarcinoma, Thyroid—Dogs 40 Aggression—Between Dogs in the Household 42 Aggression to Unfamiliar People and Unfamiliar Dogs—Dogs 44 Aggression Toward Children—Dogs 46 Aggression Toward Familiar People—Dogs 47 Aggression Toward Humans—Cats 49 Aggression, Food and Resource Guarding—Dogs 51 Aggression, Intercat Aggression 53 Aggression, Overview—Cats 56 Aggression, Overview—Dogs 58 Alkaline Hyperphosphatasemia in Dogs 61 331 client education handouts are available at www.fiveminutevet.com/canineandfeline7th for you to download and use in practice

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Alkalosis, Metabolic 63 Alopecia—Cats65 Alopecia—Dogs67 Alopecia, Noninflammatory—Dogs 69 Ameloblastoma71 Amphetamine and ADD/ADHD Medication Toxicosis 72 Amyloidosis74 Anaerobic Infections 76 Anal Sac Disorders 77 Anaphylaxis78 Anemia of Chronic Kidney Disease 80 Anemia, Aplastic 82 Anemia, Heinz Body 83 Anemia, Immune-Mediated 84 Anemia, Iron-Deficiency 86 Anemia, Nonregenerative 87 Anemia, Nuclear Maturation Defects (Anemia, Megaloblastic) 89 Anemia, Regenerative 90 Anisocoria92 Anorexia94 Antebrachial Growth Deformities 96 Anterior Uveitis—Cats 98 Anterior Uveitis—Dogs 100 Antidepressant Toxicosis—SSRIs and SNRIs 102 Antidepressant Toxicosis—Tricyclic 104 Aortic Stenosis 106 Aortic Thromboembolism 108 Apudoma111 Arteriovenous Fistula and Arteriovenous Malformation 112 Arteriovenous Malformation of the Liver 113 Arthritis (Osteoarthritis) 115 Arthritis, Septic 118 Ascites120 Aspergillosis, Disseminated Invasive 122 Aspergillosis, Nasal 124 Aspirin Toxicosis 126 Asthma, Bronchitis—Cats 127 Astrocytoma129 Ataxia130 Atlantoaxial Instability 132 Atopic Dermatitis 134 Atrial Fibrillation and Atrial Flutter 136 Atrial Premature Complexes 139 Atrial Septal Defect 141 Atrial Standstill 142 Atrial Wall Tear 144 331 client education handouts are available at www.fiveminutevet.com/canineandfeline7th for you to download and use in practice

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Atrioventricular Block, Complete (Third Degree) 146 Atrioventricular Block, First Degree 148 Atrioventricular Block, Second Degree—Mobitz Type I 150 Atrioventricular Block, Second Degree—Mobitz Type II 152 Atrioventricular Valve Dysplasia 154 Atrioventricular Valvular Stenosis 156 Azotemia and Uremia 159 Babesiosis161 Baclofen Toxicosis 163 Bartonellosis164 Basal Cell Tumor 165 Battery Toxicosis 166 Baylisascariasis167 Benign Prostatic Hyperplasia 168 Benzodiazepine and Other Sleep Aids Toxicosis 169 Beta Receptor Antagonist (Beta Blockers) Toxicosis 171 Beta-2 Agonist Inhaler Toxicosis 172 Bile Duct Carcinoma 173 Bile Duct Obstruction (Extrahepatic) 174 Bile Peritonitis 177 Bilious Vomiting Syndrome 179 Blastomycosis180 Blepharitis182 Blind Quiet Eye 184 Blood Transfusion Reactions 186 Blue‐Green Algae Toxicosis 187 Botulism188 Brachial Plexus Avulsion 189 Brachycephalic Airway Syndrome 190 Brain Injury 192 Brain Tumors 194 Breeding, Timing 196 Bronchiectasis198 Bronchitis, Chronic 200 Brucellosis202 Calcipotriene/Calcipotriol Toxicosis 204 Calcium Channel Blocker Toxicosis 205 Campylobacteriosis206 Candidiasis207 Canine Coronavirus Infections 208 Canine Degenerative Myelopathy 209 Canine Distemper 211 Canine Infectious Diarrhea 213 Canine Infectious Respiratory Disease 215 Canine Parvovirus 217 Canine Schistosomiasis (Heterobilharziasis) 219 331 client education handouts are available at www.fiveminutevet.com/canineandfeline7th for you to download and use in practice

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Car Ride Anxiety—Dogs and Cats 220 Carbon Monoxide Toxicosis 223 Carcinoid and Carcinoid Syndrome 224 Cardiac Glycoside Plant Toxicosis 225 Cardiomyopathy, Arrhythmogenic Right Ventricular—Cats 226 Cardiomyopathy, Arrhythmogenic Right Ventricular—Dogs 227 Cardiomyopathy, Dilated—Cats 229 Cardiomyopathy, Dilated—Dogs 232 Cardiomyopathy, Hypertrophic—Cats 235 Cardiomyopathy, Hypertrophic—Dogs 238 Cardiomyopathy, Nutritional 239 Cardiomyopathy, Restrictive—Cats 241 Cardiopulmonary Arrest 243 Cataracts245 Cerebellar Degeneration 247 Cerebellar Hypoplasia 248 Cerebrovascular Accidents 249 Ceruminous Gland Adenocarcinoma, Ear 251 Cervical Spondylomyelopathy (Wobbler Syndrome) 252 Chagas Disease (American Trypanosomiasis) 254 Chediak-Higashi Syndrome 255 Chemodectoma256 Cheyletiellosis257 Chlamydiosis—Cats258 Chocolate Toxicosis 260 Cholangitis/Cholangiohepatitis Syndrome 262 Cholecystitis and Choledochitis 265 Cholelithiasis267 Chondrosarcoma, Bone 269 Chondrosarcoma, Nasal and Paranasal Sinus 270 Chondrosarcoma, Oral 271 Chorioretinitis272 Chronic Kidney Disease 274 Chylothorax277 Cirrhosis and Fibrosis of the Liver 279 Claw and Clawfold Disorders 282 Clostridial Enterotoxicosis 284 Coagulation Factor Deficiency 286 Coagulopathy of Liver Disease 288 Cobalamin Deficiency 290 Coccidioidomycosis292 Coccidiosis294 Cognitive Dysfunction Syndrome 295 Cold Agglutinin Disease 297 Colibacillosis298 Colitis and Proctitis 300 331 client education handouts are available at www.fiveminutevet.com/canineandfeline7th for you to download and use in practice

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Colitis, Histiocytic Ulcerative 303 Compulsive Disorders—Cats 304 Compulsive Disorders—Dogs 306 Congenital and Developmental Renal Diseases 308 Congenital Ocular Anomalies 310 Congenital Spinal and Vertebral Malformations 313 Congestive Heart Failure, Left-Sided 315 Congestive Heart Failure, Right-Sided 317 Conjunctivitis—Cats319 Conjunctivitis—Dogs321 Constipation and Obstipation 323 Contact Dermatitis 325 Coonhound Paralysis (Acute Polyradiculoneuritis) 326 Copper Associated Hepatopathy 328 Coprophagia and Pica 332 Corneal and Scleral Lacerations 334 Corneal Opacities—Degenerations and Infiltrates 336 Corneal Opacities—Dystrophies 337 Corneal Sequestrum—Cats 338 Cough339 Craniomandibular Osteopathy 341 Cruciate Ligament Disease, Cranial 342 Cryptococcosis344 Cryptorchidism346 Cryptosporidiosis347 Crystalluria348 Cutaneous Drug Eruptions 350 Cuterebriasis351 Cyanosis352 Cyclic Hematopoiesis 354 Cylindruria355 Cytauxzoonosis356 Deafness357 Deciduous Teeth, Persistent (Retained) 359 Deep Cutaneous Mycoses 360 Demodicosis362 Dental Caries 364 Dentigerous Cyst 366 Dermatomyositis367 Dermatophilosis369 Dermatophytosis370 Dermatoses, Depigmenting Disorders 372 Dermatoses, Erosive or Ulcerative 374 Dermatoses, Exfoliative 376 Dermatoses, Neoplastic 378 Dermatoses, Papulonodular 380 331 client education handouts are available at www.fiveminutevet.com/canineandfeline7th for you to download and use in practice

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Dermatoses, Sterile Nodular/Granulomatous Dermatoses, Sun-Induced Dermatoses, Vesiculopustular Dermatoses, Viral (Non-Papillomatosis) Destructive and Scratching Behavior—Cats Destructive Behavior—Dogs Diabetes Insipidus Diabetes Mellitus With Hyperosmolar Hyperglycemic State Diabetes Mellitus With Ketoacidosis Diabetes Mellitus Without Complication—Cats Diabetes Mellitus Without Complication—Dogs Diaphragmatic Hernia Diarrhea, Antibiotic Responsive Diarrhea, Chronic—Cats Diarrhea, Chronic—Dogs Digoxin Toxicity Diisocyanate Glues Discolored Tooth/Teeth

382 384 385 387 388 389 391 393 395 397 399 401 402 403 405 407 408 409

Discospondylitis411 Disseminated Intravascular Coagulation 413 Drowning (Near Drowning) 415 Ductal Plate Malformation (Congenital Hepatic Fibrosis) 416 Dysautonomia (Key-Gaskell Syndrome) 419 Dyschezia and Hematochezia 420 Dysphagia422 Dyspnea and Respiratory Distress 425 Dystocia428 Dysuria, Pollakiuria, and Stranguria 430 Ear Mites 432 Eclampsia433 Ectopic Ureter 434 Ectropion435 Ehrlichiosis and Anaplasmosis 436 Elbow Dysplasia 438 Electric Cord Injury 440 Enamel Hypoplasia/Hypocalcification 441 Encephalitis442 Encephalitis Secondary to Parasitic Migration 444 Endocarditis, Infective 445 Endomyocardial Diseases—Cats 447 Entropion449 Eosinophilia450 Eosinophilic Granuloma Complex 451 Epididymitis/Orchitis453 Epilepsy, Genetic (Idiopathic)—Dogs 454 Epiphora456 331 client education handouts are available at www.fiveminutevet.com/canineandfeline7th for you to download and use in practice

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Episcleritis458 Epistaxis459 Erythrocytosis462 Esophageal Diverticula 464 Esophageal Foreign Bodies 465 Esophageal Stricture 467 Esophagitis469 Essential Oils Toxicosis 472 Ethanol Toxicosis 473 Ethylene Glycol Toxicosis 474 Excessive Vocalization and Waking at Night—Dogs and Cats 476 Exercise-Induced Weakness/Collapse in Labrador Retrievers 478 Exocrine Pancreatic Insufficiency 480 Eyelash Disorders (Trichiasis/Distichiasis/Ectopic Cilia) 482 Facial Nerve Paresis and Paralysis 483 False Pregnancy 485 Familial Shar-Pei Fever 487 Fanconi Syndrome 489 Fear and Aggression in Veterinary Visits—Cats 490 Fear and Aggression in Veterinary Visits—Dogs 492 Fears, Phobias, and Anxieties—Cats 494 Fears, Phobias, and Anxieties—Dogs 496 Feline Alveolar Osteitis 498 Feline Calicivirus Infection 499 Feline Herpesvirus Infection 501 Feline Hyperesthesia Syndrome 503 Feline Idiopathic Lower Urinary Tract Disease 504 Feline Immunodeficiency Virus (FIV) Infection 506 Feline Infectious Diarrhea 508 Feline Infectious Peritonitis (FIP) 510 Feline Ischemic Encephalopathy 512 Feline Leukemia Virus (FeLV) Infection 514 Feline Panleukopenia 516 Feline Paraneoplastic Alopecia 518 Feline Stomatitis—Feline Chronic Gingivostomatitis (FCGS) 519 Feline Symmetrical Alopecia 521 Feline Tooth Resorption (Odontoclastic Resorption) 522 Feline (Upper) Respiratory Infections 524 Fever526 Fiber-Responsive Large Bowel Diarrhea 528 Fibrocartilaginous Embolic Myelopathy 530 Fibrosarcoma, Bone 532 Fibrosarcoma, Gingiva 533 Fibrosarcoma, Nasal and Paranasal Sinus 534 Fipronil Toxicosis 535 Flatulence536 331 client education handouts are available at www.fiveminutevet.com/canineandfeline7th for you to download and use in practice

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Flea Bite Hypersensitivity and Flea Control 538 Food Reactions, Dermatologic 540 Food Reactions (Gastrointestinal), Adverse 542 Gallbladder Mucocele 544 Gastric Dilation and Volvulus Syndrome 546 Gastric Motility Disorders 548 Gastritis, Chronic 550 Gastroduodenal Ulceration/Erosion 552 Gastroenteritis, Acute Hemorrhagic Diarrhea Syndrome 554 Gastroenteritis, Eosinophilic 556 Gastroesophageal Reflux 558 Gastrointestinal Obstruction 559 Gestational Diabetes Mellitus 561 Giardiasis562 Gingival Enlargement/Hyperplasia 563 Glaucoma564 Glomerulonephritis566 Glucagonoma568 Glucosuria570 Gluten Enteropathy in Irish Setters 572 Glycogen Storage Disease 573 Glycogen-Type Vacuolar Hepatopathy 574 Grape and Raisin Toxicosis 577 Hair Follicle Tumors 578 Halitosis579 Head Pressing 581 Head Tilt 583 Head Tremors (Bobbing), Idiopathic—Dogs 585 Heartworm Disease—Cats 586 Heartworm Disease—Dogs 587 Heat Stroke and Hyperthermia 589 Helicobacter spp. 591 Hemangiopericytoma593 Hemangiosarcoma, Bone 594 Hemangiosarcoma, Heart 595 Hemangiosarcoma, Skin 596 Hemangiosarcoma, Spleen and Liver 598 Hematemesis600 Hematuria602 Hemoglobinuria and Myoglobinuria 604 Hemothorax606 Hemotropic Mycoplasmosis 607 Hepatic Amyloid 609 Hepatic Encephalopathy 611 Hepatic Failure, Acute 614 Hepatic Lipidosis 617 331 client education handouts are available at www.fiveminutevet.com/canineandfeline7th for you to download and use in practice

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Hepatic Nodular Hyperplasia and Dysplastic Hyperplasia 620 Hepatitis, Chronic 622 Hepatitis, Granulomatous 626 Hepatitis, Infectious (Viral) Canine 628 Hepatitis, Suppurative and Hepatic Abscess 630 Hepatocellular Adenoma 632 Hepatocellular Carcinoma 633 Hepatocutaneous Syndrome 634 Hepatomegaly636 Hepatoportal Microvascular Dysplasia 639 Hepatosupportive Therapies 642 Hepatotoxins643 Hepatozoonosis645 Hiatal Hernia 646 Hip Dysplasia 647 Histiocytic Diseases—Dogs and Cats 650 Histiocytosis, Cutaneous 652 Histoplasmosis653 Hookworms (Ancylostomiasis) 655 Horner’s Syndrome 656 Housesoiling—Cats657 Housesoiling—Dogs661 Hydrocephalus663 Hydronephrosis665 Hyperadrenocorticism (Cushing’s Syndrome)—Cats 667 Hyperadrenocorticism (Cushing’s Syndrome)—Dogs 668 Hypercalcemia672 Hypercapnia674 Hyperchloremia676 Hypercoagulability677 Hypereosinophilic Syndrome (HES) 678 Hyperestrogenism (Estrogen Toxicity) 679 Hyperglycemia681 Hyperkalemia683 Hyperlipidemia685 Hypermagnesemia687 Hypermetria and Dysmetria 689 Hypernatremia691 Hyperosmolarity692 Hyperparathyroidism694 Hyperparathyroidism, Renal Secondary 696 Hyperphosphatemia698 Hypersomatotropism/Acromegaly in Cats 700 Hypertension, Portal 701 Hypertension, Pulmonary 704 Hypertension, Systemic Arterial 706 331 client education handouts are available at www.fiveminutevet.com/canineandfeline7th for you to download and use in practice

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Hyperthyroidism709 Hypertrophic Osteodystrophy 711 Hypertrophic Osteopathy 713 Hypertrophic Pyloric Gastropathy, Chronic 714 Hyperviscosity Syndrome 716 Hyphema717 Hypoadrenocorticism (Addison’s Disease) 719 Hypoalbuminemia722 Hypocalcemia724 Hypochloremia726 Hypoglycemia727 Hypokalemia729 Hypomagnesemia731 Hypomyelination733 Hyponatremia734 Hypoparathyroidism736 Hypophosphatemia739 Hypopituitarism741 Hypopyon and Lipid Flare 742 Hyporexia743 Hyposthenuria744 Hypothermia745 Hypothyroidism747 Hypoxemia750 Icterus752 Idioventricular Rhythm 754 Ileus756 Illicit/Club Drug Toxicosis 758 Imidazoline Toxicosis 759 Immunodeficiency Disorders, Primary 760 Immunoproliferative Enteropathy of Basenjis 762 Incontinence, Fecal 763 Incontinence, Urinary 765 Infertility, Female—Dogs 767 Infertility, Male—Dogs 769 Inflammatory Bowel Disease 771 Influenza773 Insoluble Oxalate Plant Toxicosis 775 Insulinoma776 Interstitial Cell Tumor, Testicle 779 Intervertebral Disc Disease—Cats 780 Intervertebral Disc Disease, Cervical 781 Intervertebral Disc Disease, Thoracolumbar 784 Intussusception788 Iris Atrophy 790 Iron Toxicosis 791 331 client education handouts are available at www.fiveminutevet.com/canineandfeline7th for you to download and use in practice

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Ivermectin and Other Macrocyclic Lactones Toxicosis 792 Joint Luxations 793 Keratitis, Eosinophilic—Cats 795 Keratitis, Nonulcerative 796 Keratitis, Ulcerative 798 Keratoconjunctivitis Sicca 800 Kitten Behavior Problems 801 Kitten Socialization and Kitten Classes 803 Lactic Acidosis (Hyperlactatemia) 805 Lameness808 Laryngeal and Tracheal Perforation 810 Laryngeal Diseases 812 Lead Toxicosis 814 Left Anterior Fascicular Block 816 Left Bundle Branch Block 818 Legg–Calvé–Perthes Disease 820 Leiomyoma, Stomach, Small and Large Intestine 822 Leiomyosarcoma, Stomach, Small and Large Intestine 823 Leishmaniosis824 Leishmaniosis, Cutaneous 825 Lens Luxation 827 Leptospirosis828 Leukemia, Chronic Lymphocytic 830 Leukocytosis831 Leukoencephalomyelopathy in Rottweilers 833 Lily Toxicosis 834 Lipoma, Infiltrative 835 Liver Fluke Infestation 836 Lower Urinary Tract Infection, Bacterial 838 Lower Urinary Tract Infection, Fungal 840 Lumbosacral Stenosis and Cauda Equina Syndrome 841 Lung Lobe Torsion 843 Lupus Erythematosus, Cutaneous (Discoid) 844 Lupus Erythematosus, Systemic (SLE) 845 Lyme Borreliosis 847 Lymphangiectasia849 Lymphadenopathy/Lymphadenitis851 Lymphedema853 Lymphoma—Cats854 Lymphoma—Dogs856 Lymphoma, Cutaneous Epitheliotropic 858 Lysosomal Storage Diseases 859 Malassezia Dermatitis 860 Malignant Fibrous Histiocytoma 861 Malocclusions—Skeletal and Dental 862

331 client education handouts are available at www.fiveminutevet.com/canineandfeline7th for you to download and use in practice

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Mammary Gland Hyperplasia—Cats 864 Mammary Gland Tumors—Cats 865 Mammary Gland Tumors—Dogs 867 Marijuana Toxicosis 869 Marking, Roaming, and Mounting Behavior—Cats 870 Marking, Roaming, and Mounting Behavior—Dogs 872 Mast Cell Tumors 874 Mastitis876 Maternal Behavior Problems 877 Maxillary and Mandibular Fractures 879 Megacolon881 Megaesophagus883 Melanocytic Tumors, Oral 886 Melanocytic Tumors, Skin and Digit 888 Melena889 Meningioma—Cats and Dogs 891 Meningitis/Meningoencephalitis/Meningomyelitis, Bacterial 894 Meningoencephalomyelitis, Eosinophilic 896 Meningoencephalomyelitis of Unknown Etiology (MUE) 897 Mesothelioma899 Metabolic, Nutritional, and Endocrine Bone Disorders 900 Metaldehyde Toxicosis 902 Metformin Toxicosis 903 Methemoglobinemia904 Metritis906 Movement Disorders 907 Mucopolysaccharidoses908 Multidrug-Resistant Infections 909 Multiple Myeloma 911 Murmurs, Heart 912 Muscle Rupture (Muscle Tear) 914 Mushroom Toxicoses 916 Myasthenia Gravis 920 Mycobacterial Infections 922 Mycoplasmosis924 Mycotoxicosis—Aflatoxin926 Mycotoxicosis—Tremorgenic Toxins 927 Myelodysplastic Syndromes 928 Myelomalacia, Spinal Cord (Ascending, Descending, Progressive) 929 Myelopathy—Paresis/Paralysis—Cats930 Myeloproliferative Disorders 932 Myocardial Infarction 933 Myocardial Tumors 934 Myocarditis935

331 client education handouts are available at www.fiveminutevet.com/canineandfeline7th for you to download and use in practice

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Myoclonus937 Myopathy—Hereditary X-linked Muscular Dystrophy 938 Myopathy—Masticatory and Extraocular Myositis 939 Myopathy, Noninflammatory—Endocrine 941 Myopathy, Noninflammatory—Hereditary Labrador Retriever 943 Myopathy, Noninflammatory—Hereditary Myotonia 944 Myopathy, Noninflammatory—Hereditary Scottie Cramp 945 Myopathy, Noninflammatory—Metabolic 946 Myopathy—Polymyositis and Dermatomositis 948 Myxedema and Myxedema Coma 950 Myxomatous Mitral Valve Disease 951 Narcolepsy and Cataplexy 954 Nasal and Nasopharyngeal Polyps 955 Nasal Dermatoses—Canine 956 Nasal Discharge 958 Nasopharyngeal Stenosis 960 Neck and Back Pain 961 Necrotizing Encephalitis 963 Neonatal Mortality and Canine Herpesvirus 964 Neonatal Resuscitation and Early Neonatal Care 966 Neonicotinoid Toxicosis 968 Neosporosis969 Nephrolithiasis970 Nephrotic Syndrome 972 Nephrotoxicity, Drug-Induced 974 Nerve Sheath Tumors 976 Neuroaxonal Dystrophy 977 Neutropenia978 Nocardiosis/Actinomycosis—Cutaneous980 Nonsteroidal Anti-Inflammatory Drug Toxicosis 981 Notoedric Mange 983 Nystagmus984 Obesity986 Odontogenic Tumors 988 Odontoma990 Oliguria and Anuria 991 Ollulanus Infection 993 Ophthalmia Neonatorum 994 Opiates/Opioids Toxicosis 996 Optic Neuritis and Papilledema 998 Oral Cavity Tumors, Undifferentiated Malignant Tumors 1000 Orbital Diseases (Exophthalmos, Enophthalmos, Strabismus) 1001 Organophosphorus and Carbamate Toxicosis 1003 Oronasal Fistula 1005 Osteochondrodysplasia1006

331 client education handouts are available at www.fiveminutevet.com/canineandfeline7th for you to download and use in practice

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Osteochondrosis1007 Osteomyelitis1009 Osteosarcoma1011 Otitis Externa and Media 1013 Otitis Media and Interna 1015 Ovarian Remnant Syndrome 1017 Ovarian Tumors 1019 Ovulatory Failure 1020 Pain (Acute, Chronic, and Postoperative) 1021 Palatal Defects 1025 Pancreatitis—Cats1027 Pancreatitis—Dogs1029 Pancytopenia1031 Panniculitis/Steatitis1033 Panosteitis1034 Panting and Tachypnea 1036 Papillomatosis1039 Paralysis1040 Paraneoplastic Syndromes 1042 Paraphimosis, Phimosis, and Priapism 1045 Paraproteinemia1046 Patellar Luxation 1047 Patent Ductus Arteriosus 1049 Pectus Excavatum 1052 Pelger–Huët Anomaly 1053 Pelvic Bladder 1054 Pemphigus1055 Perianal Fistula 1057 Pericardial Disease 1058 Perineal Hernia 1061 Periodontal Disease 1063 Peripheral Edema 1065 Perirenal Pseudocysts 1067 Peritoneopericardial Diaphragmatic Hernia 1068 Peritonitis1069 Petechiae, Ecchymosis, Bruising 1072 Petroleum Hydrocarbon Toxicosis 1074 Pheochromocytoma1076 Phosphofructokinase Deficiency 1078 Physalopterosis1079 Plague1080 Plasmacytoma, Mucocutaneous 1081 Pleural Effusion 1082 Pneumocystosis1084 Pneumonia, Aspiration 1085 Pneumonia, Bacterial 1086 331 client education handouts are available at www.fiveminutevet.com/canineandfeline7th for you to download and use in practice

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Pneumonia, Eosinophilic 1088 Pneumonia, Fungal 1090 Pneumonia, Interstitial 1092 Pneumothorax1094 Pododermatitis1096 Poisoning (Intoxication) Therapy 1098 Polioencephalomyelitis—Cats1100 Polyarthritis, Erosive, Immune-Mediated 1101 Polyarthritis, Nonerosive, Immune-Mediated, Dogs 1103 Polycystic Kidney Disease 1105 Polycythemia Vera 1106 Polyneuropathies (Peripheral Neuropathies) 1107 Polyphagia1109 Polypoid Cystitis 1111 Polyuria and Polydipsia 1113 Portosystemic Shunting, Acquired 1115 Portosystemic Vascular Anomaly, Congenital 1118 Poxvirus Infection—Cats 1122 Pregnancy Edema in the Bitch 1123 Pregnancy Toxemia 1125 Premature Labor 1126 Prolapsed Gland of the Third Eyelid (Cherry Eye) 1127 Proptosis1128 Prostate Disease in the Breeding Male Dog 1129 Prostatic Cysts 1131 Prostatitis and Prostatic Abscess 1132 Prostatomegaly1134 Protein-Losing Enteropathy 1136 Proteinuria1138 Protothecosis1141 Pruritus1142 Pseudoephedrine/Phenylephrine Toxicosis 1144 Pseudomacrothrombocytopenia (Inherited Macrothrombocytopenia) 1145 Ptyalism1146 Pulmonary Contusions 1148 Pulmonary Edema, Noncardiogenic 1149 Pulmonary Thromboembolism 1151 Pulmonic Stenosis 1153 Puppy Behavior Problems 1155 Puppy Socialization and Puppy Classes 1157 Puppy Strangles (Juvenile Cellulitis) 1159 Pyelonephritis1160 Pyoderma1162 Pyoderma—Methicillin-Resistant1164 Pyometra1165 Pyothorax1168 331 client education handouts are available at www.fiveminutevet.com/canineandfeline7th for you to download and use in practice

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Pyrethrin and Pyrethroid Toxicosis 1170 Pyruvate Kinase Deficiency 1171 Pythiosis1172 Pyuria1174 Q Fever 1176 Quadrigeminal Cyst 1177 Rabies1178 Rectal and Anal Prolapse 1180 Rectal Stricture 1181 Rectoanal Polyps 1182 Red Eye 1183 Regurgitation1185 Renal Tubular Acidosis 1187 Renomegaly1188 Respiratory Parasites 1190 Retained Placenta 1192 Retinal Degeneration 1193 Retinal Detachment 1195 Retinal Hemorrhage 1197 Rhinitis and Sinusitis 1199 Right Bundle Branch Block 1202 Rocky Mountain Spotted Fever 1204 Rodenticide Toxicosis—Anticoagulants 1206 Rodenticide Toxicosis—Bromethalin 1208 Rodenticide Toxicosis—Cholecalciferol 1209 Rodenticide Toxicosis—Phosphides 1211 Roundworms (Ascariasis) 1212 Sago Palm Toxicosis 1213 Salivary Mucocele 1214 Salmon Poisoning Disease 1216 Salmonellosis1217 Salt Toxicosis 1219 Sarcoptic Mange 1221 Schiff–Sherrington Phenomenon 1222 Schwannoma1223 Sebaceous Adenitis, Granulomatous 1224 Seizures (Convulsions, Status Epilepticus)—Cats 1225 Seizures (Convulsions, Status Epilepticus)—Dogs 1227 Seminoma1230 Separation Anxiety Syndrome 1231 Sepsis and Bacteremia 1235 Sertoli Cell Tumor 1237 Sexual Development Disorders 1238 Shaker/Tremor Syndrome, Corticosteroid Responsive 1240 Shock, Cardiogenic 1241 Shock, Hypovolemic 1243 331 client education handouts are available at www.fiveminutevet.com/canineandfeline7th for you to download and use in practice

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Shock, Septic Shoulder Joint, Ligament, and Tendon Conditions Sick Sinus Syndrome Sinus Arrest and Sinoatrial Block Sinus Arrhythmia Sinus Bradycardia Sinus Tachycardia Sjögren-Like Syndrome Skin Fragility Syndrome, Feline Small Intestinal Dysbiosis Smoke Inhalation Snake Venom Toxicosis—Coral Snakes Snake Venom Toxicosis—Pit Vipers Sneezing, Reverse Sneezing, Gagging Soft Tissue Sarcoma Spermatocele/Sperm Granuloma Spermatozoal Abnormalities Spider Venom Toxicosis—Black Widow

1245 1247 1250 1252 1254 1256 1258 1260 1261 1262 1264 1265 1266 1268 1270 1272 1273 1274

Spider Venom Toxicosis—Brown Recluse 1275 Spinal Dysraphism 1276 Splenic Torsion 1278 Splenomegaly1279 Spondylosis Deformans 1281 Sporotrichosis1282 Squamous Cell Carcinoma, Digit 1283 Squamous Cell Carcinoma, Ear 1284 Squamous Cell Carcinoma, Gingiva 1285 Squamous Cell Carcinoma, Lung 1286 Squamous Cell Carcinoma, Nasal and Paranasal Sinuses 1287 Squamous Cell Carcinoma, Nasal Planum 1288 Squamous Cell Carcinoma, Skin 1289 Squamous Cell Carcinoma, Tongue 1290 Squamous Cell Carcinoma, Tonsil 1291 Staphylococcal Infections 1292 Steroid-Responsive Meningitis-Arteritis—Dogs 1294 Stertor and Stridor 1295 Stomatitis and Oral Ulceration 1297 Streptococcal Infections 1299 Stupor and Coma 1300 Subarachnoid Cysts (Arachnoid Diverticulum) 1302 Subinvolution of Placental Sites 1304 Submissive and Excitement Urination—Dogs 1305 Superficial Necrolytic Dermatitis 1306 Supraventricular Tachycardia 1307 Syncope1309 Synovial Cell Sarcoma 1311 331 client education handouts are available at www.fiveminutevet.com/canineandfeline7th for you to download and use in practice

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Syringomyelia and Chiari-Like Malformation 1312 Systolic Anterior Motion 1315 Tapeworms (Cestodiasis) 1317 Temporomandibular Joint Disorders 1318 Testicular Degeneration and Hypoplasia 1319 Tetanus1320 Tetralogy of Fallot 1322 Third Eyelid Protrusion 1323 Thrombocytopathies1325 Thrombocytopenia1327 Thrombocytopenia, Primary Immune-Mediated 1329 Thrombocytosis1331 Thunderstorm and Noise Phobias 1333 Thymoma1335 Tick Bite Paralysis 1336 Ticks and Tick Control 1338 Toad Venom Toxicosis 1340 Tooth—Missing1341 Tooth Formation/Structure, Abnormal 1342 Tooth Root Abscess (Apical Abscess) 1343 Torsion of the Spermatic Cord 1345 Toxoplasmosis1346 Tracheal Collapse 1348 Transitional Cell Carcinoma 1350 Transmissible Venereal Tumor 1352 Traumatic Dentoalveolar Injuries (TDI) 1353 Tremors1355 Trichomoniasis1357 Trigeminal Neuritis, Idiopathic 1358 Tularemia1359 Unruly Behaviors: Jumping, Pulling, Chasing, Stealing—Dogs 1361 Ureterolithiasis1363 Urethral Prolapse 1365 Urinary Retention, Functional 1366 Urinary Tract Obstruction 1368 Urinary Tract Parasites 1370 Urolithiasis, Calcium Oxalate 1372 Urolithiasis, Calcium Phosphate 1375 Urolithiasis, Cystine 1376 Urolithiasis, Pseudo (Dried Blood, Ossified Material)1378 Urolithiasis, Struvite—Cats 1379 Urolithiasis, Struvite—Dogs 1381 Urolithiasis, Urate 1383 Urolithiasis, Xanthine 1385 Uterine Inertia 1386 Uterine Tumors 1387 331 client education handouts are available at www.fiveminutevet.com/canineandfeline7th for you to download and use in practice

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Uveal Melanoma—Cats 1388 Uveal Melanoma—Dogs 1389 Uveodermatologic Syndrome (VKH) 1390 Vaginal Discharge 1391 Vaginal Hyperplasia and Prolapse 1393 Vaginal Malformations and Acquired Lesions 1394 Vaginal Tumors 1396 Vaginitis1397 Vascular Ring Anomalies 1399 Vasculitis, Cutaneous 1400 Vasculitis, Systemic (Including Phlebitis) 1401 Ventricular Arrhythmias and Sudden Death in German Shepherds 1404 Ventricular Fibrillation 1405 Ventricular Pre-Excitation and Wolff–Parkinson–White Syndrome 1407 Ventricular Premature Complexes 1409 Ventricular Septal Defect 1411 Ventricular Standstill (Asystole) 1413 Ventricular Tachycardia 1415 Vertebral Column Trauma Vesicourachal Diverticula Vestibular Disease, Geriatric—Dogs Vestibular Disease, Idiopathic—Cats Vomiting, Chronic Von Willebrand Disease Weight Loss and Cachexia West Nile Virus Infection Whipworms (Trichuriasis) Xylitol Toxicosis Zinc Toxicosis

1419 1421 1422 1424 1426 1429 1431 1434 1435 1436 1437

Appendix I Normal Reference Ranges for Laboratory Tests Table I-A Normal hematologic values Table I-B Normal biochemical values Table I-C Conversion table for hematologic units Table I-D Conversion table for clinical biochemical units Appendix II Endocrine Testing ­Table II-A Endocrine function testing protocols Table II-B Tests of the endocrine system Table II-C Conversion table for hormone assay units Appendix III Approximate Normal Ranges for Common Measurements in Dogs and Cats Appendix IV Normal Values for the Canine and Feline Electrocardiogram Appendix V Antidotes and Useful Drugs: Methods of Treatment Appendix VI Toxic Home and Garden Hazards for Pets Table VI-A Toxic plants and their clinical signs—antidotes and treatment Table VI-B Herbal toxicities

1441 1441 1441 1442 1443 1444 1444 1445 1446 1447 1448 1449 1452 1452 1457

331 client education handouts are available at www.fiveminutevet.com/canineandfeline7th for you to download and use in practice

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Table VI-C Household cleaners, disinfectants, and solvents—products, clinical signs, and treatment Appendix VII Pain Management Table VII-A Recommended parenteral opioid dosages and indications Table VII-B Recommended dispensable opioid dosages and indications Table VII-C Recommended parenteral local anesthetic dosages and indications Table VII-D Recommended parenteral NSAID dosages and indications Table VII-E Recommended dispensable NSAID dosages and indications Table VII-F Dosages and indications for selected drugs used to treat neuropathic pain Appendix VIII Medications and Supplements for Osteoarthritis Table VIII-A Anti-inflammatories and pain medications Table VIII-B Recommended parenteral NSAID dosages and indications Table VIII-C Recommended oral NSAID dosages and indications Table VIII-D Disease-Modifying Drugs (DMOADs) Appendix IX Glossary of Terminology for Seizures and Epileptic Disorders Appendix X Common Procedures and Testing Protocols  Abdominocentesis and Fluid Analysis

1460 1465 1465 1465 1466 1466 1467 1468 1469 1469 1470 1471 1472 1473 1475 1476

Arthrocentesis With Synovial Fluid Analysis 1479 Bacterial Culture and Sensitivity 1483 Blood Gas Interpretation 1485 Blood Pressure Determination: Noninvasive and Invasive 1488 Blood Sample Collection 1490 Blood Smear Microscopic Examination 1492 Blood Smear Preparation 1496 Blood Typing 1498 Bone Marrow Aspirate and Biopsy 1501 Bone Marrow Aspirate Cytology: Microscopic Evaluation 1503 Complete Ophthalmologic Exam 1507 Crossmatch1512 Cystocentesis1514 Electrocardiography1517 Fecal Direct Smear and Cytology 1520 Fecal Flotation 1522 Fine-Needle Aspiration 1525 Fluid Analysis 1527 Glucose Curve 1530 Impression Smear 1533 Pericardiocentesis1534 Point of Care Abdominal Ultrasonography 1538 Point of Care Pleural Space and Lung Ultrasonography 1541 Rectal Scraping and Cytology 1547 Saline Agglutination Test 1548 Thoracocentesis and Fluid Analysis 1550 Tracheal Wash 1553 Ultrasound‐Guided Mass or Organ Aspiration 1555 331 client education handouts are available at www.fiveminutevet.com/canineandfeline7th for you to download and use in practice

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Urethral Catheterization Urinalysis Overview Urine Sediment Appendix XI Conversion Tables Table XI-A Conversion table of weight to body surface area (in square meters) for dogs Table XI-B Approximate equivalents for degrees Fahrenheit and Celsius Table XI-C Weight-unit conversion factors Appendix XII Important Resources for Veterinarians

1559 1563 1565 1569 1569 1569 1570 1571

Index1573

331 client education handouts are available at www.fiveminutevet.com/canineandfeline7th for you to download and use in practice

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Contents

by Subject

Topic

Appendices Appendix I Normal Reference Ranges for Laboratory Tests 1441 Table I-A Normal hematologic values 1441 Table I-B Normal biochemical values 1441 Table I-C Conversion table for hematologic units 1442 Table I-D Conversion table for clinical biochemical units 1443 Appendix II Endocrine Testing 1444 ­Table II-A Endocrine function testing protocols 1444 Table II-B Tests of the endocrine system 1445 Table II-C Conversion table for hormone assay units 1446 Appendix III Approximate Normal Ranges for Common Measurements in Dogs and Cats 1447 Appendix IV Normal Values for the Canine and Feline Electrocardiogram 1448 Appendix V Antidotes and Useful Drugs: Methods of Treatment 1449 Appendix VI Toxic Home and Garden Hazards for Pets 1452 Table VI-A Toxic plants and their clinical signs—antidotes and treatment 1452 Table VI-B Herbal toxicities 1457 Table VI-C Household cleaners, disinfectants, and solvents—products, clinical signs, and treatment 1460 Appendix VII Pain Management 1465 Table VII-A Recommended parenteral opioid dosages and indications 1465 Table VII-B Recommended dispensable opioid dosages and indications 1465 Table VII-C Recommended parenteral local anesthetic dosages and indications1466 Table VII-D Recommended parenteral NSAID dosages and indications 1466 Table VII-E Recommended dispensable NSAID dosages and indications 1467 Table VII-F Dosages and indications for selected drugs used to treat neuropathic pain 1468 Appendix VIII Medications and Supplements for Osteoarthritis 1469 Table VIII-A Anti-inflammatories and pain medications 1469 Table VIII-B Recommended parenteral NSAID dosages and indications 1470 Table VIII-C Recommended oral NSAID dosages and indications 1471 Table VIII-D Disease-Modifying Drugs (DMOADs) 1472 Appendix IX Glossary of Terminology for Seizures and Epileptic Disorders 1473

331 client education handouts are available at www.fiveminutevet.com/canineandfeline7th for you to download and use in practice

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Appendix X Common Procedures and Testing Protocols  1475 Abdominocentesis and Fluid Analysis 1476 Arthrocentesis With Synovial Fluid Analysis 1479 Bacterial Culture and Sensitivity 1483 Blood Gas Interpretation 1485 Blood Pressure Determination: Noninvasive and Invasive 1488 Blood Sample Collection 1490 Blood Smear Microscopic Examination 1492 Blood Smear Preparation 1496 Blood Typing 1498 Bone Marrow Aspirate and Biopsy 1501 Bone Marrow Aspirate Cytology: Microscopic Evaluation 1503 Complete Ophthalmologic Exam 1507 Crossmatch1512 Cystocentesis1514 Electrocardiography1517 Fecal Direct Smear and Cytology 1520 Fecal Flotation 1522 Fine-Needle Aspiration 1525 Fluid Analysis 1527 Glucose Curve 1530 Impression Smear 1533 Pericardiocentesis1534 Point of Care Abdominal Ultrasonography 1538 Point of Care Pleural Space and Lung Ultrasonography 1541 Rectal Scraping and Cytology 1547 Saline Agglutination Test 1548 Thoracocentesis and Fluid Analysis 1550 Tracheal Wash 1553 Ultrasound‐Guided Mass or Organ Aspiration 1555 Urethral Catheterization 1559 Urinalysis Overview 1563 Urine Sediment 1565 Appendix XI Conversion Tables 1569 Table XI-A Conversion table of weight to body surface area (in square meters) for dogs 1569 Table XI-B Approximate equivalents for degrees Fahrenheit and Celsius 1569 Table XI-C Weight-unit conversion factors 1570 Appendix XII Important Resources for Veterinarians 1571

Behavior Aggression—Between Dogs in the Household Aggression to Unfamiliar People and Unfamiliar Dogs—Dogs Aggression Toward Children—Dogs Aggression Toward Familiar People—Dogs 331 client education handouts are available at www.fiveminutevet.com/canineandfeline7th for you to download and use in practice

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42 44 46 47

Aggression Toward Humans—Cats 49 Aggression, Food and Resource Guarding—Dogs 51 Aggression, Intercat Aggression 53 Aggression, Overview—Cats 56 Aggression, Overview—Dogs 58 Car Ride Anxiety—Dogs and Cats 220 Cognitive Dysfunction Syndrome 295 Compulsive Disorders—Cats 304 Compulsive Disorders—Dogs 306 Coprophagia and Pica 332 Destructive and Scratching Behavior—Cats 388 Destructive Behavior—Dogs 389 Excessive Vocalization and Waking at Night—Dogs and Cats 476 Fear and Aggression in Veterinary Visits—Cats 490 Fear and Aggression in Veterinary Visits—Dogs 492 Fears, Phobias and Anxieties—Cats 494 Fears, Phobias and Anxieties—Dogs 496 Housesoiling—Cats657 Housesoiling—Dogs661 Kitten Behavior Problems 801 Kitten Socialization and Kitten Classes 803 Marking, Roaming, and Mounting Behavior—Cats 870 Marking, Roaming, and Mounting Behavior—Dogs 872 Maternal Behavior Problems 877 Polyphagia1109 Puppy Behavior Problems 1155 Puppy Socialization and Puppy Classes 1157 Separation Anxiety Syndrome 1231 Submissive and Excitement Urination—Dogs 1305 Thunderstorm and Noise Phobias 1333 Unruly Behaviors: Jumping, Pulling, Chasing, Stealing—Dogs  1361

Cardiology Aortic Stenosis 106 Aortic Thromboembolism 108 Arteriovenous Fistula and Arteriovenous Malformation 112 Ascites120 Atrial Fibrillation and Atrial Flutter 136 Atrial Premature Complexes 139 Atrial Septal Defect 141 Atrial Standstill 142 Atrial Wall Tear 144 Atrioventricular Block, Complete (Third Degree) 146 Atrioventricular Block, First Degree 148 Atrioventricular Block, Second Degree—Mobitz Type I 150 331 client education handouts are available at www.fiveminutevet.com/canineandfeline7th for you to download and use in practice

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Atrioventricular Block, Second Degree—Mobitz Type II Atrioventricular Valve Dysplasia Atrioventricular Valvular Stenosis Cardiomyopathy, Arrhythmogenic Right Ventricular—Cats Cardiomyopathy, Arrhythmogenic Right Ventricular—Dogs Cardiomyopathy, Dilated—Cats Cardiomyopathy, Dilated—Dogs Cardiomyopathy, Hypertrophic—Cats Cardiomyopathy, Hypertrophic—Dogs Cardiomyopathy, Nutritional Cardiomyopathy, Restrictive—Cats Cardiopulmonary Arrest Congestive Heart Failure, Left-Sided Congestive Heart Failure, Right-Sided Digoxin Toxicity Electric Cord Injury Endocarditis, Infective Endomyocardial Diseases—Cats

152 154 156 226 227 229 232 235 238 239 241 243 315 317 407 440 445 447

Fever526 Heartworm Disease—Cats 586 Heartworm Disease—Dogs 587 Heat Stroke and Hyperthermia 589 Hypertension, Pulmonary 704 Hypertension, Systemic Arterial 706 Hypothermia745 Idioventricular Rhythm 754 Left Anterior Fascicular Block 816 Left Bundle Branch Block 818 Lymphedema853 Murmurs, Heart 912 Myocardial Infarction 933 Myocarditis935 Myxomatous Mitral Valve Disease  951 Patent Ductus Arteriosus 1049 Pericardial Disease 1058 Peripheral Edema 1065 Peritoneopericardial Diaphragmatic Hernia 1068 Pleural Effusion 1082 Pulmonary Thromboembolism 1151 Pulmonic Stenosis 1153 Right Bundle Branch Block 1202 Shock, Cardiogenic 1241 Shock, Hypovolemic 1243 Shock, Septic 1245 Sick Sinus Syndrome 1250

331 client education handouts are available at www.fiveminutevet.com/canineandfeline7th for you to download and use in practice

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Sinus Arrest and Sinoatrial Block 1252 Sinus Arrhythmia 1254 Sinus Bradycardia 1256 Sinus Tachycardia 1258 Supraventricular Tachycardia 1307 Syncope1309 Systolic Anterior Motion 1315 Tetralogy of Fallot 1322 Vascular Ring Anomalies 1399 Vasculitis, Systemic (Including Phlebitis) 1401 Ventricular Arrhythmias and Sudden Death in German Shepherds 1404 Ventricular Fibrillation 1405 Ventricular Pre-Excitation and Wolff–Parkinson–White Syndrome 1407 Ventricular Premature Complexes 1409 Ventricular Septal Defect 1411 Ventricular Standstill (Asystole) 1413 Ventricular Tachycardia 1415

Dentistry Deciduous Teeth, Persistent (Retained) 359 Dental Caries 364 Dentigerous Cyst 366 Discolored Tooth/Teeth 409 Enamel Hypoplasia/Hypocalcification 441 Feline Alveolar Osteitis 498 Feline Stomatitis—Feline Chronic Gingivostomatitis (FCGS) 519 Feline Tooth Resorption (Odontoclastic Resorption) 522 Gingival Enlargement/Hyperplasia 563 Halitosis579 Malocclusions—Skeletal and Dental 862 Maxillary and Mandibular Fractures 879 Odontogenic Tumors 988 Odontoma990 Oronasal Fistula 1005 Palatal Defects 1025 Periodontal Disease 1063 Stomatitis and Oral Ulceration 1297 Temporomandibular Joint Disorder 1318 Tooth—Missing1341 Tooth Formation/Structure, Abnormal 1342 Tooth Root Abscess (Apical Abscess) 1343 Traumatic Dentoalveolar Injuries (TDI) 1353

331 client education handouts are available at www.fiveminutevet.com/canineandfeline7th for you to download and use in practice

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Dermatology Acne—Cats14 Acne—Dogs15 Acral Lick Dermatitis 16 Alopecia—Cats65 Alopecia—Dogs67 Alopecia, Noninflammatory—Dogs 69 Anal Sac Disorders 77 Atopic Dermatitis 134 Cheyletiellosis257 Claw and Clawfold Disorders 282 Contact Dermatitis 325 Cutaneous Drug Eruptions 350 Deep Cutaneous Mycoses 360 Demodicosis362 Dermatomyositis367 Dermatophilosis369 Dermatophytosis370 Dermatoses, Depigmenting Disorders 372 Dermatoses, Erosive or Ulcerative 374 Dermatoses, Exfoliative 376 Dermatoses, Neoplastic 378 Dermatoses, Papulonodular 380 Dermatoses, Sterile Nodular/Granulomatous 382 Dermatoses, Sun-Induced 384 Dermatoses, Vesiculopustular 385 Dermatoses, Viral (Non-Papillomatosis) 387 Ear Mites 432 Eosinophilic Granuloma Complex 451 Feline Paraneoplastic Alopecia 518 Feline Symmetrical Alopecia 521 Flea Bite Hypersensitivity and Flea Control 538 Food Reactions, Dermatologic 540 Histiocytosis, Cutaneous 652 Leishmaniosis, Cutaneous 825 Lupus Erythematosus, Cutaneous (Discoid) 844 Lymphoma, Cutaneous Epitheliotropic  858 Malassezia Dermatitis 860 Mycobacterial Infections 922 Nasal Dermatoses—Canine 956 Nocardiosis/Actinomycosis—Cutaneous980 Notoedric Mange 983 Otitis Externa and Media 1013 Panniculitis/Steatitis1033 Papillomatosis1039 Pemphigus1055 331 client education handouts are available at www.fiveminutevet.com/canineandfeline7th for you to download and use in practice

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Pododermatitis1096 Protothecosis1141 Pruritus1142 Puppy Strangles (Juvenile Cellulitis) 1159 Pyoderma1162 Pyoderma—Methicillin-Resistant1164 Sarcoptic Mange 1221 Sebaceous Adenitis, Granulomatous 1224 Skin Fragility Syndrome, Feline 1261 Sporotrichosis1282 Superficial Necrolytic Dermatitis 1306 Ticks and Tick Control 1338 Uveodermatologic Syndrome (VKH) 1390 Vasculitis, Cutaneous 1400

Endocrinology and Metabolism Apudoma111 Carcinoid and Carcinoid Syndrome 224 Diabetes Insipidus 391 Diabetes Mellitus With Hyperosmolar Hyperglycemic State 393 Diabetes Mellitus With Ketoacidosis 395 Diabetes Mellitus Without Complication—Cats 397 Diabetes Mellitus Without Complication—Dogs 399 Glucagonoma568 Hyperadrenocorticism (Cushing’s Syndrome)—Cats 667 Hyperadrenocorticism (Cushing’s Syndrome)—Dogs 668 Hypercalcemia672 Hyperchloremia676 Hyperestrogenism (Estrogen Toxicity) 679 Hyperglycemia681 Hyperkalemia683 Hyperlipidemia685 Hypermagnesemia687 Hypernatremia691 Hyperosmolarity692 Hyperparathyroidism694 Hyperphosphatemia698 Hypersomatotropism/Acromegaly in Cats 700 Hyperthyroidism709 Hypoadrenocorticism (Addison’s Disease) 719 Hypocalcemia724 Hypochloremia726 Hypoglycemia727 Hypokalemia729 331 client education handouts are available at www.fiveminutevet.com/canineandfeline7th for you to download and use in practice

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Hypomagnesemia731 Hyponatremia734 Hypoparathyroidism736 Hypophosphatemia739 Hypopituitarism741 Hyporexia743 Hyposthenuria744 Hypothyroidism747 Insulinoma776 Lactic Acidosis (Hyperlactatemia) 805 Myxedema and Myxedema Coma 950 Pheochromocytoma1076

Gastroenterology Acute Abdomen Acute Diarrhea Acute Vomiting

18 21 27

Anorexia94 Bilious Vomiting Syndrome 179 Cobalamin Deficiency 290 Colitis and Proctitis 300 Colitis, Histiocytic Ulcerative 303 Constipation and Obstipation 323 Diarrhea, Antibiotic Responsive 402 Diarrhea, Chronic—Cats 403 Diarrhea, Chronic—Dogs 405 Dyschezia and Hematochezia 420 Dysphagia422 Esophageal Diverticula 464 Esophageal Foreign Bodies 465 Esophageal Stricture 467 Esophagitis469 Exocrine Pancreatic Insufficiency 480 Fiber-Responsive Large Bowel Diarrhea 528 Flatulence536 Food Reactions (Gastrointestinal), Adverse 542 Gastric Dilation and Volvulus Syndrome 546 Gastric Motility Disorders 548 Gastritis, Chronic 550 Gastroduodenal Ulceration/Erosion  552 Gastroenteritis, Acute Hemorrhagic Diarrhea Syndrome 554 Gastroenteritis, Eosinophilic 556 Gastroesophageal Reflux 558 Gastrointestinal Obstruction 559 Gluten Enteropathy in Irish Setters 572 331 client education handouts are available at www.fiveminutevet.com/canineandfeline7th for you to download and use in practice

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Hematemesis600 Hiatal Hernia 646 Hypertrophic Pyloric Gastropathy, Chronic 714 Ileus756 Immunoproliferative Enteropathy of Basenjis 762 Incontinence, Fecal 763 Inflammatory Bowel Disease 771 Intussusception788 Lymphangiectasia849 Megacolon881 Megaesophagus883 Melena889 Obesity986 Pancreatitis—Cats1027 Pancreatitis—Dogs1029 Perianal Fistula 1057 Perineal Hernia 1061 Protein-Losing Enteropathy 1136 Ptyalism1146 Rectal and Anal Prolapse 1180 Rectal Stricture 1181 Rectoanal Polyps 1182 Regurgitation1185 Salivary Mucocele 1214 Small Intestinal Dysbiosis  1262 Vomiting, Chronic 1426 Weight Loss and Cachexia 1431

Hematology/ Immunology Anaphylaxis78 Anemia, Aplastic 82 Anemia, Heinz Body 83 Anemia, Immune-Mediated 84 Anemia, Iron-Deficiency 86 Anemia, Nonregenerative 87 Anemia, Nuclear Maturation Defects (Anemia, Megaloblastic) 89 Anemia, Regenerative 90 Blood Transfusion Reactions 186 Chediak-Higashi Syndrome 255 Coagulation Factor Deficiency 286 Cold Agglutinin Disease 297 Cyclic Hematopoiesis  354 Disseminated Intravascular Coagulation 413 Eosinophilia450 331 client education handouts are available at www.fiveminutevet.com/canineandfeline7th for you to download and use in practice

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Erythrocytosis462 Familial Shar-Pei Fever 487 Hemotropic Mycoplasmosis 607 Hypercoagulability677 Hypereosinophilic Syndrome (HES) 678 Hyperviscosity Syndrome 716 Immunodeficiency Disorders, Primary 760 Leukocytosis831 Lupus Erythematosus, Systemic (SLE) 845 Lymphadenopathy/Lymphadenitis851 Methemoglobinemia904 Mucopolysaccharidoses908 Neutropenia978 Pancytopenia1031 Paraproteinemia1046 Pelger–Huët Anomaly 1053 Petechiae, Ecchymosis, Bruising 1072 Phosphofructokinase Deficiency 1078 Pseudomacrothrombocytopenia (Inherited Macrothrombocytopenia) 1145 Pyruvate Kinase Deficiency 1171 Sjögren-Like Syndrome 1260 Splenic Torsion 1278 Thrombocytopathies1325 Thrombocytopenia1327 Thrombocytopenia, Primary Immune-Mediated 1329 Thrombocytosis1331 Von Willebrand Disease 1429

Hepatology Alkaline Hyperphosphatasemia in Dogs 61 Arteriovenous Malformation of the Liver 113 Bile Duct Obstruction (Extrahepatic) 174 Bile Peritonitis 177 Cholangitis/Cholangiohepatitis Syndrome 262 Cholecystitis and Choledochitis 265 Cholelithiasis267 Cirrhosis and Fibrosis of the Liver 279 Coagulopathy of Liver Disease 288 Copper Associated Hepatopathy 328 Ductal Plate Malformation (Congenital Hepatic Fibrosis) 416 Gallbladder Mucocele 544 Glycogen Storage Disease 573 Glycogen-Type Vacuolar Hepatopathy 574 Hepatic Amyloid 609 Hepatic Encephalopathy 611 331 client education handouts are available at www.fiveminutevet.com/canineandfeline7th for you to download and use in practice

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Hepatic Failure, Acute 614 Hepatic Lipidosis 617 Hepatic Nodular Hyperplasia and Dysplastic Hyperplasia 620 Hepatitis, Chronic 622 Hepatitis, Granulomatous 626 Hepatitis, Infectious (Viral) Canine 628 Hepatitis, Suppurative and Hepatic Abscess 630 Hepatocutaneous Syndrome 634 Hepatomegaly636 Hepatoportal Microvascular Dysplasia 639 Hepatosupportive Therapies 642 Hepatotoxins643 Hypertension, Portal 701 Hypoalbuminemia722 Icterus752 Liver Fluke Infestation 836 Portosystemic Shunting, Acquired 1115 Portosystemic Vascular Anomaly, Congenital 1118 Splenomegaly1279

Infectious Diseases Abscessation8 Actinomycosis and Nocardia 17 Anaerobic Infections 76 Aspergillosis, Disseminated Invasive 122 Babesiosis161 Bartonellosis164 Baylisascariasis167 Blastomycosis180 Brucellosis202 Campylobacteriosis206 Candidiasis207 Canine Coronavirus Infections 208 Canine Distemper 211 Canine Infectious Diarrhea 213 Canine Parvovirus 217 Canine Schistosomiasis (Heterobilharziasis) 219 Chagas Disease (American Trypanosomiasis) 254 Chlamydiosis—Cats258 Clostridial Enterotoxicosis 284 Coccidioidomycosis  292 Coccidiosis294 Colibacillosis298 Cryptococcosis344 331 client education handouts are available at www.fiveminutevet.com/canineandfeline7th for you to download and use in practice

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Cryptosporidiosis347 Cuterebriasis351 Cytauxzoonosis356 Ehrlichiosis and Anaplasmosis 436 Feline Calicivirus Infection 499 Feline Herpesvirus Infection 501 Feline Immunodeficiency Virus (FIV) Infection 506 Feline Infectious Diarrhea 508 Feline Infectious Peritonitis (FIP) 510 Feline Leukemia Virus (FeLV) Infection 514 Feline Panleukopenia 516 Feline (Upper) Respiratory Infections 524 Giardiasis562 Helicobacter spp. 591 Hepatozoonosis645 Histoplasmosis653 Hookworms (Ancylostomiasis) 655 Influenza773 Leishmaniosis824 Leptospirosis828 Lyme Borreliosis 847 Multidrug-Resistant Infections 909 Mycoplasmosis924 Neonatal Mortality and Canine Herpesvirus 964 Neosporosis969 Ollulanus Infection 993 Peritonitis1069 Physalopterosis1079 Plague1080 Pneumocystosis1084 Poxvirus Infection—Cats 1122 Pythiosis1172 Q Fever 1176 Rabies1178 Rocky Mountain Spotted Fever 1204 Roundworms (Ascariasis) 1212 Salmon Poisoning Disease 1216 Salmonellosis1217 Sepsis and Bacteremia 1235 Staphylococcal Infections 1292 Streptococcal Infections 1299 Tapeworms (Cestodiasis) 1317 Tetanus1320 Toxoplasmosis1346 Trichomoniasis1357 Tularemia1359 331 client education handouts are available at www.fiveminutevet.com/canineandfeline7th for you to download and use in practice

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West Nile Virus Infection Whipworms (Trichuriasis)

1434 1435

Musculoskeletal Antebrachial Growth Deformities 96 Arthritis (Osteoarthritis) 115 Arthritis, Septic 118 Atlantoaxial Instability 132 Craniomandibular Osteopathy 341 Cruciate Ligament Disease, Cranial 342 Discospondylitis411 Elbow Dysplasia 438 Hip Dysplasia 647 Hypertrophic Osteodystrophy 711 Hypertrophic Osteopathy 713 Intervertebral Disc Disease, Cervical 781 Intervertebral Disc Disease, Thoracolumbar 784 Joint Luxations 793 Lameness808 Legg–Calvé–Perthes Disease 820 Metabolic, Nutritional, and Endocrine Bone Disorders 900 Muscle Rupture (Muscle Tear) 914 Myasthenia Gravis 920 Myopathy—Hereditary X-linked Muscular Dystrophy 938 Myopathy—Masticatory and Extraocular Myositis 939 Myopathy, Noninflammatory—Endocrine 941 Myopathy, Noninflammatory—Hereditary Labrador Retriever 943 Myopathy, Noninflammatory—Hereditary Myotonia 944 Myopathy, Noninflammatory—Hereditary Scottie Cramp 945 Myopathy, Noninflammatory—Metabolic 946 Myopathy—Polymyositis and Dermatomositis 948 Osteochondrodysplasia1006 Osteochondrosis1007 Osteomyelitis1009 Panosteitis1034 Patellar Luxation 1047 Polyarthritis, Erosive, Immune-Mediated 1101 Polyarthritis, Nonerosive, Immune-Mediated, Dogs 1103 Shoulder Joint, Ligament, and Tendon Conditions 1247

Nephrology/ Urology Acidosis, Metabolic Acute Kidney Injury 

12 23

331 client education handouts are available at www.fiveminutevet.com/canineandfeline7th for you to download and use in practice

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Alkalosis, Metabolic 63 Amyloidosis74 Anemia of Chronic Kidney Disease 80 Azotemia and Uremia 159 Benign Prostatic Hyperplasia  168 Chronic Kidney Disease 274 Congenital and Developmental Renal Diseases 308 Crystalluria348 Cylindruria355 Dysuria, Pollakiuria, and Stranguria 430 Ectopic Ureter 434 Fanconi Syndrome 489 Feline Idiopathic Lower Urinary Tract Disease 504 Glomerulonephritis566 Glucosuria570 Hematuria602 Hemoglobinuria and Myoglobinuria 604 Hydronephrosis665 Hyperparathyroidism, Renal Secondary 696 Incontinence, Urinary 765 Lower Urinary Tract Infection, Bacterial 838 Lower Urinary Tract Infection, Fungal 840 Nephrolithiasis970 Nephrotic Syndrome 972 Nephrotoxicity, Drug-Induced 974 Oliguria and Anuria 991 Pelvic Bladder 1054 Perirenal Pseudocysts 1067 Polycystic Kidney Disease 1105 Polypoid Cystitis 1111 Polyuria and Polydipsia 1113 Prostatic Cysts 1131 Prostatitis and Prostatic Abscess 1132 Prostatomegaly1134 Proteinuria1138 Pyelonephritis1160 Pyuria1174 Renal Tubular Acidosis 1187 Renomegaly1188 Ureterolithiasis1363 Urethral Prolapse 1365 Urinary Retention, Functional 1366 Urinary Tract Obstruction 1368 Urinary Tract Parasites 1370 Urolithiasis, Calcium Oxalate 1372 Urolithiasis, Calcium Phosphate 1375 331 client education handouts are available at www.fiveminutevet.com/canineandfeline7th for you to download and use in practice

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Urolithiasis, Cystine Urolithiasis, Pseudo (Dried Blood, Ossified Material) Urolithiasis, Struvite—Cats Urolithiasis, Struvite—Dogs Urolithiasis, Urate Urolithiasis, Xanthine Vesicourachal Diverticula

1376 1378 1379 1381 1383 1385 1421

Neurology Ataxia130 Botulism188 Brachial Plexus Avulsion 189 Brain Injury 192 Brain Tumors 194 Canine Degenerative Myelopathy 209 Cerebellar Degeneration 247 Cerebellar Hypoplasia 248 Cerebrovascular Accidents 249 Cervical Spondylomyelopathy (Wobbler Syndrome) 252 Congenital Spinal and Vertebral Malformations 313 Coonhound Paralysis (Acute Polyradiculoneuritis) 326 Deafness357 Dysautonomia (Key-Gaskell Syndrome) 419 Encephalitis442 Encephalitis Secondary to Parasitic Migration 444 Epilepsy, Genetic (Idiopathic)—Dogs 454 Exercise-Induced Weakness/Collapse in Labrador Retrievers 478 Facial Nerve Paresis and Paralysis 483 Feline Hyperesthesia Syndrome 503 Feline Ischemic Encephalopathy 512 Fibrocartilaginous Embolic Myelopathy 530 Head Pressing 581 Head Tilt 583 Head Tremors (Bobbing), Idiopathic—Dogs 585 Hydrocephalus663 Hypermetria and Dysmetria 689 Hypomyelination733 Intervertebral Disc Disease—Cats 780 Leukoencephalomyelopathy in Rottweilers 833 Lumbosacral Stenosis and Cauda Equina Syndrome 841 Lysosomal Storage Diseases 859 Meningioma—Cats and Dogs 891 Meningitis/Meningoencephalitis/Meningomyelitis, Bacterial 894 Meningoencephalomyelitis, Eosinophilic 896 Meningoencephalomyelitis of Unknown Etiology (MUE) 897 331 client education handouts are available at www.fiveminutevet.com/canineandfeline7th for you to download and use in practice

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Movement Disorders 907 Myelomalacia, Spinal Cord (Ascending, Descending, Progressive) 929 Myelopathy—Paresis/Paralysis—Cats930 Myoclonus937 Narcolepsy and Cataplexy 954 Neck and Back Pain 961 Necrotizing Encephalitis 963 Nerve Sheath Tumors 976 Neuroaxonal Dystrophy 977 Nystagmus984 Otitis Media and Interna 1015 Pain (Acute, Chronic, and Postoperative) 1021 Paralysis1040 Polioencephalomyelitis—Cats1100 Polyneuropathies (Peripheral Neuropathies) 1107 Quadrigeminal Cyst 1177 Schiff–Sherrington Phenomenon 1222 Seizures (Convulsions, Status Epilepticus)—Cats 1225 Seizures (Convulsions, Status Epilepticus)—Dogs 1227 Shaker/Tremor Syndrome, Corticosteroid Responsive 1240 Spinal Dysraphism 1276 Spondylosis Deformans 1281 Steroid-Responsive Meningitis-Arteritis—Dogs 1294 Stupor and Coma 1300 Subarachnoid Cysts (Arachnoid Diverticulum) 1302 Syringomyelia and Chiari-Like Malformation 1312 Tick Bite Paralysis 1336 Tremors1355 Trigeminal Neuritis, Idiopathic 1358 Vertebral Column Trauma 1419 Vestibular Disease, Geriatric—Dogs 1422 Vestibular Disease, Idiopathic—Cats 1424

Oncology Adenocarcinoma, Anal Sac 29 Adenocarcinoma, Lung 31 Adenocarcinoma, Nasal 32 Adenocarcinoma, Pancreas 34 Adenocarcinoma, Prostate 35 Adenocarcinoma, Renal 36 Adenocarcinoma, Salivary Gland 37 Adenocarcinoma, Skin (Sweat Gland, Sebaceous) 38 Adenocarcinoma, Stomach, Small and Large Intestine, Rectal 39 Adenocarcinoma, Thyroid—Dogs 40 Ameloblastoma71 331 client education handouts are available at www.fiveminutevet.com/canineandfeline7th for you to download and use in practice

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Astrocytoma129 Basal Cell Tumor 165 Bile Duct Carcinoma 173 Ceruminous Gland Adenocarcinoma, Ear 251 Chemodectoma256 Chondrosarcoma, Bone 269 Chondrosarcoma, Nasal and Paranasal Sinus 270 Chondrosarcoma, Oral 271 Fibrosarcoma, Bone 532 Fibrosarcoma, Gingiva 533 Fibrosarcoma, Nasal and Paranasal Sinus 534 Hair Follicle Tumors 578 Hemangiopericytoma593 Hemangiosarcoma, Bone 594 Hemangiosarcoma, Heart 595 Hemangiosarcoma, Skin 596 Hemangiosarcoma, Spleen and Liver 598 Hepatocellular Adenoma 632 Hepatocellular Carcinoma 633 Histiocytic Diseases—Dogs and Cats 650 Interstitial Cell Tumor, Testicle 779 Leiomyoma, Stomach, Small and Large Intestine 822 Leiomyosarcoma, Stomach, Small and Large Intestine 823 Leukemia, Chronic Lymphocytic 830 Lipoma, Infiltrative 835 Lymphoma—Cats854 Lymphoma—Dogs856 Malignant Fibrous Histiocytoma 861 Mammary Gland Tumors—Cats 865 Mammary Gland Tumors—Dogs 867 Mast Cell Tumors 874 Melanocytic Tumors, Oral 886 Melanocytic Tumors, Skin and Digit 888 Mesothelioma899 Multiple Myeloma 911 Myelodysplastic Syndromes 928 Myeloproliferative Disorders 932 Myocardial Tumors 934 Oral Cavity Tumors, Undifferentiated Malignant Tumors 1000 Osteosarcoma1011 Ovarian Tumors 1019 Paraneoplastic Syndromes 1042 Plasmacytoma, Mucocutaneous 1081 Polycythemia Vera  1106 Schwannoma1223 Seminoma1230 331 client education handouts are available at www.fiveminutevet.com/canineandfeline7th for you to download and use in practice

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Sertoli Cell Tumor 1237 Soft Tissue Sarcoma 1270 Squamous Cell Carcinoma, Digit 1283 Squamous Cell Carcinoma, Ear 1284 Squamous Cell Carcinoma, Gingiva 1285 Squamous Cell Carcinoma, Lung 1286 Squamous Cell Carcinoma, Nasal and Paranasal Sinuses 1287 Squamous Cell Carcinoma, Nasal Planum 1288 Squamous Cell Carcinoma, Skin 1289 Squamous Cell Carcinoma, Tongue 1290 Squamous Cell Carcinoma, Tonsil 1291 Synovial Cell Sarcoma 1311 Thymoma1335 Transitional Cell Carcinoma 1350 Transmissible Venereal Tumor 1352 Uterine Tumors 1387 Vaginal Tumors 1396

Ophthalmology Anisocoria92 Anterior Uveitis—Cats  98 Anterior Uveitis—Dogs  100 Blepharitis  182 Blind Quiet Eye 184 Cataracts  245 Chorioretinitis  272 Congenital Ocular Anomalies  310 Conjunctivitis—Cats  319 Conjunctivitis—Dogs  321 Corneal and Scleral Lacerations  334 Corneal Opacities—Degenerations and Infiltrates  336 Corneal Opacities—Dystrophies  337 Corneal Sequestrum—Cats  338 Ectropion435 Entropion449 Epiphora  456 Episcleritis  458 Eyelash Disorders (Trichiasis/Distichiasis/Ectopic Cilia)  482 Glaucoma564 Horner’s Syndrome  656 Hyphema717 Hypopyon and Lipid Flare 742 Iris Atrophy  790 Keratitis, Eosinophilic—Cats 795 Keratitis, Nonulcerative 796 331 client education handouts are available at www.fiveminutevet.com/canineandfeline7th for you to download and use in practice

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Keratitis, Ulcerative Keratoconjunctivitis Sicca Lens Luxation  Ophthalmia Neonatorum Optic Neuritis and Papilledema Orbital Diseases (Exophthalmos, Enophthalmos, Strabismus)  Prolapsed Gland of the Third Eyelid (Cherry Eye)  Proptosis  Red Eye  Retinal Degeneration  Retinal Detachment  Retinal Hemorrhage  Third Eyelid Protrusion  Uveal Melanoma—Cats  Uveal Melanoma—Dogs

798 800 827 994 998 1001 1127 1128 1183 1193 1195 1197 1323 1388 1389

Respiratory Acute Respiratory Distress Syndrome 25 Aspergillosis, Nasal 124 Asthma, Bronchitis—Cats 127 Brachycephalic Airway Syndrome 190 Bronchiectasis198 Bronchitis, Chronic 200 Canine Infectious Respiratory Disease 215 Chylothorax277 Cough339 Cyanosis352 Diaphragmatic Hernia 401 Drowning (Near Drowning) 415 Dyspnea and Respiratory Distress 425 Epistaxis459 Hemothorax606 Hypercapnia674 Hypoxemia750 Laryngeal and Tracheal Perforation 810 Laryngeal Diseases 812 Lung Lobe Torsion 843 Nasal and Nasopharyngeal Polyps 955 Nasal Discharge  958 Nasopharyngeal Stenosis 960 Panting and Tachypnea 1036 Pectus Excavatum 1052 Pneumonia, Aspiration 1085 Pneumonia, Bacterial 1086 Pneumonia, Eosinophilic 1088 331 client education handouts are available at www.fiveminutevet.com/canineandfeline7th for you to download and use in practice

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Pneumonia, Fungal 1090 Pneumonia, Interstitial  1092 Pneumothorax1094 Pulmonary Contusions 1148 Pulmonary Edema, Noncardiogenic 1149 Pyothorax1168 Respiratory Parasites  1190 Rhinitis and Sinusitis 1199 Smoke Inhalation 1264 Sneezing, Reverse Sneezing, Gagging 1268 Stertor and Stridor 1295 Tracheal Collapse 1348

Theriogenology Abortion, Spontaneous (Early Pregnancy Loss)—Cats Abortion, Spontaneous (Early Pregnancy Loss)—Dogs Abortion, Termination of Pregnancy

2 4 6

Breeding, Timing 196 Cryptorchidism346 Dystocia428 Eclampsia433 Epididymitis/Orchitis453 False Pregnancy 485 Gestational Diabetes Mellitus 561 Infertility, Female—Dogs 767 Infertility, Male—Dogs  769 Mammary Gland Hyperplasia—Cats 864 Mastitis876 Metritis906 Neonatal Resuscitation and Early Neonatal Care 966 Ovarian Remnant Syndrome 1017 Ovulatory Failure 1020 Paraphimosis, Phimosis, and Priapism 1045 Pregnancy Edema in the Bitch 1123 Pregnancy Toxemia 1125 Premature Labor 1126 Prostate Disease in the Breeding Male Dog 1129 Pyometra  1165 Retained Placenta 1192 Sexual Development Disorders 1238 Spermatocele/Sperm Granuloma 1272 Spermatozoal Abnormalities 1273 Subinvolution of Placental Sites 1304 Testicular Degeneration and Hypoplasia 1319 Torsion of the Spermatic Cord  1345 331 client education handouts are available at www.fiveminutevet.com/canineandfeline7th for you to download and use in practice

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Uterine Inertia 1386 Vaginal Discharge 1391 Vaginal Hyperplasia and Prolapse 1393 Vaginal Malformations and Acquired Lesions 1394 Vaginitis1397

Toxicology 5-Fluorouracil (5-FU) Toxicosis  Acetaminophen (APAP) Toxicosis  Amphetamine and ADD/ADHD Medication Toxicosis  Antidepressant Toxicosis—SSRIs and SNRIs Antidepressant Toxicosis—Tricyclic  Aspirin Toxicosis Baclofen Toxicosis  Battery Toxicosis  Benzodiazepine and Other Sleep Aids Toxicosis Beta Receptor Antagonist (Beta Blockers) Toxicosis

1 10 72 102 104 126 163 166 169 171

Beta-2 Agonist Inhaler Toxicosis  Blue-Green Algae Toxicosis  Calcipotriene/Calcipotriol Toxicosis  Calcium Channel Blocker Toxicosis Carbon Monoxide Toxicosis  Cardiac Glycoside Plant Toxicosis  Chocolate Toxicosis Diisocyanate Glues Essential Oils Toxicosis  Ethanol Toxicosis Ethylene Glycol Toxicosis Fipronil Toxicosis Grape and Raisin Toxicosis Illicit/Club Drug Toxicosis  Imidazoline Toxicosis  Insoluble Oxalate Plant Toxicosis  Iron Toxicosis  Ivermectin and Other Macrocyclic Lactones Toxicosis  Lead Toxicosis  Lily Toxicosis Marijuana Toxicosis  Metaldehyde Toxicosis  Metformin Toxicosis  Mushroom Toxicoses Mycotoxicosis—Aflatoxin  Mycotoxicosis—Tremorgenic Toxins Neonicotinoid Toxicosis Nonsteroidal Anti-Inflammatory Drug Toxicosis

172 187 204 205 223 225 260 408 472 473 474 535 577 758 759 775 791 792 814 834 869 902 903 916 926 927 968 981

331 client education handouts are available at www.fiveminutevet.com/canineandfeline7th for you to download and use in practice

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Opiates/Opioids Toxicosis Organophosphorus and Carbamate Toxicosis Petroleum Hydrocarbon Toxicosis  Poisoning (Intoxication) Therapy  Pseudoephedrine/Phenylephrine Toxicosis Pyrethrin and Pyrethroid Toxicosis  Rodenticide Toxicosis—Anticoagulants Rodenticide Toxicosis—Bromethalin Rodenticide Toxicosis—Cholecalciferol Rodenticide Toxicosis—Phosphides Sago Palm Toxicosis Salt Toxicosis Snake Venom Toxicosis—Coral Snakes Snake Venom Toxicosis—Pit Vipers Spider Venom Toxicosis—Black Widow Spider Venom Toxicosis—Brown Recluse  Toad Venom Toxicosis  Xylitol Toxicosis

996 1003 1074 1098 1144 1170 1206 1208 1209 1211 1213 1219 1265 1266 1274 1275 1340 1436

Zinc Toxicosis

1437

Index1573

331 client education handouts are available at www.fiveminutevet.com/canineandfeline7th for you to download and use in practice

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Preface Keeping abreast of advances in veterinary internal medicine is extremely difficult, especially for the busy general practitioner. To keep current with all the veterinary journals while practicing medicine is impossible. The veterinarian in practice can be overwhelmed by all of the findings and conclusions of thousands of studies conducted by veterinary specialists. Blackwell’s Five-Minute Veterinary Consult is designed to provide the busy veterinary practitioner and student of veterinary medicine with concise practical reviews of almost all the diseases and clinical problems in dogs and cats. Our goal in creating this textbook was also to provide up-to-date information in an easy-to-use format. Emphasis is placed on diagnosis and treatment of problems and diseases likely to be seen by veterinarians. Our fondest dream was realized when the first six editions of this book were chosen as a comprehensive reference source for canine and feline medicine by veterinary students, practicing veterinarians, and board-certified specialists. The format has proven easy to use and very popular with busy practitioners. The scope of the book and the number of Consulting Editors and authors have been expanded. We have also increased the number of authors from outside North America, to provide the best advice in the world. The number of topics has been increased, and every topic has been updated to provide you with the most current information possible in a textbook. The appendixes have also been expanded to include more useful tables. Several good veterinary internal medicine textbooks are available. The uniqueness and value of Blackwell’s Five-Minute Veterinary Consult as a quick reference is the consistency of presentation, the breadth of coverage, the contribution of large numbers of experts, and the timely preparation of the manuscript. The format of every topic is identical, making it easy to find information. An extensive list of topic headings ensures complete coverage of each topic. As the title implies, one objective of this book is to make information quickly available. To this end, we have organized topics alphabetically from A to Z. Most topics can be found without using the index. A table of contents broken out by organ system and a detailed index are provided. Large volumes of useful information are summarized in charts in the appendixes. Included in the appendixes are normal laboratory values, endocrine testing protocols, common procedures and testing protocols, toxicology tables, pain management tables, Rx for Osteoarthritis, disease-modifying drugs table, an epilepsy classification table, conversion tables, and other information pages with important resources for veterinarians. For this new edition, an appendix has been added to include common procedures and testing protocols used in veterinary medicine. We are delighted and privileged to have had the assistance of numerous experts in veterinary internal medicine from around the world. More than 450 veterinary specialists contributed to this text, allowing each chapter to be written by an expert on the subject. In addition to providing outstanding information, this large pool of experts allowed us to publish this major text in a timely manner. Many large textbooks take several years to write, making some of the information outdated by the time the book is published. We are indebted to the many contributors and Consulting Editors whose hard work allowed us to write, edit, and publish this work in 3 years, with most chapters completed within a year of publication. Our goal is to revise the text every 3–4 years, so that the contents will always be current. Blackwell’s Five-Minute Veterinary Consult: Canine and Feline, Seventh Edition is available in a variety of digital formats. Visit www.wiley.com/go/5MVC for more information. This edition also includes Client Education Handouts based on the content of Blackwell’s Five-Minute Veterinary Consult. The complimentary Client Education Handouts are available on a companion website at www.fiveminutevet.com/ canineandfeline featuring 331 Client Education Handouts for you to customize and use in practice. These Handouts can be edited to reflect your practice preferences and then printed on your letterhead to distribute to your clients.

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The book will also be published as an e-book, in downloadable ePub/ePDF formats. Now veterinarians can quickly access information about necessary clinical skills and new developments in diagnosis and treatment on their computers or mobile versions. The electronic versions offer fast, affordable access to  much of the accumulated wisdom in veterinary medicine. This technology brings to the clinic examination room and doctor’s office an easy-to-use resource that will markedly improve the quality of continuing education and clinical practice, and a companion website offers client education handouts to be downloaded and used in practice. The seventh edition of this textbook constitutes an important, up-to-date medical reference source for your practice and clinical education. We strived to make it complete yet practical and easy to use. Our dreams are realized if this text helps you to quickly locate and use the “momentarily important” information that is essential to the practice of high-quality veterinary medicine. We would appreciate your input so that we can make future editions even more useful. If you would like to see any changes in content or format, additions, or deletions, please let us know. Send comments to the following: Drs. Tilley, Smith, Sleeper and Brainard c/o John Wiley & Sons 1606 Golden Aspen Dr Ste 104 Ames, IA 50010, USA

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Acknowledgments The completion of this textbook provides a welcome opportunity to recognize in writing the many individuals who have helped along the way. The Editors gratefully acknowledge the Consulting Editors and the contributors who, by their expertise, have so unmistakably enhanced the quality of this textbook. We would also like to acknowledge and thank our families for their support of this project and the sacrifices they made to allow us the time to complete the book. In addition to thanking veterinarians who have referred patients to us, we would like to express our gratitude to all the veterinary students, interns, and residents who we have had the privilege to teach. Their curiosity and intellectual stimulation have enabled us to grow and have prompted us to undertake the task of writing this book. Finally, a special acknowledgment goes to everyone at Wiley Blackwell. The marketing and sales departments also must be acknowledged for generating such an interest in this book. They are all meticulous workers and kind people who have made the final stages of preparing this book both inspiring and fun. We would also like to thank copy-editors Sally Osborn and Harriet Stewart-Jones, and Erica Judisch, Executive Editor. A special thank you goes to Mirjana Misina, Editorial Project Manager, who spent hours and days keeping track of all the contributors and the deadline dates for manuscripts. This edition would not have taken place without her. An important life goal of ours has been fulfilled: to provide expertise in small animal internal medicine worldwide and to teach the principles contained in this textbook to veterinarians and students everywhere. Larry P. Tilley, Francis W.K. Smith, Jr., Meg M. Sleeper and Benjamin M. Brainard

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­Consulting Editors MICHAEL AHERNE, MVB, GradDipVetStud, MS, MANZCVS (Small Animal Surgery) Diplomate ACVIM (Cardiology) Clinical Assistant Professor Department of Small Animal Clinical Sciences College of Veterinary Medicine University of Florida Gainesville, Florida, USA Subject: Cardiology

KATE HOLAN, BS, DVM Diplomate ACVIM (Small Animal Internal Medicine) Assistant Professor and Head Small Animal Internal Medicine Department of Small Animal Clinical Sciences Michigan State University East Lansing, Michigan, USA Subject: Hepatology

MELINDA S. CAMUS, DVM Diplomate ACVP (Clinical Pathology) Associate Professor Department of Pathology College of Veterinary Medicine University of Georgia Athens, Georgia, USA Subject: Hematology/Immunology

LYNN R. HOVDA, RPH, DVM, MS Diplomate ACVIM (Large Animal Internal Medicine) Director of Veterinary Medicine SafetyCall International & Pet Poison Helpline Bloomington, Minnesota; Assistant Adjunct Professor Department of Veterinary Biomedical Sciences College of Veterinary Medicine University of Minnesota St. Paul, Minnesota, USA Subject: Toxicology

TIMOTHY M. FAN, DVM, PhD Diplomate ACVIM (Small Animal Internal Medicine, Oncology) Professor Department of Veterinary Clinical Medicine College of Veterinary Medicine University of Illinois at Urbana-Champaign Urbana, Illinois, USA Subject: Oncology J.D. FOSTER, VMD Diplomate ACVIM (Small Animal Internal Medicine) Nephrology/Urology & Internal Medicine Friendship Hospital for Animals Washington, DC, USA Subject: Nephrology MATHIEU M. GLASSMAN, VMD Diplomate ACVS Chief of Surgery Friendship Surgical Specialists Friendship Hospital for Animals Washington, DC, USA Subject: Musculoskeletal

AMIE KOENIG, DVM Diplomate ACVIM (Small Animal Internal Medicine), Diplomate ACVECC Professor of Emergency and Critical Care Department of Small Animal Medicine and Surgery College of Veterinary Medicine University of Georgia Athens, Georgia, USA Subject: Infectious Diseases GARY M. LANDSBERG, BSc, DVM Diplomate ACVB, ECAWBM Veterinary Behaviourist Vice-President CanCog Incorporated Fergus, Ontario; Head Fear Free Research Canada Subject: Behavior

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PATTY A. LATHAN, VMD, MS Diplomate ACVIM (Small Animal Internal Medicine) Associate Professor Department of Clinical Sciences Mississippi State University Mississippi State, Mississippi, USA Subject: Endocrinology/Metabolism HEIDI B. LOBPRISE, DVM Diplomate AVDC (Dentistry) Main Street Veterinary Dental Clinic Flower Mound, Texas, USA Subject: Dentistry KATHERN E. MYRNA, DVM, MS Diplomate ACVO Associate Professor of Ophthalmology Department of Small Animal Medicine and Surgery College of Veterinary Medicine University of Georgia Athens, Georgia, USA Subject: Ophthalmology MARK P. RONDEAU, DVM Diplomate ACVIM (Small Animal Internal Medicine) Professor of Clinical Medicine Department of Clinical Sciences and Advanced Medicine School of Veterinary Medicine University of Pennsylvania Philadelphia, Pennsylvania, USA Subject: Gastroenterology ELIZABETH ROZANSKI, DVM Diplomate ACVECC Diplomate DACVIM (Small Animal Internal Medicine) Associate Professor Department of Clinical Science Cummings School of Veterinary Medicine Tufts University North Grafton, Massachusetts, USA Subject: Respiratory

ERIN E. RUNCAN, DVM Diplomate ACT Associate Professor—Clinical Theriogenology and Reproductive Medicine Department of Veterinary Clinical Sciences The Ohio State University College of Veterinary Medicine Columbus, Ohio, USA Subject: Theriogenology

ALEXANDER H. WERNER RESNICK, VMD Diplomate ACVD Staff Dermatologist Animal Dermatology Center Studio City & Westlake Village California, USA Subject: Dermatology

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Acknowledgment The Book Editors acknowledge the prior contribution of the following Consulting Editors: Stephen C. Barr (Infectious Diseases) Deborah S. Greco (Endocrinology) Sara K. Lyle (Theriogenology) Stanley L. Marks (Gastroenterology) Paul E. Miller (Ophthalmology) Joane M. Parent (Neurology) Carl A. Osborne (Nephrology/Urology) Alan H. Rebar (Hematology/Immunology) Walter C. Renberg (Musculoskeletal)

­Contributors JONATHAN A. ABBOTT, DVM Diplomate ACVIM (Cardiology) Associate Professor Department of Small Animal Clinical Sciences College of Veterinary Medicine University of Tennessee Knoxville, Tennessee USA ANTHONY C.G. ABRAMS-OGG, DVM, DVSc Diplomate ACVIM (Small Animal Internal Medicine) Professor Department of Clinical Studies University of Guelph Ontario Veterinary College Guelph, Ontario Canada LARRY G. ADAMS, DVM, PhD Diplomate ACVIM (Small Animal Internal Medicine) Professor of Small Animal Internal Medicine Department of Veterinary Clinical Sciences College of Veterinary Medicine Purdue University West Lafayette, Indiana USA DARCY B. ADIN, DVM Diplomate ACVIM (Cardiology) Clinical Associate Professor College of Veterinary Medicine Department of Large Animal Clinical Sciences University of Florida Gainesville, Florida USA MICHAEL AHERNE, MVB, GradDipVetStud, MS, MANZCVS (Small Animal Surgery) Diplomate ACVIM (Cardiology) Clinical Assistant Professor Department of Small Animal Clinical Sciences College of Veterinary Medicine University of Florida Gainesville, Florida USA

HASAN ALBASAN, DVM, MS, PhD Associate Veterinarian Nephrology & Urology Veterinary Care Specialists Milford, Michigan USA RACHEL A. ALLBAUGH, DVM, MS Diplomate ACVO (Ophthalmology) Associate Professor Department of Veterinary Clinical Sciences College of Veterinary Medicine Iowa State University Ames, Iowa USA KARIN ALLENSPACH, Dr.med.vet, PhD, FHEA, AGAF Diplomate ECVIM-CA Professor Department of Clinical Sciences College of Veterinary Medicine Iowa State University Ames, Iowa USA

GENNA ATIEE, DVM Diplomate ACVIM (Small Animal Internal Medicine) Interventional Radiology Fellow College of Veterinary Medicine University of Georgia Veterinary Medical Center Athens, Georgia USA MELISSA J. BAIN, DVM, MS Diplomate ACVB (Behavior) Diplomate ACAW (Welfare) Professor, Clinical Animal Behavior Department of Veterinary Medicine and Epidemiology School of Veterinary Medicine University of California, Davis Davis, California USA TOMAS W. BAKER Pound Sound Consulting Three Rivers, California USA

COLLEEN M. ALMGREN, DVM, PhD Diplomate DABT Diplomate DABVT Veterinary Toxicologist Pet Poison Helpline/SafetyCall International Bloomington, Minnesota USA

CHERYL E. BALKMAN, DVM Diplomate ACVIM (Small Animal Internal Medicine, Oncology) Senior Lecturer Department of Clinical Sciences College of Veterinary Medicine Cornell University Ithaca, New York USA

SARAH R. ALPERT, DVM Diplomate ABT Consulting Veterinarian, Clinical Toxicology Pet Poison Helpline & SafetyCall International Bloomington, Minnesota USA

GAD BANETH, DVM, PhD Diplomate ECVCP Professor Koret School of Veterinary Medicine The Hebrew University Rehovot Israel

SOPHIE ASCHENBROICH, DVM, PhD Diplomate ACVP (Anatomic Pathology) Assistant Professor Department of Pathobiological Sciences School of Veterinary Medicine University of Wisconsin-Madison Madison, Wisconsin USA

KRISTIN M. BANNON, DVM, FAVD Diplomate AVDC Veterinary Dentistry and Oral Surgery of New Mexico, LLC Algodones, New Mexico USA

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RENEE BARBER, DVM, PhD Diplomate ACVIM (Neurology) Assistant Professor of Neurology and Neurosurgery Department of Small Animal Medicine and Surgery College of Veterinary Medicine University of Georgia Athens, Georgia USA LAURA A. BARBUR, DVM Diplomate ACVS (Small Animal) Small Animal Surgeon Department of Surgery Friendship Hospital for Animals Washington, DC USA ADRIENNE M. BARCHARD COUTS, DVM Resident ACVECC (SA) Westford Veterinary Emergency and Referral Center Westford, Massachusetts USA HEIDI L. BARNES HELLER, DVM Diplomate ACVIM (Neurology) Clinical Associate Professor, Neurology/ Neurosurgery School of Veterinary Medicine University of Wisconsin-Madison Madison, Wisconsin USA MARGARET C. BARR, DVM, PhD Associate Dean for Academic Affairs Professor of Virology and Immunology College of Veterinary Medicine Western University of Health Sciences Pomona, California USA CARLA BARSTOW, DVM, MS Diplomate ACT (Theriogenology) Highland Pet Hospital Lakeland, Florida USA JOSEPH W. BARTGES, DVM, PhD Diplomate ACVIM (Small Animal Internal Medicine) Diplomate ACVN Professor of Medicine and Nutrition Department of Small Animal Medicine and Surgery College of Veterinary Medicine The University of Georgia Athens, Georgia USA

KRISTEN BARTHOLOMEW, DVM Emergency Clinician Veterinary Referral Center Malvern, Pennsylvania USA FIONA L. BATEMAN, BVSc Diplomate ACVD Assistant Professor of Dermatology Department of Small Animal Medicine and Surgery College of Veterinary Medicine University of Georgia Athens, Georgia USA REBECCA M. BATES, DVM Cardiology Resident Department of Small Animal Medicine and Surgery College of Veterinary Medicine University of Georgia Athens, Georgia USA ADRIENNE C. BAUTISTA, DVM, PhD Diplomate ABVT Scientific Services Veterinarian Royal Canin Davis, California USA ASHLEY E. BAVA, BVetMed (Hons) Emergency Clinician Garden State Veterinary Specialists Tinton Falls, New Jersey USA SARAH S.K. BEATTY, DVM Diplomate ACVP (Clincial Pathology) Clinical Assistant Professor Department of Comparative, Diagnostic, and Population Medicine College of Veterinary Medicine University of Florida Gainesville, Florida USA JAN BELLOWS, DVM Diplomate AVDC Diplomate ABVP All Pets Dental Weston, Florida USA

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ELSA BELTRAN, Ldo Vet, PGDipVetEd, MRCVS Diplomate ECVN Associate Professor in Veterinary Neurology & Neurosurgery Department of Clinical Science & Services The Royal Veterinary College University of London North Mymms Hatfield, Herts United Kingdom MARIAN E. BENITEZ, DVM, MS Diplomate ACVS-SA Surgeon/Owner Dogwood Veterinary Surgical Care, PLLC Huntersville, North Carolina USA KIA BENSON, DVM Associate Veterinarian, Clinical Toxicology SafetyCall International & Pet Poison Helpline Bloomington, Minnesota USA ELLISON BENTLEY, DVM Diplomate ACVO Clinical Professor, Comparative Ophthalmology Department of Surgical Sciences School of Veterinary Medicine University of Wisconsin-Madison Madison, Wisconsin USA ALLYSON BERENT, DVM, DACVIM Director, Interventional Endoscopy Services Staff Internal Medicine Specialist Animal Medical Center New York, NY USA JEANNINE BERGER, DVM, CAWA Diplomate ACVB (Behavior) Diplomate ACAW (Welfare) Senior VP of Rescue and Welfare The Society for Prevention of Cruelty to Animals (SPCA) San Francisco, California USA MATTHEW R. BERRY, DVM Medical Oncology Resident Department of Veterinary Clinical Medicine; PhD Candidate Department of Pathobiology University of Illinois at Urbana-Champaign Urbana, Illinois USA

CHRISTINE F. BERTHELIN-BAKER, DVM Diplomate ACVIM (Neurology) Diplomate ECVN Neurologist Atlanta, Georgia USA

LINDSAY BOOZER, DVM Diplomate ACVIM (Neurology) Staff Neurologist Friendship Hospital for Animals Washington, DC USA

JEAN M. BETKOWSKI, VMD Diplomate ACVIM (Cardiology) Staff Cardiologist Cape Cod Veterinary Specialists S. Dennis, Massachusetts USA

DWIGHT D. BOWMAN, MS, PhD Diplomate ACVM (Parasitology, Honorary) Professor Department of Microbiology and Immunology College of Veterinary Medicine Cornell University Ithaca, New York USA

ADAM J. BIRKENHEUER, DVM, PhD Diplomate ACVIM Professor of Internal Medicine Department of Clinical Medicine North Carolina State University Raleigh, North Carolina USA KARYN BISCHOFF, DVM, MS Diplomate ABVT Diagnostic Toxicologist New York State Animal Health Diagnostic Laboratory Department of Population Medicine and Diagnostic Sciences College of Veterinary Medicine Cornell University Ithaca, New York USA MARIE-CLAUDE BLAIS, DVM Diplomate ACVIM (Small Animal Internal Medicine) Associate Professor Department of Clinical Sciences Faculty of Veterinary Medicine Université de Montréal St-Hyacinthe, Quebec Canada APRIL E. BLONG, DVM Diplomate ACVECC Assistant Professor Department of Veterinary Clinical Sciences College of Veterinary Medicine Iowa State University Ames, Iowa USA JOHN D. BONAGURA, DVM, MS Diplomate ACVIM (Cardiology, Internal Medicine) Department of Clinical Sciences College of Veterinary Medicine North Carolina State University Raleigh, North Carolina; Professor Emeritus of Veterinary Clinical Sciences The Ohio State University Columbus, Ohio USA

SØREN BOYSEN, DVM Diplomate ACVECC Professor Veterinary Emergency and Critical Care Department of Veterinary Clinical and Diagnostic Sciences Faculty of Veterinary Medicine University of Calgary Calgary, Alberta Canada BENJAMIN M. BRAINARD, VMD Diplomate ACVAA and ACVECC Edward H. Gunst Professor of Small Animal Critical Care Department of Small Animal Medicine and Surgery College of Veterinary Medicine University of Georgia Athens, Georgia USA RANDI BRANNAN, DVM, FAVD Diplomate AVDC (Dentistry) Animal Dental Clinic Portland, Oregon USA MATT BREWER, DVM, PhD Diplomate ACVM (Parasitology) Associate Professor Department of Veterinary Pathology College of Veterinary Medicine Iowa State University Ames, Iowa USA ALYSSA J. BROOKER, DVM Resident, Clinical Pathology Department of Pathology College of Veterinary Medicine University of Georgia Athens, Georgia USA

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MARJORY B. BROOKS, DVM Diplomate ACVIM (Small Animal) Director Comparative Coagulation Section, Animal Health Diagnostic Laboratory Department of Population Medicine and Diagnostic Sciences Cornell University Ithaca, New York USA AHNA G. BRUTLAG, DVM, MS Diplomate ABT Diplomate ABVT Director, Veterinary Services & Senior Veterinary Toxicologist Pet Poison Helpline & SafetyCall International Bloomington, Minnesota; Adjunct Assistant Professor Department of Veterinary and Biomedical Sciences College of Veterinary Medicine University of Minnesota St. Paul, Minnesota USA JÖRG BUCHELER, DVM, PhD, FTA Diplomate ACVIM (IM) Diplomate ECVIM-CA Veterinary Specialty Hospital of Palm Beach Gardens Palm Beach Gardens, Florida USA ANDREW C. BUGBEE, DVM Diplomate ACVIM (Small Animal Internal Medicine) Associate Clinical Professor of IM Department of Small Animal Medicine & Surgery College of Veterinary Medicine University of Georgia Athens, Georgia USA ANNE E. BUGLIONE, DVM Postdoctoral Associate Department of Neurobiology and Behavior Cornell University Ithaca, New York USA KARAH BURNS DEMARLE, DVM Staff Internist, Small Animal Internal Medicine Northstar VETS Robbinsville, New Jersey USA

JENNA H. BURTON, DVM, MS Diplomate ACVIM (Oncology) Associate Professor Clinical Oncology Department of Surgical and Radiological Sciences School of Veterinary Medicine University of California, Davis Davis, California USA

AUDE M.H. CASTEL, DV, MSc Diplomate ACVIM (Neurology) Assistant Professor, Neurology and Neurosurgery Department of Clinical Sciences Faculty of Veterinary Medicine University of Montreal St-Hyacinthe, Quebec Canada

JULIE K. BYRON, DVM, MS Diplomate ACVIM (Small Animal Medicine) Professor—Clinical Department of Veterinary Clinical Sciences College of Veterinary Medicine The Ohio State University Columbus, Ohio USA

MEGAN N. CAUDILL, DVM, MS Diplomate ACVP (Clinical Pathology) Department of Comparative, Diagnostic, and Population Medicine College of Veterinary Medicine University of Florida Gainesville, Florida

LAURA CAGLE, DVM Diplomate ACVECC PhD Candidate – Integrative Pathobiology School of Veterinary Medicine University of California, Davis Davis, California USA KAREN L. CAMPBELL, DVM, MS Diplomate ACVIM (Small Animal Internal Medicine) Diplomate ACVD Professor Emerita University of Illinois; Clinical Professor Department of Veterinary Sciences College of Veterinary Medicine University of Missouri Veterinary Health Center-Wentzville Wentzville, Missouri USA MELINDA S. CAMUS, DVM Diplomate ACVP (Clinical Pathology) Associate Professor Department of Pathology College of Veterinary Medicine University of Georgia Athens, Georgia USA RENEE T. CARTER, DVM Diplomate ACVO Associate Professor, Ophthalmology Department of Veterinary Clinical Sciences School of Veterinary Medicine Louisiana State University Baton Rouge, Louisiana USA

JULIE T. CECERE, DVM, MS, DACT Clinical Associate Professor, Theriogenology Department of Small Animal Clinical Sciences Virginia-Maryland College of Veterinary Medicine Blacksburg, Virginia USA SHARON A. CENTER, DVM Diplomate ACVIM (Small Animal Internal Medicine) Professor Department of Clinical Sciences Cornell University Cornell University Hospital for Animals Ithaca, New York USA SERGE CHALHOUB, DVM Diplomate ACVIM (Small Animal Internal Medicine) Senior Instructor, Small Animal Internal Medicine Department of Veterinary Clinical and Diagnostic Sciences Faculty of Veterinary Medicine University of Calgary Calgary, Alberta Canada GEORGINA CHILD, BVSc Diplomate ACVIM (Neurology) Consultant Small Animal Specialist Hospital North Ryde; Senior Lecturer School of Veterinary Science University of Sydney Sydney, NSW Australia

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BRUCE W. CHRISTENSEN, DVM, MS Diplomate ACT Kokopelli Assisted Reproductive Services Franklin Ranch Pet Hospital Elk Grove, California USA E’LISE CHRISTENSEN BELL Diplomate ACVB Owner Behavior Vets New York and Colorado USA JOHN A. CHRISTIAN, DVM, PhD Associate Professor of Clinical Pathology Department of Comparative Pathobiology College of Veterinary Medicine Purdue University West Lafayette, Indiana USA RUTHANNE CHUN, DVM Diplomate ACVIM (Oncology) Clinical Professor Department of Medical Sciences University of Wisconsin School of Veterinary Medicine Madison, Wisconsin USA DAVID B. CHURCH, BVSc, PhD, MACVSc, FHEA, MRCVS Professor of Small Animal Studies and Deputy Principal The Royal Veterinary College Hatfield, Herts United Kingdom JOHN J. CIRIBASSI, DVM Diplomate ACVB Chicagoland Veterinary Behavior Consultants Schererville, Indiana USA CÉCILE CLERCX, DVM, PhD Diplomate ECVIM-CA Professor Department of Companion Animal Clinical Sciences Faculty of Veterinary Medicine University of Liège Belgium ANDREANNE CLEROUX Diplomate ACVIM (Small Animal Internal Medicine) Lecturer in Internal Medicine & Interventional Radiology Department of Clinical Sciences & Advanced Medicine School of Veterinary Medicine University of Pennsylvania Philadelphia, Pennsylvania USA

CRAIG A. CLIFFORD, DVM, MS Diplomate ACVIM (Oncology) Medical Oncologist Director of Clinical Trials Hope Veterinary Specialists Malvern, Pennsylvania USA JOAN R. COATES, BS, DVM, MS Diplomate ACVIM (Neurology) Professor of Veterinary Neurology & Neurosurgery Department of Veterinary Medicine and Surgery College of Veterinary Medicine University of Missouri Columbia, Missouri USA SUSAN M. COCHRANE, BSc, MSc, DVM, DVSc Diplomate ACVIM (Neurology) Veterinary Emergency Clinic and Referral Centre Toronto, Ontario Canada STEVEN M. COGAR, DVM Diplomate ACVS-SA Carolina Veterinary Specialists Winston-Salem, North Carolina USA WILLIAM M. COLE, DVM Small Animal Internal Medicine Metropolitan Animal Specialty Hospital Los Angeles, California USA AMANDA E. COLEMAN, DVM, DACVIM (Cardiology) Associate Professor of Cardiology Department of Small Animal Medicine and Surgery University of Georgia College of Veterinary Medicine Athens, Georgia USA HEATHER E. CONNALLY, DVM, MS Diplomate ACVECC Veterinary Specialty Center on Tucson (retired) Associate Veterinarian Tucson, Arizona USA FRANCISCO O. CONRADO, DVM, MSc Diplomate ACVP (Clinical Pathology) Assistant Professor Department of Biomedical Sciences Cummings School of Veterinary Medicine Tufts University North Grafton, Massachusetts USA

AUDREY K. COOK, BVM&S, MSc VetEd, MRCVS Diplomate ACVIM (Small Animal Internal Medicine) Diplomate ECVIM-CA Diplomate ABVP (Feline Practice) Professor, Small Animal Internal Medicine Department of Small Animal Clinical Sciences College of Veterinary Medicine and Biomedical Sciences Texas A&M University College Station, Texas USA LESLIE LARSON COOPER, DVM Diplomate ACVB Animal Behavior Counseling and Therapy Davis, California USA EDWARD S. COOPER, VMD, MS Diplomate ACVECC Professor—Clinical Department of Veterinary Clinical Sciences College of Veterinary Medicine Ohio State University Columbus, Ohio USA RHIAN COPE, BVSc, BSc(Hon1), PhD, FACTRA Diplomate ABT Diplomate ABVT Principal Toxicologist Australian Pesticides and Veterinary Medicines Authority Symonston Australia JOHN M. CRANDELL, DVM Diplomate ACVIM (Small Animal Internal Medicine) Veterinary Internist MedVet Akron Akron, Ohio USA SIGNE E. CREMER, DVM, PhD Associate Professor, Clinical Pathology Department of Veterinary Clinical Sciences Faculty of Health and Medical Sciences University of Copenhagen Frederiksberg Denmark

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SUZANNE M. CUNNINGHAM, DVM Diplomate ACVIM (Cardiology) Associate Professor Department of Clinical Sciences Cummings School of Veterinary Medicine Tufts University North Grafton, Massachusetts USA ELIZABETH A. CURRY-GALVIN, DVM Barrington Hills, Illinois USA TERRY MARIE CURTIS, DVM, MS Diplomate ACVB Veterinary Behaviorist St. Augustine, Florida USA SARAH L. CZERWINSKI, BSc, DVM Diplomate ACVO Clinical Assistant Professor Department of Small Animal Medicine and Surgery College of Veterinary Medicine University of Georgia Athens, Georgia USA RONALDO CASIMIRO DA COSTA, DMV, MSc, PhD Diplomate ACVIM (Neurology) Professor and Service Head, Neurology and Neurosurgery Department of Veterinary Clinical Sciences College of Veterinary Medicine The Ohio State University Columbus, Ohio USA AUTUMN P. DAVIDSON, DVM, MS Diplomate ACVIM (Small Animal Internal Medicine) Clinical Professor VMTH School of Veterinary Medicine University of California Davis, California USA THOMAS K. DAY, DVM, MS Diplomate ACVAA Diplomate ACVECC Emergency and Critical Care Specialist Anesthesiology and Pain Management Specialist VCA Veterinary Emergency Service and Specialty Center Middleton, Wisconsin USA

ALEXANDER DE LAHUNTA, DVM, PhD Retired Professor of Veterinary Anatomy at Cornell University Ithaca, New York USA HELIO S. AUTRAN DE MORAIS, DVM, PhD Diplomate ACVIM (Internal Medicine and Cardiology) Director Lois Bates Acheson Veterinary Teaching Hospital College of Veterinary Medicine Oregon State University Corvallis, Oregon USA JONATHAN D. DEAR, DVM, MAS Diplomate ACVIM (Small Animal Internal Medicine) Assistant Professor of Clinical Internal Medicine Department of Medicine and Epidemiology School of Veterinary Medicine University of California, Davis Davis, California USA TERESA C. DEFRANCESCO, DVM Diplomate ACVIM (Cardiology), ACVECC Department of Clinical Sciences College of Veterinary Medicine North Carolina State University Raleigh, North Carolina USA VICTORIA A. DEMELLO, DVM Nashville Veterinary Specialists Nashville, Tennessee USA SAGI DENENBERG, DVM, MRCVS Veterinary Psychiatrist Diplomate ACVB Diplomate ECAWBM RCVS Recognized Specialist in Veterinary Behavioural Medicine North Toronto Veterinary Behaviour Specialty Clinic Thornhill, Ontario Canada THERESA L. DEPORTER, BSc, DVM, MRCVS Diplomate DECAWBM Diplomate ACVB (Behavior) Veterinary Behaviorist Behavioral Medicine Department Oakland Veterinary Referral Services Bloomfield Hills, Michigan USA

NICK DERVISIS, DVM, PhD DACVIM (Oncology) Medical Oncology Associate Professor Department of Small Animal Clinical Sciences; Associate Professor Faculty of Health Sciences VA-MD College of Veterinary Medicine DSACS, Phase II Blacksburg, Virginia USA IAN DESTEFANO, DVM Resident, Emergency & Critical Care Foster Hospital for Small Animals Tufts University North Grafton, Massachusetts USA SHARON M. DIAL, DVM, PhD Diplomate ACVP (Clinical and Anatomic Pathology) Research Scientist College of Veterinary Medicine University of Arizona Tucson, Arizona USA STEPHEN P. DIBARTOLA, DVM Diplomate ACVIM (Small Animal Internal Medicine) Professor Emeritus of Internal Medicine Department of Veterinary Clinical Sciences College of Veterinary Medicine Ohio State University Columbus, Ohio USA DAVID C. DORMAN, DVM, PhD Diplomate ABVT Diplomate ABT Professor of Toxicology Department of Molecular Biomedical Sciences College of Veterinary Medicine North Carolina State University Raleigh, North Carolina USA ELIZABETH R. DRAKE, DVM Diplomate ACVD Associate Professor Department of Small Animal Clinical Sciences College of Veterinary Medicine University of Tennessee Knoxville, Tennessee USA

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EDWARD J. DUBOVI, PhD Professor of Virology Department of Population Medicine and Diagnostic Sciences Animal Health Diagnostic Center College of Veterinary Medicine Cornell University Ithaca, New York USA DAVID D. DUCLOS, DVM Diplomate ACVD Clinical Dermatologist—Animal Skin & Allergy Clinic Lynnwood, Washington USA CEDRIC P. DUFAYET, DVM Associate Veterinarian Advanced Urinary Disease and Extracorporeal Therapies Service University of California Veterinary Medicine Center San Diego, California USA STÉPHANIE DUGAS, DVM, MSc Diplomate ACVIM (Neurology) Medical Neurologist BluePearl Specialty & Emergency Hospital Irvine, California USA ERIC K. DUNAYER, MS, VMD Diplomate ABT Diplomate ABVT Senior Toxicologist ASPCA Animal Poison Control Center Urbana, Illinois USA CAROLINA DUQUE, DVM, MSc, DVSc Diplomate ACVIM (Neurology) Mississauga Oakville Emergency Hospital and Referral Group Oakville, Ontario Canada DAVID DYCUS, DVM, MS, CCRP Diplomate ACVS (Small Animal) Chief of Orthopedics Nexus Veterinary Bone & Joint Center Medical Director Nexus Veterinary Specialists Baltimore, Maryland USA HEATHER D. EDGINTON, DVM Diplomate ACVD Animal Medical Center of Seattle Shoreline, Washington USA

MELISSA N.C. EISENSCHENK, DVM, MS Diplomate ACVD Owner, Veterinary Dermatologist Pet Dermatology Clinic Maple Grove, Minnesota USA

LEAH FERGUSON, DVM, MS Diplomate ACVIM (Internal Medicine) Veterinary Internist VCA Great Lakes Veterinary Specialists Warrensville Heights, Ohio USA

MARC ELIE, DVM Diplomate ACVIM (Internal Medicine) Staff Internist Small Animal Internal Medicine BluePearl Veterinary Partners Southfield, Michigan USA

LLUÍS FERRER, BVSc, PhD Diplomate ECVD Professor Department of Animal Medicine and Surgery Veterinary School Universitat Autònoma de Barcelona, Bellaterra, Barcelona Spain

ROBYN ELLERBROCK, DVM, PhD Diplomate ACT Assistant Professor Department of Large Animal Medicine College of Veterinary Medicine University of Georgia Athens, Georgia USA NAHVID M. ETEDALI, DVM Diplomate ACVIM (Small Animal Internal Medicine) Staff Internist Head of Hemodialysis and Extracorporeal Therapies Animal Medical Center New York, New York USA TIMOTHY M. FAN, DVM, PhD Diplomate ACVIM (Small Animal Internal Medicine, Oncology) Professor Department of Veterinary Clinical Medicine College of Veterinary Medicine University of Illinois at Urbana-Champaign Urbana, Illinois USA JUSTIN FARRIS, DVM Clinical Pathology Resident Department of Pathology College of Veterinary Medicine University of Georgia Athens, Georgia USA RICHARD A. FAYRER-HOSKEN, BVSc, PhD Diplomate ACT (Theriogenology) Diplomate ECAR Research Scientist Institute for Conservation Research San Diego Zoo Global Escondido, California USA

MARIA SOLEDAD FERRER, DVM, MS Diplomate DACT (Theriogenology) Associate Professor Department of Large Animal Medicine College of Veterinary Medicine University of Georgia Athens, Georgia USA TESSA FIAMENGO, DVM, MS Diplomate ACT Slade Veterinary Hospital Framingham, Massachusetts USA ANDREA M. FINNEN, DVM, DES, MSc Diplomate ACVIM (Neurology) Mississauga Oakville Veterinary Emergency Hospital Neurology Service Oakville, Ontario Canada ANDREA FISCHER, DVM, Dr.med.vet., Dr. habil. Diplomate ACVIM (Neurology) Diplomate ECVN Professor Centre for Clinical Veterinary Medicine LMU University of Munich Munich Germany GERRARD FLANNIGAN, DVM, MSc Diplomate ACVB Kernersville, North Carolina USA LINDA M. FLEEMAN, BVSc, PhD, MANZCVS Animal Diabetes Australia Melbourne, Victoria Australia CHARLOTTE FLINT, DVM, DABT Senior Consulting Veterinarian, Clinical Toxicology Pet Poison Helpline & SafetyCall International Bloomington, Minnesota USA

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J.D. FOSTER, VMD Diplomate ACVIM (Small Animal Internal Medicine) Nephrology/Urology & Internal Medicine Friendship Hospital for Animals Washington, DC USA DANIEL S. FOY, MS, DVM Diplomate ACVIM (Small Animal Internal Medicine) Diplomate ACVECC Clinical Assistant Professor College of Veterinary Medicine Midwestern University Glendale, Arizona USA LINDA A. FRANK, MS, DVM Diplomate ACVD Professor Department of Small Animal Clinical Sciences College of Veterinary Medicine University of Tennessee Knoxville, Tennessee USA JONI L. FRESHMAN, DVM MS CVA Diplomate ACVIM (Internal Medicine) Owner Canine Consultations Peyton, Colorado USA CANNY FUNG, DVM Surgery Intern Southwest Veterinary Surgical Service Phoenix Arizona USA EVA FURROW, VMD, PhD Diplomate ACVIM (Small Animal Internal Medicine) Associate Professor Department of Veterinary Clinical Sciences College of Veterinary Medicine University of Minnesota St. Paul, Minnesota USA LUIS GAITERO, DVM Diplomate ECVN Associate Professor and Head Neurology and Neurosurgery Service HSC Chief Medical Officer Department of Clinical Studies Ontario Veterinary College University of Guelph Guelph, Ontario Canada

JOAO FELIPE DE BRITO GALVAO, MV, MS Diplomate ACVIM (Small Animal Internal Medicine) Internal Medicine Specialist VCA Arboretum View Animal Hospital Downers Grove, Illinois; Adjunct Assistant Professor The Ohio State University Columbus, Ohio USA BRIDGET C. GARNER, DVM, PhD Diplomate ACVP (Clinical Pathology) Associate Professor Department of Pathology College of Veterinary Medicine University of Georgia Athens, Georgia USA LAURENT GAROSI, DVM, FRCVS Diplomate ECVN RCVS and EBVS® European Specialist in Veterinary Neurology Clinical Director Vet Oracle Teleneurology Bedford United Kingdom

ANNE J. GEMENSKY METZLER, DVM, MS Diplomate ACVO Professor—Clinical Department of Veterinary Clinical Sciences College of Veterinary Medicine The Ohio State University Columbus, Ohio USA KATHERINE GERKEN, DVM, MS Diplomate ACVECC Assistant Clinical Professor Small Animal Emergency and Critical Care Department of Clinical Sciences Bailey Small Animal Teaching Hospital College of Veterinary Medicine Auburn University Auburn, Alabama USA VIRGINIA L. GILL, DVM Diplomate DACVIM (Oncology) Medical Director Maine Veterinary Medical Center Scarborough, Maine USA

LAURA D. GARRETT, DVM Diplomate ACVIM (Oncology) Clinical Professor Department of Veterinary Clinical Medicine College of Veterinary Medicine University of Illinois Urbana, Illinois USA

MARGI A. GILMOUR, DVM Diplomate ACVO Professor Department of Veterinary Clinical Sciences College of Veterinary Medicine Oklahoma State University Stillwater, Oklahoma USA

CATHY J. GARTLEY, DVM, DVSc Diplomate ACT Assistant Professor Department of Population Medicine Ontario Veterinary College University of Guelph Guelph, Ontario Canada

ERIC N. GLASS, MS, DVM Diplomate ACVIM (Neurology) Section Head, Neurology and Neurosurgery Red Bank Veterinary Hospital Tinton Falls, New Jersey; Chief of Neurology and Neurosurgery Compassion First Pet Hospital Tinton Falls, New Jersey USA

ANNA R.M. GELZER, Dr.med.vet., PhD Diplomate ACVIM Diplomate ECVIM-CA-Cardiology Professor of Cardiology Department of Clinical Sciences & Advanced Medicine School of Veterinary Medicine University of Pennsylvania Philadelphia, Pennsylvania USA

MATHIEU M. GLASSMAN, VMD Diplomate ACVS Chief of Surgery Friendship Surgical Specialists Friendship Hospital for Animals Washington, DC USA

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RITA GONÇALVES, DVM, MVM, FHEA, MRCVS Diplomate ECVN European and RCVS Recognized Specialist in Veterinary Neurology Senior Lecturer in Veterinary Neurology Small Animal Clinical Science University of Liverpool Neston, Cheshire United Kingdom SARA E. GONZALEZ, DVM, MS Clinical Assistant Professor of Community Practice Department of Small Animal Medicine and Surgery University of Georgia College of Veterinary Medicine Athens, Georgia USA JENNIFER GOOD, DVM Diplomate ACVECC (Emergency and Critical Care) Assistant Clinical Professor Department of Emergency and Critical Care College of Veterinary Medicine University of Georgia Athens, Georgia USA SHARON FOOSHEE GRACE, M Agric, MS, DVM Diplomate ACVIM (Small Animal) Diplomate ABVP (Canine/Feline) Clinical Professor Department of Clinical Sciences College of Veterinary Medicine Mississippi State University Mississippi State, Mississippi USA W. DUNBAR GRAM, DVM, MRCVS Diplomate ACVD Clinical Associate Professor and Dermatology Service Chief Small Animal Clinical Sciences, University of Florida Gainesville, Florida USA JENNIFER L. GRANICK, DVM, PhD Diplomate ACVIM (Small Animal Internal Medicine) Associate Professor Department of Veterinary Clinical Sciences College of Veterinary Medicine University of Minnesota St. Paul, Minnesota USA

GREGORY F. GRAUER, DVM, MS Diplomate ACVIM (Small Animal Internal Medicine) Professor Emeritus Department of Clinical Sciences College of Veterinary Medicine Kansas State University Manhattan, Kansas USA SARAH L. GRAY, DVM Diplomate ACVECC (Emergency and Critical Care) Horizon Veterinary Specialist Ventura, California USA KURT A. GRIMM, DVM, MS, PhD Diplomate ACVCP Diplomate ACVAA Owner Veterinary Specialist Services, PC Conifer, Colorado USA AMY M. GROOTERS, DVM Diplomate ACVIM (Small Animal Internal Medicine) Professor, Companion Animal Medicine Veterinary Clinical Sciences Louisiana State University Baton Rouge, Louisiana USA MARGARET E. GRUEN, DVM, PhD Diplomate ACVB Assistant Professor, Behavioral Medicine Department of Clinical Sciences College of Veterinary Medicine North Carolina State University Raleigh, North Carolina USA SOPHIE A. GRUNDY, BVSc (Hons), MANZCVS (Small Animal Internal Medicine) Diplomate ACVIM (Small Animal Internal Medicine) Internal Medicine Consultant IDEXX Laboratories, Inc. Westbrook, Maine USA REBEKAH G. GUNN-CHRISTIE, DVM Diplomate ACVP (Clinical Pathology) Veterinary Clinical Pathologist Antech Diagnostics Cary, North Carolina USA

TALIA GUTTIN, VMD Diplomate ACVIM (Small Animal Internal Medicine) Assistant Professor Small Animal Medicine and Surgery Department School of Veterinary Medicine St. George’s University True Blue Campus St. George, Grenada West Indies SHARON GWALTNEY-BRANT, DVM, PhD Diplomate ABVT Diplomate ABT Consultant Veterinary Information Network Mahomet, Illinois USA TIMOTHY B. HACKETT, DVM, MS Diplomate ACVECC Professor Department of Clinical Sciences College of Veterinary Medicine and Biomedical Sciences Colorado State University Fort Collins, Colorado USA DEBORAH J. HADLOCK, VMD Diplomate ABVP (Canine and Feline) Certified Veterinary Acupuncturist—CVA (IVAS) Certified Veterinary Spinal Manipulative Therapist—CVSMT (HOWC) Owner Hadlock Integrative Veterinary Consulting Salt Lake City, Utah USA JENS HÄGGSTRÖM, DVM, PhD Diplomate ECVIM-CA (Cardiology) Professor Department of Clinical Sciences Faculty of Veterinary Medicine and Animal Science Swedish University of Agricultural Sciences Uppsala Sweden FRASER A. HALE, DVM, FAVD Diplomate AVC Hale Veterinary Clinic Guelph, Ontario Canada

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EDWARD J. HALL, MA, VetMB, PhD, FRCVS Diplomate ECVIM-CA Emeritus Professor of Small Animal Internal Medicine Langford Vets Bristol Veterinary School University of Bristol Langford United Kingdom STEVEN R. HANSEN, DVM, MS, MBA Diplomate ACAW Diplomate ABVT President and CEO Arizona Humane Society Phoenix, Arizona USA TISHA A.M. HARPER, DVM, MS, CCRP Diplomate ACVS-SA Diplomate ACVSMR Clinical Associate Professor Department of Veterinary Clinical Medicine University of Illinois College of Veterinary Medicine Urbana, Illinois USA JOHN W. HARVEY, DVM, PhD Diplomate ACVP (Clinical Pathology) Professor Emeritus Department of Physiological Sciences College of Veterinary Medicine University of Florida Gainesville, Florida USA LORE I. HAUG, DVM, MS Diplomate ACVB Texas Veterinary Behavior Services Sugar Land, Texas USA ELEANOR C. HAWKINS, DVM Diplomate ACVIM (Small Animal Internal Medicine) Professor Department of Clinical Sciences College of Veterinary Medicine North Carolina State University Raleigh, North Carolina USA CRISTINE L. HAYES, DVM Diplomate ABVT Diplomate ABT Medical Director ASPCA Animal Poison Control Center Urbana, Illinois USA

IAN P. HERRING, DVM, MS Diplomate ACVO (Ophthalmology) Associate Professor VA-MD Regional College of Veterinary Medicine Virginia Tech Blacksburg, Virginia USA MEGHAN E. HERRON, DVM Diplomate ACVB Senior Director Behavioral Medicine, Education, and Outreach Gigi’s (Shelter for Dogs) Canal Winchester, Ohio USA MILAN HESS, DVM, MS Diplomate ACT (Theriogenology) Colorado Veterinary Specialty Group Littleton, Colorado USA STEVE HILL, DVM, MS Diplomate ACVIM (Small Animal Internal Medicine) Small Animal Internal Medicine Consultant Flagstaff Veterinary Internal Medicine Consulting Flagstaff, Arizona USA TRACY HILL, DVM PhD Diplomate ACVIM (Small Animal Internal Medicine) Assistant Professor Department of Small Animal Medicine and Sur gery College of Veterinary Medicine University of Georgia Athens, Georgia USA LORA S. HITCHCOCK, DVM Diplomate ACVIM (Cardiology) Clinical Cardiologist Ohio Veterinary Cardiology, Ltd Metropolitan Veterinary Hospital Akron, Ohio USA KATE HOLAN, BS, DVM Diplomate ACVIM (Small Animal Internal Medicine) Assistant Professor and Head Small Animal Internal Medicine Department of Small Animal Clinical Sciences Michigan State University East Lansing, Michigan USA

MASON HOLLAND, VMD Diplomate ACVR Staff Radiologist Port City Veterinary Referral Hospital Portsmouth, New Hampshire USA

TYNE HOVDA, DVM Anesthesia Intern College of Veterinary Medicine North Carolina State University Raleigh, North Carolina USA

SUSAN HOLLAND, DVM Associate Veterinarian, Clinical Toxicology Pet Poison Helpline Bloomington, Minnesota USA

JUNE C. HUANG, DVM, PhD Diplomate ACVP (Clinical Pathology) Veterinary Clinical Pathologist ANTECH Diagnostics Atlanta, Georgia USA

FIONA HOLLINSHEAD, BVSc (Hons), PhD, MANZCVS Diplomate ACT (Theriogenology) Registered Specialist in Small Animal Reproduction Glenbred, Matamata Veterinary Services Ltd Matamata New Zealand STEPHEN B. HOOSER, DVM, PhD Diplomate ABVT Professor of Veterinary Toxicology & Head Toxicology Section Department of Comparative Pathobiology & ADDL College of Veterinary Medicine Purdue University West Lafayette, Indiana USA KATE HOPPER, BVSc, PhD Diplomate ACVECC Associated Professor, Small Animal Emergency & Critical Care Department of Veterinary Surgical & Radiological Sciences School of Veterinary Medicine University of California, Davis Davis, California USA DEBRA F. HORWITZ, DVM Diplomate ACVB Veterinary Behavior Consultations St. Louis, Missouri USA LYNN R. HOVDA, RPH, DVM, MS Diplomate ACVIM (Large Animal Internal Medicine) Director of Veterinary Medicine SafetyCall International & Pet Poison Helpline Bloomington, Minnesota; Assistant Adjunct Professor Department of Veterinary and Biomedical Sciences College of Veterinary Medicine University of Minnesota St. Paul, Minnesota USA

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WAYNE HUNTHAUSEN, DVM Director Animal Behavior Consultations Westwood, Kansas USA CASSANDRA O. JANSON, DVM Diplomate ACVECC Staff Criticalist Mount Laurel Animal Hospital Mount Laurel, New Jersey USA NICK D. JEFFERY, BVSc, PhD, MSc, FRCVS Diplomate ECVS Diplomate ECVN Professor, Neurology & Neurosurgery Department of Small Animal Clinical Sciences College of Veterinary Medicine Texas A&M University College Station, Texas USA ALBERT E. JERGENS, DVM, PhD, AGAF Diplomate ACVIM (Small Animal Internal Medicine) Professor, Associate Chair for Research and Graduate Studies and Donn E. and Beth M. Bacon Professor in Small Animal Medicine and Surgery Department of Veterinary Clinical Sciences College of Veterinary Medicine Iowa State University Ames, Iowa USA JEBA R.J. JESUDOSS CHELLADURAI, BVSc, MS, PhD Diplomate ACVM (Parasitology) Postdoctoral Associate Department of Veterinary Pathology College of Veterinary Medicine Iowa State University Ames, Iowa USA

AIME K. JOHNSON, DVM Diplomate American College of Theriogenology Associate Professor Department of Clinical Sciences Auburn University College of Veterinary Medicine Auburn, Alabama USA JESSICA JOHNSON, DVM Senior Dental & Oral Surgery Resident Elevate Your Small Animal Dental Team, LLC Main Street Veterinary Hospital & Dental Clinic Dallas, Texas USA LYNELLE R. JOHNSON, DVM, MS, PhD Diplomate ACVIM (Small Animal Internal Medicine) Professor Department of Medicine and Epidemiology University of California, Davis Davis, California USA SPENCER A. JOHNSTON, VMD Diplomate ACVS James and Marjorie Waggoner Professor Head Department of Small Animal Medicine and Surgery College of Veterinary Medicine University of Georgia Athens, Georgia USA RICHARD J. JOSEPH, DVM Diplomate ACVIM (Neurology) Founder, CEO AnimalMR.com VetsOnCall.org Katonah, New York USA RONNIE KAUFMANN, BSc, DVM Diplomate ECVD (Dermatology) Head of Dermatology Service The Veterinary Teaching Hospital Koret School of Veterinary Medicine The Hebrew University of Jerusalem Israel BRUCE W. KEENE, DVM, MSc Diplomate ACVIM (Cardiology) Jane Lewis Seaks Distinguished Professor of Companion Animal Medicine Department of Clinical Sciences College of Veterinary Medicine North Carolina State University Raleigh, North Carolina USA

LISA S. KELLY, DVM, PhD Diplomate ACVP (Clinical Pathology) Veterinary Clinical Pathologist Antech Diagnostics Atlanta, Georgia USA DANIEL E. KEYLER, BS, PharmD, FAACT Senior Clinical Toxicologist SafetyCall International Bloomington, Minnesota; Adjunct Professor Experimental & Clinical Pharmacology University of Minnesota Minneapolis, Minnesota USA YUNJEONG KIM, DVM, PhD Diplomate ACVM (Immunology) Associate Professor Department of Diagnostic Medicine and Pathobiology College of Veterinary Medicine Kansas State University Manhattan, Kansas USA SHAWNA L. KLAHN, DVM Diplomate ACVIM (Oncology) Associate Professor Department of Small Animal Clinical Sciences Virginia-Maryland College of Veterinary Medicine Virginia Tech Blacksburg, Virginia USA MARY P. KLINCK, DVM, PhD Diplomate ACVB Veterinary Behavioural Medicine Consultant Sainte-Anne-de-Bellevue, Quebec Canada MARGUERITE F. KNIPE, DVM Diplomate ACVIM (Neurology) Health Sciences Associate Clinical Professor, Neurology/Neurosurgery Department of Surgical and Radiological Sciences UC Davis School of Veterinary Medicine Davis, California USA JOYCE S. KNOLL, VMD, PhD Diplomate ACVP (Clinical Pathology) Associate Professor and Interim Chair Department of Biomedical Sciences Cummings School of Veterinary Medicine Tufts University North Grafton, Massachusetts USA

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AMIE KOENIG, DVM Diplomate ACVIM (Small Animal Internal Medicine) Diplomate ACVECC Professor of Emergency and Critical Care Department of Small Animal Medicine and Surgery College of Veterinary Medicine University of Georgia Athens, Georgia USA CASEY J. KOHEN, DVM Diplomate ACVECC Emergency and Critical Care Specialist MarQueen Veterinary Emergency and Specialty Roseville, California USA BARBARA KOHN, Prof. Dr. med. vet Diplomate ECVIM-CA Clinic for Small Animals Faculty of Veterinary Medicine Freie Universität Berlin Germany MARC S. KRAUS, DVM Professor of Clinical Cardiology Diplomate ACVIM (Cardiology, Internal Medicine) Diplomate ECVIM-CA (Cardiology) University of Pennsylvania Department of Clinical Sciences and Advanced Medicine Philadelphia, Pennsylvania USA NATALI KREKELER, Dr. med. vet., PhD Diplomate ACT Senior Lecturer in Veterinary Reproduction Melbourne Veterinary School The University of Melbourne Werribee, Victoria Australia ERIKA L. KRICK, VMD Diplomate ACVIM (Oncology) Medical Oncologist and Oncology Department Head Mount Laurel Animal Hospital Mount Laurel, New Jersey USA PAULA M. KRIMER, DVM, DVSc Diplomate ACVP (Clinical Pathology) Professor & Outreach Services Chief Athens Veterinary Diagnostic Laboratory and Department of Pathology College of Veterinary Medicine University of Georgia Athens, Georgia USA

ANNEMARIE T. KRISTENSEN, DVM, PhD Diplomate ACVIM (Small Animal) Diplomate ECVIM-CA & Oncology Professor, Companion Animal Clinical Oncology Department of Veterinary Clinical Sciences Faculty of Health and Medical Sciences University of Copenhagen Frederiksberg Denmark JOHN M. KRUGER, DVM, PhD Diplomate ACVIM- SAIM Professor and Carrigan Chair in Feline Health Department of Small Animal Clinical Sciences College of Veterinary Medicine Michigan State University East Lansing, Michigan USA STEPHANIE KUBE, DVM, CCRT, CVPP Diplomate ACVIM (Neurology) Veterinary Neurology and Pain Management Center of New England Walpole, Massachusetts USA KAREN A. KUHL, DVM Diplomate ACVD Midwest Veterinary Dermatology Center Veterinary Specialty Center Buffalo Grove, Illinois USA LEIGH A. LAMONT, DVM, MS Diplomate ACVAA Associate Dean of Academic and Student Affairs Atlantic Veterinary College University of Prince Edward Island Charlottetown, Prince Edward Island Canada GARY M. LANDSBERG, BSc, DVM Diplomate ACVB, ECAWBM Veterinary Behaviorist Vice-President CanCog Incorporated Fergus, Ontario; Head Fear Free Research Canada SELENA LANE, DVM Diplomate ACVECC Clinical Assistant Professor of Small Animal Emergency and Critical Care Small Animal Medicine and Surgery University of Georgia College of Veterinary Medicine Athens, Georgia USA

CATHY E. LANGSTON, DVM Diplomate ACVIM (Small Animal Internal Medicine) Professor - Clinical Veterinary Medical Center College of Veterinary Medicine The Ohio State University Columbus, Ohio USA PATTY A. LATHAN, VMD, MS Diplomate ACVIM (Small Animal Internal Medicine) Associate Professor Department of Clinical Sciences Mississippi State University Mississippi State, Mississippi USA KENNETH S. LATIMER, DVM, PhD Diplomate ACVP (Clinical Pathology) Lanexa Veterinary & Consulting Services, LLC Toano, Virginia USA ROBIN LAZARO, RVT, VTS(ECC) ICU Supervisor North Carolina State Veterinary Hospital College of Veterinary Medicine Raleigh, North Carolina USA AMY LEARN, VMD Resident in Clinical Behavior Medicine Animal Behavior Wellness Center Richmond, Virginia USA MYLÈNE-KIM LECLERC, DMV Diplomate ACVIM (Neurology) Head of the Neurology Service Centre Veterinaire Rive Sud Brossard, Quebec Canada RICHARD A. LECOUTEUR, BVSc, PhD Diplomate ACVIM (Neurology) Diplomate ECVN Professor Emeritus Department of Surgical & Radiological Sciences School of Veterinary Medicine University of California, Davis Davis, California USA

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MICHAEL S. LEIB, DVM, MS Diplomate ACVIM (Small Animal Internal Medicine) Emeritus Professor of Internal Medicine Department of Small Animal Clinical Sciences Virginia-Maryland College of Veterinary Medicine Virginia Tech Blacksburg, Virginia USA MATTHEW S. LEMMONS, DVM Diplomate AVDC Dentistry and Oral Surgery MedVet Carmel, Indiana USA JOSE A. LEN, DVM, MS, PhD Diplomate ACT Assistant Professor, Theriogenology College of Veterinary Medicine North Carolina State University Raleigh, North Carolina USA SOPHIE LE PODER, DVM, MS, PhD Professor in Virology Unity of Bacteriology, Immunology and Virology Ecole Nationale Vétérinaire d’Alfort Maisons-Alfort France JOHN R. LEWIS, VMD, FAVD Diplomate AVDC Veterinary Dentistry Specialists Silo Academy Education Center Chadds Ford, Pennsylvania USA ELLEN M. LINDELL, VMD Diplomate ACVB Veterinary Behaviorist Central Hospital for Veterinary Medicine North Haven, Connecticut USA MERYL P. LITTMAN, VMD Diplomate ACVIM (Small Animal Internal Medicine) Professor Emerita of Medicine Department of Clinical Sciences & Advanced Medicine School of Veterinary Medicine University of Pennsylvania Philadelphia, Pennsylvania USA

INGRID LJUNGVALL, DVM, PhD Diplomate ECVIM-CA (Cardiology) Associate Professor Department of Clinical Sciences Faculty of Veterinary Medicine Swedish University of Agricultural Sciences Uppsala Sweden HEIDI B. LOBPRISE, DVM Diplomate AVDC (Dentistry) Main Street Veterinary Dental Clinic Flower Mound, Texas USA JOHN P. LOFTUS, PhD, DVM Diplomate ACVIM (Small Animal Internal Medicine) Assistant Professor Department of Clinical Sciences College of Veterinary Medicine Cornell University Ithaca, New York USA DAWN E. LOGAS, DVM Diplomate ACVD Owner/Staff Dermatologist Veterinary Dermatology Center Maitland, Florida USA JAYME S. LOOPER, DVM Diplomate ACVR (Radiation Oncology) Associate Professor Department of Veterinary Clinical Sciences School of Veterinary Medicine Louisiana State University Baton Rouge, Louisiana USA CHERYL LOPATE, MS, DVM Diplomate ACT Veterinarian and Owner Reproductive Revolutions and Wilsonville Veterinary Clinic Wilsonville, Oregon USA BIANCA N. LOURENÇO, DVM, MSc, PhD Diplomate ACVIM (Small Animal Internal Medicine) Assistant Professor Department of Small Animal and Surgery College of Veterinary Medicine University of Georgia Athens, Georgia USA

VIRGINIA LUIS FUENTES, MA, VetMB, PhD, CertVR, DVC, MRCVS Diplomate ACVIM (Cardiology) Diplomate ECVIM-CA (Cardiology) Professor Department of Veterinary Clinical Science and Services Royal Veterinary College North Mymms United Kingdom JODY P. LULICH, DVM, PhD Diplomate ACVIM (Internal Medicine) Professor Department of Veterinary Clinical Sciences Director of the Minnesota Urolith Center College of Veterinary Medicine University of Minnesota St. Paul, Minnesota USA ALYCEN P. LUNDBERG, DVM Diplomate ACVIM (Oncology) Assistant Professor Department of Veterinary Clinical Medicine College of Veterinary Medicine University of Illinois at UrbanaChampaign Urbana, Illinois USA CANDACE C. LYMAN, DVM Diplomate DACT (Theriogenology) Associate Professor Department of Clinical Sciences College of Veterinary Medicine Auburn University Auburn, Alabama USA

ORLA MAHONY, MVB Diplomate ACVIM (Internal Medicine) Diplomate ECVIM Clinical Assistant Professor Department of Clinical Sciences Cummings School of Veterinary Medicine at Tufts University North Grafton, Massachusetts USA SEAN B. MAJOY, DVM, MS Diplomate ACVECC Clinical Assistant Professor Department of Clinical Sciences Cummings School of Veterinary Medicine at Tufts University North Grafton, Massachusetts USA GUILLERMINA MANIGOT, DMV UBA Diplomate CPMV (Dermatology) Dermlink Buenos Aires Buenos Aires Argentina KATIA MARIONI-HENRY, DMV, PhD, MRCVS Diplomate ACVIM (Neurology) and ECVN EBVS® European Veterinary Specialist in Small Animal Neurology RCVS Specialist in Veterinary Neurology; Senior Lecturer Neurology/Neurosurgery Service Hospital for Small Animals Royal (Dick) School of Veterinary Studies University of Edinburgh Roslin, Midlothian United Kingdom

KASEY E. MABRY, DVM Resident, Small Animal Internal Medicine Department of Small Animal Medicine and Surgery College of Veterinary Medicine University of Georgia Athens, Georgia USA

STANLEY L. MARKS, BVSc, PhD Diplomate ACVIM (Internal Medicine, Oncology) Diplomate ACVN Professor Department of Medicine & Epidemiology University of California, Davis School of Veterinary Medicine Davis, California USA

CATRIONA M. MACPHAIL, DVM, PhD Diplomate ACVS ACVS Founding Fellow, Surgical Oncology Professor, Small Animal Surgery Department of Clinical Sciences Colorado State University Fort Collins, Colorado USA

STEVEN L. MARKS, BVSc, MS, MRCVS Diplomate ACVIM (Small Animal Internal Medicine) Associate Dean, Director of Veterinary Medical Services College of Veterinary Medicine NC State University Raleigh, North Carolina USA

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SINA MARSILIO, Dr.med.vet., PhD Diplomate ACVIM (Small Animal Internal Medicine) Diplomate ECVIM-CA Assistant Professor University of California, Davis School of Veterinary Medicine Department of Veterinary Medicine and Epidemiology Davis, California USA DEBBIE MARTIN, LVT, VTS (Behavior) Veterinary Technician Specialist (Behavior) TEAM Education in Animal Behavior, LLC Veterinary Behavior Consultations, LLC Spicewood, Texas USA KATY A. MARTIN, DVM, MPH USDA Resident in Veterinary Parasitology Graduate Research Assistant Department of Veterinary Pathology College of Veterinary Medicine Iowa State University Ames, Iowa USA KENNETH M. MARTIN, DVM Diplomate ACVB (Veterinary Behaviorists) TEAM Education in Animal Behavior, LLC Veterinary Behavior Consultations, LLC Spicewood, Texas USA PAULA MARTÍN VAQUERO, DVM, PhD Diplomate ACVIM (Neurology) FCB Health Europe FCB Health Madrid Madrid Spain KENNETH V. MASON, BSc, MVSc, FACVSc Veterinary Dermatologist Managing Director Dermcare-Vet Pty Ltd Springwood, Queensland Australia PHILIPP D. MAYHEW, BVM&S, MRCVS Diplomate ACVS Professor, Small Animal Surgery Department of Surgical and Radiological Sciences University of California, Davis Davis, California USA

TERRI L. MCCALLA, DVM, MS Diplomate ACVO Animal HealthQuest Solutions LLC Bellingham, Washington USA MEGAN MCCLOSKY, DVM Clinical Assistant Professor Small Animal Internal Medicine Department of Clinical Sciences and Advanced Medicine University of Pennsylvania School of Veterinary Medicine Philadelphia, Pennsylvania USA PATRICK L. MCDONOUGH, MS, PhD Atkinson Center for a Sustainable Future Faculty Fellow Professor Emeritus of Veterinary Microbiology Animal Health Diagnostic Center Department of Population Medicine and Diagnostic Sciences College of Veterinary Medicine Cornell University Ithaca, New York USA KATHRYN M. MCGONIGLE, MPH DVM Diplomate ACVIM (Internal Medicine) Assistant Professor Clinical Small Animal Internal Medicine Department of Clinical Sciences and Advanced Medicine University of Pennsylvania School of Veterinary Medicine Philadelphia, Pennsylvania USA ANNA K. MCMANAMEY, DVM Cardiology Resident North Carolina State University Veterinary Hospital Raleigh, North Carolina USA STEPHEN MEHLER, DVM Diplomate ACVS Chief Medical Officer Veterinarian Recommended Solutions Blue Bell, Pennsylvania USA KRISTINA MEICHNER, DVM Diplomate ECVIM-CA (Oncology) Diplomate ACVP (Clinical Pathology) Assistant Professor Department of Pathology College of Veterinary Medicine University of Georgia Athens, Georgia USA

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KATHRYN M. MEURS, DVM, PhD Diplomate ACVIM (Cardiology) Professor Department of Clinical Sciences North Carolina State University College of Veterinary Medicine Raleigh, North Carolina USA LYNDA M.J. MILLER, DVM, PhD Diplomate ACT Director of Large Animal Clinical Skills Associate Professor of Theriogenology Lincoln Memorial University College of Veterinary Medicine Harrogate, Tennessee USA MATTHEW W. MILLER, DVM, MS Diplomate ACVIM (Cardiology) Staff Cardiologist and Cardiology Section Head VetMed Emergency and Specialty Care Phoenix, Arizona USA PAUL E. MILLER, DVM Diplomate ACVO Clinical Professor of Comparative Ophthalmology Department of Surgical Sciences School of Veterinary Medicine University of Wisconsin-Madison Madison, Wisconsin USA MELISSA L. MILLIGAN, VMD Resident in Internal Medicine The Animal Medical Center New York, New York USA KELLY MOFFAT, DVM Diplomate ACVB (Behavior) Medical Director VCA Mesa Animal Hospital Mesa, Arizona USA SARAH A. MOORE, DVM Diplomate ACVIM (Neurology) Professor Department of Veterinary Clinical Sciences College of Veterinary Medicine The Ohio State University Columbus, Ohio USA ANDREW R. MOORHEAD, DVM, MS, PhD Diplomate ACVM (Parasitology) Assistant Professor Department of Infectious Diseases University of Georgia College of Veterinary Medicine Athens, Georgia USA

DANIEL O. MORRIS, DVM, MPH Diplomate ACVD Professor of Dermatology & Allergy Department of Clinical Studies School of Veterinary Medicine University of Pennsylvania Philadelphia, Pennsylvania USA BRADLEY L. MOSES, DVM Diplomate ACVIM (Cardiology) Staff Clinician VCA Roberts Animal Hospital and VCA South Shore Animal Hospital South Weymouth, Massachusetts USA JOCELYN MOTT, DVM Diplomate ACVIM (Small Animal Internal Medicine) VCA TLC Pasadena Veterinary Specialty and Emergency South Pasadena, California USA CHRISTINE MULLIN, VMD Diplomate ACVIM (Oncology) Medical Oncologist Hope Veterinary Specialists Malvern, Pennsylvania USA JENNIFER M. MULZ, DVM Diplomate ACVIM (Cardiology) BluePearl Veterinary Partners Sarasota, Florida USA KAREN R. MUÑANA, DVM, MS Diplomate ACVIM (Neurology) Professor, Neurology Department of Clinical Sciences College of Veterinary Medicine North Carolina State University Raleigh, North Carolina USA LISA A. MURPHY, VMD Diplomate ABT Associate Professor of Toxicology Department of Pathobiology University of Pennsylvania School of Veterinary Medicine PADLS New Bolton Center Toxicology Laboratory Kennett Square, Pennsylvania USA

ANTHONY J. MUTSAERS, DVM, PhD Diplomate ACVIM (Oncology) Associate Professor Department of Clinical Studies Department of Biomedical Sciences Ontario Veterinary College University of Guelph Guelph, Ontario Canada KATHERN E. MYRNA, DVM, MS Diplomate ACVO Associate Professor of Ophthalmology Department of Small Animal Medicine and Surgery College of Veterinary Medicine University of Georgia Athens, Georgia USA GEORGINA M. NEWBOLD, DVM Diplomate ACVO Assistant Professor- Ophthalmology Department of Veterinary Clinical Sciences College of Veterinary Medicine The Ohio State University Columbus, Ohio USA REBECCA G. NEWMAN, DVM, MS Diplomate ACVIM (Oncology) Medical Oncologist Pittsburgh Veterinary Medical Specialist and Emergency Center Pittsburgh, Pennsylvania USA DENNIS P. O’BRIEN, DVM, PhD Diplomate ACVIM (Neurology) Professor Emeritus Department of Veterinary Medicine and Surgery College of Veterinary Medicine University of Missouri Columbia, Missouri USA LINDA K. OKONKOWSKI, DVM Internal Medicine Resident, ACVIM (Small Animal Internal Medicine) Small Animal Clinical Sciences Michigan State University College of Veterinary Medicine East Lansing, Michigan USA

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NATASHA J. OLBY, Vet MB, PhD, MRCVS Diplomate ACVIM (Neurology) Professor of Neurology/Neurosurgery Dr. Kady M. Gjessing and Rahna M. Davidson Distinguished Chair in Gerontology Department of Clinical Sciences Member of the Comparative Medicine Institute North Carolina State CVM Raleigh, North Carolina USA GAVIN L. OLSEN, DVM Diplomate ACVIM (Small Animal Internal Medicine) Staff Internist Carolina Veterinary Specialists Greensboro, North Carolina USA JENNIFER L. OWEN, DVM, PhD Diplomate ACVP (Clinical Pathology) Assistant Professor Department of Physiological Sciences College of Veterinary Medicine University of Florida Gainesville, Florida USA JOANE M. PARENT, DVM, MVetSc ACVIM Neurology Professor Centre Hospitalier Universitaire Vétérinaire Faculté de Médecine Vétérinaire Université de Montréal Montréal Canada VALERIE J. PARKER, DVM Diplomate ACVIM Diplomate ACVN Associate Professor, Clinical Department of Veterinary Clinical Sciences College of Veterinary Medicine The Ohio State University Columbus, Ohio USA THOMAS PARMENTIER, DVM Diplomate ACVIM (Neurology) PhD Candidate Department of Biomedical Sciences Ontario Veterinary College University of Guelph Guelph, Ontario Canada

R. MICHAEL PEAK, DVM Diplomate AVCD The Pet Dentist at Tampa Bay Largo, Florida USA KATHERINE L. PETERSON, DVM Diplomate ACVECC Diplomate ABT Emergency and Critical Care Specialist Pet Poison Helpline & SafetyCall International Bloomington, Minnesota USA MICHAEL E. PETERSON, DVM, MS Gem Veterinary Clinic Emmett, Idaho USA JASON PIEPER, DVM, MS Diplomate ACVD Assistant Professor Department of Veterinary Clinical Medicine University of Illinois at UrbanaChampaign Urbana, Illinois USA SARAH B. PIERARD, BVSc, PgCertVS, MVS Animal Diabetes Australia Melbourne, Victoria Australia AMY L. PIKE, DVM Diplomate ACVB Owner, Animal Behavior Wellness Center Fairfax, Virginia USA KATHRYN A. PITT, DVM, MS Diplomate ACVS-SA Assistant Professor of Small Animal Soft Tissue Surgery Small Animal Clinical Sciences Michigan State University East Lansing, Michigan Bloomington, Minnesota USA AMANDA L. POLDOSKI, DVM Senior Consulting Veterinarian, Clinical Toxicology Associate Manager of Veterinary & Regulatory Affairs Pet Poison Helpline & SafetyCall International Bloomington, Minnesota USA

DAVID J. POLZIN, DVM, PhD Diplomate ACVIM (Internal Medicine) Professor and Chief of Small Animal Internal Medicine University of Minnesota College of Veterinary Medicine Department of Veterinary Clinical Sciences St. Paul, Minnesota USA JILL S. POMRANTZ, DVM Diplomate ACVIM (Small Animal Internal Medicine) Small Animal Internal Medicine Consultant IDEXX Laboratories, Inc. Westbrook, Maine USA ERIC R. POPE, DVM, MS Diplomate ACVS Professor of Surgery Department of Clinical Sciences Ross University School of Veterinary Medicine Basseterre St Kitts ROBERT H. POPPENGA, DVM, PhD Diplomate ABVT Head, Toxicology Section California Animal Health and Food Safety Laboratory School of Veterinary Medicine University of California Davis, California USA

BIRGIT PUSCHNER, DVM, PhD Diplomate ABVT Dean and Professor College of Veterinary Medicine Michigan State University East Lansing, Michigan USA ANDHIKA PUTRA, DVM, MS Dermatology Specialty Intern Department of Small Animal Medicine and Surgery University of Georgia Athens, Georgia USA BARBARA QUROLLO, MS, DVM Associate Research Professor Department of Clinical Sciences-CVM North Carolina State University Raleigh, North Carolina USA MARYANN G. RADLINSKY, DVM, MS Diplomate ACVS Founding Fellow Minimally Invasive Surgery, Small Animal Soft Tissue Surgeon Salt River Veterinary Specialists Scottsdale, Arizona USA LISA RADOSTA, DVM Diplomate ACVB Florida Veterinary Behavior Service West Palm Beach, Florida USA

SIMON A. POT, DVM Diplomate ACVO Diplomate ECVO Associate Professor of Ophthalmology Equine Department Vetsuisse Faculty University of Zurich Zurich Switzerland

ELEANOR RAFFAN, BVM&S, PhD, CertSAM, MRCVS Diplomate ECVIM-CA University Lecturer in Systems Physiology Department of Physiology, Development and Neuroscience University of Cambridge Cambridge United Kingdom

SILVIA G. PRYOR, DVM Diplomate ACVO Ophthalmology Service BluePearl Emergency and Specialty Hospital-Irvine Irvine, California USA

MERL F. RAISBECK, DVM, MS, PhD Diplomate ABVT Emeritus Professor Department Veterinary Sciences University of Wyoming Laramie, Wyoming USA

DAVID A. PUERTO, DVM Diplomate ACVS Chief of Surgery Center for Animal Referral and Emergency Services Langhorne, Pennsylvania USA

LAURA RAYHEL, DVM Assistant Professor Department of Medicine College of Veterinary Medicine Midwestern University Glendale, Arizona USA

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JONJO REECE, DVM, ECFVG, BSc Small Animal Internal Medicine Resident Department of Clinical Sciences Cummings School of Veterinary Medicine Tufts University North Grafton, Massachusetts USA

SHARON L. RIPPEL, DVM Diplomate ABVT Diplomate ABT Clinical Toxicologist Pet Poison Helpline Bloomington, Minnesota USA

TABATHA J. REGEHR, DVM Consulting Veterinarian, Clinical Toxicology SafetyCall International & Pet Poison Helpline Bloomington, Minnesota USA

WESLEY J. ROACH, DVM Diplomate ACVS Head of Surgery Department Nashville Veterinary Specialists Nashville, Tennessee USA

MARSHA R. REICH, DVM Diplomate ACVB Veterinary Behaviorist Maryland-Virginia Veterinary Behavioral Consulting Silver Spring, Maryland USA

TRACIE D. ROMSLAND, DVM, MS Diplomate ACVP (Clinical Pathology) Staff Clinical Pathologist Friendship Hospital for Animals Washington, DC USA

JENNIFER M. REINHART, DVM, PhD Diplomate ACVIM (Small Animal Internal Medicine) Diplomate ACVCP Assistant Professor Department of Veterinary Clinical Medicine College of Veterinary Medicine University of Illinois Urbana-Champaign Urbana, Illinois USA ILANA R. REISNER, DVM, PhD Diplomate ACVB (Behavior) Reisner Veterinary Behavior Services, LLC Wallingford, Pennsylvania USA ALEXANDER M. REITER, Dipl.Tzt., Dr.med.vet Diplomate AVDC, Diplomate EVDC Professor of Dentistry and Oral Surgery Department of Clinical Sciences and Advanced Medicine School of Veterinary Medicine University of Pennsylvania Philadelphia, Pennsylvania USA LISA RESTINE, DVM Associate Veterinarian Alamo Feline Health Center San Antonio, Texas USA AUSTIN RICHMAN, DVM Diplomate ACVD Los Angeles, California USA

KATHRYN A. ROOK, VMD Diplomate ACVD Assistant Professor of Clinical Dermatology Department of Clinical Sciences and Advanced Medicine School of Veterinary Medicine University of Pennsylvania Philadelphia, Pennsylvania USA SHERI ROSS, BSc, DVM, PhD Diplomate ACVIM (Internal Medicine) Coordinator Advanced Urinary Disease and Extracorporeal Therapies Service University of California Veterinary Medical Center - San Diego San Diego, California USA JAMES K. ROUSH, DVM, MS Diplomate ACVS Doughman Chair Professor Department of Clinical Sciences College of Veterinary Medicine Kansas State University Manhattan, Kansas USA ELIZABETH ROZANSKI, DVM Diplomate ACVECC Diplomate DACVIM (Small Animal Internal Medicine) Associate Professor Department of Clinical Science Cummings School of Veterinary Medicine Tufts University North Grafton, Massachusetts USA

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RENEE RUCINSKY, DVM Diplomate ABVP (Feline Practice) Medical Director Mid Atlantic Cat Hospital Mid Atlantic Feline Thyroid Center Queenstown, Maryland USA ELKE RUDLOFF, DVM, CVMA Diplomate ACVECC Clinical Specialist Emergency and Critical Care Lakeshore Veterinary Specialists Glendale, Wisconsin USA HÉLÈNE L.M. RUEL, DVM, DES, MSc Diplomate ACVIM (Neurology) PhD Candidate Department of Clinical Sciences Faculty of Veterinary Medicine Université de Montréal Saint-Hyacinthe, Québec Canada WILSON K. RUMBEIHA, BVM, PhD, ATS Diplomate ABT Diplomate ABVT Professor of One Environmental Health Toxicology Department of Molecular Biosciences School of Veterinary Medicine University of California, Davis Davis, California USA ERIN E. RUNCAN, DVM Diplomate ACT Associate Professor, Clinical Theriogenology and Reproductive Medicine Department of Veterinary Clinical Sciences The Ohio State University College of Veterinary Medicine Columbus, Ohio USA

CLARE RUSBRIDGE, BVMS, PhD, FRCVS Diplomate ECVN Professor in Veterinary Neurology University of Surrey School of Veterinary Medicine Faculty of Health & Medical Sciences Guildford, Surrey United Kingdom

JOHN E. RUSH, DVM, MS Diplomate ACVIM (Cardiology) Diplomate ACVECC Professor Department of Clinical Sciences Tufts University Cummings School of Veterinary Medicine North Grafton, Massachusetts USA KAREN E. RUSSELL, DVM, PhD Diplomate ACVP (Clinical Pathology) Professor and Associate Department Head for Clinical Services and Residency Programs Department of Veterinary Pathobiology College of Veterinary Medicine & Biomedical Sciences Texas A&M University College Station, Texas USA SHERISSE A. SAKALS, DVM Diplomate ACVS-SA VCA Vancouver Animal Emergency & Referral Center Vancouver, WA Canada CARL D. SAMMARCO, BVSc MRCVS Diplomate ACVIM (Cardiology) Head of Cardiology Red Bank Veterinary Hospital Tinton Falls, New Jersey USA SHERRY LYNN SANDERSON, BS, DVM, PhD Diplomate ACVIM (Small Animal Internal Medicine) Diplomate ACVN Associate Professor Department of Veterinary Biosciences and Diagnostic Imaging College of Veterinary Medicine The University of Georgia Athens, Georgia USA DOMENICO SANTORO, DVM, MS, DrSc, PhD Diplomate ACVD Diplomate ECVD Diplomate ACVM (Bacteriology/Mycology/ Immunology) Assistant Professor Department of Small Animal Clinical Sciences College of Veterinary Medicine University of Florida Gainesville, Florida USA

ASHLEY B. SAUNDERS, DVM Diplomate ACVIM (Cardiology) Professor of Cardiology Department of Veterinary Small Animal Clinical Sciences College of Veterinary Medicine & Biomedical Sciences Texas A&M University College Station, Texas USA BRIAN A. SCANSEN, DVM, MS Diplomate ACVIM (Cardiology) Associate Professor and Service Head, Cardiology & Cardiac Surgery Department of Clinical Sciences Colorado State University Fort Collins, Colorado USA MICHAEL SCHAER, DVM Diplomate ACVIM (Small Animal Internal Medicine) Diplomate ACVECC Emeritus Professor Adjunct Professor, Emergency and Critical Care Medicine University of Florida College of Veterinary Medicine Gainesville, Florida USA THOMAS SCHERMERHORN, VMD Diplomate ACVIM (Small Animal Internal Medicine) Professor and Jarvis Chair Department of Clinical Sciences College of Veterinary Medicine Kansas State University Manhattan, Kansas USA PHILIP SCHISSLER, DVM Diplomate ACVIM (Neurology) Staff Neurologist/Neurosurgeon Veterinary Neurology Center Tustin, California USA RENEE D. SCHMID, DVM Diplomate ABVT Diplomate ABT Senior Consulting Veterinarian, Clinical Toxicology Pet Poison Helpline & SafetyCall International Bloomington, Minnesota USA

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KARSTEN E. SCHOBER, DVM, MS, PhD Diplomate ECVIM-CA (Cardiology) Professor Head, Cardiology and Interventional Medicine Department of Veterinary Clinical Sciences College of Veterinary Medicine The Ohio State University Columbus, Ohio USA GRETCHEN L. SCHOEFFLER, DVM Diplomate ACVECC Chief, Emergency and Critical Care Department of Clinical Sciences College of Veterinary Medicine Cornell University Ithaca, New York USA JOHAN P. SCHOEMAN, BVSc, MMedVet(Med)(Pretoria), PhD(Cantab), DSAM(RCVS-UK) Diplomate ECVIM-CA EBVS® European Veterinary Specialist in Internal Medicine RCVS Recognized Specialist in Small Animal Medicine; Professor Department of Companion Animal Clinical Studies Chair, Pathobiology Research Faculty of Veterinary Science University of Pretoria Onderstepoort South Africa DONALD P. SCHROPE, DVM Diplomate ACVIM (Cardiology) Department of Cardiology Oradell Animal Hospital Paramus, New Jersey USA ERIN M. SCOTT, VMD Diplomate ACVO Department of Small Animal Clinical Sciences College of Veterinary Medicine Texas A&M University College Station, Texas USA CHRISTOPHER J. SCUDDER, BVSc, MVetMed, PhD, MRCVS Diplomate ACVIM-SAIM Diplomate ECVIM-CA Head of Internal Medicine Southfields Veterinary Specialists Essex United Kingdom

LYNNE M. SEIBERT, DVM, MS, PhD Diplomate ACVB Veterinary Behavior Consultants LLC Lawrenceville, Georgia USA ASHLEIGH SEIGNEUR, DVM, MVSc Diplomate ACVIM Associate Veterinarian Internal Medicine Department South Carolina Veterinary Specialists and Emergency Care Columbia, South Carolina USA KIM A. SELTING, DVM, MS Diplomate ACVIM (Oncology) Diplomate ACVR (Radiation Oncology) Associate Professor Department of Veterinary Clinical Medicine College of Veterinary Medicine University of Illinois at Urbana-Champaign Urbana, Illinois USA LINDA G. SHELL, DVM Diplomate ACVIM (Neurology) Veterinary Neurology Education and Consulting Pilot, Virginia USA BARBARA L. SHERMAN, MS, PhD, DVM Diplomate ACVB (Behavior) & ACAW (Animal Welfare) Clinical Professor Emerita Department of Clinical Sciences College of Veterinary Medicine North Carolina State University Raleigh, North Carolina USA TRACI A. SHREYER, MA Applied Animal Behaviorist Consultant Department of Comparative Pathobiology Purdue University West Lafayette, Indiana USA DEBORAH C. SILVERSTEIN, DVM Diplomate ACVECC Professor of Critical Care Department of Clinical Sciences and Advanced Medicine University of Pennsylvania School of Veterinary Medicine Philadelphia, Pennsylvania USA

LESLIE SINN, DVM Diplomate ACVB Specialist in Behavior Behavior Solutions Hamilton, Virginia USA KIM SLENSKY, DVM Diplomate ACVECC Assistant Professor of Clinical Emergency and Critical Care Department of Clinical Sciences and Advanced Medicine School of Veterinary Medicine University of Pennsylvania Philadelphia, Pennsylvania USA FRANCIS W.K. SMITH, JR., DVM Diplomate, ACVIM (Small Animal Internal Medicine and Cardiology) Vice-President VetMed Consultants, Inc. Lexington, Massachusetts USA MARK M. SMITH, VMD Diplomate ACVS Diplomate AVDC Founding Fellow, ACVS Oral & Maxillofacial Surgery Founding Fellow, AVDC Oral & Maxillofacial Surgery Center for Veterinary Dentistry and Oral Surgery Gaithersburg, Maryland USA PATRICIA J. SMITH, MS, DVM, PhD Diplomate ACVO PJSmith Animal Eye Consulting Adjunct Ophthalmologist Animal Eye Care Milpitas, California USA CHRISTOPHER J. SNYDER, DVM Diplomate AVDC Clinical Associate Professor Dentistry and Oral Surgery, Department of Surgical Sciences University of Wisconsin-Madison School of Veterinary Medicine Madison, Wisconsin USA PAUL W. SNYDER, DVM, PhD Diplomate ACVP (Anatomical Pathology) Fellow, International Academy Toxicologic Pathologists Senior Pathologist Experimental Pathology Laboratories, Inc. Bonita Springs, Florida USA

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LAIA SOLANO-GALLEGO, DVM, PhD Diplomate ECVCP Professora Agregada (Associate Professor) Departament de Medicina i Cirurgia Animals Facultat de Veterinària Universitat Autònoma de Barcelona Barcelona Spain MITCHELL D. SONG, DVM Diplomate ACVD Animal Dermatology, PC Phoenix, Arizona; Adjunct Assistant Clinical Professor Midwestern University College of Veterinary Medicine Glendale, Arizona USA JASON W. SOUKUP, DVM Diplomate AVDC Founding Fellow, AVDC Oral & Maxillofacial Surgery Clinical Associate Professor Dentistry and Oromaxillofacial Surgery Department of Surgical Sciences School of Veterinary Medicine University of Wisconsin-Madison Madison, Wisconsin USA SAMANTHA B. SOUTHER, DVM Diplomate ACT Associate Veterinarian, Theriogenology Mohnacky Animal Hospitals Carlsbad, California USA CLARISSA P. SOUZA, DVM, MS, PhD Diplomate ACVD Assistant Professor of Dermatology and Otology Department of Veterinary Clinical Medicine College of Veterinary Medicine University of Illinois Urbana-Champaign, Illinois USA JÖRG M. STEINER, MedVet, DrVetMed, PhD, AGAF Diplomate ACVIM Diplomate ECVIM-CA University Distinguished Professor Dr. Mark Morris Chair in Small Animal Gastroenterology and Nutrition Director, Gastrointestinal Laboratory Department of Small Animal Clinical Sciences College of Veterinary Medicine and Biomedical Sciences Texas A&M University College Station, Texas USA

KEVIN S. STEPANIUK, DVM, FAVD Diplomate AVDC Veterinary Dentistry Education and Consulting Services Ridgefield, Washington USA JOSHUA A. STERN, DVM, PhD Diplomate ACVIM (Cardiology) Associate Professor Department of Medicine & Epidemiology School of Veterinary Medicine University of California, Davis Davis, California USA VICTOR J. STORA, DVM Postdoctoral Fellow Transgenesis & Large Animal Model Creation Vite Lab, Referral Center for Animal Models Department of Clinical Sciences and Advanced Medicine School of Veterinary Medicine University of Pennsylvania Philadelphia, Pennsylvania USA JAN S. SUCHODOLSKI, MedVet, DrVetMed, PhD, AGAF Diplomate ACVM (Immunology) Associate Professor Small Animal Medicine Associate Director for Research Head of Microbiome Sciences Gastrointestinal Laboratory Texas A&M University College of Veterinary Medicine Department of Small Animal Clinical Sciences College Station, Texas USA ALYSSA M. SULLIVANT, DVM, MS Diplomate ACVIM (Small Animal Internal Medicine) Assistant Professor Department of Clinical Sciences College of Veterinary Medicine Mississippi State University Mississippi State, Mississipi USA ANNIKA SUNDBY, DVM Rotating Intern Nashville Veterinary Specialists Nashville, Tennessee USA

WAILANI SUNG, MS, PhD, DVM Diplomate ACVB Veterinary Behaviorist Behavior Service The San Francisco Society for the Prevention of Cruelty to Animals (SPCA) San Francisco, California USA

JAIME L. TARIGO, DVM, PhD Diplomate ACVP (Clinical Pathology) Associate Professor Department of Pathology College of Veterinary Medicine University of Georgia Athens, Georgia USA

STEVEN E. SUTER, VMD, MS, PhD Diplomate ACVIM (Oncology) Professor Department of Clinical Sciences North Carolina State University College of Veterinary Medicine Raleigh, North Carolina USA

DOMINIC A. TAUER, DVM Diplomate ABT Consulting Veterinarian in Clinical Toxicology Pet Poison Helpline and SafetyCall International, PLLC Bloomington, Minnesota USA

JANE E. SYKES, BVSc(Hons), PhD Diplomate ACVIM (Small Animal Internal Medicine) Professor of Small Animal Internal Medicine Department of Medicine & Epidemiology University of California, Davis Davis, California USA JOSEPH TABOADA, DVM Diplomate ACVIM Professor and Associate Dean Department of Veterinary Clinical Sciences School of Veterinary Medicine Louisiana State University Baton Rouge, Louisiana USA LAUREN TALARICO, BS, DVM Diplomate ACVIM (Neurology) Section Head Neurology/Neurosurgery VCA Southpaws Veterinary Specialty & Emergency Center Fairfax, Virginia USA PATRICIA A. TALCOTT, MS, DVM, PhD Diplomate ABVT Professor Department of Integrative Physiology and Neuroscience College of Veterinary Medicine Washington State University Pullman, Washington USA KENDALL TANEY, DVM Diplomate AVDC Center for Veterinary Dentistry and Oral Surgery Gaithersburg, Maryland USA

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SUSAN M. TAYLOR, DVM Diplomate ACVIM Professor Emeritus Department of Small Animal Clinical Sciences Western College of Veterinary Medicine University of Saskatchewan Saskatoon, Saskatchewan Canada MICHELLE C. TENSLEY, DVM, MS Diplomate ACVIM (Neurology) Associate Neurologist The Animal Neurology and Imaging Center Algodones, New Mexico USA VINCENT J. THAWLEY, VMD Diplomate ACVECC Clinical Assistant Professor Emergency and Critical Care Medicine Department of Clinical Sciences and Advanced Medicine School of Veterinary Medicine University of Pennsylvania Philadelphia, Pennsylvania USA JUSTIN D. THOMASON, DVM Diplomate ACVIM (Cardiology; SAIM) Clinical Associate Professor Department of Clinical Sciences College of Veterinary Medicine Kansas State University Manhattan, Kansas USA CRAIG A. THOMPSON, DVM Diplomate ACVP Clinical Associate Professor - Clinical Pathology Department of Comparative Pathobiology Purdue University- College of Veterinary Medicine West Lafayette, Indiana USA

JERRY A. THORNHILL, DVM Diplomate ACVIM Director, Nephrology & Dialysis Division of Internal Medicine Veterinary Specialty Center Buffalo Grove, Illinois USA

VALARIE V. TYNES, DVM Diplomate ACVB (Veterinary Behavior) Diplomate ACAW (Animal Welfare) Veterinary Services Specialist Ceva Animal Health Lenexa, Kansas USA

MARY ANNA THRALL, BA, DVM, MS Diplomate ACVP (Clinical Pathology) Professor Department of Biomedical Sciences Ross University School of Veterinary Medicine Basseterre, St. Kitts West Indies

YU UEDA, DVM, PhD Clinical Assistant Professor Small Animal Emergency and Critical Care Department of Clinical Sciences College of Veterinary Medicine North Carolina State University Raleigh, North Carolina USA

LARRY P. TILLEY, DVM Diplomate ACVIM (Small Animal Internal Medicine) President VetMed Consultants, Inc. Santa Fe, New Mexico USA

STEFAN UNTERER, Dr.med.vet., Dr. habil. Diplomate ECVIM Head of Gastroenterology Service Clinic of Small Animal Internal Medicine Ludwig-Maximilians-University Munich Germany

ANDREA TIPOLD, DVM Diplomate ECVN (Veterinary Neurology) Department of Small Animal Medicine and Surgery University of Veterinary Medicine Hannover Hannover Germany

SHELLY VADEN, DVM, PhD Diplomate ACVIM (Internal Medicine) Professor, Small Animal Nephrology and Urology Department of Clinical Sciences College of Veterinary Medicine North Carolina State University Raleigh, North Carolina USA

SHEILA M.F. TORRES, DVM, MS, PhD Diplomate ACVD (Dermatology) Professor Department of Veterinary Clinical Sciences College of Veterinary Medicine University of Minnesota St. Paul, Minnesota USA SANDRA P. TOU, DVM Diplomate ACVIM (Cardiology and Internal Medicine) Clinical Assistant Professor of Cardiology Department of Clinical Sciences North Carolina State University College of Veterinary Medicine Raleigh, North Carolina USA WILLIAM J. TRANQUILLI, Bs in Ed, Ms, DVM Diplomate ACVAA Professor Emeritus Departments of Clinical Science, Biological Sciences, and Pathobiology University of Illinois-Urbana Illinois USA

SUZY Y.M. VALENTIN, DVM, MS Diplomate ACVIM Diplomate ECVIM-CA (Internal Medicine) Internal Medicine Specialist Internal Medicine Service Centre Hospitalier Vétérinaire Pommery Reims France MEGHAN VAUGHT, DVM Diplomate ACVECC Staff Criticalist; ECC Medical Director Maine Veterinary Medicine Center Scarborough, Maine USA GUILHERME G. VEROCAI, DVM, MSc, PhD Diplomate ACVM (Parasitology) Clinical Assistant Professor Director Parasitology Diagnostic Laboratory Department of Veterinary Pathobiology College of Veterinary Medicine and Biomedical Sciences Texas A&M University College Station, Texas USA

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MARIA VIANNA, DVM Diplomate DACVS Veterinary Specialty Hospital of Palm Beach Gardens Palm Beach Gardens, Florida USA ALYSHA VINCENT, DVM Internal Medicine Resident (Small Animal Internal Medicine) Department of Small Animal Clinical Sciences College of Veterinary Medicine Michigan State University East Lansing, Michigan USA KAREN A. VON DOLLEN, DVM, MS Diplomate ACT Hagyard Equine Medical Institute Lexington, Kentucky USA DIRSKO J.F. VON PFEIL, Dr.med.vet, DVM Diplomate ACVS Diplomate ECVS Diplomate ACVSMR Sirius Veterinary Orthopedic Center Omaha, Nebraska; Small Animal Surgery Locum, PLLC Dallas, Texas USA LORI S. WADDELL, DVM Diplomate ACVECC Professor, Clinical Critical Care Department of Clinical Studies and Advancement of Medicine School of Veterinary Medicine University of Pennsylvania Philadelphia, Pennsylvania USA LIORA WALDMAN, BVM&S, MRCVS CertSAD Dermatology and Allergy Clinic Haifa Israel JULIE M. WALKER, DVM Diplomate ACVECC Clinical Associate Professor Department of Medical Sciences School of Veterinary Medicine University of Wisconsin-Madison Madison, Wisconsin USA

REBECCA A.L. WALTON, DVM Diplomate ACVECC Clinical Assistant Professor Department of Veterinary Clinical Sciences College of Veterinary Medicine Iowa State University Ames, Iowa USA STUART A. WALTON, BVSc, BScAgr MANZCVS (Small Animal Internal Medicine) Diplomate ACVIM (Small Animal Internal Medicine) Clinical Assistant Professor Department of Small Animal Clinical Sciences College of Veterinary Medicine University of Florida Gainesville, Florida USA ANDREA WANG MUNK, MA, DVM Diplomate ACVIM (Small Animal Internal Medicine) Small Animal Internal Medicine Consultant IDEXX Laboratories, Inc. Westbrook, Maine USA KIRSTEN E. WARATUKE, DVM Diplomate ABT Toxicologist ASPCA Animal Poison Control Center Urbana, Illinois USA BRETT A. WASIK, DVM Diplomate ACVIM (Small Animal Internal Medicine) Antech Diagnostics - Internal Medicine/ Endocrinology Consultant Veterinary Information Network - Internal Medicine/Endocrinology Consultant UC Davis Endocrinology Post-doctorate Allen, Texas USA NICOLE M. WEINSTEIN, DVM Diplomate ACVP (Clinical Pathology) Associate Professor Department of Pathobiology School of Veterinary Medicine University of Pennsylvania Philadelphia, Pennsylvania USA GLADE WEISER, DVM Diplomate ACVP Emeritus Clinical Pathologist Loveland, Colorado USA

SARA A. WENNOGLE, DVM, PhD Diplomate ACVIM-SAIM Assistant Professor Small Animal Clinical Sciences Michigan State University East Lansing, Michigan USA MICHAEL D. WILLARD, DVM, MS Diplomate ACVIM (Small Animal) Senior Professor Department of Small Animal Clinical Sciences College of Veterinary Medicine Texas A&M University College Station, Texas USA LAUREL E. WILLIAMS, DVM Diplomate ACVIM (Oncology) Adjunct Professor Department of Clinical Sciences College of Veterinary Medicine North Carolina State University Raleigh, North Carolina; Oncologist​, Medical Director Veterinary Specialty Center of Seattle Lynwood, Washington USA

R. DARREN WOOD, DVM, DVSc Diplomate ACVP (Clinical Pathology) Associate Professor Department of Pathobiology Ontario Veterinary College University of Guelph Guelph, Ontario Canada J. PAUL WOODS, DVM, MS Diplomate ACVIM (Internal Medicine, Oncology) Professor of Internal Medicine and Oncology Department of Clinical Studies Ontario Veterinary College; Co-Director Institute for Comparative Cancer Investigation University of Guelph Guelph, Ontario Canada CORRY K. YEUROUKIS, DVM, MS Diplomate ACVP (Clinical) Clinical Pathologist ANTECH Diagnostics Annapolis, Maryland USA

HEATHER M. WILSON-ROBLES, DVM Diplomate ACVIM (Oncology) Professor Department of Veterinary Small Animal Clinical Sciences College of Veterinary Medicine Texas A&M University College Station, Texas USA

HANY YOUSSEF, BVSc, MS, DVM Diplomate ABT Diplomate ABVT Watseka Animal Hospital Watseka, Illinois; Iroquois County Animal Control Director Watseka, Illinois USA

TINA WISMER, DVM, MS Diplomate ABVT Diplomate ABT Medical Director ASPCA Animal Poison Control Center Urbana, Illinois USA

DANIELLE ZWUESTE, DVM Diplomate ACVIM (Neurology) Vancouver Animal Emergency and Referral Centre Vancouver British Columbia Canada

EWAN D.S. WOLFF, PhD, DVM Diplomate ACVIM Small Animal Internist BluePearl - Affiliated Veterinary Specialists USA MICHAEL W. WOOD, DVM, PhD Diplomate ACVIM (Small Animal Internal Medicine) Assistant Professor Department of Medical Sciences School of Veterinary Medicine University of Wisconsin-Madison Madison, Wisconsin USA

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About the Companion Website This book is accompanied by a companion website: www.fiveminutevet.com/canineandfeline7th The website includes: •  Videos •  Images •  Client Education Handouts •  Additional references and internet resources

The password for the companion website: pl58ez690xle

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Canine and Feline, Seventh Edition

5-Fluorouracil (5-FU) Toxicosis

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 BASICS

OVERVIEW •  Antimetabolite, antineoplastic agent; it is metabolized to thymidine, which blocks the methylation reaction of deoxyuridylic and thymidylic acids, resulting in thymine deficiency; thymine is critical for DNA and to a lesser extent RNA replication; the result is cell death due to interruption of normal DNA and RNA synthesis; this mechanism targets rapidly growing cells like bone marrow and intestinal crypts; 5-FU has various active metabolites resulting in delayed clearance from bone marrow and γ-aminobutyric acid (GABA) depletion in the brain. •  Labeled for human use only. •  Topical preparation for actinic and solar keratoses: Efudex® (5% cream, 2% and 5% solution), Carac® (0.5% cream), Fluoroplex® (1% cream), Tolak® (4% cream). •  IV preparation used for a variety of neoplastic conditions: Adrucil® (50 mg/m: IV solution). •  Causes acute and severe gastroenteritis and seizures; seizures can develop within 30 minutes to 6 hours post exposure; bone marrow suppression occurs 7–21 days after acute presentation. •  Patients may survive acute toxicity to succumb to bone marrow suppression later. •  Any suspected exposure in animals warrants immediate veterinary evaluation.

iron, metaldehyde, mushrooms (Amanita, Galerina, and Lepiota spp.), sodium fluoroacetate (Compound 1080), strychnine. •  Metabolic—hepatic failure, hepatic encephalopathy. •  Nervous—idiopathic epilepsy, meningitis, neoplasia. CBC/BIOCHEMISTRY/URINALYSIS

•  CBC—baseline, then continue to monitor

q3–4 days post exposure for 21 days; monitor for echinocytes; leukopenia develops by day 7 and continues to day 13; thrombocytopenia develops by day 7 and can continue for 21 days; acute anemia due to blood loss can be secondary to bone marrow suppression by day 9, persisting until day 21. •  Chemistry—baseline; hepatic values may increase. •  Electrolytes—baseline; recheck PRN based on GI losses. OTHER LABORATORY TESTS

•  Blood gases—metabolic acidosis can occur;

monitor PRN.

•  Packed cell volume (PCV)/total protein

(TP) q6–24h.

•  Blood glucose q2–4h.

•  Antiemetic—maropitant 1 mg/kg IV, SC

q24h; ondansetron 0.1–0.2 mg/kg IV q6–12h; metoclopramide 0.1–0.5 mg/kg IV, SC q6–8h. •  GI protection—proton pump inhibitors, H2 blockers, sucralfate. •  Analgesia—buprenorphine 0.005–0.03 mg/kg IM or IV q6–12h, butorphanol 0.1–0.5 mg/kg SC, IV, or IM. •  Antibiotic—broad-spectrum antibiotic therapy if total white blood cell count is below 2000. •  Bone marrow stimulation—filgrastim (Neupogen®) 4–6 μg/kg SQ q24h. •  Transfusion therapy may be indicated if PCV 5 years old; increased risk in purebred cats with high inbreeding.

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SIGNS General Comments

Frequently no clinical symptoms other than lack of pregnancy or reduced litter size. Historical Findings

Failure to deliver kittens at expected due date, return to estrus sooner than expected (approximately 45 days), discovery of fetal tissues or placenta, behavior change, systemic illness. Physical Examination Findings

Signs range from normal to dehydration, fever, abdominal straining, and discomfort to presence of purulent, mucoid, watery, or sanguineous vaginal discharge.

 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Early pregnancy loss—failure to ovulate, failure to conceive, chromosomal disorder, or disorder of sexual development. •  Vaginal discharge—pyometra, uterine stump pyometra, mucometra, vaginitis, neoplasia, cystitis, active labor or impending abortion, trauma to urogenital tract. •  Mass or tissue from vaginal vault—dystocia, neoplasia, hemorrhage/blood clot, uterine prolapse.

confirm positive results with Western blot.

•  FPLV—viral isolation from fetuses

submitted for necropsy; document serocon­ version in queen.

Noninfectious Causes

•  To rule out anovulatory cycle, confirm

progesterone >2 ng/mL one week following mating. •  Hypoluteoidism—serum progesterone level 200 bpm). Visualization of fetal kidney and intestinal peristalsis indicates fetal maturity. •  Abdominal radiographs—after 45 days, can evaluate fetal number, relative size, and position; also assess fetal death (gas pockets) or fetal malformation. DIAGNOSTIC PROCEDURES

•  Submit aborted, stillborn, mummified

fetuses and fetal membranes (fresh or refrigerated on ice) for gross necropsy, histopathology, cultures, and viral isolation. Submit culture of reproductive tract or entire tract if removed (uterus, ovaries, oviducts). Submit samples from aborted and stillborn fetus for karyotyping. •  Pedigree analysis— evaluate COI. •  Evaluate cattery management for vaccination protocols, feeding regime, sanitation procedures, and quarantine procedures. •  Nutrition—nutritional analysis of diet: of particular importance when queen is fed homemade and/or raw diet. PATHOLOGIC FINDINGS Variable with etiology.

CBC/BIOCHEMISTRY/URINALYSIS

•  Generally normal. •  Inflammatory leuko-

­gram with infection or systemic disease. •  Anemia of pregnancy; hemoconcentration and azotemia may be seen with dehydration or hypovolemia.

CAUSES

OTHER LABORATORY TESTS

Infectious

Infectious Causes

abortion via ascending infection through the vaginal vault and cervix include E. coli, Staphylococcus spp., Streptococcus spp., Chlamydia spp., Pasteurella spp., Klebsiella spp., Pseudomonas spp., Salmonella spp., Mycoplasma spp., and Ureaplasma spp. •  Protozoal— Toxoplasma gondii. •  Viral— feline leukemia

discharge, fetus, fetal membranes, or uterine contents (aerobic and mycoplasma). •  FeLV—test for antigens in queens using ELISA or indirect fluorescent antibody (IFA). •  FHV-1—IFA or PCR from corneal or conjunctival swabs, viral isolation from conjunctival, nasal, or pharyngeal swabs.

•  Bacterial—organisms implicated in causing

•  FIP—submit fetal tissue for histopathology and immunohistochemistry. •  FIV—ELISA:

•  Cytology and bacterial culture of vaginal

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 TREATMENT

APPROPRIATE HEALTH CARE None, for noninfectious, stable queens; primary hypoluteoidism—managed on outpatient basis. NURSING CARE Inpatient management if systemically ill, debilitated, severely dehydrated, or for medical management of ongoing fetal loss or pyometra. ACTIVITY •  Isolation for queens with infectious disease. •  No activity restrictions for most; restrict activity as indicated if due to trauma.

(continued)

Abortion, Spontaneous (Early Pregnancy Loss)—Cats

DIET •  Feed commercially available diet labeled for use in pregnancy. •  Correct diets with inappropriate taurine or vitamin A concen­ trations. •  Avoid feeding raw meats or allowing queens to hunt during pregnancy to reduce risk for ingestion of pathogenic bacteria and T. gondii. CLIENT EDUCATION

•  Infectious diseases—verify vaccination

status (vaccinate prior to pregnancy) and disease surveillance measures; ensure use of quarantine facilities for pregnant queens and new arrivals. •  Breeding management—keep detailed records of reproductive performance, pedigree analysis, and social behavior of queens (including when not receptive to male). •  Nutrition—advise feeding commercial cat food during pregnancy. •  Genetic disease— discuss COI and value of introducing new genetics. •  Discuss risk of zoonotic disease from T. gondii. SURGICAL CONSIDERATIONS Ovariohysterectomy (OHE) may be considered if queen is systemically ill from uterine infection or deceased fetuses. If valuable breeding animal, Cesarean section can be performed to remove deceased fetuses.

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Canine and Feline, Seventh Edition

 MEDICATIONS

DRUG(S) OF CHOICE •  Depends on etiology. •  Amoxicillin– clavulanic acid 13.75 mg/kg PO q12h—safe for pregnancy. •  Enrofloxacin 5 mg/kg/day PO— excellent penetration to uterus; contraindicated if live fetuses present. •  Prostaglandin F2α (PGF2α; dinoprost/Lutalyse®) 80–100 μg/kg IM q8–12h—promotes uterine contractions, loss of corpus luteum, and cervical opening to expulse aborted materials. •  Tocolytics— prevent uterine contractions: terbutaline 0.03–1.0 mg PO as needed based on tocodyna­ mometry (www.whelpwise.com); 0.03 mg/kg PO q8h if tocodynamometry not available. •  Hypoluteoidism—oral progestogene (altrenogest) 0.088 mg/kg PO q24h to maintain pregnancy; can monitor queen’s progesterone, as altrenogest will not interfere with progesterone assay. CONTRAINDICATIONS •  Terbutaline—cardiac disease, pyometra, infectious disease, hypertension. •  Altrenogest—contaminated uterus with systemically ill queen. •  Prostaglandin-cats with previously diagnosed respiratory disease. PRECAUTIONS

•  Use of tocolytics requires accurate breeding

dates to know when to stop treatment; most successful in combination with tocodyna­ mometry. •  Terbutaline can cause

hypertension leading to hemorrhage from placental sites during parturition or at time of Cesarean section. •  Altrenogest can cause agalactia and failure of parturition, leading to death of litter; discontinue use 2 days before due date. •  Caution with use of altrenogest with infectious processes or necrotic fetuses in uterus; may keep infection within uterus, causing metritis and systemic illness; monitor pregnancy often with ultrasound. •  PGF2α— side effects vomiting, hypersalivation, defecation, urination, and tachypnea; dose dependent and self-limiting. POSSIBLE INTERACTIONS

•  Progesterone administration during

pregnancy associated with masculinization of female fetuses; do not administer in first half of pregnancy and use with informed consent thereafter. •  Tocolytics associated with increased risk of dystocia, failure of placental separation, lack of milk production, and poor maternal behavior for first days postpartum. ALTERNATIVE DRUG(S) Dopamine agonists (e.g., cabergoline 5 μg/kg PO q24h) can be used to lower progesterone and facilitate uterine emptying. Use in conjunction with low dose of PGF2α.

CEH. •  Fair prognosis for successful pregnancy with treatment for primary hypoluteoidism; significant monitoring required for good outcome. •  Pregnancy loss due to genetic abnormalities likely to recur if queen is bred to tom with similar pedigree.

­

 MISCELLANEOUS

ASSOCIATED CONDITIONS Severe systemic disease otf any kind, malnutrition. AGE-RELATED FACTORS Queens >6 years old—higher incidence of lower litter size and infertility. ZOONOTIC POTENTIAL T. gondii. PREGNANCY/FERTILITY/BREEDING Queens with previous pregnancy loss are at higher risk of subsequent pregnancy loss or infertility and should be monitored intensively. SYNONYMS •  Pregnancy loss. •  Abortion. •  Fetal mummification. •  Early embryonic loss. SEE ALSO

­

 FOLLOW-UP

PATIENT MONITORING •  Serial ultrasound—follow pregnancy loss, uterine emptying, or viability of remaining fetuses; initially daily; decrease frequency when stable, continue until birth (with partial loss) or uterus is free of fluid (complete abortion). •  Monitor health and attitude of queen. •  If live fetuses are present—delayed parturition my occur with progesterone or terbutaline treatment; Cesarean section may be necessary. PREVENTION/AVOIDANCE

•  Institute infectious disease prevention, control, and surveillance. •  Replace subfertile

queens with more reproductively fit individ­ uals. •  Avoid exposure to abortifacient, teratogenic, or fetotoxic drugs. •  Serial progesterone assays and fetal ultrasound during next pregnancy. POSSIBLE COMPLICATIONS

•  Loss of entire litter. •  Metritis, chronic

endometritis, uterine rupture, sepsis, shock. •  Uterine pathology. •  Masculinization of female fetuses with progesterone therapy. EXPECTED COURSE AND PROGNOSIS •  Poor prognosis for live kittens for current litter, even with aggressive monitoring and treatment. •  May recur in future pregnancies depending on cause and treatment. •  Poor prognosis for normal pregnancy with severe

•  Breeding, Timing. •  Sexual Development Disorders.

ABBREVIATIONS

•  CEH = cystic endometrial hyperplasia. •  COI = coefficient of inbreeding. •  FeLV = feline leukemia virus. •  FHV-1 = feline herpesvirus 1. •  FIPV = feline infectious peritonitis virus. •  FIV = feline immuno­deficiency virus. •  FPLV = feline panleukopenia virus. •  IFA = indirect fluorescent antibody. •  OHE = ovariohysterectomy. •  PGF2α = prostaglandin F2α.

­Suggested Reading

Lamm CG. Clinical approach to abortion, stillbirth, and neonatal death in dogs and cats. Vet Clin North Am Small Anim Pract 2012, (42)3:501–513. Verstegen J, Dhaliwal G, Verstegen-Onclin K. Canine and feline pregnancy loss due to viral and non-infectious causes: a review. Theriogenology 2008, 70(3):304–319. Author Aime K. Johnson Consulting Editor Erin E. Runcan Acknowledgment The author and editors acknowledge the prior contribution of Milan Hess.  Client Education Handout available online

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Blackwell’s Five-Minute Veterinary Consult

Abortion, Spontaneous (Early Pregnancy Loss)—Dogs CAUSES Infectious

­

 BASICS

DEFINITION Loss of a fetus because of resorption in early stages or expulsion in later stages of pregnancy. PATHOPHYSIOLOGY •  Direct—congenital abnormality, infectious disease, trauma. •  Indirect—infectious placentitis, abnormal ovarian function, abnormal uterine environment. SYSTEMS AFFECTED

•  Reproductive. •  Any major body system dysfunction can

adversely affect pregnancy. GENETICS

•  No genetic basis for most causes. •  Lymphocytic hypothyroidism—single-gene

recessive trait in Borzois.

INCIDENCE/PREVALENCE

•  True incidence unknown. •  Resorption estimated between 11% and

13%, up to 30% (at least one resorption).

•  Brucella canis. •  Canine herpesvirus. •  Toxoplasma gondii, Neospora caninum. •  Mycoplasma and Ureaplasma. •  Bacteria—Escherichia coli, Streptococcus,

Campylobacter, Salmonella.

•  Viruses—distemper, parvovirus, adenovirus.

Uterine

•  Cystic endometrial hyperplasia and pyometra. •  Trauma—acute and chronic. •  Neoplasia.

Ovarian

•  Hypoluteoidism—abnormal luteal function

in absence of fetal, uterine, or placental disease: progesterone concentrations 6

years old.

Predominant Sex

Intact bitches. SIGNS

Historical Findings

•  Failure to whelp on time. •  Expulsion of recognizable fetuses or

placental tissues.

•  Decrease in abdominal size; weight loss. •  Anorexia, vomiting, diarrhea. •  Behavioral changes.

Physical Examination Findings

•  Sanguineous or purulent vulvar discharge. •  Disappearance of previously documented

vesicles or fetuses. •  Abdominal straining, discomfort. •  Depression. •  Dehydration. •  Fever.

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Differentiate infectious from noninfectious causes—B. canis immediate and zoonotic concern. •  Differentiate resorption from infertility— helped by early diagnosis of pregnancy. •  History of drug use during pregnancy— particularly during first trimester, or use of drugs (e.g., dexamethasone, prostaglandins, ketoconazole, griseofulvin, doxycycline, tetracycline, dantrolene) known to cause fetal death. •  Vulvar discharge during diestrus—may mimic abortion; evaluate discharge and origin to differentiate uterine from distal reproduc­ tive tract disease.

•  Necropsy of aborted fetus, stillborn puppies,

and placenta(s)—enhance chances of definitive diagnosis. •  Systemic or endocrine disease—problems with maternal environment. CBC/BIOCHEMISTRY/URINALYSIS

•  Usually normal. •  Systemic disease, uterine infection, viral

infection, or endocrine abnormalities—may produce changes in CBC, biochemistries, or urinalysis. OTHER LABORATORY TESTS

•  Serologic testing—B. canis, canine

herpesvirus, Toxoplasma, Neospora; collect serum as soon as possible after abortion; repeat testing for paired titers for canine herpesvirus, Toxoplasma, Neospora. •  B. canis— ◦  Slide test (D-Tec CB®, Zoetis) very sensitive; negative results reliable; prevalence of false positives as high as 60%. ◦  PCR best to use on abortive discharge (Kansas State Veterinary Diagnostic Laboratory). ◦  Definitive diagnosis made via culture of abortive discharge or dam serum. ◦  Tube agglutination—titers >1 : 200 considered positive; titers 1 : 50–1 : 200 suspicious. ◦  Agar gel immunodiffusion—differen­ tiates between false positives and true positives in agglutination tests; detects cytoplasmic and cell surface antigens. •  Baseline T4 serum concentration— hypothyroidism possible cause for fetal wastage; role in pregnancy loss unclear. •  Serum progesterone concentration (hypoluteoidism; if no infectious cause); dogs depend on ovarian progesterone production throughout gestation (minimum of 2 ng/mL required to maintain pregnancy); determine as soon as possible after abortion; in subsequent pregnancies, start weekly monitoring at week 3 (may be before pregnancy documented with ultrasound); start biweekly sampling around gestational age of prior loss. Pregnancy loss typically occurs during seventh week of gestation (see Premature Labor). •  Vaginal culture—B. canis with positive serologic test; Mycoplasma, Ureaplasma, other bacterial agents; all except B. canis can be normal flora, so diagnosis difficult from vaginal culture alone; limited benefit unless heavy growth of single organism; Salmonella associated with systemic illness. IMAGING

•  Radiography—identifies fetal structures

after 45 days of gestation; earlier determines uterine enlargement but not uterine contents. •  Ultrasonography—identify uterine size and contents; assess fluid and its consistency; assess fetal viability (heartbeats: normal, >200 bpm; stress, 280 bpm).

(continued)

Abortion, Spontaneous (Early Pregnancy Loss)—Dogs

DIAGNOSTIC PROCEDURES •  Vaginoscopy—identify source of vulvar discharge and vaginal lesions; use scope of sufficient length (16–20 cm) to examine entire length of vagina. •  Cytologic examination, bacterial culture— may reveal inflammatory process (e.g., uterine infection): use guarded swab to ensure anterior sample (distal reproductive tract is heavily contaminated with bacteria), or collect secretions by transcervical catheterization.

•  Prostaglandin treatment—discuss side

PATHOLOGIC FINDINGS Histopathologic examination and culture of fetal and placental tissue—may reveal infectious organisms; tissue culture, particularly of stomach contents, may identify infectious bacteria.

DRUG(S) OF CHOICE •  Prostaglandin F2α (PGF2α; Lutalyse®, dinoprost tromethamine)—uterine evacuation after abortion; 0.05–0.1 mg/kg SC q8–24h; cloprostenol (Estrumate®, cloprostenol)—1–5 μg/ kg SC q24h; not approved for use in dogs, but adequate documentation for use; use only if all living fetuses expelled. •  Antibiotics—broad-spectrum agent appropriate pending culture and sensitivity of vaginal tissue or fetus. •  Progesterone (altrenogest) at 0.088 mg/kg (1 mL/25 kg PO q24h); progesterone in oil at  2 mg/kg IM q48–72h; progesterone (Prometrium®; 10 mg/kg PO q24h, adjust daily dosage based on serum progesterone)— for documented hypoluteoidism only to maintain pregnancy; must have accurate due date to know when to discontinue therapy; inadvertently prolonging gestation results in fetal death.

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 TREATMENT

APPROPRIATE HEALTH CARE •  Most bitches should be isolated pending diagnosis. •  Hospitalization of infectious patients preferred. •  B. canis—highly infective; shed in high numbers during abortion; suspected dogs should be isolated. •  Outpatient—medically stable patients with noninfectious pregnancy loss. •  Partial abortion—attempt to salvage live fetuses; antibiotics indicated if bacterial component. NURSING CARE Dehydration—isotonic crystalloid fluids, electrolyte supplementation as indicated. ACTIVITY Partial abortion—cage rest, but effect on reducing further abortion unknown. DIET No special considerations; abortions have been associated with raw diets. CLIENT EDUCATION

•  Critical for B. canis—if confirmed, euthanasia

recommended due to lack of successful treatment and to prevent spread; may try ovariohysterectomy (OHE) and long-term antibiotics with surveillance program for kennel situations (monthly serology, culling any positive animals until three consecutive negative tests are obtained); discuss zoonotic potential. •  Primary uterine disease—OHE is indicated in nonbreeding patients; cystic endometrial hyperplasia (CEH) is irreversible. •  Infertility or pregnancy loss—may recur in subsequent estrous cycles despite successful immediate treatment; pedigree analysis may be beneficial in highly linebred animals if pregnancy loss and small litter size due to inbreeding depression.

effects (e.g., abortion). •  Infectious disease—establish surveillance and control measures. SURGICAL CONSIDERATIONS OHE preferred for stable nonbreeding patients.

for consistency (increasing mucoid content prognostically good). •  PGF2α—continued for 5 days or until most of discharge ceases (range 3–15 days). •  B. canis—monitor after neutering and antibiotic therapy; yearly serologic testing (identify recrudescence). •  Hypothyroidism—see Hypothyroidism. PREVENTION/AVOIDANCE

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 MEDICATIONS

CONTRAINDICATIONS Progestogen supplementation contraindicated with endometrial or mammary gland disease. PRECAUTIONS

•  PGF2α—dose-related side effects related to

smooth muscle contraction, diminish with each injection; panting, salivation, vomiting, and defecation common; caution in brachyce­ phalics; dosing critical (LD50 for dinoprost—5 mg/kg). •  Progesterone supplementation will prevent whelping—administration needs to be discontinued before 2–3 days prior to due date; risk of masculinization of female fetuses if used before day 45 of gestation. ALTERNATIVE DRUG(S) Oxytocin—1 U/5 kg SC q6–24h for uterine evacuation; consider only where uterine evacuation solely through uterine contraction desired.

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 FOLLOW-UP

PATIENT MONITORING •  Partial abortion—monitor viability of remaining fetuses with ultrasonography; monitor systemic health of dam for rest of pregnancy. •  Vulvar discharges—daily; for decreasing amount, odor, and inflammatory component;

•  Brucellosis, other infectious agents—

surveillance programs to prevent spread to kennel. •  OHE—for nonbreeding bitches. •  Use of modified-live vaccines (e.g., some distemper, parvovirus), currently unavailable in United States. POSSIBLE COMPLICATIONS

•  Untreated pyometra—septicemia, death. •  Brucellosis—discospondylitis, endophthal­

mitis, uveitis, zoonotic.

EXPECTED COURSE AND PROGNOSIS

•  Pyometra—recurrence during subsequent

cycle likely (up to 70%) unless pregnant.

•  CEH—recovery of fertility unlikely;

pyometra common complication.

•  Hormonal dysfunction—manageable;

heritability should be considered.

•  Brucellosis—guarded; extremely difficult to

eliminate infection even with neutering.

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 MISCELLANEOUS

AGE-RELATED FACTORS Older bitches more likely to have CEH. ZOONOTIC POTENTIAL B. canis—can be transmitted to humans (especially if immunosuppressed), particularly when handling bitch and expelled tissues. Notify pathologists if B. canis is suspected. SEE ALSO •  Brucellosis. •  Hypothyroidism. •  Infertility, Female—Dogs. •  Premature Labor. •  Pyometra. ABBREVIATIONS

•  CEH = cystic endometrial hyperplasia. •  OHE = ovariohysterectomy. •  PGF2α = prostaglandin F2α.

­Suggested Reading

Verstegen J, Dhaliwal G, Verstegen-Onclin K. Canine and feline pregnancy loss due to viral and non-infectious causes: a review. Theriogenology 2008, 70(3):304–319. Author Julie T. Cecere Consulting Editor Erin E. Runcan  Client Education Handout available online

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Abortion, Termination of Pregnancy RISK FACTORS N/A

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 BASICS

DEFINITION Termination of an unwanted pregnancy. May be accomplished by drugs that alter embryo transport in the oviduct, impeding establishment of a pregnancy, and/or cause luteal regression, terminating an established pregnancy. Due to their possible side effects (cystic endometrial hyperplasia, aplastic anemia, and bone marrow suppression), drugs that impair embryonic transit through the oviduct (estrogens) are not commonly used or recommended. PATHOPHYSIOLOGY After fertilization the embryo travels the oviduct in a timely manner before entering the uterus. Impaired embryo transport through the oviduct leads to embryonic degeneration and implantation abnormalities. In the dog and cat, pregnancy maintenance is dependent on progesterone production from the corpora lutea. In dogs and cats, maintenance of the corpora lutea during the second half of gestation is also supported by prolactin (PRL). Drugs that cause luteal regression, antagonize PRL, and/or compete with progesterone receptors will terminate pregnancy. SYSTEMS AFFECTED •  Cardiovascular. •  Digestive. •  Neurologic (caused by drugs used for treatment). •  Reproductive. •  Respiratory. GENETICS N/A INCIDENCE/PREVALENCE N/A GEOGRAPHIC DISTRIBUTION N/A SIGNALMENT Species

Dog and cat. Breed Predilections

N/A

Mean Age and Range

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 DIAGNOSIS

•  Confirm pregnancy first, ~60% of

mismated bitches do not become pregnant: ◦  Abdominal palpation—bitch: 31–33 days after luteinizing hormone (LH) surge; queen: 21–25 days after breeding. ◦  Transabdominal ultrasound—bitch: >25 days after LH surge; queen: >16 days after breeding. ◦  Abdominal radiographs—bitch: >45 days after LH surge; queen: >38 days after breeding. ◦  Serum relaxin concentration in the bitch (>28 days after LH surge; Witness® Relaxin, Synbiotics/Zoetis).

DIFFERENTIAL DIAGNOSIS •  Hydrometra. •  Mucometra. •  Hematometra. •  Pyometra. •  Pseudopregnancy. CBC/BIOCHEMISTRY/URINALYSIS •  Within normal limits during first half of pregnancy in healthy patients. •  Decrease in hematocrit during second half of pregnancy in bitches and queens is normal. •  Recommended as screening tests prior to treatment in patients with suspected under­lying disease. OTHER LABORATORY TESTS •  Vaginal cytology—determines stage of estrous cycle and presence of sperm (absence does not rule out previous breeding). •  Serum progesterone concentration deter­mines if female in diestrus and monitors luteal regression during treatment. IMAGING

•  Transabdominal ultrasound (method of

choice)—diagnose pregnancy and monitor uterine evacuation during treatment. •  Abdominal radiographs. DIAGNOSTIC PROCEDURES N/A PATHOLOGIC FINDINGS N/A

Postpubertal bitch and queen. Predominant Sex

Female

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SIGNS •  Depends on stage of gestation: ◦  None. ◦  Vaginal discharge. ◦  Fetal expulsion.

APPROPRIATE HEALTH CARE •  Physical examination before initiation of treatment. •  Monitor 30–60 minutes after treatment for side effects (vomiting, defecation, hypersalivation, hyperpnea, micturition, tachycardia). •  Pregnancy status in early diestrus is unknown; ultrasound confirmation of pregnancy not possible until ~4 weeks after breeding.

CAUSES

•  Impaired oviductal transport. •  Luteal regression. •  Progesterone receptor antagonism.

 TREATMENT

•  Treatment on day 6–10 of diestrus—may

have reduced efficacy compared to mid-gestation, but can be less distasteful to client (less discharge and recognizable fetuses are not passed). •  Multimodal treatment improves efficacy of drugs given alone. NURSING CARE N/A ACTIVITY Normal DIET Avoid feeding prior to each treatment and for 1–2 hours after treatments (reduces nausea and vomiting). CLIENT EDUCATION

•  Discuss patient’s reproductive future with

owner. If no litters are desired, then ovario­ hysterectomy (OHE) is the best option. •  Discuss with client potential side effects of treatment options; reach mutual agreement on treatment plan. SURGICAL CONSIDERATIONS OHE recommended for patients with no reproductive value or when owners do not desire future litters.

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 MEDICATIONS

DRUG(S) OF CHOICE •  Confirmation of pregnancy before initiating any of treatment protocols suggested below is recommended. Duration of suggested treatment may vary; treatments should be continued until abortion is complete. •  Prostaglandin F2α (PGF2α)—causes luteal regression with subsequent decline in progesterone concentration, cervical relax­ation, and uterine contractions. Higher doses necessary prior to day 28 of gestation. ◦  Bitch low dose protocol—10 μg/kg SC q6h for 7–10 days or until pregnancy termination. ◦  Bitch standard dose protocol—100 μg/kg SC q8h for 2 days, then 200 μg/kg SC q8h until pregnancy termination. ◦  Queen low dose protocol—25 μg/kg SC q6h for 1–2 days, then 50 μg/kg SC q6h for 3–4 days (queen more resistant to luteolytic effects of PGF2α than bitches; often higher doses for longer periods are required). ◦  Queen standard protocol—0.5–1 mg/kg SC q12h every other day (>day 40), or 2 mg/cat SC q24h for 5 days (>day 33). •  Cloprostenol (prostaglandin analogue): ◦  Bitch—2.5 μg/kg SC q8–12h every 48 hours until pregnancy termination (~6 days after start of treatment). •  Dexamethasone—mode of action unknown: ◦  Bitch—0.2 mg/kg PO q8–12h for 5 days, then decreasing incrementally from



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Abortion, Termination of Pregnancy

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0.16 to 0.02 mg/kg over last 5 days; treatment failures not uncommon. •  Cabergoline (PRL antagonist)—causes luteal regression: ◦  Bitch—1.65 μg/kg SC q24h for 5 days or 5 μg/kg PO q24h for 5 days (>day 40). ◦  Queen—1.65 μg/kg SC for 5 days (>day 30) or 5 μg/kg PO q24h for 5 days (>day 35). •  Bromocriptine (PRL antagonist)—causes luteal regression: ◦  Bitch—50–100 μg/kg IM/PO q12h for 4–7 days >day 35 (50% effective); common side effect vomiting; reduce dose and give with meal. •  Cloprostenol and cabergoline combination: ◦  Bitch—cabergoline 5 μg/kg PO q24h for 10 days plus cloprostenol 2.5 μg/kg SC at start of treatment or 1 μg/kg SC at start of treatment and at day 5 of treatment; treatment should be initiated >28 days post-LH surge. ◦  Queen—cabergoline 5 μg/kg PO q24h plus cloprostenol 5 μg/kg SC q48h (>30 days after breeding) until abortion complete (~9 days). •  Cloprostenol and bromocriptine combination: ◦  Bitch—bromocriptine 30 μg/kg PO q8h for 10 days plus cloprostenol 2.5 μg/kg SC or 1 μg/kg SC at start of treatment and at day 5 of treatment; treatment should be initiated >28 days post-LH surge. CONTRAINDICATIONS •  PGF2α and analogues—animals with respiratory disease (bronchoconstriction); do not administer intravenously. Use with caution in brachycephalic breeds. •  Cabergoline and bromocriptine—avoid administration in animals hypersensitive to ergot alkaloids; use with caution in patients with impaired liver function. •  Estrogens may cause cystic endometrial hyperplasia (CEH), pyometra, and bone marrow suppression leading to pancytopenia.

impaired liver function; side effects may include vomiting and anorexia; prolonged use (>2 weeks) may cause coat color changes.

for breeding.

POSSIBLE INTERACTIONS •  PGF2α and analogues—effect may be reduced by concomitant administration of progestins; use may enhance effects of oxytocin. •  Cabergoline and bromocriptine—cabergoline effects may be reduced with concomitant treatment with dopamine (D2) antagonists; avoid concomitant treatment with drugs causing hypotension.

•  Estrus suppression or confinement of

ALTERNATIVE DRUG(S)

prostaglandins and PRL inhibitors may be shortened (~1 month). Queens may resume estrous behavior 7–10 days after pregnancy termination. •  Subsequent estrus fertility not affected.

•  The following drugs are recommended for

use in bitches but are not readily available in the United States: ◦  Aglepristone (progestin and glucocorticoid receptors antagonist)—10 mg/kg SC q24h for 2 days >14 days post-LH surge; highly effective in preventing pregnancy (>95% treatment efficacy); abdominal ultrasound at 28–30 days essential to insure treatment success; if pregnancy still present, repeat injection protocol. Mild reactions at injection site have been reported; mild vaginal discharge may be observed; slight risk (3.4%) of development of pyometra in field studies. ◦  Aglepristone and cloprostenol combination—aglepristone (10 mg/kg SC) combined with cloprostenol (1 μg/kg SC) q24h for 2 days >25 days’ pregnancy; pregnancy terminated within 6 days. Side effects after treatment include vomiting and diarrhea; vaginal discharge may be observed. ◦  Aglepristone (10 mg/kg SC q24h for 2 days) with intravaginal misoprostol (200–400 μg depending on body size) daily until abortion complete; abortion complete within 7 days. Vomiting, diarrhea, polydipsia, anorexia not observed with this regimen.

bitches and queens intended for breeding during a later cycle to avoid mismating. POSSIBLE COMPLICATIONS Pregnancy termination may not be achieved after one treatment protocol and continuation or change in treatment protocol may be necessary. EXPECTED COURSE AND PROGNOSIS

•  Interestrous interval in bitches treated with

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 MISCELLANEOUS

ASSOCIATED CONDITIONS N/A AGE-RELATED FACTORS N/A ZOONOTIC POTENTIAL N/A PREGNANCY/FERTILITY/BREEDING N/A SYNONYMS Induced abortion. SEE ALSO Breeding, Timing. ABBREVIATIONS •  CEH = cystic endometrial hyperplasia. •  LH = luteinizing hormone. •  OHE = ovariohysterectomy. •  PGF2α = prostaglandin F2α. •  PRL = prolactin.

­Suggested Reading

PRECAUTIONS

­

dependent and include vomiting, defecation, dyspnea, tachycardia, salivation, restlessness, and anxiety; side effects subside within 60 minutes; use extreme caution in dogs and cats with preexisting cardiopulmonary, liver, and renal diseases. •  Dexamethasone—polydipsia, polyuria, and polyphagia are reported side effects; longterm administration can result in signs of hyperadrenocorticism. •  Cabergoline and bromocriptine—should be administered with caution in patients with

PATIENT MONITORING In animals treated with luteolytic drugs (prostaglandins and PRL antagonists), progesterone assays and transabdominal ultrasound examinations should be performed to monitor decrease of serum progesterone concentration and complete evacuation of uterine contents. In patients treated with progesterone receptor antagonist drugs, transabdominal ultrasound examinations are recommended to monitor complete evacu­ ation of the uterus.

•  PGF2α and analogues—side effects dose

PREVENTION/AVOIDANCE

•  OHE for bitches and queens not intended

 FOLLOW-UP

Eilts BE. Pregnancy termination in the bitch and queen. Clin Tech Small Anim Pract 2002, 17:116–123. Fieni F, Dumon C, Tainturier D, Bruyas JF. Clinical protocol for pregnancy termination in bitches using prostaglandin F2α. J Reprod Fertil Suppl 1997, 51:245–250. Author Jose A. Len Consulting Editor Erin E. Runcan  Client Education Handout available online

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Abscessation

­

 BASICS

DEFINITION An abscess is a focal collection of purulent exudate within a confined tissue space or cavity. PATHOPHYSIOLOGY •  Bacterial organisms may enter tissue by penetrating trauma, spread from another source of infection (hematogenous or adjacent infected tissues), or migration of a contaminated object (e.g., plant awn). •  Most often, bacteria are inoculated under the skin via puncture or bite wounds. •  When bacteria or foreign objects persist in tissue, purulent exudate accumulates. •  If exudate not quickly resorbed or drained, fibrous capsule forms to “wall off ” infection; abscess may eventually rupture. •  With fibrous capsule—to heal, the cavity must fill with granulation tissue from which causative agent may not be totally eliminated; may lead to chronic or intermittent discharge of exudate from a draining tract. •  Sterile abscesses can occur when irritants (injectable medications, venom) or inflamm­ atory processes (pancreatitis, immune mediated, decreased blood supply) lead to local collection of purulent exudate. SYSTEMS AFFECTED

•  Skin/exocrine—percutaneous (cats > dogs);

anal sac (dogs > cats).

•  Reproductive—prostate gland (dogs > cats);

mammary gland.

•  Ophthalmic—periorbital tissues. •  Hepatobiliary—liver parenchyma. •  Gastrointestinal—pancreas (dogs > cats). •  Respiratory—pulmonary parenchyma.

GENETICS N/A INCIDENCE/PREVALENCE N/A GEOGRAPHIC DISTRIBUTION N/A SIGNALMENT Species

Cat and dog. Breed Predilections

N/A

Mean Age and Range

N/A

Predominant Sex

Mammary glands (female); prostate gland (male). SIGNS General Comments

•  Determined by organ system and/or tissue

affected.

•  Associated with combination of inflamm­

ation (pain, swelling, redness, heat, and loss

of function), tissue destruction, and/or organ system dysfunction caused by accumulation of exudates. Historical Findings

•  Often nonspecific signs (e.g., lethargy,

­

 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS

anorexia).

Mass Lesions

without discharge, if affected area is visible.

•  Fibrous scar tissue—firm, nonpainful. •  Granuloma—less painful, slower growing,

•  History of trauma or prior infection. •  Rapidly appearing painful swelling with or

Physical Examination Findings

•  Determined by organ system or tissue

•  Cyst—transiently painful, slower growing,

no overt signs of inflammation.

firmer without fluctuant center.

affected. •  Classic signs of inflammation (heat, pain, swelling, and loss of function) associated with specific anatomic location of abscess. •  Inflammation and discharge from fistulous tract may be visible if abscess has ruptured to an external surface. •  Variably sized, painful mass of fluctuant to firm consistency attached to surrounding tissues. •  Fever common, but may be absent if abscess has ruptured. •  Sepsis or infection of body cavity (e.g., pyothorax) may be seen if abscess ruptures internally.

•  Hematoma/seroma—variable pain,

CAUSES •  Foreign objects. •  Pyogenic bacteria—Staphylococcus spp., Escherichia coli, β-hemolytic Streptococcus spp., Pseudomonas, Mycoplasma and Mycoplasma-like organisms (l-forms), Pasteurella multocida, Corynebacterium, Actinomyces spp., Nocardia, Bartonella. •  Obligate anaerobes—Bacteroides spp., Clostridium spp., Peptostreptococcus, Fusobacterium. •  Noninfectious—pancreatitis, suture reaction, vaccination, other injectable drug administration, stinging insects, snake envenomation, immune-mediated panniculitis, dermatitis, neoplasia (especially when blood supply outgrown).

•  CBC—normal, neutrophilia with or

RISK FACTORS •  Anal sac—impaction, anal sacculitis. •  Brain—otitis interna, sinusitis, oral infection. •  Liver—omphalophlebitis, sepsis. •  Lung—foreign object aspiration or migration, bacterial pneumonia. •  Mammary gland—mastitis. •  Periorbital—dental disease, chewing of wood or other plant material. •  Percutaneous—fighting, trauma, or surgery. •  Prostate gland—bacterial prostatitis. •  Immunosuppression—feline leukemia virus (FeLV) or feline immunodeficiency virus (FIV) infection, immunosuppressive chemo­therapy, acquired or inherited immune system dysfunctions, underlying predisposing disease (e.g., diabetes mellitus, chronic renal failure, hyperadrenocorticism).

nonencapsulated, rapid initial growth but slows once full size attained, fluctuant initially, may become more firm over time. •  Neoplasia—variable growth, variable pain. Draining Tracts

•  Fungal infection—blastomycosis,

coccidioidomycosis, cryptococcosis, histoplasmosis, sporotrichosis. •  Mycobacterial disease. •  Mycetoma—botryomycosis, actinomycotic mycetoma, eumycotic mycetoma. •  Neoplasia. •  Phaeohyphomycosis. CBC/BIOCHEMISTRY/URINALYSIS

without left shift, neutropenia and degenerative left shift (severe infection). •  Serum chemistry profile—depends on severity, system affected. Signs of cholestasis if pancreatic abscess causes obstruction, hyperglycemia if diabetes mellitus, etc. •  Urinalysis—pyuria (prostatic abscess). OTHER LABORATORY TESTS

•  FeLV, FIV testing—recurrent or slow-

healing abscesses (cats).

•  Cerebrospinal fluid evaluation—increased

cellularity and protein with brain abscess.

•  Adrenal function—hyperadrenocorticism.

IMAGING

•  Radiography—soft-tissue density mass in

affected area, may reveal foreign material.

•  Ultrasonography—determine if mass is

fluid filled; may reveal foreign object; echogenic fluid suggests purulent exudate. •  Echocardiography—pericardial abscess, endocarditis. •  CT or MRI—pulmonary or brain abscess. DIAGNOSTIC PROCEDURES Fine-Needle Aspiration

•  Red, white, yellow, or greenish liquid. •  Protein content >2.5–3.0 g/dL. •  Nucleated cell count—3,000–100,000 (or

more) cells/μL; primarily degenerate neutrophils, fewer macrophages, lymphocytes. •  Bacteria—intra- and extracellular: ◦  Gram stain to classify organism for empiric therapy. ◦  If causative agent not readily identified with a Romanowsky-type stain, acid-fast



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Abscessation

(continued)

stain to detect mycobacteria or Nocardia and periodic acid-Schiff stain to detect fungus. Biopsy

•  Sample should contain both normal and

abnormal tissue.

•  Impression smears. •  Tissue—for histopathologic examination

and culture. •  Necessary to confirm nodular panniculitis.

•  Early drainage—to prevent further tissue

damage and abscess wall formation. •  Remove foreign objects(s), necrotic tissue, nidus of infection. •  Complications to discuss include progressive tissue damage, necrosis, dehiscence of wound, prolonged healing times in high-motion areas (axillary, inguinal).

Culture and Susceptibility Testing

•  Affected tissue and/or exudate—aerobic

and anaerobic bacterial and fungal. •  Blood and/or urine if systemic disease.

PATHOLOGIC FINDINGS •  Exudate-containing mass lesion accom­ panied by inflammation. •  Causative agent may be detectable.

­

 TREATMENT

APPROPRIATE HEALTH CARE •  Establish and maintain adequate drainage. •  Surgical removal of nidus of infection or foreign object(s) if necessary. •  Initiate appropriate antimicrobial therapy. •  Outpatient—minor abscesses, localized infection, nodular panniculitis. •  Inpatient—sepsis or systemic inflammation, extensive surgical procedures, treatment requiring hospitalization. NURSING CARE

•  Depends on location of abscess. •  Apply hot packs to inflamed area as needed. •  Use protective bandaging, Elizabethan

collar as needed.

•  Accumulated exudate—surgical drainage,

debridement of necrotic tissue. •  Sepsis, peritonitis, pyothorax—fluid therapy, antimicrobial therapy, intensive care. ACTIVITY Restrict until abscess has resolved and adequate healing occurs. DIET N/A CLIENT EDUCATION

•  Correct or prevent risk factors. •  Maintain adequate drainage and continue

antimicrobial therapy for adequate period of time.

SURGICAL CONSIDERATIONS •  Appropriate debridement and drainage— may need to leave wound open to external surface; may need drain placement. ◦  Penrose drains must exit ventrally to encourage drainage; may be bandaged, if bandage is changed regularly. ◦  If no ventral drainage, use active drains (e.g., Jackson-Pratt drain).

­

intrathoracic abscess ruptures.

•  Compromise of organ function. •  Delayed evacuation may lead to chronic,

draining fistulous tracts.

EXPECTED COURSE AND PROGNOSIS Depends on cause, organ system involved, and amount of tissue destruction.

 MEDICATIONS

DRUG(S) OF CHOICE •  Antimicrobial drugs that are effective against infectious agent and penetrate site of infection. •  Broad-spectrum agent—bactericidal with both aerobic and anaerobic activity until results of culture and sensitivity are known; Gram stain of exudate may guide therapy. ◦  Dogs and cats—amoxicillin (22 mg/kg PO q12h); amoxicillin–clavulanic acid (22 mg/kg PO q12h); clindamycin (5–10 mg/kg PO q12h); trimethoprim– sulfadiazine (15 mg/kg PO q12h). ◦  Cats only—pradofloxacin (7.5 mg/kg PO q24 for 7 days). ◦  Cats with Mycoplasma and L-forms— doxycycline (5 mg/kg PO q12h). •  Aggressive IV antimicrobial therapy— sepsis, peritonitis, pyothorax. •  Antimicrobials not required for confirmed sterile abscesses. CONTRAINDICATIONS N/A PRECAUTIONS N/A POSSIBLE INTERACTIONS N/A ALTERNATIVE DRUG(S) Sterile nodular panniculitis—corticosteroids.

­

POSSIBLE COMPLICATIONS

•  Sepsis. •  Peritonitis/pleuritis if intra-abdominal or

 FOLLOW-UP

PATIENT MONITORING Monitor for progressive decrease in drainage, resolution of inflammation, and improvement of clinical signs. PREVENTION/AVOIDANCE •  Percutaneous abscesses—prevent fighting; consider castration to reduce roaming or aggressive behavior. •  Anal sac abscesses—prevent impaction; consider anal saculectomy for recurrent cases. •  Prostatic abscesses—consider castration. •  Mastitis—prevent lactation (spay). •  Periorbital abscesses—do not allow chewing on foreign objects.

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 MISCELLANEOUS

ASSOCIATED CONDITIONS •  FeLV or FIV infection. •  Immunosuppression. AGE-RELATED FACTORS N/A ZOONOTIC POTENTIAL

•  Mycobacteria and systemic fungal

infections carry some potential.

•  If prostatitis secondary to Brucella canis.

PREGNANCY/FERTILITY/BREEDING N/A SEE ALSO

•  Actinomycosis and Nocardia. •  Anaerobic Infections. •  Colibacillosis. •  Mycoplasmosis. •  Nocardiosis/Actinomycosis—Cutaneous. •  Sepsis and Bacteremia.

ABBREVIATIONS

•  FeLV = feline leukemia virus. •  FIV = feline immunodeficiency virus.

­Suggested Reading

Green CE, Goldstein EJC. Bite wound infections. In: Greene CE, ed., Infectious Diseases of the Dog and Cat, 4th ed. St. Louis, MO: Elsevier Saunders, 2012, pp. 528–542. Singh A, Scott Weese J. Wound infections and antimicrobial use. In: Johnston SA, Tobias KM, eds., Veterinary Surgery Small Animal, 2nd ed. St. Louis, MO: Elsevier, 2018, pp. 148–155. Author Selena Lane Consulting Editor Amie Koenig Acknowledgment The author and editors acknowledge the prior contribution of Adam J. Birkenheuer.  Client Education Handout available online

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Acetaminophen (APAP) Toxicosis SIGNALMENT Species

­

 BASICS

Cats more often than dogs.

DEFINITION Results from accidental animal ingestion or owner administration of over-the-counter acetaminophen-containing analgesic and antipyretic medications.

SIGNS

PATHOPHYSIOLOGY When the normal biotransformation mechanisms for detoxification (glucuronidation and sulfation) are saturated, cytochrome P450–mediated oxidation produces a toxic metabolite (N-acetyl-p-benzoquinone imine) that is electrophilic, conjugates with glutathione, and binds to sulfhydryl groups, leading to hepatic necrosis.

•  Depression. •  Hyperventilation. •  Darkened mucous membranes. •  Signs may develop 1–4 hours after dosing.

Dogs

•  Liver is most susceptible to toxicity. •  Signs commonly observed at exposures

>75–100 mg/kg.

General Comments

Relatively common—owing to widespread human use. Historical Findings

Physical Examination Findings

•  Progressive depression. •  Salivation. •  Vomiting. •  Abdominal pain. •  Tachypnea and cyanosis or muddy mucous

membranes—reflect methemoglobinemia.

•  Edema—face, paws, and possibly forelimbs;

after several hours.

•  Methemoglobinemia may develop at doses

•  Chocolate-colored urine—hematuria and

Cats

•  Icterus. •  Hypothermia. •  Shock. •  Death.

>200 mg/kg.

•  Cannot effectively glucuronidate; more

limited capacity for acetaminophen elimination than dogs. •  Saturate glucuronidation and sulfation biotransformation routes. •  Red blood cells (RBCs) are most susceptible to oxidative injury following glutathione depletion. •  Develop toxic cytochrome P450 metabolite at much lower doses than dogs. •  Poisoned by as little as 50–60 mg/kg (often as little as one half tablet); deacetylation of acetaminophen to p-aminophenol (PAP) causes oxidative damage to RBCs, rapidly producing methemoglobinemia by binding to sulfhydryl groups on hemoglobin. •  Slower-developing hepatotoxicosis may not be fully expressed before development of fatal methemoglobinemia. SYSTEMS AFFECTED

•  Hemic/lymph/immune—RBCs damaged

by glutathione depletion, allowing oxidation of hemoglobin to methemoglobin. •  Hepatobiliary—liver necrosis (more common in dogs). •  Cardiovascular (primarily cats)—edema of face, paws, and (to lesser degree) forelimbs through undefined mechanism. GENETICS Cats—genetic deficiency in the glucuronide conjugation pathway makes them vulnerable. INCIDENCE/PREVALENCE Common drug toxicity in cats; less frequent in dogs. GEOGRAPHIC DISTRIBUTION N/A

methemoglobinuria; especially in cats.

CAUSES Acetaminophen toxicosis. RISK FACTORS •  Nutritional deficiencies of glucose and/or sulfate. •  Simultaneous administration of other glutathione-depressing drugs.

(alanine aminotransferase [ALT], aspartate transaminase [AST])—characteristic. •  As hepatic function becomes impaired— decreased blood urea nitrogen (BUN), cholesterol, and albumin, and increased serum bilirubin. •  Heinz bodies (cats)—prominent in RBCs within 72 hours. •  Anemia, hemoglobinemia, and hemoglob­ inuria or hematuria. OTHER LABORATORY TESTS Acetaminophen plasma, serum, or urine concentrations. IMAGING N/A DIAGNOSTIC PROCEDURES N/A PATHOLOGIC FINDINGS

•  Methemoglobinemia. •  Pulmonary edema. •  Centrilobular necrosis and congestion of

the liver.

•  Renal tubular edema and degeneration with

proteinaceous tubular casts.

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 TREATMENT

APPROPRIATE HEALTH CARE •  With methemoglobinemia—must evaluate promptly. •  With dark or bloody colored urine or icterus—inpatient. NURSING CARE

•  Gentle handling—imperative for clinically

affected patients.

•  Induced emesis and gastric lavage—useful

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS Other Causes of Liver Injury

•  Hepatotoxic mushrooms. •  Blue-green algae. •  Aflatoxins. •  Iron, copper, zinc. •  Xylitol. •  Cycad palms. •  Nonsteroidal anti-inflammatory drugs

(NSAIDs).

Other Causes of Methemoglobinemia •  Onions/garlic. •  Naphthalene. •  Chlorates. •  Nitrites. •  Sulfites. •  Phenol. •  Benzocaine. •  Propylene glycol (cats).

CBC/BIOCHEMISTRY/URINALYSIS •  Methemoglobinemia and progressively rising serum concentrations of liver enzymes

within 4–6 hours of ingestion.

•  Anemia, hematuria, or hemoglobinuria—

may require whole blood transfusion.

•  Fluid therapy—maintain hydration and

electrolyte balance.

•  Oxygen therapy may be needed. •  Drinking water—available at all times. •  Food—offered 24 hours after initiation of

treatment.

ACTIVITY Restricted DIET N/A CLIENT EDUCATION

•  Warn client that treatment in clinically

affected patients may be prolonged and expensive. •  Inform client that patients with liver injury may require prolonged and costly management. SURGICAL CONSIDERATIONS N/A



Acetaminophen (APAP) Toxicosis

(continued)

PREVENTION/AVOIDANCE

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 MEDICATIONS

DRUG(S) OF CHOICE •  Activated charcoal 1–2 g/kg PO with a cathartic; immediately after completion of emesis or gastric lavage. •  N-acetylcysteine (Mucomyst®) 140 mg/kg diluted in 5% dextrose injection (D5W) as loading dose PO/IV; then 70 mg/kg diluted in D5W PO/IV q6h for 7 additional treatments. Large overdoses may require up to 17 treatments. •  S-adenosylmethionine (SAMe) as a glutathione donor; 40 mg/kg PO × 1 dose, then 20 mg/kg q24h PO × 7 days. •  Added benefit of using methylene blue, cimetidine, and/or ascorbic acid is controversial. CONTRAINDICATIONS Drugs that contribute to methemoglobinemia or hepatotoxicity. PRECAUTIONS Drugs requiring extensive liver metabolism or biotransformation—use with caution; expect their half-lives to be extended. POSSIBLE INTERACTIONS Drugs requiring activation or metabolism by the liver have reduced effectiveness.

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 FOLLOW-UP

PATIENT MONITORING •  Continual clinical monitoring of methemo­ globinemia—vital for effective management; laboratory determination of methemoglobin percentage every 2–3 hours. •  Serum liver enzyme activities (ALT, ALP) every 12 hours; monitor liver damage.

•  Never give acetaminophen to cats. •  Give careful attention to acetaminophen

dose in dogs.

POSSIBLE COMPLICATIONS Liver necrosis and resulting fibrosis—may compromise long-term liver function in recovered patients. EXPECTED COURSE AND PROGNOSIS

•  Rapidly progressive methemoglobinemia—

serious sign.

•  Methemoglobin concentrations ≥50%—

grave prognosis.

•  Progressively rising serum liver enzymes

12–24 hours after ingestion—serious concern.

•  Expect clinical signs to persist 12–48 hours;

death owing to methemoglobinemia possible at any time. •  Dogs and cats receiving prompt treatment that reverses methemoglobinemia and prevents excessive liver necrosis—may recover fully. •  Dogs—death as a result of liver necrosis may occur within 72 hours. •  Cats—death as a result of methemoglobinemia occurs 18–36 hours after ingestion.

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 MISCELLANEOUS

ASSOCIATED CONDITIONS Keratoconjunctivitis sicca may develop in small-breed dogs as a sequela. AGE-RELATED FACTORS Young and small dogs and cats—greater risk from owner-given single-dose acetaminophen medications. PREGNANCY/FERTILITY/BREEDING Imposes additional stress and higher risk on exposed animals.

SYNONYMS

•  Paracetamol. •  Tylenol®.

SEE ALSO Poisoning (Intoxication) Therapy. ABBREVIATIONS •  ALT = alanine aminotransferase. •  AST = aspartate transaminase. •  BUN = blood urea nitrogen. •  D5W = 5% dextrose injection. •  NSAID = nonsteroidal anti-inflammatory drug. •  PAP = p-aminophenol. •  RBC = red blood cell. •  SAMe = S-adenosylmethionine. INTERNET RESOURCES https://www.aspca.org/pet-care/ animal-poison-control

­Suggested Reading

Plumb DC. Acetaminophen. In: Plumb DC, ed., Plumb’s Veterinary Drug Handbook, 9th ed. Ames, IA: Wiley-Blackwell, 2018, pp. 6–8. Plumlee KH. Hematic system. In: Plumlee KH, ed., Clinical Veterinary Toxicology. St. Louis, MO: Mosby, 2004, p. 59. Schell MM, Gwaltney-Brant S. OTC drugs. In: Poppenga RH, Gwaltney-Brant SM, eds., Small Animal Toxicology Essentials. Chichester: Wiley-Blackwell, 2011, pp. 231–233. Sellon RK. Acetaminophen. In: Peterson ME, Talcott PA, eds. Small Animal Toxicology, 3rd ed. St. Louis, MO: Elsevier, 2013, pp. 423–429. Stockham SL, Scott MA. Fundamentals of Veterinary Clinical Pathology, 2nd ed. Oxford: Blackwell, 2008, p. 186. Author Lisa A. Murphy Consulting Editor Lynn R. Hovda  Client Education Handout available online

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Acidosis, Metabolic

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 BASICS

DEFINITION A process in the body that leads to a decrease in pH below the reference interval. A decline in blood pH is specifically termed acidemia. Associated with a decrease in plasma bicarb­onate concentration ( HCO3 ; dogs, 15 minutes have low pH because of increased PCO2. •  Hypoalbuminemia lowers AG; negative charges of albumin are main component of AG. Valid if Run in Human Laboratory?

Yes

CBC/BIOCHEMISTRY/URINALYSIS •  Low total CO2—total CO2 in serum samples handled aerobically closely approximates serum HCO3 concentration; unfortunately, patients with chronic respiratory alkalosis also have low total CO2, and distinction cannot be made without blood gas analysis. •  Metabolic acidoses traditionally divided into hyperchloremic and high AG by means of AG. Anion gap, the difference between the measured cations and the measured anions, is calculated as AG = [Na+] – ( HCO3 + [Cl–]) or AG = ([Na+] + [K+]) – ( HCO3 + [Cl–]), depending on preference of clinician or laboratory. Normal values with potassium included in calculation usually 12–24 mEq/L



Acidosis, Metabolic

(continued)

in dogs and 13–27 mEq/L in cats. Negative charges of albumin are major contributors to normal AG; this should be taken into account when evaluating AG in patients with hypo­albuminemia. At pH 7.4 in dogs, decrease of 1 g/dL in albumin associated with decrease of 4.1 mEq/L in AG. •  Normal AG (i.e., hyperchloremic metabolic acidosis). •  High AG (i.e., normochloremic metabolic acidosis). •  Hyperglycemia. •  Azotemia. •  Hyperphosphatemia. •  High lactate concentration. •  Hyperkalemia (formulas to adjust potassium concentration based on pH changes should not be used). OTHER LABORATORY TESTS Blood gas analysis reveals low HCO3 , low PCO2, and low pH. DIAGNOSTIC PROCEDURES None TREATMENT

•  Acid-base disturbances are secondary

phenomena; successful resolution depends on diagnosis and treatment of underlying disease process. •  Restore blood volume and perfusion deficits before considering sodium bicarbonate (NaHCO3). •  Treat patients with blood pH ≤7.1 aggressively while pursuing definitive diagnosis. •  Discontinue drugs that may cause metabolic acidosis. •  Nursing care—isotonic, buffered electrolyte solution is fluid of choice for patients with mild metabolic acidosis and normal liver function.

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 MEDICATIONS

DRUG(S) OF CHOICE •  NaHCO3 may help patients with hyper­ chloremic, hyperhosphatemic, or uremic acidosis, but not patients with lactic acidosis or diabetic ketoacidosis. •  NaHCO3 may be considered for alkaline diuresis in salicylate toxicity. ° Estimation of HCO3 dose—dogs, 0.3 × body weight (kg) × (21 – patient HCO3 ); cats, 0.3 × body weight (kg) × (19 – patient HCO3 ). Give half of this dose slowly IV and reevaluate blood gases before deciding on need for additional administration. Empirical dose of 1–2 mEq/kg followed by reevaluation of blood gas status is safe in most patients. ° Potential complications of NaHCO3 administration—volume overload resulting from administered Na+, tetany from low ionized calcium concentration, increased

affinity of hemoglobin for oxygen, paradoxical CNS acidosis, overshoot metabolic alkalosis, hypokalemia. •  Hyperchloremic acidosis—NaHCO3 may be effective and considered whenever pH 50% dogs, ~40% cats). ◦  Dyspnea (may be related to pneumo­ thorax or pleural effusion). ◦  Tachypnea. ◦  Hemoptysis. •  Paraneoplastic signs: ◦  Lameness—bone metastasis or hypertrophic

osteopathy (dogs or cats), weight‐bearing lytic digit metastasis (cats). ◦  Polyuria or polydipsia— hypercalcemia or hyperadrenocorticism from ectopic production of adrenocorticotrophic hormone (ACTH). ◦  Fever. Physical Examination Findings

•  May be asymptomatic or lack respiratory signs (~25% dogs, 9% cats). •  Tachypnea, dyspnea. •  Fever. •  Limb swelling. •  Ascites,

IMAGING •  Thoracic radiography—usually demonstrates focal, solitary, well‐circumscribed mass in dogs, often in caudal lung lobes; caudal lobes most common in cats, though radiographic patterns vary more and can include diffuse interstitial disease; radiographs must be performed in cats presenting with multiple digit tumors to screen for primary lung tumor (lung‐digit syndrome). •  Ultrasonography—to obtain aspirate or biopsy specimen if mass in contact with chest wall, or evaluate abdomen for primary tumor. •  CT—to assess surgical feasibility, lymphadenopathy (93% accuracy), metastatic disease; can see cavitated areas, irregular margins, bronchial invasion. DIAGNOSTIC PROCEDURES •  Thoracocentesis with cytologic examination (for pleural effusion). •  Cytology—transthoracic fine‐needle aspiration (83% agreement with histopathology). •  Percutaneous tissue biopsy— use Tru‐Cut instrument, not commonly performed. •  Open lung biopsy—via thoraco­ tomy, or minimally invasive thoracoscopy. PATHOLOGIC FINDINGS •  Adenocarcinoma—classified by location (bronchial, bronchiolar, bronchiolar‐alveolar, or alveolar) and degree of differentiation. •  Immunohistochemistry on biopsy for thyroid transcription factor‐1 (TTF‐1), surfactant protein A, and napsin A to confirm pulmonary carcinoma, especially adenocarcinoma. TTF‐1 and napsin A can also be seen in thyroid tumors. •  Cats tend to have less differentiated tumors, corresponding to more aggressive behavior.

pleural effusion.

CAUSES & RISK FACTORS Some (controversial) evidence correlates risk to urban environment; secondhand environ­ mental tobacco smoke not definitively linked to primary lung cancer in dogs, though weak association seen in dogs with short and medium‐length noses.

­

 DIAGNOSIS

•  Cytology of mass aspirate. •  Tissue biopsy/

definitive resection.

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 TREATMENT

•  Surgery—mainstay of treatment: partial or

complete lobectomy with tracheobronchial lymph node biopsy or removal; thoracoscopic removal possible at limited centers and offers less postoperative morbidity. •  Radiotherapy— reports anecdotal, but certain patients may benefit. •  Chemotherapy should be considered following surgery for tumors that are high grade, undifferentiated, and/or have nodal involvement, though no benefit confirmed. Intracavitary chemotherapy can be used to treat malignant pleural effusion.

DIFFERENTIAL DIAGNOSIS

•  Granulomatous lesion (fungal, foreign body, parasitic). •  Pulmonary abscess. •  Other primary lung tumor: ◦  Squamous cell carcinoma. ◦  Sarcomas (osteo‐, chondro‐, lipo‐). •  Metastatic lung tumor. •  Pneumonia. •  Asthma. •  Pulmonary thromboembolism. •  Congenital cyst. •  Lung torsion/hematoma.

CBC/BIOCHEMISTRY/URINALYSIS No specific abnormalities.

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 MEDICATIONS

DRUG(S) OF CHOICE •  Chemotherapy—vinorelbine concentrates in lungs and responses have been seen. ◦  Doxorubicin, cisplatin, carboplatin, mitoxantrone, vinorelbine, and/or vindesine: rational choices for primary or adjuvant therapy. ◦  Platinum‐based or gemcitabine

chemotherapy may be superior. ◦  Toceranib phosphate (Palladia) has shown some anecdotal success. •  Chemotherapy can be toxic; seek advice if unfamiliar with cytotoxic drugs. CONTRAINDICATIONS/POSSIBLE INTERACTIONS •  Doxorubicin—cardiotoxic, avoid in dogs with myocardial disease (arrhythmias); nephrotoxic in cats. •  Cisplatin—do not give to cats (fatal); do not use in dogs with preexisting renal disease; never use without appropriate and concurrent diuresis.

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 FOLLOW‐UP

PATIENT MONITORING •  Serial thoracic radiographs—every 3 mths; administer minimum two cycles of chemo­ therapy before evaluating response. •  Perform CBC (with any chemotherapy), biochemical analysis (cisplatin), and urinalysis (cisplatin) before each chemotherapy. POSSIBLE COMPLICATIONS

•  Following diagnostic procedures or

thoracotomy—pneumo‐ or hemothorax.

•  Resulting from chemotherapy—myelo­

suppression, fever, sepsis, nausea.

EXPECTED COURSE AND PROGNOSIS

•  Metastasis to tracheobronchial lymph

nodes—single best prognostic indicator; median survival without metastasis approaches 1 yr and with metastasis, 60 days. More common (75%) in cats. •  Postoperative survival around 2 yrs in both cats and dogs if positive prognostic factors present, and ~1 yr overall in dogs, 4 mths overall in cats. •  Other patient, tumor, and treatment factors positively influencing prognosis—complete surgical excision; size of primary tumor (1–2 cm margins is recommended as a curative treatment option. Always submit resected tissue for histopathology, in order to confirm the original diagnosis, and evaluate soft tissue and bone margins. •  Radiation therapy may provide long-term control in large tumors, or when owners decline surgery. •  Intralesional chemotherapy with bleomycin has been reported, but results are generally inferior to those of surgery or radiation.

gingival mass that is usually nonulcerated.

•  May be incidental finding during dental

prophylaxis/procedures. If involving rostral dental arcade, incisor teeth can be displaced and enveloped by proliferative tissue. CAUSES & RISK FACTORS N/A

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 MEDICATIONS

DRUG(S) OF CHOICE N/A CONTRAINDICATIONS/POSSIBLE INTERACTIONS N/A

 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Epulis. •  Gingival hyperplasia. •  Squamous cell carcinoma. •  Amelanotic melanoma. •  Plasma cell tumor. •  Other tumors related to the odontogenic apparatus. CBC/BIOCHEMISTRY/URINALYSIS Unaffected OTHER LABORATORY TESTS N/A IMAGING •  Dental radiographs may show bone lysis deep to the superficial mass. Not particularly useful for diagnostic or treatment planning. •  Regional and distant metastasis has not been described. •  CT is ideal for planning surgery or radiation therapy, especially in large or caudal tumors. DIAGNOSTIC PROCEDURES

•  Deep tissue biopsies are necessary and

recommended for definitive diagnosis.

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 FOLLOW-UP

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 MISCELLANEOUS

Careful oral examination at 1, 3, 6, 9, and 12 months after definitive treatment is recommended to monitor for local recurrence.

­Suggested Reading

Amory JT, Reetz JA, Sanchez MD, et al. Computed tomographic characteristics of odontogenic neoplasms in dogs. Vet Radiol Ultrasound 2014, 55(2):147–158. Fiani N, Verstraete FJ, Kass PH, Cox DP. Clinicopathologic characterization of odontogenic tumors and focal fibrous hyperplasia in dogs: 152 cases (1995–2005). J Am Vet Med Assoc 2011, 238(4):495–500. Goldschmidt SL, Bell CM, Hetzel S, Soukup J. Clinical characterization of canine acanthomatous ameloblastoma (CAA) in 263 dogs and the influence of postsurgical

histopathological margin on local recurrence. J Vet Dent 2017, 34(4):241–247. Author Nick Dervisis Consulting Editor Timothy M. Fan

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Amphetamine and ADD/ADHD Medication Toxicosis •  Gastrointestinal (GI)—anorexia, vomiting,

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 BASICS

DEFINITION Acute neurologic, neuromuscular, and cardiac toxicosis as the result of excessive consumption of amphetamine or a derivative. May be due to ingestion of prescription medications or illegal drugs. PATHOPHYSIOLOGY •  Amphetamine and its derivatives belong to the CNS stimulant class phenylethylamines. Various substitutions of the basic phenylethylamine structure account for many pharmaceutical and illicit compounds found today. •  Amphetamine is a sympathomimetic that is structurally related to norepinephrine. •  Central action—stimulates cortical centers including cerebral cortex, medullary respiratory center, and reticular activating systems. •  Peripheral action—directly stimulates alpha and beta receptors and stimulates release of norepinephrine from stores in adrenergic nerve terminals. •  Amphetamine may slow catecholamine metabolism by inhibition of monoamine oxidase. •  Several different product formulations, including immediate and extended release and topical patch. •  Amphetamines are well absorbed orally; peak plasma levels are generally reached in 1–3 hours; this may be delayed with extended release formulations. •  Metabolism is minimal. •  The half-life, which varies from 7 to 34 hours, and rate of excretion of unchanged amphetamine in the urine are both dependent upon urine pH, with shorter half-lives associated with more acidic urine. •  Clinical signs may be seen at doses below 1 mg/kg. •  Oral lethal dose in dogs for most amphetamines ranges from 10 mg/kg to 23 mg/kg and for methamphetamine sulfate it is 9–11 mg/kg. Oral lethal dose for amphetamine sulfate is 20–27 mg/kg. •  Amphetamine and its derivatives are used in humans to treat attention deficit disorder (ADD)/attention deficit hyperactivity disorder (ADHD), narcolepsy, and obesity. •  Illicit use of amphetamines in humans is also prevalent. SYSTEMS AFFECTED

•  Cardiovascular—stimulation most

common: tachycardia and hypertension.

•  Nervous—stimulation most common,

depression uncommon.

•  Neuromuscular—stimulation: muscle

tremors and seizures.

•  Respiratory—stimulation, tachypnea. •  Ophthalmic—mydriasis.

diarrhea.

•  5-fluorouracil. •  Ma huang, guarana, or ephedra.

INCIDENCE/PREVALENCE N/A

•  CBC—generally normal with mild to

SIGNALMENT Species

Dogs and cats, although more prevalent in dogs. Breed Predilections

N/A

Mean Age and Range

N/A

Predominant Sex

N/A

SIGNS Historical Findings

•  Abnormal behavior—usually hyperactivity,

anxiety or pacing, anorexia, fast heart rate, panting; observed or evidence of exposure by owner/caretaker. •  Onset of signs typically begins within 30 minutes to 6 hours post ingestion; depends on product formulation. Physical Examination Findings

•  Nervous—hyperactivity, agitation,

restlessness, head bobbing, pacing, circling, vocalization, disorientation, hyperesthesia, ataxia, lethargy or depression (less common). •  Cardiovascular—tachycardia or bradycardia (less common, may be reflexive), hypertension. •  Neuromuscular—muscle fasciculation or tremors, seizures. •  Gastrointestinal—vomiting, diarrhea, anorexia, excessive salivation. •  Respiratory—tachypnea. •  Ophthalmic—mydriasis with possibly poor to unresponsive pupillary light response. •  Other—hyperthermia. CAUSES Accidental ingestion or administration, malicious poisoning. RISK FACTORS Households with children or adults currently taking prescription or illicit amphetamine or derivative.

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Strychnine. •  Organochlorine insecticides. •  Methylxanthine. •  4-aminopyridine. •  Metaldehyde. •  Phenylpropanolamine. •  Albuterol. •  Nicotine. •  Tremorgenic mycotoxins. •  Hypernatremia. •  Pseudoephedrine, phenylephrine.

CBC/BIOCHEMISTRY/URINALYSIS

moderate intoxications; disseminated intravascular coagulopathy secondary to severe hyperthermia (rare). •  Chemistry—generally normal with mild to moderate intoxications. •  Azotemia—prerenal: secondary to dehydration; renal: secondary to rhabdomyolysis and myoglobinuria (rare). •  Elevated liver enzymes—secondary to seizures and/or hyperthermia (rare). •  Hypoglycemia. •  Urinalysis—evidence of myoglobinuria, urine specific gravity (high: prerenal azotemia; isosthenuria: renal failure). OTHER LABORATORY TESTS

•  Electrolytes—imbalances secondary to GI

effects.

•  Acid-base status—acidosis may occur. •  Over-the-counter urine drug screens—

watch for false positive or negative; consult user handbook for further information. •  Amphetamines are present in blood, urine, and saliva; consult with local veterinary diagnostic lab or human hospital for availability and proper sample submission. IMAGING N/A DIAGNOSTIC PROCEDURES

•  ECG for presence of any tachyarrhythmia

or less commonly bradyarrhythmia.

•  Blood pressure—identification of

hypertension.

PATHOLOGIC FINDINGS On necropsy presence of amphetamines may be found in gastric contents, urine, plasma, liver, kidney, or muscle.

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 TREATMENT

APPROPRIATE HEALTH CARE Majority of cases require emergency inpatient intensive care management. NURSING CARE •  Intravenous fluid therapy to correct dehydration and electrolyte imbalances as well as support renal function and promote excretion of amphetamines; use blood pressure to help guide fluid rate. •  Cool intravenous fluids, fans, cool water baths for hyperthermia. ACTIVITY Minimize activity and stimuli. DIET Withhold food if moderately to severely affected. Bland diet for few days post exposure if significant GI signs were noted.



Canine and Feline, Seventh Edition



(continued)

Amphetamine and ADD/ADHD Medication Toxicosis

CLIENT EDUCATION In case of exposure, owner should contact local veterinarian or veterinary poison center immediately. SURGICAL CONSIDERATIONS N/A

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 MEDICATIONS

DRUG(S) OF CHOICE Decontamination

•  Induce emesis—if recent exposure and pet

is not already symptomatic.

PRECAUTIONS N/A POSSIBLE INTERACTIONS •  Amphetamines inhibit metabolism of adrenergic blockers (doxazosin, phenoxy­ benzamine, prazosin, terazosin), phenobarbital, and phenytoin. •  Amphetamines potentiate metabolism of coumarin anticoagulants, monoamine oxidase inhibitors, opioid analgesics, and tricyclic antidepressants. ALTERNATIVE DRUG(S) Phenobarbital, pentobarbital, and propofol for CNS stimulatory signs.

•  Apomorphine—0.04 mg/kg IV, subcon-

junctival.

•  Hydrogen peroxide 3%—2.2 mL/kg,

­

•  Gastric lavage if extremely large ingestion

PATIENT MONITORING •  Monitor in hospital until resolution of clinical signs. •  If severely affected, monitor liver and kidney values every 24 hours for 72 hours or until resolution.

maximum dose 45 mL.

or patient is already symptomatic. •  Activated charcoal with cathartic. CNS Signs of Stimulation

•  Acepromazine 0.05–1.0 mg/kg IV/IM, start

low and titrate to effect.

•  Chlorpromazine 0.5 mg/kg IV, titrate up as

needed.

•  Cyproheptadine (serotonin antagonist)—

dogs, 1.1 mg/kg orally or rectally, may be repeated q8h as needed for signs consistent with serotonin syndrome; cats, 2–4 mg/cat, may repeat q12h as needed for signs consistent with serotonin syndrome. •  Methocarbamol (for muscle tremors)— 50–220 mg/kg IV, titrate to effect; do not exceed 330 mg/kg/day. Cardiovascular Signs

•  Tachyarrhythmia—beta blockers such as

propranolol 0.02–0.04 mg/kg IV or esmolol or metoprolol; caution using propranolol in significantly hypertensive patient. •  Ventricular premature contractions— lidocaine: dogs at 2–4 mg/kg IV (to maximum of 8 mg/kg over 10-minute period); cats: start with 0.1–0.4 mg/kg and increase cautiously to 0.25–0.75 mg/kg IV slowly if no response; cats are reportedly very sensitive to lidocaine, so monitor carefully if used. Promote Elimination

Ascorbic acid or ammonium chloride—for urinary acidification to promote elimination; however, only use if can measure acid-base status. CONTRAINDICATIONS •  While diazepam has been successfully used to treat amphetamine exposures, there is evidence that benzodiazepines may intensify neurologic signs. •  Urinary acidification if unable to monitor acid-base status or if myoglobinuria is present. •  Inducing emesis in symptomatic patient.

 FOLLOW-UP

PREVENTION/AVOIDANCE All medications and illicit drugs should be kept out of pets’ reach at all times. POSSIBLE COMPLICATIONS Acute renal failure secondary to myoglobinuria or disseminated intravascular coagulation (DIC; rare). EXPECTED COURSE AND PROGNOSIS •  Expected course of clinical signs is 12–72 hours, depending on dose, product formulation, effectiveness of decontamination and treatment, and rate of elimination. •  Prognosis—most patients do well with prompt and appropriate veterinary care. Seizures or severe hyperthermia may be poor prognostic indicator.

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 MISCELLANEOUS

ASSOCIATED CONDITIONS N/A AGE-RELATED FACTORS N/A ZOONOTIC POTENTIAL Pets exposed to human waste products from those taking amphetamines or derivatives could become symptomatic. PREGNANCY/FERTILITY/BREEDING Amphetamines are a known teratogen in humans. They have been found to cross the placenta in animals and may also be found in milk.

SYNONYMS

•  Common brand names of prescription

amphetamine drugs and their active ingredient—Adderall® (amphetamine and dextroamphetamine); Ritalin®, Metadate®, and Concerta® (methylphenidate); Daytrana® (methylphenidate transdermal patch); Focalin® (dexmethylphenidate); Vyvanse® (lisdexamfetamine); Cylert® (pemoline); Adipex-P® (phentermine); Dexedrine® (dextroamphetamine). •  Illicit drug street names—ice, glass, crank, speed, uppers, ecstasy, meth, and many others. SEE ALSO •  Antidepressant Toxicosis—SSRIs and SNRIs. •  Antidepressant Toxicosis—Tricyclics. •  Pseudoephedrine/Phenylephrine Toxicosis. ABBREVIATIONS

•  ADD = attention deficit disorder. •  ADHD = attention deficit hyperactivity

disorder.

•  DIC = disseminated intravascular

coagulation.

•  GI = gastrointestinal.

INTERNET RESOURCES

•  https://www.aspcapro.org/animal-health/

toxicology-poison-control

•  http://www.petpoisonhelpline.com

­Suggested Reading

Stern LA, Schell M. Management of attentiondeficit disorder and attention-deficit/ hyperactivity disorder drug intoxication in dogs and cats. Vet Clin North Am Small Anim Pract 2012, 42(2):279–287. Teitler JB. Evaluation of a human on-site urine multi drug test for emergency use with dogs. J Am Anim Hosp Assoc 2009, 45(2):59–66. Volmer PA. Human drugs of abuse. In: Bonagua JD, Twedt DC, eds., Current Veterinary Therapy XIV. St. Louis, MO: Elsevier, 2009, pp. 144–145. Volmer PA. “Recreational” drugs. In: Peterson ME, Talcott PA, eds., Small Animal Toxicology, 3rd ed. St. Louis, MO: Elsevier, 2013, pp. 309–334. Wismer T. Amphetamines. In: Osweiler GD, Hovda LR, Brutlag AG, Lee JL, eds. Blackwell’s Five-Minute Veterinary Consult Clinical Companion Small Animal Toxicology. Ames, IA: Wiley-Blackwell, 2011, pp. 125–130. Author Kirsten E. Waratuke Consulting Editor Lynn R. Hovda

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Amyloidosis SIGNALMENT Species

­

 BASICS

DEFINITION Group of conditions of diverse causes in which extracellular deposition of insoluble fibrillar proteins (amyloid) in various organs and tissues compromises normal function. PATHOPHYSIOLOGY •  Patients usually affected by reactive (secondary) amyloidosis; tissue deposits contain amyloid A protein (AA), fragment of acute‐phase reactant protein called serum amyloid A protein (SAA). •  Macrophage‐derived cytokines, e.g., IL‐1 and IL‐6, stimulate hepatocytes to synthesize SAA. •  Cellular and extracellular components involved in formation and deposition of AA. •  Specific pathophysiology varies among different species and breeds; reactive amyloidosis occurs as familial disease in Chinese Shar-Pei dog and Abyssinian cat. •  Chinese Shar-Pei dog—mutation involving overexpression of HAS2 results in overproduction of hyaluronic acid, which acts as danger signal activating inflammasome pathway and IL‐1 production; this mutation linked to increased likelihood of developing shar‐pei autoinflammatory disease (SPAID), and also responsible for breed’s meat‐mouth phenotype; amyloid deposition occurs in medulla of all dogs, with majority of dogs also having glomerular involvement. •  Non‐shar‐ pei dogs—amyloid deposits found more commonly in glomeruli than medulla. •  Abyssinian cat—amyloid deposits usually found in medulla, but may occur in glomeruli. •  Siamese and oriental shorthair cats with familial amyloidosis—amyloid deposition occurs in liver. •  Pancreatic islet amyloid polypeptide, or amylin, deposits in pancreas of old cats; amylin secreted with insulin by pancreatic beta cells; chronic increased stimulus for secretion of amylin by beta cells (e.g., states of insulin resistance) leads to pancreatic islet cell amyloidosis. SYSTEMS AFFECTED •  Renal/urologic—predilection for renal AA deposition. •  Liver, spleen, adrenal glands, pancreas, tracheobronchial tree, gastrointestinal tract also may be affected. GENETICS •  Familial amyloidosis occurs in Chinese Shar-Pei, English foxhound, and beagle dogs, and in Abyssinian, oriental shorthair, and Siamese cats. •  A genetic mutation that increases likelihood of SPAID in shar‐pei dogs has been identified; chronic inflammatory episodes in SPAID result in renal amyloid deposition. INCIDENCE/PREVALENCE Uncommon, occurs mostly in dogs; rare in cats, except Abyssinian, Siamese, and oriental shorthair.

Dog and cat. Breed Predilections

•  Dog—Chinese Shar-Pei, beagle, English foxhound, Walker hound, collies. •  Cat—

Abyssinian, Siamese, oriental shorthair.

Mean Age and Range

•  Cats—mean age at diagnosis 7 years; range

1–17 years; Abyssinian cats with familial renal amyloidosis usually die by 5 years of age; Siamese cats with familial amyloidosis of liver and thyroid gland usually develop signs of liver disease when 1–4 years old. •  Dogs— mean age at diagnosis 9 years; range 1–15 years; Chinese Shar-Pei affected younger, with median age at diagnosis of 5 years, range 3.6–17 years. •  Prevalence increases with age.

Predominant Sex

None

SIGNS General Comments

Clinical signs depend on organs affected; usually caused by kidney involvement. Historical Findings

•  No clear history of predisposing disorder in most cases. •  Anorexia, lethargy, polyuria/ polydipsia, weight loss, vomiting. •  Owners

may appreciate ascites and peripheral edema in animals with glomerular amyloidosis. •  Chinese Shar-Pei dogs may have history of previous episodic joint swelling and high fever that resolves spontaneously within few days (SPAID). •  Siamese and oriental shorthair cats may present with acute collapse and hemoabdomen due to spontaneous hepatic fracture. Physical Examination Findings

•  Related to primary inflammatory or neoplastic disease process. •  Animals with renal disease may have muscle wasting, abnormal renal palpation, uremic ulceration, hypertensive fundic lesions. •  Fluid retention may be present (ascites, peripheral edema). •  Chinese Shar-Pei dogs may have evidence of SPAID if present during active flare‐up (joint effusion and pain, fever). •  Signs of thromboembolic disease may be present in up to 40% of dogs with renal amyloidosis (dyspnea with pulmonary embolism, caudal paresis with aortic embolism). •  Siamese and oriental shorthair cats with hepatic dysfunction may have jaundice; pallor and abdominal fluid wave may be present with hepatic fracture and hemoabdomen.

CAUSES •  Neoplasia and chronic infectious and noninfectious inflammatory conditions can be found in 30–50% of dogs with reactive amyloidosis. •  Chronic inflammation— systemic mycoses, chronic bacterial infections, parasitic infections (dirofilariasis, leishmaniasis, hepatozoonosis), inflammatory and

immune‐mediated diseases (SPAID, systemic lupus erythematosus, juvenile polyarteritis of beagle); amyloid deposits can be found in up to 35% of feline immunodeficiency virus (FIV)‐positive cats. •  Neoplasia (lymphoma, plasmacytoma, multiple myeloma, mammary tumors, testicular tumors). •  Familial— Chinese Shar-Pei, English foxhound, and beagle dogs; Abyssinian, Siamese, and oriental shorthair cats. •  Other—cyclic hematopoiesis in gray collies.

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Depends on organ affected. •  Renal (glomerular) amyloidosis—immune‐complex glomerulonephritis (GN; e.g., membranoproliferative GN [MPGN], membranous GN [MGN]), non‐immune‐complex GN, glomerulosclerosis, focal segmental glomerulosclerosis, other glomerulopathies. •  Renal (medullary) amyloidosis—other causes of medullary renal disease (e.g., pyelonephritis, chronic interstitial nephritis). •  Hepatic amyloidosis—other causes of hepatic dysfunction (e.g., infectious, inflammatory, portosystemic shunt, neoplasia); in animals with hepatic fracture and hemoabdomen, consider other causes of hemoabdomen (e.g., hemangiosarcoma, hematoma). CBC/BIOCHEMISTRY/URINALYSIS

•  CBC—nonregenerative anemia found in some dogs and cats. •  Chemistry profile—

changes reflect distribution of amyloid deposition; with renal medullary amyloidosis, azotemia, hyperphosphatemia, metabolic acidosis may be seen; hypoalbuminemia common with glomerular amyloidosis; hyperglobulinemia may be seen due to underlying inflammatory condition resulting in reactive amyloidosis. •  Urinalysis— isosthenuria, proteinuria, cylindruria common with renal amyloidosis; proteinuria may be mild or absent in patients without glomerular amyloidosis; isosthenuria may not be present in patients without medullary involvement. OTHER LABORATORY TESTS

•  Urine protein–creatinine ratio (UPC) should

be performed for quantification of proteinuria. •  Urine sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS‐PAGE)—can differentiate between high and low molecular weight proteinuria; high molecular weight proteinuria expected with glomerular disease. IMAGING Abdominal Radiographic Findings

Kidneys—usually small in affected cats; small, normal size, or large in affected dogs.



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Abdominal Ultrasonographic Findings

•  Renal size, shape, and architecture variable;

kidneys usually hyperechoic and small in affected cats; may be small, normal size, or large in affected dogs. •  Echogenic effusion may be present in cats with hepatic amyloidosis, due to hepatic fracture and hemoabdomen. DIAGNOSTIC PROCEDURES Renal biopsy—histopathology required for definitive diagnosis, and to rule out other causes of GN; ultrasound‐guided sampling preferred over surgical methods; samples should be assessed under dissecting microscope to ensure glomeruli present; risk factors for hemorrhage include body weight 5 mg/dL. PATHOLOGIC FINDINGS •  Amyloid deposits appear homogeneous and eosinophilic when stained by hematoxylin and eosin and viewed by conventional light micro­scopy. •  Demonstrate green birefringence after Congo red staining when viewed under polarized light; AA amyloid loses Congo red affinity after permanganate oxidation. •  Ultrastructurally, fibrils are 9–11 nm in diameter, nonbranching, haphazardly arranged.

therapy (heparin, low molecular weight heparin, or factor Xa inhibitors). Management of Renal Insufficiency and Hypertension

•  As indicated by IRIS guidelines for stage of renal disease. •  Amlodipine (0.3–0.8 mg/kg

PO SID) as first‐line therapy for management of hypertension.

Management of Amyloid Deposition

•  Dimethylsulfoxide (DMSO; dogs—90%

DMSO diluted 1 : 4 with sterile water subcutaneously at dosage of 90 mg/kg 3 times per week) may help patients by solubilizing amyloid fibrils, reducing serum concentration of SAA, and reducing interstitial inflammation and fibrosis in affected kidneys, though benefit of DMSO is controversial. •  Colchicine (dogs—0.01–0.04 mg/kg PO q24h) impairs release of SAA from hepatocytes, and used for amyloidosis in humans with familial Mediterranean fever (familial amyloidosis similar in pathology to SPAID); no evidence for benefit once patient develops renal amyloidosis and dysfunction; colchicine used particularly in shar‐pei dogs with episodic fever or polyarthritis before development of renal failure. PRECAUTIONS

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 TREATMENT

APPROPRIATE HEALTH CARE •  Identify underlying inflammatory and neoplastic processes and treat if possible. •  Animals symptomatic from uremia or clinically dehydrated may require hospitalization. •  Stable, euhydrated animals can be managed as outpatients with standard therapy for proteinuria. DIET •  Low‐protein, low‐phosphorous renal diets recommended for animals with proteinuria and/or renal dysfunction. •  Esophageal feeding tube placement should be considered for enteral hydration and nutritional support. CLIENT EDUCATION •  Discuss progression of disease and potential for underlying primary disease process. •  Discuss familial predisposition in susceptible breeds.

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 MEDICATIONS

DRUG(S) OF CHOICE Management of Proteinuria

•  Animals with proteinuria should be

treated with standard therapy for proteinuria (see Glomerulonephritis and Proteinuria). •  Patients with evidence of active thromboembolic disease require antiplatelet drugs (clopidogrel or aspirin) and/or anticoagulant

•  Dose reduction of drugs may be needed in patients with renal insufficiency. •  Use of

nonsteroidal anti‐inflammatory drugs (NSAIDs) should be avoided in patients with renal insufficiency; SPAID flare‐ups usually resolve on their own, do not require NSAIDs. •  Animals with glomerular disease are prone to overhydration due to abnormal renal sodium handling; fluid therapy should be used judiciously, only to correct dehydration; even patients with mild hypoalbuminemia can become significantly overhydrated from inappropriate fluid therapy.

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 FOLLOW‐UP

PATIENT MONITORING BUN, creatinine, albumin, electrolyte concentrations, 3-day pooled UPC, and blood pressure 1 month following medication changes, and every 3-4 months in stable patients. PREVENTION/AVOIDANCE Do not breed affected animals. POSSIBLE COMPLICATIONS •  Renal insufficiency and progressive chronic kidney disease. •  Nephrotic syndrome and fluid overload. •  Thromboembolic disease occurs in up to 40% of dogs, but uncommon in cats. •  Hepatic rupture causing hemoabdomen (hepatic amyloidosis). •  Otic and airway hemorrhage (vascular amyloidosis) reported.

EXPECTED COURSE AND PROGNOSIS

•  Disease is progressive and usually advanced at

time of diagnosis. In one study, median survival time for all dogs with renal amyloidosis 5 days (range: 0–443 days), shorter in Chinese Shar-Pei dogs (2 days, range: 0–368 days). •  Serum creatinine concentration has significant negative association with survival. •  Cats with renal insufficiency because of amyloidosis usually survive 90%; sensitivity greater with urine test; cross-reacts with other fungal infections (e.g., histoplasmosis). •  Agar gel immunodiffusion (AGID)—not sensitive early in disease, but very specific for infection.

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 MEDICATIONS

DRUG(S) OF CHOICE Itraconazole

•  Dogs—5 mg/kg PO q12h with a fat-rich

meal (e.g., canned dog food) for the first 3 days, then reduce to 5 mg/kg PO q24h.



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Canine and Feline, Seventh Edition

Blastomycosis

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•  Cats—5 mg/kg PO q12h; open the 100 mg

Thoracic Radiographs

Fluconazole

changes (fibrosis/scarring) may occur after the infection resolves, making determination of persistent active disease difficult. •  At 90 days of treatment—if active pulmonary disease, continue treatment for additional 30 days. •  If lungs appear normal, stop treatment and repeat radiographs again in 30 days. •  At 120 days of treatment—if the lungs appear the same as day 90, changes are residual (fibrosis); if clearer than day 90, continue treatment for 30 more days. If lesions are significantly worse than at 90 days, consider a change in therapeutic agent. •  Continue treatment as long as improvement is noted in the lungs; if there is no further improvement and no indication of active disease, the lesions are likely the result of scarring.

capsules containing pellets and mix with palatable food. •  Avoid antacid drugs as absorption best in acidic environment. •  Treat for minimum 90 days, or for 1 month after all signs of disease have resolved (which­ever is longer). •  Absorption of compounded itraconazole is unreliable and use is not recommended. •  Dogs—5 mg/kg PO q12h. •  Cats—5–10 mg/kg PO q12–24h; 50 mg/cat. •  Inexpensive, but may require longer

treatment duration.

Amphotericin B

•  For dogs with neurologic signs or life-

threatening disease.

•  0.5–1.0 mg/kg IV q48h; use lipid complex

for dogs with renal dysfunction.

CONTRAINDICATIONS Corticosteroids—may allow continued proliferation of organisms; patients with previous steroid therapy require longer treatment duration; for dogs with lifethreatening dyspnea, dexamethasone (0.1–0.2 mg/kg/day IV) for 2–3 days may be given with itraconazole treatment; taper and discontinue corticosteroids as soon as possible. PRECAUTIONS Itraconazole and Fluconazole Toxicity

•  Anorexia—most common sign; attributed

to liver toxicity; monitor serum alanine aminotransferase (ALT) activity monthly or when anorexia occurs; temporarily discontinue drug for patients with anorexia and moderate ALT activity elevation; after appetite improves, restart at half the previous dose. •  Ulcerative dermatitis—in some dogs due to vasculitis; dose related; temporarily discontinue drug until ulcers resolve, then restart at half the previous dose. Amphotericin B Toxicity

•  Only absolute contraindication to therapy

is anaphylaxis, but major limiting factor is cumulative nephrotoxicity. •  Monitor serum creatinine concentration throughout therapy—elevation above normal or 20% greater than baseline considered significant.

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 FOLLOW-UP

PATIENT MONITORING Serum chemistry—monthly to monitor for hepatic toxicity, or if anorexia develops.

•  Considerable permanent pulmonary

Urine Antigen Testing

•  Positive test is generally related to active disease. •  If other signs have resolved, a negative test

supports treatment discontinuation.

PREVENTION/AVOIDANCE •  Location of environmental growth of Blastomyces organisms unknown, thus difficult to avoid exposure; exposure to lakes and streams may be restricted (but limited practicality). •  Dogs that recover from the infection may be immune to reinfection. EXPECTED COURSE AND PROGNOSIS

•  Death—25% of dogs die during first week

of treatment; early diagnosis improves chance of survival. •  Severe pulmonary disease and CNS involvement decrease prognosis. •  Recurrence—approximately 20% of dogs; usually within 3–6 months after completion of treatment; may occur >1 year after treatment; a second course of azole treatment cures most patients; drug resistance has not been observed. •  With early detection of blastomycosis, the prognosis in cats appears similar to dogs.

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 MISCELLANEOUS

ZOONOTIC POTENTIAL •  Yeast form is not spread from animals to humans, except through bite wounds; inoculation of organisms from dog bites has occurred. •  Avoid cuts during necropsy of infected dogs and avoid needle sticks when aspirating lesions.

•  Warn clients that blastomycosis is acquired

from an environmental source and that they may have been exposed to the source; the incidence in dogs is 10 times that in humans. •  Encourage clients with respiratory and skin lesions to inform their physicians that they may have been exposed to blastomycosis. PREGNANCY/FERTILITY/BREEDING Azole drugs can have teratogenic effects (embryotoxicity found at high doses) and should ideally be avoided during pregnancy (but the risk of not treating the mother must be balanced with the theoretical risk of azole therapy to the fetuses). ABBREVIATIONS

•  AGID = agar gel immunodiffusion. •  ALT = alanine transaminase. •  AV = atrioventricular.

INTERNET RESOURCES Information on antigen testing: www. miravistalabs.com

­Suggested Reading

Crews LJ, Feeney DA, Jessen CR, et al. Radiographic findings in dogs with pulmonary blastomycosis: 125 cases (1989–2006). J Am Vet Med Assoc 2008, 232:215–221. Foy DS, Trepanier LA, Kirsch EJ, et al. Serum and urine Blastomyces antigen concentrations as markers of clinical remission in dogs treated for systemic blastomycosis. J Vet Intern Med 2014, 28:305–310. Legendre AM, Rohrbach BW, Toal RL, et al. Treatment of blastomycosis with itraconazole in 112 dogs. J Vet Intern Med 1996, 10:365–371. Mazepa AS, Trepanir LA, Foy DS. Retrospective comparison of the efficacy of fluconazole or itraconazole for the treatment of systemic blastomycosis in dogs. J Vet Intern Med 2011, 25:440–445. Spector D, Legendre AM, Wheat J, et al. Antigen and antibody testing for the diagnosis of blastomycosis in dogs. J Vet Intern Med 2008, 22:839–843. Author Daniel S. Foy Consulting Editor Amie Koenig  Client Education Handout available online

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Blepharitis

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erythematosus (SLE), SH, drug eruption.

•  Type IV (cell mediated)—contact and flea

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 BASICS

DEFINITION Inflammation of outer (skin) and middle (muscle, connective tissue, and glands) portions of eyelid, usually with secondary inflammation of palpebral conjunctiva. PATHOPHYSIOLOGY •  Inflammation—immune mediated, infectious, endocrine mediated, self- and external trauma, parasitic, radiation, nutritional. Inflammatory response often exaggerated because conjunctiva is rich in mast cells and densely vascularized. •  Meibomian gland dysfunction—bacterial lipases alter meibomian lipids and plug gland; produce irritating fatty acids, enhance bacterial growth, and destabilize tear film. SYSTEMS AFFECTED Ophthalmic SIGNALMENT See Causes. SIGNS

•  Serous, mucoid, or mucopurulent ocular discharge. •  Blepharospasm. •  Eyelid

hyperemia, edema, and thickening. •  Pruritus. •  Excoriation. •  Depigmentation— skin, hair (in Siamese-type cats with color points, lightening of hair on affected lids due to increased skin temperature). •  Alopecia. •  Swollen, cream-colored meibomian glands. •  Elevated, pinpoint meibomian gland orifices. •  Abscesses. •  Scales, crusts, papules, or pustules. •  Single or multiple nodular hyperemic swellings. •  Concurrent conjunctivitis and/or keratitis. CAUSES Congenital

•  Eyelid abnormalities—may promote self-trauma or moist dermatitis. •  Prominent nasal folds, medial trichiasis, and lower lid entropion—shih tzu, Pekingese, English bulldog, Lhasa apso, pug; Persian and Himalayan cat. •  Distichia—shih tzu, pug, golden retriever, Labrador retriever, poodle, English bulldog. •  Ectopic cilia. •  Lateral lid entropion—Chinese Shar-Pei, chow chow, Labrador retriever, Rottweiler. •  Lagophthalmos—brachycephalic dogs; Persian, Himalayan, and Burmese cats. •  Deep medial canthal pocket—dolichocephalic dogs. •  Dermoids—Rottweiler, dachshund, and others; Burmese cat.

Allergic

•  Type I (immediate)—atopy, food, insect

bite, inhalant, Staphylococcus hypersensitivity (SH). •  Type II (cytotoxic)—pemphigus, pemphigoid, drug eruption •  Type III (immune complex)—systemic lupus

bite hypersensitivity; drug eruption.

Bacterial

•  Hordeolum—localized abscess of eyelid glands, usually staphylococcal; may be external (sty in young dogs, glands of Zeis) or internal (in old dogs, meibomian glands). •  Generalized bacterial blepharitis and meibomianitis—usually Staphylococcus or Streptococcus. •  Bartonella henselae—chronic blepharoconjunctivitis in cats. •  Pyogranulomas. •  SH—young and old dogs.

Neoplastic

•  Sebaceous adenomas and

adenocarcinomas—from meibomian gland.

•  Squamous cell carcinoma—white cats. •  Mast cell—may appear as swollen, hyper­-

emic lesion.

Other

•  External trauma—eyelid lacerations, thermal or chemical burns. •  Mycotic—

dermatophytosis; systemic fungal granulomas.

•  Parasitic—demodicosis; sarcoptic mange;

Cuterebra and Notoedres cati. Note: Demodex injai has a propensity for sebaceous glands and can be associated with meibomian gland dysfunction in dogs, including chalazia and granulomatous blepharitis. •  Chalazia—sterile, yellow-white, painless meibomian gland swellings caused by granulomatous inflammatory response to meibum in surrounding eyelid tissue. •  Nutritional—zinc-responsive dermatosis (Siberian husky, Alaskan Malamute, puppies), fatty acid deficiency. •  Endocrine—hypothyroidism (dogs); hyperadrenocorticism (dogs); diabetic dermatosis. •  Viral—chronic blepharitis in cats (feline herpesvirus type 1 [FHV-1]). •  Irritant—drug reaction (e.g., neomycin); smoke in environment; post-parotid duct transposition. •  Familial canine dermato­ myositis—collie and Shetland sheepdog. •  Nodular granulomatous episclerokeratitis— fibrous histiocytoma and collie granuloma; may affect eyelids, cornea, or conjunctiva. •  Eosinophilic granuloma—cats; may affect eyelids, cornea, or conjunctiva. •  Eyelid contact with tear overflow and purulent exudate (tear burn). •  Keratitis, conjunctivitis, dacryocystitis. •  Dry eye. •  Orbital disease. •  Radiotherapy. •  Idiopathic— especially Persians and Himalayans. RISK FACTORS

•  Breed predisposition to eyelid abnormalities

(e.g., entropion, ectropion).

•  Hypothyroidism—may promote chronic bacterial disease in dogs. •  Canine seborrhea—

may promote chronic generalized meibomianitis, with predisposition for Demodex injai infection.

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS Clinical signs are diagnostic. CBC/BIOCHEMISTRY/URINALYSIS Usually normal unless metabolic cause (e.g., diabetic dermatosis). OTHER LABORATORY TESTS Indicated for systemic disorders, including hypothyroidism. DIAGNOSTIC PROCEDURES •  Eye examination—inciting cause, corneal ulcer, foreign body, distichia, ectopic cilia, keratoconjunctivitis sicca (KCS). •  Ancillary ocular tests— fluorescein, Schirmer tear test. •  Thorough history and dermatologic exam: ◦  Cytology—deep skin scrape, conjunctival scrape, or exudate from glands and pustules. ◦  Wood’s light evaluation, dermatophyte culture. ◦  KOH preparation. ◦  Intradermal skin testing, other testing for hypersensitivityinduced disease. ◦  Consider referral to a dermatologist for refractory cases. •  Aerobic bacterial culture and sensitivity—of exudate from skin, conjunctiva, expressed meibomian glands, or pustules; often will not recover Staphylococcus from patients with chronic meibomianitis and suspected SH. •  Immuno­ fluorescent antibody assay or PCR for FHV-1 and Chlamydia—in conjunctival scrapings from cats with primary conjunctivitis or keratitis. •  Full-thickness wedge biopsy of eyelid. PATHOLOGIC FINDINGS Routine histopathology often nondiagnostic in chronic disease.

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 TREATMENT

APPROPRIATE HEALTH CARE See Nursing Care. NURSING CARE •  Prevent self-trauma—Elizabethan collar. •  Cleanse eyelids—to remove crusts; warm compresses applied for 5–15 minutes 3–4 times daily, avoiding ocular surfaces. Use saline, lactated Ringer’s solution, or a commercial ocular cleansing agent (e.g., I-Lid ’n Lash®); clip periocular hair short. •  Common underlying cause in cats is FHV-1 infection; minimize stress. DIET Only if food allergy. CLIENT EDUCATION In cats with FHV-1-related blepharitis, inform client that there is no cure and that clinical signs often recur when animal is stressed.



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Blepharitis

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SURGICAL CONSIDERATIONS •  Temporary everting eyelid sutures—spastic entropion; or in puppies before permanent surgical correction. •  Repair eyelid lacerations. •  Lancing—large abscesses only; lance and curette hordeola that resist medical treatment and chalazia that have hardened and cause keratitis; manually express infected meibomian secretions.

affected dogs might also require treatment for demodecosis. •  Eyelid lesions associated with puppy strangles—treat generalized condition. •  Atopy—see Atopic Dermatitis. Bacterial

•  Based on culture and sensitivity or serologic testing. •  Pending results—topical polymyxin

B and neomycin with 0.1% dexamethasone ointment (q4–6h) and systemic broadspectrum antibiotic.

Mycotic

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 MEDICATIONS

DRUG(S) OF CHOICE Antibiotics

•  Systemic—for bacterial eyelid infections

(e.g., cephalexin 20 mg/kg IV q8h). For Bartonella henselae infection in cats, therapy may include doxycycline (10 mg/kg PO q12h for 3 weeks), pradofloxacin (5–10 mg/kg PO q12–24h for 28–42 days), or azithromycin (10 mg/kg PO q24h for 3 weeks). •  Topical— neomycin, polymyxin B, and bacitracin combination or chloramphenicol.

Congenital

•  Topical antibiotic ointment—q6–12h to

prevent frictional rubbing of eyelid hairs or cilia on ocular surface. •  Regularly flush debris from deep medial canthal pocket using saline, lactated Ringer’s solution, or ocular irrigant.

External Trauma

•  Topical antibiotic ointment—q6–12h; in

patients with spastic entropion and blepharo­ spasm until surgical correction. •  Systemic antibiotics.

Allergic

•  SH blepharitis—systemic broad-spectrum

antibiotics and systemic corticosteroids (prednisolone 0.5 mg/kg PO q12h for 3–5 days, then taper); many patients respond to systemic corticosteroids alone; systemic cyclosporine (5 mg/kg PO q24h until remission, then q48–72h) if refractory to corticosteroids; failure of treatment—consider injections of Staphylococcus aureus bacterin (Staphage Lysate®). •  Infected meibomian glands—oral tetracycline (15–20 mg/kg PO q8h), doxycycline (3–5 mg/kg PO q12h), or cephalexin (22 mg/kg PO q8h) for 3 weeks (the former two are lipophilic and cause decreased production of bacterial lipases and irritating fatty acids); topical polymyxin B and neomycin with 0.1% dexamethasone (q6–8h) or topical 0.02% tacrolimus compounded ointment (q8–12h). Some

Microsporium canis infection—see Dermatophytosis. Parasitic

Demodicosis, Notoedres infection, sarcoptic mange—see relevant chapters. Idiopathic

Clinical signs often controlled with topical polymyxin B and neomycin with 0.1% dexamethasone (q8–24h or as needed); occasionally may need prednisolone (0.5 mg/ kg PO q12h for 3–5 days, then taper) and/or systemic antibiotic. CONTRAINDICATIONS •  Topical corticosteroids—do not use with corneal ulceration. •  Many cats with presumed idiopathic blepharoconjunctivitis have FHV-1 infection; topical and systemic corticosteroids may exacerbate infection. •  Oral tetracycline and doxycycline—do not use in puppies and kittens. •  Neomycin— avoid topical use if possible cause of blepharitis. •  Neomycin, bacitracin, and polymyxin—avoid topical ophthalmic use in cats due to rare but potentially fatal anaphy­ lactic reaction. PRECAUTIONS •  Ectoparasitism—wear gloves; do not contact ocular surfaces with a drug topically applied to skin; apply artificial tear ointment to eyes for protection. •  Topical gentamicin, neomycin, terramycin, and most ointments— may cause irritant blepharoconjunctivitis (rare); withdrawal may resolve condition. POSSIBLE INTERACTIONS Staphylococcal bacterin may cause anaphy­ lactic reaction (rare).

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 FOLLOW-UP

PATIENT MONITORING •  Depends on cause, therapy. •  Bacterial— systemic and topical treatment for at least 3

weeks; should notice improvement within 10 days. •  Most common causes of treatment failure—use of subinhibitory antibiotic dosages, failure to correct one or more predisposing factors, early discontinuation of medications. PREVENTION/AVOIDANCE Depends on cause. POSSIBLE COMPLICATIONS

•  Cicatricial lid contracture—results in

trichiasis, ectropion, or lagophthalmos.

•  Spastic entropion—because of blepharo­ spasm and pain. •  Qualitative tear film

deficiency—loss of proper meibum secretion.

•  Recurrence of bacterial infection or FHV-1

blepharoconjunctivitis.

EXPECTED COURSE AND PROGNOSIS Depend on cause.

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 MISCELLANEOUS

ZOONOTIC POTENTIAL •  Dermatophytosis. •  Sarcoptic mange. SEE ALSO

•  Atopic Dermatitis. •  Conjunctivitis—Cats. •  Conjunctivitis—Dogs. •  Dermatophytosis. •  Epiphora. •  Keratitis—Nonulcerative. •  Keratitis—Ulcerative. •  Red Eye.

ABBREVIATIONS

•  FHV-1 = feline herpesvirus type 1. •  KCS = keratoconjunctivitis sicca. •  SH = Staphylococcus hypersensitivity. •  SLE = systemic lupus erythematosus.

­Suggested Reading

Bettany S, Mueller R, Maggs D. Diseases of the eyelids. In: Maggs DJ, Miller PE, Ofri R, eds., Slatter’s Fundamentals of Veterinary Ophthalmology, 6th ed. St. Louis, MO: Saunders, 2018, pp. 127–157. Author Terri L. McCalla Consulting Editor Kathern E. Myrna  Client Education Handout available online

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Blind Quiet Eye

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RISK FACTORS

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  BASICS

DEFINITION Loss of vision in one or both eyes without ocular vascular injection or other externally apparent signs of ocular inflammation.

•  Poorly regulated diabetes mellitus—cataracts. •  Related animals with genetic cataracts or PRA. •  Systemic hypertension—retinal detachment. •  CNS hypoxia—blindness may become

apparent after excessively deep anesthesia or revival from cardiac arrest.

PATHOPHYSIOLOGY Results from abnormalities in focusing images on the retina, the retina detecting an image, optic nerve transmission, or the brain not interpreting images correctly.

­

SYSTEMS AFFECTED •  Nervous. •  Ophthalmic.

•  Anterior segment inflammation and

SIGNALMENT •  Dog and cat. •  Any age, breed, or sex. •  Many causes (e.g., cataracts and progressive retinal atrophy) have a genetic basis and are often highly breed and age specific. •  Sudden acquired retinal degeneration syndrome (SARDS)—tends to occur in older dogs. •  Optic nerve hypoplasia— congenital. SIGNS Historical Findings

•  Vary with underlying cause. •  Bumping into objects. •  Clumsy behavior. •  Reluctance to move. •  Impaired vision in dim light.

Physical Examination Findings

•  Vary with underlying cause. •  Decreased or absent menace or dazzle response. •  Impaired

visual placing responses. CAUSES

•  Cataracts—entire lens must become opaque

to produce complete blindness; incomplete opacification may reduce performance of visually demanding tasks. •  Loss of focusing power of the lens—rarely completely blinding; substantial hyperopia (far-sightedness) occurs when the optical power of the lens is not replaced after lens extraction or if the lens luxates posteriorly out of the pupillary plane and into the vitreous. •  Retina—SARDS, progressive retinal atrophy (PRA), retinal detachment, taurine deficiency (cats), enrofloxacin toxicity (cats), ivermectin toxicity (dogs, cats). •  Optic nerve—optic neuritis, neoplasia of the optic nerve or adjacent tissues, trauma, optic nerve hypoplasia, lead toxicity, excessive traction on the optic nerve during enucleation resulting in trauma to the contralateral optic nerve or optic chiasm (especially cats and brachycephalic dogs). •  CNS (amaurosis)—lesions of the optic chiasm or tract, optic radiation, or visual cortex. CNS-associated vision loss that occurs at a level higher than the optic chiasm often has vague visual disturbances in which the patient has some vision, but clearly does not have normal vision.

  DIAGNOSIS

DIFFERENTIAL DIAGNOSIS Signs

glaucoma—conjunctiva typically injected.

•  Young patients—may lack menace responses,

but will successfully navigate a maze or visually track hand movements or cotton balls. •  Postictal period—transient vision loss. •  Abnormal mentation—may be difficult to determine whether an animal is visual; other neurologic abnormalities help localize the lesion.

IMAGING

•  Ocular ultrasound—may demonstrate

retinal detachment (especially if the ocular media are opaque) or optic nerve mass lesion. •  Plain skull radiographs—seldom inform­ ative. •  CT or MRI—often helpful with orbital or CNS lesions. DIAGNOSTIC PROCEDURES See Figure 1. •  Ophthalmic examination with a penlight— usually permits diagnosis of cataracts or retinal detachments severe enough to cause blindness. •  Ophthalmoscopy—may show PRA, late SARDS, or optic nerve disease; normal exam suggests early SARDS, retrobulbar optic neuritis, or a CNS lesion. •  Systemic arterial blood pressure—determine in patients with retinal detachment. •  Electroretinography— differentiates retinal from optic nerve or CNS disease. •  Cerebrospinal fluid (CSF) tap— may be of value with a neurogenic cause of vision loss.

Causes

•  Optic neuritis, retinal detachment, SARDS,

or visual cortex hypoxia—sudden vision loss (over hours to weeks). •  SARDS—often preceded by polyuria, polydipsia, polyphagia, and weight gain. •  PRA—gradual vision loss, especially in dim light; apparently acute vision loss with sudden change in environ­ ment. •  Cataract—either gradual or rapidly increasing opacification and vision loss in a quiet eye. •  Optic nerve hypoplasia— congenital; may be unilateral or bilateral. •  Optic neuropathy or CNS disease—other signs of neurologic abnormalities. •  Pupillary light responses—usually normal with cataracts or visual cortex lesions; sluggish to absent with retinal or optic nerve diseases. •  Ophthalmoscopy—normal with early SARDS, retrobulbar optic neuritis, and higher visual pathway lesions; abnormal with retinal detachment and disorders of optic nerve head. CBC/BIOCHEMISTRY/URINALYSIS

•  Usually normal, unless underlying systemic disease. •  Hyperglycemia or glucosuria—may note with diabetic cataracts. •  Elevated alkaline

phosphatase (ALP) enzyme activity and changes consistent with hyperadrenocorticism (Cushing’s syndrome)—suggest SARDS. •  Retinal detachment secondary to systemic hypertension (cats)—azotemia or changes consistent with hyperthyroidism.

OTHER LABORATORY TESTS •  Blood lead and serology for deep fungal or viral infections—consider for suspected optic neuritis (see Optic Neuritis and Papilledema). •  Low-dose dexamethasone suppression test—may help rule out Cushing’s syndrome with SARDS. •  Sex hormone abnormalities are common in patients with SARDS.

­

  TREATMENT

•  Try to obtain a definitive diagnosis on an

outpatient basis before initiating treatment.

•  Consider referral before attempting empirical therapy. •  Most causes are not

fatal, but must perform a workup to rule out potentially fatal diseases. •  Reassure client that most causes of a blind quiet eye are not painful and that blind animals can lead relatively normal and functional lives. •  Warn client that the environment should be examined for potential hazards to a blind animal. •  Advise client that patients with PRA or genetic cataracts should not be bred and related animals should be examined. •  Retinal detachment—restrict exercise until the retina is firmly reattached. •  Calorierestricted diet—to prevent obesity owing to reduced activity level. •  Cats with nutritionally induced retinopathy—ensure diet has adequate levels of taurine. •  SARDS, PRA, optic nerve atrophy, and optic nerve hypoplasia—no effective treatment. •  Cataracts, luxated lenses, and some forms of retinal detachment—best treated surgically.

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 MEDICATIONS

DRUG(S) OF CHOICE •  Depend on cause. •  If workup is declined, infectious disease is unlikely, and the likely diagnosis is either SARDS or retrobulbar optic neuritis—consider systemic prednisolone (1–2 mg/kg/day PO for 7–14 days, then taper); may concurrently administer oral broad-spectrum antibiotic.



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Canine and Feline, Seventh Edition



Blind Quiet Eye

(continued)

Blind Quiet Eye History, physical examination Ophthalmic examination

Opaque ocular media Cataracts Check blood glucose +/– lens extraction

Is the ocular media opaque? CLEAR OCULAR MEDIA Is the fundus normal?

YES

NO

Retinal Detachment Retinal Degeneration PRA Consider • CBC • Examine related animals • Chemistry profile Do not breed • Urinalysis Late SARDS • Deep fungal serology • Systemic blood pressure Postinflammatory • No Rx for any • Chest radiographs

Optic Neuropathy Congenltal Hypoplasia Optic Neuritis Consider • CBC • Chemistry profile • Urinalysis • Deep fungal serology • CSF tap • CT/MRI • Blood lead

Pupillary light response Abnormal NORMAL CNS blindness Rule out hypoxia Consider • CSF tap • CT/MRI

ERG NORMAL Optic Neuritls

ABNORMAL SARDS Consider • CBC • Chemistry profile • Urinalysis • LDDST

Figure 1.  CONTRAINDICATIONS Do not use systemic corticosteroids or other immunosuppressive drugs with optic neuritis and retinal detachments that are infectious in origin. PRECAUTIONS Pretreatment with corticosteroids may mimic or mask liver enzyme changes in SARDS.

neuritis; may occur weeks, months, or years after initial presentation.

SEE ALSO Optic Neuritis and Papilledema.

POSSIBLE COMPLICATIONS •  Death. •  Permanent vision loss. •  Loss of the eye. •  Chronic ocular inflammation and pain. •  Obesity from inactivity or as a sequela of SARDS.

ABBREVIATIONS •  ALP = alkaline phosphatase. •  CSF = cerebrospinal fluid. •  PRA = progressive retinal atrophy. •  SARDS = sudden acquired retinal degeneration syndrome.

POSSIBLE INTERACTIONS N/A

INTERNET RESOURCES

ALTERNATIVE DRUG(S) Oral azathioprine 1–2 mg/kg/day PO for 3–7 days, then taper; may be used to treat immune-mediated retinal detachments if systemic corticosteroids are not effective; perform a CBC, platelet count, and liver enzyme every 1–2 weeks for the first 8 weeks, then periodically.

ASSOCIATED CONDITIONS •  SARDS (dogs)—signs similar to those of hyperadrenocorticism. •  Neurologic disease— may note seizures, behavior or personality changes, circling or other CNS signs. •  Cardiomyopathy (cats)—taurine deficiency.

­

AGE-RELATED FACTORS •  PRA and many cataracts—breed-specific ages of onset. •  SARDS—tends to occur in older dogs. •  Optic nerve hypoplasia—congenital.

  FOLLOW-UP

PATIENT MONITORING •  Repeat ophthalmic examinations—as required to ensure that ocular inflammation is controlled and, if possible, vision is maintained. •  Recurrence of vision loss—common in optic

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  MISCELLANEOUS

ZOONOTIC POTENTIAL N/A PREGNANCY/FERTILITY/BREEDING Corticosteroids and immunosuppressive drugs may complicate pregnancy.

•  https://muffinshalo.com •http://www. pepedog.com •https://www.akc.org/expert-

advice/health/seven-ways-to-keep-the-light-inyour-blind-dogs-life

­Suggested Reading

Maggs DJ, Miller PE, Ofri R. Fundamentals of Veterinary Ophthalmology, 6th ed. St Louis, MO: Elsevier, 2018. Rubin LF. Inherited Eye Disease in Purebred Dogs. Baltimore, MD: Williams & Wilkins, 1989. Author Paul E. Miller Consulting Editor Kathern E. Myrna  Client Education Handout available online

B

186

Blackwell’s Five-Minute Veterinary Consult

Blood Transfusion Reactions

B

Delayed Hemolysis

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 BASICS

OVERVIEW •  Reaction to donor blood cells can result in minor (fever, urticaria) or major (hemolysis, anaphylactic shock) reactions, usually acute but can be delayed. •  Can occur with admini­stration of any blood‐derived product. SIGNALMENT •  Dogs and cats. •  No sex predilection. •  All ages affected. SIGNS Acute Nonhemolytic Reaction

•  Fever, urticaria, erythema, pruritus (in 10–25% of transfusions). •  Septic shock from bacterial contamination of blood products. •  Transfusion‐associated circulatory overload (TACO)—dyspnea, cough, cyanosis (congestive heart failure). •  Transfusion‐associated acute lung injury (TRALI)—dyspnea, cyanosis. •  Citrate toxicity—facial pruritis, weakness. •  Hyperammonemia—encephalopathy.

Acute Hemolytic Reaction

•  Occurs in 1–5% of transfusions. •  Tachycardia, shock, anaphylaxis, death. •  Collapse, lethargy, weakness. •  Vomiting, diarrhea. •  Pigmenturia, potential for pigmentary nephropathy. •  Restlessness,

hypersalivation, urticaria, facial swelling. •  Hemolysis of transfused red blood cells (RBCs). Delayed Hemolytic Reaction

Clinical signs of anemia may recur. Delayed Nonhemolytic Reaction

Signs of blood‐borne disease (e.g., Babesia, Mycoplasma haemofelis, Ehrlichia). CAUSES & RISK FACTORS Cats and previously transfused dogs have higher risk of transfusion reactions. Acute Nonhemolytic Reaction

•  Anaphylaxis/immune reaction to donor

cells, major histocompatibility complex (MHC) or plasma antigens, release of inflammatory mediators and pyrogens. •  RBC membrane fragility (from depleted adenosine triphosphate [ATP]) can result in mechanical destruction during transfusion; degradation of ATP causes hyperammonemia in stored blood. •  Contamination of blood can result from lack of aseptic collection or poor storage conditions. •  TACO results from rapid transfusion or excessive transfusion volume. •  Citrate toxicity causes hypocalcemia. Acute Hemolysis

•  Type II hypersensitivity reaction caused by

naturally occurring or acquired antibodies against donor RBCs (cats have existing alloantibodies against other blood type, dogs require prior sensitization). •  Transfusion of damaged RBCs.

Immune reaction to RBC antigens (5–14 days after transfusion). Delayed Nonhemolytic Reaction

Transmission of blood‐borne disease.

­

 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Hemolysis—other hemolytic disease (e.g., immune‐mediated hemolytic anemia, Babesia, zinc toxicity). •  Fever, hypotension— infectious/inflammatory disease, contamination of IV catheter sites. •  Urticaria/pruritis— allergic reaction; avoid coadministration of medications during transfusion to distinguish drug vs. transfusion reaction. •  Pigmenturia— hematuria or myoglobinuria vs. hemoglobinuria. CBC/BIOCHEMISTRY/URINALYSIS Hemoglobinemia, leukocytosis, thrombocytopenia possible, bilirubinemia, pigmenturia (hemoglobin/bilirubinuria).

­

 FOLLOW‐UP

PATIENT MONITORING •  Check attitude, rectal temperature, and vital signs before, during, and after transfusion. •  For acute hemolytic reactions or septicemia— intensive monitoring and supportive care required. •  Measure PCV or hematocrit 2 hours post transfusion, sooner if clinical signs warrant. PREVENTION/AVOIDANCE •  Record any transfusion reaction in the medical file. •  Pretransfusion testing: ∘ Screen donors for infectious disease. ∘  Blood type donors and recipients (imperative in cats). ∘  Cross‐match patients receiving repeated transfusions. •  Have standard transfusion protocols, dedicated storage for blood products. •  Transfusion administration should start slowly but be completed within 4 hours. •  Leukoreduction of RBC‐containing products may decrease incidence of reactions. •  Older stored blood more likely to result in reaction.

ination of blood may reveal contamination.

POSSIBLE COMPLICATIONS Fulminant hemolysis may cause acute renal failure, multiorgan dysfunction, coagulopathies, and cardiac arrhythmias.

hemolysis.

•  Acute course in most animals;

OTHER LABORATORY TESTS

•  Cross‐match to confirm incompatibility. •  Bacterial culture or microscopic exam­

•  Centrifugation of donor blood may show

EXPECTED COURSE AND PROGNOSIS nonhemolytic reactions have good prognosis.

•  Prognosis guarded in animals with severe

­

 TREATMENT

reactions or hemolysis.

•  Acute, nonhemolytic reaction—stop

transfusion: if signs resolve, restart at slower rate, if signs recur, discontinue transfusion; if dyspnea, supplemental oxygen; if volume overload/congestive heart failure, furosemide; animals with TRALI may require mechanical ventilation. •  Acute, hemolytic reaction—stop transfusion and administer IV fluids to maintain blood pressure and treat shock; in hypotensive patients, administer isotonic crystalloids (20–30 mL/kg, repeat as necessary); epinephrine and vasopressor therapy for severe anaphylaxis.

­

 MEDICATIONS

DRUG(S) OF CHOICE •  For anaphylaxis—IV crystalloid as above, epinephrine 0.01 mg/kg IV. •  For urticaria, fever—diphenhydramine (1–2 mg/kg IM); dexamethasone sodium phosphate (0.1 mg/kg IV once). •  If septic shock suspected—broad‐ spectrum IV antibiotics, IV fluid therapy. •  Volume overload—furosemide 2–4 mg/kg IV, oxygen. •  Hypocalcemia—calcium gluconate 50–150 mg/kg IV slowly (monitor ECG).

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 MISCELLANEOUS

SEE ALSO Sepsis and Bacteremia. ABBREVIATIONS •  ATP = adenosine triphosphate. •  MHC = major histocompatibility complex. •  RBC = red blood cells. •  TACO = transfusion‐ associated circulatory overload. •  TRALI = transfusion‐associated acute lung injury.

­Suggested Reading

Hann L, Brown DC, King LG, Callan MB. Effect of duration of packed red blood cell storage on morbidity and mortality in dogs after transfusion: 3,095 cases (2001–2010). J Vet Intern Med 2014, 28(6):1830–1837. Maglaras CH, Koenig A, Bedard DL, Brainard BM. Retrospective evaluation of the effect of red blood cell product age on occurrence of acute transfusion‐related complications in dogs: 210 cases (2010– 2012). JVECC 2017, 27(1):108–120. Wardrop KJ. Update on canine and feline blood donor screening for blood‐borne pathogens. J Vet Intern Med 2016, 30(1):15–35. Author Jörg Bucheler Consulting Editor Melinda S. Camus



187

Canine and Feline, Seventh Edition

Blue‐Green Algae Toxicosis Neurotoxic

­

 BASICS

OVERVIEW •  Cyanobacterial blooms can occur in fresh and brackish waters, and in backyard ponds where algal material is concentrated. •  Nutrient‐rich runoff, increased water temperatures, and stagnant water conditions favor toxic bloom formation. •  Blue‐green algae exposure can lead to acute hepato‐ or neurotoxicosis in animals and humans. •  Skin irritation following exposure to cyanobacteria‐ contaminated water may occur. •  Hepatotoxic blue‐green algae poisonings are more frequently reported than neurotoxic algal intoxication. •  Toxin‐producing cyanobacteria include Microcystis, Anabena, Aphanizomenon, Oscillatoria, Lyngbya, and Planktothrix spp. •  Microcystins are hepatotoxic blue‐green algae toxins that have been found worldwide. •  Anatoxins, which include anatoxin‐a and anatoxin‐as, are neurotoxic blue‐green algae toxins. SIGNALMENT

•  Dogs—no breed, sex, or age predilection. •  Cats—no cases reported.

SIGNS Hepatotoxic

•  Diarrhea, weakness, shock. •  Rapid progression to depression, coma, and death.

Neurotoxic

•  Onset of rigidity and muscle tremors within

minutes to a few hours after exposure.

•  Rapid progression to paralysis, cyanosis,

and death.

•  Strychnine, metaldehyde, avitrol, pyrethrins/ pyrethroids, zinc phosphide, bromethalin. •  Organophosphorus, carbamate, and organochlorine insecticides. •  Penitrem A, methylxanthines. •  Poisonous plants (Brunfelsia spp., cyanide, oleander, poison hemlock). •  Illicit substances (amphetamine and derivatives), ephedra‐containing compounds. •  Neurotoxic mushrooms.

Dermatotoxic

Other causes of pruritus—allergies, infec­ tious, parasitic, dietary, endocrine. CBC/BIOCHEMISTRY/URINALYSIS Hepatotoxic

•  Elevated serum liver enzymes—alanine

transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), bilirubin. •  Hypoalbuminemia. •  Hypoglycemia.

hemostatic test results. •  Diazepam (2–5 mg/ kg IV, repeat in 30 min if necessary) for seizure control. •  Phenobarbital (2–5 mg/kg IV q6–12h) for seizure control. •  Methocarbamol (55–220 mg/kg IV) for muscle relaxation. Alternative Drugs

•  S‐adenosylmethionine (SAMe)—antioxidant and hepatoprotectant; no data on efficacy in hepatotoxic cyanotoxin toxicosis available; dose 20 mg/kg PO q24h. •  Ascorbic acid and cimetidine—hepatocyte protectors; no data on efficacy in hepatotoxic cyanotoxin poisoning available. •  N‐acetylcysteine (NAC)— antioxidant; no data on efficacy in hepatotoxic cyanotoxin toxicosis available; glutathione precursor that can be included in treatment regimen for acute hepatic failure at 140 mg/kg IV load, followed by 70 mg/kg IV q6h for 7 treatments.

Neurotoxic and Dermatotoxic

No specific changes.

DIAGNOSTIC PROCEDURES Morphologic algal ID in suspect water, algal material, or stomach content. Positive ID confirms hazard but is not confirmatory for the toxin because toxicity is strain specific. Hepatotoxic

•  Detection of algal material on fur or in stomach contents. •  Analysis of stomach contents and water/algal source for microcystins.

­

 FOLLOW‐UP

PATIENT MONITORING •  Hepatotoxic—liver enzymes/function, coagulation status. •  Neurotoxic— thermoregulation, respiratory function, blood gases. PREVENTION/AVOIDANCE

•  Deny access to water with visible algal blooms. •  Remove algal blooms from ponds

Neurotoxic

immediately and discard material safely.

urine, bile, and suspect source material. •  Depressed blood cholinesterase activity with anatoxin‐as poisoning.

•  Prognosis poor to guarded for hepatotoxic

­

­

•  Detection of anatoxin‐a in gastric contents,

EXPECTED COURSE AND PROGNOSIS and neurotoxic; good for dermatotoxic.

•  Rapid onset and progression; often lethal.

Dermatotoxic

•  Pruritus, erythema, urticaria. •  Secondary

skin infection.

CAUSES & RISK FACTORS •  Access to and ingestion of toxin‐ contaminated water and/or algal material. •  Exposure to dietary supplements containing the blue‐green algae Spirulina platensis and Aphanizomenon flos aquae that are contam­ inated with microcystins. •  Blooms more common in nutrient‐rich water in warmer months. •  Blooms concentrated through wind or by removal into containers. •  Certain algae reside in the benthic zone, e.g., in sediment; dogs mouthing material such as rocks from sediment can be at risk.

prevents timely therapeutic intervention.

•  Gastrointestinal decontamination with

activated charcoal can be attempted, but efficacy not known. •  Hepatotoxic—supportive care, close monitoring, and case‐specific IV fluids to correct electrolytes and hypoglycemia, vitamin K1, and plasma transfusions. •  Neurotoxic— supportive care and seizure control. •  Dermatotoxic—supportive care and treatment for secondary skin infections.

­ ­

 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS Hepatotoxic

•  Amanitins, xylitol, cycad palms,

acetaminophen, manganese, pennyroyal oil, cocklebur. •  Other causes of acute liver failure—infectious, metabolic, dietary.

 TREATMENT

•  No antidote available. •  Rapid onset typically

 MEDICATIONS

DRUG(S) OF CHOICE •  Activated charcoal—1 g/kg PO q6-8h until 2–3 days post ingestion; mix activated charcoal in water at 1 g/5 mL of water. •  IV fluids— maintain hydration, induce diuresis, correct hypoglycemia. •  Dextrose—50% dextrose 1 mL/kg IV slow bolus (1–3 min). •  Vitamin K1—0.5–1.5 mg/kg SC/IM q12h; 1–5 mg/kg PO q24h. •  Blood products—dependent on

 MISCELLANEOUS

ABBREVIATIONS •  ALP = alkaline phosphatase. •  ALT = alanine transaminase. •  AST = aspartate transaminase. •  NAC = N‐acetylcysteine. •  SAMe = S‐adenosylmethionine. INTERNET RESOURCES http://www.cdc.gov/habs

­Suggested Reading

Bautista AC, Moore CE, Lin Y, et al. Hepatopathy following consumption of a commercially available blue‐green algae dietary supplement in a dog. BMC Vet Res 2015, 11:136. Puschner B, Bautista AC, Wong C. Debromoaplysiatoxin as the causative agent of dermatitis in a dog after exposure to freshwater in California. Front Vet Sci 2017, 4:50. Authors Birgit Puschner and Adrienne C. Bautista Consulting Editor Lynn R. Hovda  Client Education Handout available online

B

188

Blackwell’s Five-Minute Veterinary Consult

Botulism

B

OTHER LABORATORY TESTS

•  Definitive diagnosis is based on detection

­

  BASICS

OVERVIEW •  Paralytic illness caused by preformed neurotoxin produced by bacterium Clostridium botulinum (Gram +, anaerobe) contained in uncooked food, carrion, and contaminated or improperly stored silage. •  Most cases in dogs caused by Clostridium botulinum neurotoxin serotype C; neurotoxin interferes with release of acetylcholine at neuromuscular junction, resulting in diffuse lower motor neuron signs. •  Heavy molecular weight of the toxin seems to preclude its transfer to placenta. SIGNALMENT Dogs (naturally infected) and cats (experiment­ ally infected except for one case report of natural Clostridium botulinum type C toxicosis).

of botulinum toxin in serum, feces, vomitus, or ingested food sample; by neutralization test in small rodents; or by in vitro test that measures toxin antigenicity rather than toxicity. •  Detection of anti-C botulinum neurotoxin antibodies may help support clinical diagnosis. IMAGING Thoracic radiographs—possible megaesophagus and/or signs of aspiration pneumonia. DIAGNOSTIC PROCEDURES

•  Electromyography may reveal fibrillation

potentials and positive sharp waves in affected muscles. •  Motor nerve conduction velocity may be normal or decreased, with reduced amplitude of evoked muscle action potentials; compound muscle action potentials can be decreased after low-frequency repetitive nerve stimulations.

SIGNS

  FOLLOW-UP

PATIENT MONITORING Monitor patients for respiratory failure, aspiration pneumonia, progressive lower motor neuron signs, urinary tract infection, and ocular complications. PREVENTION/AVOIDANCE •  Prevent access to carrion and feed dogs cooked food. •  Avoid contact with spoiled raw meat. •  Samples should be refrigerated (not frozen) and manipulated with caution, since humans are also sensitive to the toxin. POSSIBLE COMPLICATIONS

•  Respiratory failure and death in severe cases. •  Aspiration pneumonia from megaesophagus and regurgitations. •  Keratoconjunctivitis sicca and corneal ulceration. •  Prolonged

recumbence—pulmonary atelectasia and infection; decubital sores; urine scalding.

EXPECTED COURSE AND PROGNOSIS

Historical Findings

•  Signs appear a few hours to 6 days after toxin ingestion. •  Other dogs living in the same environment may be affected. •  Acute,

symmetric, progressive weakness develops, starting in the pelvic limbs and ascending to the trunk, thoracic limbs, neck, and muscles innervated by the cranial nerves; severe tetraparesis or tetraplegia ensues.

Physical Examination

•  Possible increased or decreased heart rate. •  In severe cases—diaphragmatic respiration.

Neurologic Examination Findings

•  Mental status—normal. •  Cranial nerves— may reveal sluggish pupillary light reflexes (PLR), diminished palpebral reflexes, decreased jaw tone, decreased gag reflex, salivation, and dysphonia. •  Gait and posture—a stiff, short-stride gait (no ataxia) is initially observed until recumbence develops (usually within 12–24 hours). •  Spinal reflexes—decreased to absent with decreased muscle tone (to atonia) and muscle atrophy. •  Autonomic signs—mydriasis with decreased PLR, decreased lacrimation, ileus, and urine retention or frequent voiding of small volumes. •  No hyperesthesia.

­

­

  DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Acute canine polyradiculoneuritis (coonhound paralysis). •  Myasthenia gravis. •  Tick bite paralysis. •  Coral snake venom toxicity. •  Dumb form of rabies. •  Lasalocid (growth promoter in ruminants) toxicosis. CBC/BIOCHEMISTRY/URINALYSIS Usually normal.

­

  TREATMENT

•  If recent ingestion—gastric lavage,

cathartics (avoid agents containing magnesium), or enemas may be useful. •  Mildly affected dogs recover over a period of several days with supportive treatment including physical therapy, frequent turning, good bedding (to prevent decubital sores), bladder care (catheterization), artificial tears (to prevent corneal ulceration), and feeding from an elevated position (when megaesophagus present). •  Dogs with respiratory difficulties require intensive care monitoring with arterial blood gas, intermittent esophageal suction, alimentation by nasogastric or gastrotomy tube, and eventually ventilatory support.

­

  MEDICATIONS

DRUG(S) OF CHOICE •  Type C antitoxin may cause anaphylaxis; not effective when the toxin is already fixed at the nerve ending. •  Antibiotics are not recommended since they might increase the release of toxins through bacterial lysis or by promoting intestinal infection; to be used only if secondary infections occur. CONTRAINDICATIONS/POSSIBLE INTERACTIONS Aminoglycosides, procaine penicillin, tetracyclines, phenothiazines, antiarrhythmic agents, and magnesium should be avoided (neuromuscular transmission blockade).

•  Maximum severity of signs usually reached within 12–24 hours. •  Neurologic signs disappear

in reverse order of appearance; complete recovery usually occurs within 1–3 weeks, and requires the formation of new nerve terminals and functional neuromuscular junctions.

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  MISCELLANEOUS

SEE ALSO •  Coonhound Paralysis (Acute Polyradiculoneuritis). •  Myasthenia Gravis. •  Snake Venom Toxicosis—Coral Snakes. •  Tick Bite Paralysis. ABBREVIATIONS

•  PLR = pupillary light reflex.

­Suggested Reading

Añor S. Acute lower motor neuron tetrapare­ sis. Vet Clin North Am Small Anim Pract 2014, 44(6):1201–1222, Barsanti J, Greene C, eds. Infectious Diseases of the Dog and Cat, 4th ed. St. Louis, MO: Saunders Elsevier, 2012, pp. 416–422. Elad D, Yas-Natan E, Aroch I, et al. Natural Clostridium type C toxicosis in a group of cats. J Clin Microbiol 2004, 42(11):5406–5408. Lamoureux A, Pouzot-Nevoret C, Escriou C. A case of type B botulism in a pregnant bitch. J Small Anim Pract 2015, 56(5):348–350. Silva R, Martins R, Assis R, et al. Type C botulism in domestic chickens, dogs and black-pencilled marmoset (Callithrix penicillata) in Minas Gerais, Brazil. Anaerobe 2018, 51:47–49. Uriarte A, Thibaud J, Blot S. Botulism in 2 urban dogs. Can Vet J 2010, 51:1139–1142. Author Hélène L.M. Ruel Acknowledgment The author and book editors acknowledge the prior contribution of Roberto Poma (deceased).



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Canine and Feline, Seventh Edition

Brachial Plexus Avulsion

­

  BASICS

OVERVIEW •  Trauma with traction and/or severe abduction of a forelimb causes avulsion of nerve rootlets from their spinal cord attachment. •  Ventral (motor) nerve roots are more susceptible than dorsal (sensory) roots. •  It is important to rule out nerve root avulsions in traumatized animals that are not able to bear weight on a forelimb, especially before surgical repair of orthopedic injuries. SIGNALMENT •  Dogs and cats. •  No age, sex, or breed predilection. SIGNS •  Depend on the extent and distribution of rootlet damage. •  Motor signs—paresis/ weakness (partial damage) to paralysis (complete ventral root avulsion). •  Sensory signs—decreased to absent pain perception (dorsal root damage). •  Muscle atrophy— begins within a week of injury. •  Complete avulsion—spinal nerves C5 to T2; most common; combines cranial and caudal avulsion deficits. •  Cranial avulsion—C5 to C7 nerves: supraspinatus and infraspinatus muscle atrophy, loss of shoulder and elbow movement flexion (dropped elbow), analgesia of craniodorsal scapula and medial forearm, possible diaphragm hemiplegia detected by fluoroscopy (phrenic nerve roots C5 to C7); if roots C8 to T2 are preserved, weight bearing remains almost normal. •  Caudal avulsion—spinal nerves C7 to T2: inability to bear weight with knuckling over dorsum of paw; if C5 to C7 are spared, the limb is held in a flexed position and there is analgesia distal to the elbow (except for a small area on the medial aspect of the forearm); T1 to T2 involvement causes an ipsilateral partial Horner’s syndrome (anisocoria only) and lack of ipsilateral cutaneous trunci reflex (reflex present contralaterally). •  Bilateral avulsion— rarely encountered, caused by a significant fall with sternal landing and splaying of limbs. •  Over time, complications of self-trauma may occur as a result of paresthesia in the most severe cases. CAUSES & RISK FACTORS Trauma—road accident; hung by foot; dragged; fall.

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  DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Brachial plexus trauma without avulsion— rare; temporary deficit owing to root

contusion (neurapraxia). •  Brachial plexus tumor—usually chronic, progressive onset. •  Brachial plexus neuritis or neuropathy— rare, bilateral deficits, unknown etiology; acute onset; no trauma. •  Fibrocartilaginous embolic myelopathy—deficits of ipsilateral hind limb and mild deficits of contralateral forelimb and hind limb are usually present. •  Migrating foreign body – slow onset and no history of trauma. •  Pure radial nerve paralysis caused by fracture of humerus or first rib—no nerve root sign. •  Lateralized intervertebral disc protrusion. IMAGING CT or MRI—visualize lesion; rarely needed for diagnosis. DIAGNOSTIC PROCEDURES

•  Clinical—history of trauma with sudden onset of typical neurologic deficits. •  Define

involved spinal nerve roots—map motor and sensory deficits; note signs of Horner’s syndrome; determine if cutaneous trunci reflex is present. •  Electromyography (EMG) and nerve conduction studies (NCS) may help further define deficits and detect signs of recovery—from 5–7 days post injury, EMG shows denervation in affected muscles. PATHOLOGIC FINDINGS

•  Ventral and dorsal root avulsions—

intradurally at level of root–spinal cord junction (most fragile area because it lacks protective perineurium). •  Neuroma formation may develop over time on pial surface of spinal cord.

motion, massage therapy. •  Monitor noncomplicated cases for 4–6 months before considering amputation.

­

­

  TREATMENT

Appropriate Health Care

•  No specific treatment. •  Outcome depends on initial damage. •  Amputation of limb—

may be necessary for patients showing complications (infections/self-mutilation, likely as a result of paresthesia) and no improvement. •  Carpal fusion (arthrodesis) and transposition of biceps muscle tendon— consider only with adequate function of triceps and musculocutaneous muscles.

Nursing Care

•  Protective wrap or boot to protect distal

paw if patient walks a lot/walks on rough surfaces—increased skin fragility and lack of protective reflexes due to sensory deficits can result in severe excoriations when animal walks on affected limb. •  Early and sustained physical therapy—crucial to prevent severe muscle atrophy and tendon contraction to keep joints and muscles mobile during recovery of reversible injuries; passive range of

  FOLLOW-UP

POSSIBLE COMPLICATIONS •  Skin excoriation and secondary infection— from trauma to unprotected paw. •  Trophic ulcers—thin, traumatized skin, especially over arthrodesis sites. •  Paresthesia may lead to self-mutilation. EXPECTED COURSE AND PROGNOSIS

•  Preserved pain sensation (dorsal roots

intact)—suggests less severe injury to ventral nerve roots. •  Cranial avulsion—better prognosis with preserved sensation to distal limb and ability to bear weight. •  Complete avulsion—poor prognosis for recovery, amputation likely. •  Rarely, mild cases may resolve after 2–3 months.

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  MEDICATIONS

DRUG(S) OF CHOICE Prednisolone (prednisone)—1-week antiinflammatory course may decrease early edema and favor healing of reversible injuries.

  MISCELLANEOUS

SEE ALSO Polyneuropathies (Peripheral Neuropathies). ABBREVIATIONS •  EMG = electromyography. •  NCS = nerve conduction studies.

­Suggested Reading

Bailey CS. Patterns of cutaneous anesthesia associated with brachial plexus avulsions in the dog. JAVMA 1984, 185:889–899. Braund KG. Neuropathic disorders. In: Braund KG, ed., Clinical Neurology in Small Animals: Localization, Diagnosis and Treatment. Ithaca, NY: IVIS, 2003. http:// www.ivis.org/advances/Vite/braund20b/ chapter_frm.asp. Walmsley G, Scurrell E, Summers B, et al. Foreign body induced neuritis masquerading as a canine brachial plexus nerve sheath tumour. Vet Comp Orthop Traumatol 2009, 22(5):427–429. Author Christine F. Berthelin-Baker

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Brachycephalic Airway Syndrome

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concurrent disease or exacerbating circumstances.

•  Laryngeal collapse reported in brachycephalic

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  BASICS

DEFINITION Partial upper airway obstruction in brachy­ cephalic dogs and cats caused by any of the following: stenotic nares, overlong soft palate, everted laryngeal saccules, and laryngeal collapse. Hypoplastic trachea can also be present and worsen respiratory distress. PATHOPHYSIOLOGY •  In normal dogs, the upper airway accounts for 50–70% of total airway resistance. Brachy­cephalic breeds have increased upper airway resistance due to stenosis of nares, aberrant formation of nasal conchae, and presence of nasopharyngeal turbinates. Skull bones are shortened in length but normal in width, and soft tissues are not proportionately reduced, resulting in redundant tissue and narrowed air passages. •  Increased airway resistance leads to more negative intra-airway pressures—may result in secondary eversion of laryngeal saccules, further elongation of palate, and laryngeal collapse. •  Recruitment of pharyngeal dilator muscles (sternohyoid) becomes necessary to maintain airway patency; sleep apnea may occur secondary to relaxation of these muscles. SYSTEMS AFFECTED

•  Respiratory—respiratory distress, hypox­

emia, hypercarbia, hyperthermia, aspiration pneumonia, noncardiogenic pulmonary edema from airway obstruction. •  Cardiovascular—cardiovascular collapse if complete airway obstruction or severe hyperthermia occurs. •  Gastrointestinal—may be reluctant to eat or drink; increased airway resistance can exacerbate hiatal hernia, gastroesophageal reflux, and esophagitis. GENETICS Brachycephalic head shape—inherited defect in development of skull bones perpetuated by selective breeding. INCIDENCE/PREVALENCE

•  Dogs—common in brachycephalic breeds. •  Cats—less commonly severe enough to

require treatment.

GEOGRAPHIC DISTRIBUTION Worldwide SIGNALMENT Species

Dog and cat. Breed Predilections

•  Dogs—brachycephalic breeds (English

bulldogs most common—up to 55% of breed, French bulldog, pug, Boston terrier); Norwich terriers and Cavalier King Charles spaniels affected by a variant of the syndrome. •  Cats—Persians and Himalayans. Mean Age and Range

•  Young adults, most diagnosed by 2–3 years. •  If diagnosed later than 4 years, look for

breed puppies as young as 6–7 months. Predominant Sex

No sex predilection. SIGNS Historical Findings

•  Snoring, stridor, stertorous breathing. •  Tachypnea, frequent panting. •  Coughing and gagging. •  Difficulty eating and swallowing. •  Ptyalism, regurgitation, and vomiting. •  Syncope or collapse.

Physical Examination Findings

•  Stridor and stertorous breathing. •  Stenotic nares—medial collapse of lateral nasal cartilage. •  Increased respiratory

effort—retraction of the commissures of lips, open-mouth breathing or constant panting, increased respiratory rate, abduction of forelimbs, increased abdominal component of respiration, recruitment of secondary muscles of respiration. •  In severe distress, may see paradoxical abdominal movement, inward collapse of intercostal muscles during inspiration, orthopnea, and cyanosis. Hyperthermia may be present. CAUSES

•  Inherited or congenital defects in conformation. •  Elongated soft palate—over 90% of surgical cases in dogs. •  Stenotic

nares—about 50% of dogs; most common defect in cats. •  Aberrant formation of rostral and caudal nasal conchae. •  Presence of nasopharyngeal turbinates (20% of dogs) and 100% of English bulldogs. •  Laryngeal disease—everted laryngeal saccules (>50% of dogs) and/or laryngeal collapse (∼10% of dogs).

RISK FACTORS •  Breed. •  Obesity—worsens airway obstruction, associated with poorer outcome postoperatively, and may contribute to gastro­esophageal reflux and aspiration pneumonia. •  Excitement and/or warm, humid weather— increased panting can lead to airway edema, further compromise of the lumen, and hyperthermia. •  Exercise—dogs are often exercise intolerant due to airway compromise and hypoxia. •  Sedation—relaxation of muscles of pharynx and palate can cause complete airway obstruction. •  Respiratory infection or concurrent pulmonary disease— will cause further respiratory compromise. •  Endocrine disease (hypothyroidism and hyperadrenocorticism)—could worsen weight gain and panting.

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  DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Foreign bodies of nasopharynx, larynx, or trachea. •  Infection—upper respiratory

infection, nasopharyngeal abscess. •  Neoplasia obstructing the nasopharynx, glottis, larynx, or trachea. •  Laryngeal paralysis. •  Pharyngeal mucocoele. •  Nasopharyngeal polyp or cyst. CBC/BIOCHEMISTRY/URINALYSIS CBC—usually normal, but polycythemia can occur with chronic hypoxia, and leukocytosis if concurrent infection or severe stress. OTHER LABORATORY TESTS •  Arterial blood gas—to diagnose respiratory acidosis and hypoxemia, and response to oxygen supplementation. •  Pulse oximetry— to diagnose hypoxemia. IMAGING Radiographic Findings

•  If stable, cervical and thoracic radiographs recommended. •  Cervical radiographs may

show thickened, elongated soft palate and suggest tracheal hypoplasia. •  Thoracic radiographs can reveal aspiration pneumonia, pulmonary edema, air in esophagus, and hypoplastic trachea (TD/TI = tracheal diameter at the level of thoracic inlet/thoracic inlet distance, which is the distance from the sternum to the ventral surface of TI. A ratio 90 mmHg and partial pressure of carbon dioxide (PCO2) at 35–40 mmHg; with suspected elevated ICP, hyperventilation to 32–35 mmHg. •  Maintain partial pressure of oxygen (PaO2) >60 mmHg, arterial oxygen saturation (SaO2) >90%, peripheral oxygen saturation (SpO2) >94%. •  Avoid cough or sneeze reflex during intubation or nasal oxygen supplementation; lidocaine (dogs: topical and 1–2 mg/kg IV) before. •  Do not compress jugular veins. •  Orotracheal intubation if gag reflex lost. NURSING CARE

•  Aggressive therapy for midbrain/brainstem lesion or declining neurologic signs. •  Overzealous

fluid resuscitation can contribute to brain edema. •  Small‐volume fluid resuscitation techniques to maintain systolic BP >90 mmHg with normal heart rate. •  Combination of



Brain Injury

(continued)

isotonic crystalloids (10–20 mL/kg increments) with hydroxyethyl starch (5 mL/kg increments) over 5–8 minutes. •  Avoid hypertension. •  Level head with body or elevate head and neck to 20° angle. •  Keep airway unobstructed; use suction and humidify if intubated; hyperoxygenate, consider IV lidocaine prior to suctioning. •  Lubricate eyes. •  Reposition every 2–4 hours to avoid hypostatic pulmonary congestion, pressure sores. •  Prevent fecal/urine soiling. •  Maintain normal body temperature. •  Maintain hydration with balanced crystalloid solution. •  Rehabilitation exercises. ACTIVITY •  Restricted. •  Consult rehabilitation specialist for appropriate exercises to maintain muscle tone. CLIENT EDUCATION •  Neurologic signs may worsen before improving. •  Neurologic recovery may not be evident for several days; possibly >6 months for residual neurologic deficits. •  Serious systemic abnormalities contribute to CNS instability. SURGICAL CONSIDERATIONS Depressed skull fracture, penetrating foreign body, uncontrollable ICP elevation (insufficient CSF drainage, hematoma/mass evacuation, herniation).

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 MEDICATIONS

DRUG(S) OF CHOICE Elevated ICP

•  Ensure systolic BP >90 mmHg; lower ICP by hyperventilation, drug therapy, drainage of CSF from ventricles, or surgical decompression. •  7% hypertonic saline—2–4 mL/kg IV. •  Furosemide—0.75 mg/kg IV; may decrease CSF production. •  Mannitol—0.5–1 g/kg IV bolus repeated at 2h intervals 3–4 times in dogs, and 2–3 three times in cats; repeated doses must be given on time; improves CBF and lowers ICP; may exacerbate hemorrhage. •  Glucocorticosteroids—no benefit in acute management and long‐term outcome in human traumatic brain injury (TBI); anti‐ inflammatory doses (prednisone 1 mg/kg/day) may be of benefit with brain edema related to intracranial neoplasia and infectious meningo­ encephalomyelitis (MEM); immunosuppressive doses (2 mg/kg/day) in combination with additional immunosuppressive drugs in immune‐mediated MEM. •  Provide analgesia/ sedatives (e.g., fentanyl 3–5 μg/kg IV, then 3–5 μg/kg/h CRI ± lidocaine 3–5 mg/kg/h) as indicated; avoid agents that can reduce CPP. Avoid ketamine with obstructive intracranial lesions. •  Thrashing, seizures, or uncontrolled motor activity—diazepam CRI (0.5–1 mg/kg/h), midazolam CRI (0.2–0.4 mg/kg IV), or propofol (3–6 mg/kg IV titrated to effect; 0.1–0.6 mg/ kg/min CRI); monitor for hypotension; intubate if unable to protect airway.

•  Levetiracetam—20–30 mg/kg IV/IM/PO/

rectal q8h if seizure activity.

Other

•  Reducing cerebral metabolic rate with heavy sedation using dexmedetomidine (3 μg/kg slow bolus followed by 3–7 μg/kg/h CRI IV) with ketamine (1 μg/kg slow bolus followed by 1 μg/ kg/h CRI IV) with uncontrolled seizures or propofol (2–4 mg/kg IV then 0.1–0.4 mg/kg/ min); must intubate and support blood pressure, oxygenation, and ventilation. •  Cooling patient to 32–33 °C (89–91 °F) for 48h may provide cerebral protection when administered within 6 hours of global ischemia or severe brain injury. •  Glucose regulation. •  Careful nasogastric tube feeding for early trickle flow feeding; cisapride (0.5 mg/kg PO q8–12h) and metoclopramide (1–2 mg/kg/day) may promote gastrointestinal motility. •  Desmopressin for refractory hyper­natremia; emergency dosage not established for animals (dogs: 4 μg topical conjunctival q12h; cats: 5 μg SC q12h).

CONTRAINDICATIONS Drugs that cause hypertension, hypotension, hyperexcitability, or increase in metabolic rate. PRECAUTIONS

•  Avoid hypotension, hypoxemia, hyper­

tension, hyperglycemia, hypoglycemia, hypernatremia, hypo‐ or hypervolemia. •  Keep head and neck above plane of body. •  Do not compress jugular veins. •  Furosemide, mannitol, and hypertonic saline—can cause hypovolemia and hypo­ tension. •  Maintain PCO2 >32 mmHg; avoid hyperventilation in the first 24–8h and do not perform therapeutic hyperventilation (32–35 mmHg) for extended periods (>48h).

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 FOLLOW‐UP

PATIENT MONITORING •  Repeated neurologic examinations— deterioration warrants aggressive therapeutic intervention. •  BP—maintain systolic BP >90 mmHg. •  Blood gases, pulse oximetry, end‐tidal CO2—to assess need for oxygen supplementation or ventilation. •  Blood glucose—avoid severe persistent hyperglycemia and hypoglycemia. •  ECG—arrhythmias may affect perfusion, oxygenation, and CBF. •  ICP—to detect elevations and monitor response to therapy. PREVENTION/AVOIDANCE Keep pets in a confined area or leashed. POSSIBLE COMPLICATIONS

•  Seizures. •  Brain herniation. •  Intracranial hemorrhage. •  Progression from cerebral cortical to midbrain signs. •  Malnutrition. •  Aspiration pneumonia. •  Hypostatic pulmonary congestion. •  Corneal desiccation. •  Urine scalding. •  Airway obstruction from mucus.

•  Arrhythmias. •  Hypotension. •  Hypernatremia. •  Hypokalemia. •  Respiratory failure. •  Residual neurologic deficits. •  Death.

EXPECTED COURSE AND PROGNOSIS •  Young animals, minimal primary brain injury, secondary injury consisting of cerebral edema—best prognosis. •  No deterioration for 48 hours—better prognosis. •  Rapid resuscitation of systolic BP to >90 mmHg and avoiding hypoxemia—better neurologic outcome. •  Modified Glasgow Coma Score may offer prognostic insight.

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 MISCELLANEOUS

SYNONYMS •  Head trauma. •  TBI. SEE ALSO Stupor and Coma. ABBREVIATIONS •  ADH = antidiuretic hormone. •  CBF = cerebral blood flow. •  CPP = cerebral perfusion pressure. •  CRI = continuous rate infusion •  CSF = cerebrospinal fluid. •  ICP = intracranial pressure. •  MAP = mean arterial pressure. •  MEM = meningoencephalomyelitis. •  PaO2 = partial pressure of oxygen. •  PCO2 = partial pressure of carbon dioxide. •  SaO2 = arterial oxygen saturation. •  SpO2 = peripheral oxygen saturation. •  TBI = traumatic brain injury. INTERNET RESOURCES http://www.traumaticbraininjury.com

­Suggested Reading

Dewey CW, Downs MO, Aron DN, et al. Acute traumatic intracranial haemorrhage in dogs and cats. Vet Comp Orthop Traumatol 1993, 6:29–35. Dewey CW, Fletcher DJ. Head trauma management. In: Dewey CW, ed., A Practical Guide to Canine and Feline Neurology, 2nd ed. Ames, IA: Wiley, 2008, pp. 221–235. Fletcher D, Syring R. Traumatic brain injury. In: Silverstein D, Hopper K, eds., Small Animal Critical Care Medicine. St. Louis, MO: W.B. Saunders, 2014, pp. 723–727. Freeman C, Platt SR. Head trauma, In: Platt SR, Garosi LS, eds., Small Animal Neurological Emergencies. London: Manson, 2012, pp. 363–382. Sande A, West C. Traumatic brain injury: a review of pathophysiology and management. J Vet Emerg Crit Care 2010, 20:177–190. Author Elke Rudloff Acknowledgment The author and book editors acknowledge the prior contribution of Rebecca Kirby.  Client Education Handout available online

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Brain Tumors

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 BASICS

DEFINITION •  Brain tumors of cats and dogs may be classified as either primary or secondary, depending on the cell type of origin. •  Primary brain tumors originate from cells normally found within the brain and meninges, including the neuroepithelium, lymphoid tissues, germ cells, endothelial cells, and malformed tissues. •  Secondary tumors are either neoplasms that have reached the brain by hematogenous metastasis from a primary tumor outside the nervous system, or neoplasms that affect the brain by local invasion, or extension, from adjacent non-neural tissues such as bone. •  Pituitary gland neoplasms (adenomas or carcinomas) and tumors arising from cranial nerves (e.g., nerve sheath tumor of trigeminal, oculomotor, or vestibulocochlear nerves) are considered secondary brain tumors. PATHOPHYSIOLOGY •  Brain tumors result in cerebral dysfunction by causing both primary effects, such as infiltration of nervous tissue or compression of adjacent anatomic structures, and secondary effects, such as hydrocephalus. •  Additional primary effects include disruption of cerebral circulation and local necrosis, which may result in further damage to neural tissue. •  The most important secondary effects of a primary brain tumor include disturbance of cerebrospinal fluid (CSF) flow dynamics, elevated intracranial pressure (ICP), cerebral edema, or brain herniation. •  Secondary effects usually are more diffuse or generalized in their clinical manifestations and may mask the precise location of a focal intracranial lesion. SYSTEMS AFFECTED Nervous (brain). GENETICS

•  An unusually high incidence of

meningiomas has been reported in cats with mucopolysaccharidosis type I. •  Specific genetic factors associated with breed predisposition have not been identified. •  Brachycephaly provisionally has been associated with the SMOC-2 and thrombospondin-2 genes on canine chromosome 1, and a component of glioma susceptibility provisionally has been mapped to a region on canine chromosome 2. •  Molecular and genetic classification of brain tumors may permit targeted therapies in the future. INCIDENCE/PREVALENCE

•  Brain tumors appear to be more common

in dogs than in other domestic species.

•  Reported incidence in dogs is 10–20 per

100,000 animals, or 1–3% of all deaths where necropsy was done. •  Primary nervous system tumors in dogs account for 60–80% of all such tumors reported in domestic animals (10–20% in cats; 10–20% in other species). •  The most common sites for neoplasia to occur in immature dogs (5 years of age.

•  Median age for diagnosis of meningiomas,

gliomas, and choroid plexus tumors in dogs has been reported as 10–11 years, 8 years, and 5–6 years, respectively.

Predominant Sex

Older male cats appear to be most susceptible to meningiomas. SIGNS •  Vary with tumor location. •  The most frequently recognized clinical sign associated with a brain tumor of a dog or cat is seizures, particularly should first seizure occur after 5 years of age. •  Other clinical signs frequently associated with brain tumor are abnormal behavior and mentation, visual deficits, circling, ataxia, head tilt, and cervical spinal hyperesthesia. •  Signs that result from disease in given location in nervous system are similar, regardless of precise cause. •  On basis of signalment, history, and results of complete physical and neurologic examinations, it is possible to localize a problem to the brain and, in some cases, to determine the approx­imate location. CAUSES

•  Uncertain. •  Dietary, environmental,

genetic, chemical, viral, traumatic, and immunologic factors may be considered.

­

  DIAGNOSIS

DIFFERENTIAL DIAGNOSIS Categories of disease that may result in clinical signs similar to those of a brain tumor include congenital disorders, infections,

immunologic and metabolic disorders, toxicities, nutritional disorders, trauma, vascular disorders, degeneration, and idiopathic disorders. CBC/BIOCHEMISTRY/URINALYSIS The major objective in the completion of these tests is to eliminate extracranial causes for signs of cerebral dysfunction. OTHER LABORATORY TESTS N/A IMAGING

•  Survey radiographs of the thorax and

abdominal ultrasound—to rule out primary malignancy elsewhere in body. •  Skull radiographs—of limited value; may detect neoplasms of skull or nasal cavity that involve brain by local extension. •  Occasionally, lysis or hyperostosis of skull may accompany primary brain tumor (e.g., meningioma of cats), or there may be radiographically visible mineralization within a neoplasm. •  CT— provides accurate determination of presence, location, size, and anatomic relationships of many intracranial neoplasms. •  MRI— considered superior to CT in localization and characterization of most brain tumors. DIAGNOSTIC PROCEDURES

CSF Analysis

•  CSF—may help to rule out inflammatory

causes of cerebral dysfunction: in some cases may support diagnosis of brain tumor. •  Care should be used in collection of CSF, because increased ICP may be present in association with brain tumor, and pressure alterations associated with CSF collection may lead to brain herniation. •  CSF collection usually delayed until advanced imaging has been completed to evaluate factors such as presence of cerebral edema or hemorrhage. •  In general, increased CSF protein content and normal to increased CSF white blood cell count have been considered “typical” of a brain neoplasm.

Biopsy

•  Cytologic evaluation of smear preparations

from biopsy tissue, rapidly fixed in 95% alcohol and stained with hematoxylin and eosin, may be done within minutes of biopsy collection. •  Tissue biopsy remains sole method available for definitive diagnosis of brain tumor type in cats or dogs, and is essential consideration prior to any type of therapy. •  Biopsy not always attempted because of practical considerations, such as cost and morbidity. •  CT-guided stereotactic biopsy systems provide relatively rapid and extremely accurate means of tumor biopsy, with low rate of complications. PATHOLOGIC FINDINGS

•  Classification of CNS tumors in dogs and

cats primarily is based on the characteristics of their constituent cell type, pathologic





Brain Tumors

(continued)

behavior, topographic pattern, and secondary changes present within and surrounding the tumor. •  Meningioma is most common intracranial neoplasm of dogs and cats. •  Classification of glial subset of neuroepi­ thelial tumors is based on predominant cell type (e.g., astrocyte or oligodendrocyte). Dogs

•  Embryonal tumors have been consolidated

under single term “primitive neuroecto­ dermal tumors” (or PNETs) to accommodate their anaplastic nature. •  Brain tumors arising from lymphoreticular cells traditionally have been grouped under a heading of reticulosis or histiocytic lymphoma. •  Skull tumors that affect the brain by local extension include osteosarcoma, chondro­ sarcoma, and multilobular osteochondro­ sarcoma. •  The most frequently seen secondary tumors of dogs include local extension of nasal adenocarcinoma; metastases from mammary, prostatic, or pulmonary adenocarcinoma; metastases from hemangiosarcoma; and extension of pituitary adenoma or carcinoma. •  Nerve sheath tumors arising from cranial nerves (particularly oculomotor nerve and trigeminal nerve) may occur in dogs. Cats

•  Meningiomas involving multiple

intracranial sites (including third ventricle) relatively common in cats. •  Primary brain tumors other than meningiomas occur infrequently in cats. •  Tumors that have been reported include astrocytoma, ependymoma, oligodendroglioma, choroid plexus papilloma, medulloblastoma, lymphoma, olfactory neuroblastoma, and gangliocytoma. •  Lymphoma of the brain may be primary or secondary, or may be an aspect of multicentric lymphoma of cats. •  Secondary tumors that have been reported to occur in the brain of cats include pituitary macroadenomas and macrocarcinomas, and metastatic carcinoma. •  Local extension may occur either from tumors of middle ear cavity (e.g., squamous cell carcinoma), nasal cavity (e.g., nasal adenocarcinoma), or skull (e.g., osteosarcoma).

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  TREATMENT

APPROPRIATE HEALTH CARE •  Beyond general efforts to maintain homeo­stasis, major goals of therapy for brain tumor are to control secondary effects, such as increased ICP or cerebral edema, and to eradicate the tumor or reduce its size. •  Beyond palliative care, three methods of therapy for a brain tumor currently are

available for use in dogs and cats: surgery, irradiation, and chemotherapy. Surgery

•  Neurosurgical intervention is an essential

consideration in management of brain tumors in cats or dogs, whether for complete excision, partial removal, or biopsy. •  Meningiomas, particularly those located over cerebral convexities or in frontal lobes of cerebrum, may be completely (or almost completely) removed by surgery, especially in cats. •  Primary calvarial tumors also may be removed surgically prior to other types of therapy. Radiation Therapy

•  Irradiation may be used either alone or in

combination with other treatments for either primary or secondary brain tumors. •  Careful treatment planning by qualified and experienced radiation therapist is essential to success of radiation therapy. •  A major development in radiation therapy is emergence of more precise protocols that spare tissues surrounding the brain tumor (e.g., stereotactic radiotherapy).

Chemotherapy

Alkylating agents (e.g., carmustine [BCNU], lomustine [CCNU], and temozolomide), antimetabolic agents (e.g., cytosine arabinoside), and ribonucleotide reductase inhibitors (e.g., hydroxuurea) may result in reduction of tumor size and improvement of clinical signs in dogs with glial cell tumors; however, evidence of efficacy in animals is lacking.

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  MEDICATIONS

DRUG(S) OF CHOICE •  Glucocorticoids may be used for edema reduction and, in some cases (e.g., lymphoma), for retardation of tumor growth. •  Some animals with brain tumor demonstrate dramatic improvement in clinical signs for weeks or months with sustained gluco­ corticoid therapy. •  Antiepileptic drugs (e.g., phenobarbital, bromide, levetiracetam) may be utilized for control of generalized seizures. •  Mannitol and hypertonic saline are agents best suited for effective reduction of increased ICP.

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  FOLLOW-UP

PATIENT MONITORING •  Serial neurologic examinations. •  Serial CT or MRI examinations.

POSSIBLE COMPLICATIONS •  Aspiration pneumonia due to depressed swallowing reflexes associated with increased ICP. •  Seizures. EXPECTED COURSE AND PROGNOSIS

•  Little information available concerning

survival times of dogs or cats with brain tumor that have received only palliative therapy (i.e., therapy to control secondary effects of a tumor without an attempt to eradicate the tumor). •  Results of one study indicate mean and median survival of 81 days and 56 days, respectively, following CT diagnosis of primary brain tumor in each of 8 dogs. •  Results from several studies confirm that prognosis for a dog or cat with a primary brain tumor may be significantly improved by surgical removal and irradiation, either alone or in combination.

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  MISCELLANEOUS

ASSOCIATED CONDITIONS Dogs that have been treated for a brain tumor may develop a second type of tumor elsewhere in the body. ABBREVIATIONS •  CSF = cerebrospinal fluid. •  ICP = intracranial pressure. •  PNET = primitive neuroectodermal tumor.

­Suggested Reading

Dickinson PJ. Advances in diagnostic and treatment modalities for intracranial tumors. J Vet Intern Med 2014, 28:1165–1185. Dickinson PJ. Intracranial tumors in dogs. Vet Focus 2014, 24(2):2–10. Hicks J, Platt S, Kent M, Haley A. Canine brain tumors: a model for human disease? Vet Comp Oncol 2017, 15(1):252–272. Kohler RJ, Arnold SA, Eck DJ, et al. Incidence of and risk factors for major complications or death in dogs undergoing cytoreductive surgery for treatment of suspected primary intracranial masses. J Am Vet Med Assoc 2018, 253(12):1594–1603. Rossmeisl JH. New treatment modalities for brain tumors in dogs and cats. Vet Clin Small Anim 2014, 44:1013–1038. Author Richard A. LeCouteur  Client Education Handout available online

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Breeding, Timing

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DEFINITION Timing of insemination(s) to maximize pregnancy risk and litter size.

continue during estrus and cease only at the onset of diestrus. •  Physical signs alone— unreliable for precise determination of fertile period. •  Receptivity—may be detected by touching the perineum near the vulva; if receptive, female will “flag” by elevating the tail to one side and lifting the vulva dorsally.

PATHOPHYSIOLOGY

Cats

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  BASICS

Dogs

•  Must determine ovulation day so that breeding(s) occur(s) at proper time. •  Fresh,

chilled, or frozen semen—usually limited to one or two inseminations; insemination must be timed relative to ovulation for maximum fertility. •  Ovulation may vary relative to onset of heat (proestrus), standing heat (estrus), vaginal cytology. •  Luteinizing hormone (LH)—controls ovulation; peaks on same day or after full cornification is observed; ovulation occurs approximately 2 days after peak; 2–3 days (54–72 hours) more required for oocyte maturation; mature oocytes viable for minimum 2–3 days; thus fertile period is 4–8 days after LH peak, and maximum fertility is 5–6 days after LH peak. •  Serum progesterone concentration— increase closely associated with LH peak. Cats

•  Ovulation—usually induced; timing of breeding is not as critical as with dogs; depends on adequate gonadotropin-releasing hormone (GnRH) and then LH release triggered by vaginal stimulation. •  Adequate stimulation— characterized by copulatory cry and postcoital reaction; frequency of coital stimuli important in determining adequacy of coital contact. •  LH—peak concentration and duration of elevation determine number of follicles ovulating; higher concentration with multiple copulations; response to copulation depends on day of estrus (greater release on estrus day 3 than on estrus day 1); release partially depends on duration of exposure to estrogen.

SYSTEMS AFFECTED Reproductive GENETICS N/A INCIDENCE/PREVALENCE N/A GEOGRAPHIC DISTRIBUTION N/A SIGNALMENT Dog and cat. SIGNS General Comments

Dogs

•  Onset of estrus—usually associated with a

change in the vaginal discharge from sanguineous to barely red and decreased vulvar edema; sanguineous discharge may

LH response to a single mating—may vary substantially. Historical Findings

Dogs

Sanguineous vulvar discharge during estrus.

Cats

Return to estrus in EDTA plasma).

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  MEDICATIONS

DRUG(S) OF CHOICE Cats—hCG (100–500 IU/cat IM); GnRH (25–50 μg/cat IM).

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  FOLLOW-UP

PATIENT MONITORING •  Dogs—serial vaginal cytology to determine D1; ovulation is ~6 days before D1. •  Dogs— whelping is 65 ± 1 days from LH peak, 63 ± 1 days from ovulation, or 57 ± 1 days from D1; for fresh, chilled, or frozen semen: repeat quantitative serum progesterone measurement after initial progesterone rise or LH peak to verify >10 ng/mL (32 nmol/L). •  Cats—use serum progesterone assay 1 week post insemination to verify ovulation. •  Cats— queening is 62–71 days from first breeding. PREVENTION/AVOIDANCE N/A POSSIBLE COMPLICATIONS Dogs

•  Vaginal cytologic examinations—compare

D1 with prospective estimation based on progesterone; if estimates differ, pregnancy rates are reduced. •  Semi-quantitative progesterone kits—must come to room temperature before use; concentrations falsely elevated when using a cold kit. •  Serum progesterone concentration—allow blood to clot at room temperature; separate cells from serum 20 minutes after collection; falsely low concentrations occur when using serum mixed with red blood cells (progesterone binds to erythrocytes). •  Hemolyzed or lipemic specimen—may give falsely low progesterone concentration. •  Quantitative

  MISCELLANEOUS

AGE-RELATED FACTORS Split heats in young bitches—period of proestrus (may be prolonged to 6 weeks or more), followed by cessation of signs, and subsequent resumption of estrus cycle (1–3 weeks later); no initial rise in progesterone or LH concentration occurs with first proestrus/ estrus; subsequent estrus usually normal. PREGNANCY/FERTILITY/BREEDING Ultrasound—conceptuses can first be detected 18–20 days after LH peak (requires high-resolution, high-frequency probe, easier in toy breeds) or 2–3 days earlier in cats; commonly done 4 weeks post breeding; recommend earlier exam in bitches with history of pregnancy loss or infertility. SEE ALSO •  Infertility, Female—Dogs. •  Ovulatory Failure. •  Vaginal Discharge. •  Vaginal Malformations and Acquired Lesions. ABBREVIATIONS •  AI = artificial insemination. •  D1 = first day of diestrus. •  GnRH = gonadotropin-releasing hormone. •  hCG = human chorionic gonadotropin. •  LH = luteinizing hormone. •  TCI = endoscopic transcervical insemination.

­Suggested Reading

Johnston SD, Root Kustritz MV, Olson PN. Breeding management, artificial insemination, in vitro fertilization, and embryo transfer in the queen. In: Johnston SD, Root Kustritz MV, Olson-Schultz P, eds., Canine and Feline Theriogenology. Philadelphia, PA: Saunders, 2001, pp. 406–413. Author Cathy J. Gartley Consulting Editor Erin E. Runcan

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Bronchiectasis

B

•  Foreign body pneumonia. •  Neoplasia.

­

  BASICS

OVERVIEW •  Clinical condition seen primarily in dogs; irreversible dilatation of the bronchi; caused by chronic infectious or inflammatory airway disease, foreign body pneumonia, or associated with primary ciliary dyskinesia. •  Occurs in cats as a sequela to longstanding inflammatory lung disease or neoplasia. •  Airways are pulled open by surrounding lung tissue; pooling of secretions can occur, which perpetuates lung damage and allows colonization by bacteria. •  Can be cylindrical or saccular, focal or diffuse.

CBC/BIOCHEMISTRY/URINALYSIS

•  Neutrophilia and monocytosis. •  Hyperglobulinemia. •  Proteinuria—can be seen with secondary

amyloidosis, glomerulonephritis, or sepsis. OTHER LABORATORY TESTS Arterial blood gas analysis—hypoxemia; widened alveolar–arterial oxygen gradient. IMAGING

•  Radiography—insensitive for the diagnosis.

ciliary dyskinesia.

Abnormalities visible late in the course of disease include dilatation of the lobar bronchi with lack of normal tapering in the periphery; diffuse thickening of bronchial walls; mixed bronchial, interstitial, and alveolar pattern. •  Changes can be focal or diffuse. •  CT—bronchus >2 times the width of the adjacent pulmonary artery in dogs, abnormally dilated bronchi near the lung periphery; thickened airways; cystic dilatations of the bronchi with or without pulmonaray consolidation.

pulmonary disease.

•  Bronchoscopy—saccular or tubular

SIGNALMENT

•  Primarily dogs but radiographically

detected in many cats.

•  Cocker spaniels and perhaps West

Highland white terriers predisposed.

•  Young animals (1.7 × 103 colony-forming units (CFU) for infection in dogs. Anaerobic and Mycoplasma cultures recommended as well. •  Cytology— inflammation primary finding; most cells are neutrophils, eosinophils, or macrophages; evaluate for bacteria, parasites, neoplastic cells, and contamination with foreign material. •  Recurrent infections—implicated in patho­genesis of bronchitis; however, positive cultures are not frequently reported; Mycoplasma infection discussed but rarely confirmed as a cause. PATHOLOGIC FINDINGS See Bronchoscopy under Diagnostic Procedures.





Bronchitis, Chronic

(continued)

mask (e.g., AeroDawg); however, the most adequate dose is not clearly established.

­

  TREATMENT

APPROPRIATE HEALTH CARE •  Usually outpatient—oxygen can be given at home in chronic cases. •  Inpatient—if requires oxygen therapy, parenteral medication, or aerosol therapy; patients that owners cannot keep calm at home during initial stages of therapy. NURSING CARE Consider saline nebulization followed by coupage and/or gentle exercise to encourage removal of airway secretions. ACTIVITY •  Exercise—moderate (not forced) useful in clearing secretions; assists with weight loss. •  Limit if exertion causes excessive coughing. •  Use a harness instead of a collar. DIET Weight loss critical—improves PaO2, attitude, and exercise tolerance in obese patients; reduces cough frequency. CLIENT EDUCATION •  Warn client that chronic bronchitis is an incurable disease and complete suppression of all coughing is an unattainable goal. •  Stress that aggressive treatment (including weight control, avoiding risk factors, and medical treatment) minimizes the severity of the coughing and slows disease progression in most patients. SURGICAL CONSIDERATIONS Treat severe dental disease to minimize secondary bacterial complications.

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  MEDICATIONS

Bronchodilators

Commonly prescribed, although limited evidence of efficacy. Antibiotics

•  Select on basis of quantitated culture and

sensitivity test results.

Antitussives

•  Indicated for nonproductive, paroxysmal, continuous, or debilitating cough. •  Dogs—

butorphanol (0.55 mg/kg PO q6–12h; 0.055–0.11 mg/kg SC); hydrocodone (0.1–0.3 mg/kg q6–8h PO). Over-thecounter cough suppressants are rarely effective; gabapentin 2–5mg.kg by mouth every eight hours (but unestablished efficacy). CONTRAINDICATIONS Lasix and atropine—do not use because of drying effects on tracheobronchial secretions.

PRECAUTIONS •  Beta agonists (e.g., terbutaline and albuterol)—may cause tachycardia, nervousness, and muscle tremors; typically transient. •  Theophylline—may cause tachycardia, restlessness, excitability, vomiting, and diarrhea; evaluate ethylene diamine tetra-acetate (EDTA) plasma sample for peak plasma concentration (ideally 5–20 μg/mL); toxicity may be more common with generic formulations. POSSIBLE INTERACTIONS Fluoroquinolones decrease theophylline clearance in dogs and can result in theophylline toxicity. ALTERNATIVE DRUG(S) Maropitant (some antitussive properties suggested, but not advised yet).

DRUG(S) OF CHOICE Corticosteroids

•  Diminish airway inflammation and

coughing regardless of the underlying cause. •  Indicated for noninfectious conditions. •  With allergic or hypersensitivity reactions— require long-term administration; attempt to wean off steroids or determine lowest effective dosage. •  Prednisolone preferred in cats. •  Prednisone or prednisolone usually initiated at 0.5–1 mg/kg PO q12h for a variable time, with tapering of the dosage based on clinical signs. •  Inhaled agents (e.g., budenoside or fluticasone 1–3 puffs using metered dose inhalers [variable concentrations exist] a day) are often effective and can be used to reduce systemic side effects of corticosteroids; they are delivered via a spacer chamber and face

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  FOLLOW-UP

PATIENT MONITORING •  Follow abnormalities revealed by physical examination and selected diagnostic tests— determine response to treatment. •  Monitor weight; arterial blood gases usually improve after significant weight loss. PREVENTION/AVOIDANCE Avoid and address risk factors (see Risk Factors). POSSIBLE COMPLICATIONS

•  Syncope—possible complication of

chronic coughing, particularly in toybreed dogs. •  Pulmonary hypertension and cor pulmonale—most serious

complications. •  Bronchectasis and airway remodeling. EXPECTED COURSE AND PROGNOSIS

•  Progressive airway changes—syncopal

episodes, chronic hypoxia, right ventricular hypertrophy, and pulmonary hypertension. •  Acute exacerbations—common with seasonal changes, air quality changes, worsened inflammation, and potentially development of secondary infection.

­

  MISCELLANEOUS

ASSOCIATED CONDITIONS •  Syncope—secondary to chronic coughing or development of pulmonary hypertension. •  Increased susceptibility to airway infection, chronic hypoxia, pulmonary hypertension, and cor pulmonale. PREGNANCY/FERTILITY/BREEDING Safety in pregnant animals not established for most of the recommended drugs. SYNONYMS Chronic bronchitis. SEE ALSO

•  Asthma, Bronchitis—Cats. •  Bronchiectasis. •  Cough. •  Hypoxemia. •  Tracheal Collapse.

ABBREVIATIONS •  BAL = bronchoalveolar lavage. •  CFU = colony-forming unit. •  EDTA = ethylene diamine tetra-acetate. •  PaO2 = partial pressure of oxygen.

­Suggested Reading

Grotheer M, Hirschberger J, Hartmann K, et al., Comparison of signalment, clinical, laboratory and radiographic parameters in cats with feline asthma and chronic bronchitis. J Feline Med Surg. 2020, 22(7):649–655. Reinero CR, Masseau I, Grobman M, et al., Perspectives in veterinary medicine: Description and classification of bronchiolar disorders in cats. J Vet Intern Med. 2019, 33(3):1201–1221. Rozanski E. Canine chronic bronchitis. An update . Vet Clin N Am Small Anim Pract 2020, 50:393–404. Author Cécile Clercx Consulting Editor Elizabeth Rozanski  Client Education Handout available online

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Brucellosis

B

Physical Examination Findings

•  Peripheral lymphadenopathy. •  Males—

­

  BASICS

DEFINITION •  Contagious disease of dogs caused by Brucella canis. •  Rarely caused by B. suis, B. abortus, or B. mellitensis. •  Characterized by abortion and infertility in females, epididymitis and testicular atrophy in males. PATHOPHYSIOLOGY B. canis—a small, intracellular Gram-negative bacterium; has propensity for growth in lymphatic, placental, and male genital (epididymis and prostate) tissues. SYSTEMS AFFECTED

•  Hemic/lymph/immune—lymph nodes,

swollen scrotum with scrotal dermatitis, enlarged firm epididymides, orchitis, prostatitis. •  Chronic infection—unilateral or bilateral testicular atrophy, spinal pain, discospondylitis, posterior weakness, ataxia. •  Chronic recurrent anterior uveitis without signs of systemic disease; also iris hyperpig­ mentation, vitreal infiltrates, multifocal chorioretinitis. •  Vaginal discharge—may last several weeks after abortion. •  Fever (rare). CAUSES B. canis—Gram-negative coccobacillus; morphologically indistinguishable from other members of genus. RISK FACTORS

spleen, bone marrow, mononuclear leukocytes. •  Reproductive—target tissues of gonadal steroids (gravid uterus, fetus, testes epididymides, prostate gland). •  Other tissues—intervertebral discs, anterior uvea, meninges (uncommon).

•  Breeding kennels, pack hounds. •  Contact

GENETICS No known genetic predisposition.

DIFFERENTIAL DIAGNOSIS •  Abortions—maternal, fetal, or placental abnormalities. •  Systemic infections—canine distemper, canine herpesvirus, B. abortus, hemolytic streptococci, E. coli, leptospirosis, toxoplasmosis. •  Inguinal hernia. •  Discospondylitis—fungal infections, actinomycosis, staphylococcal infections, nocardiosis, streptococci, or Corynebacterium diphtheroids.

INCIDENCE/PREVALENCE •  Incidence unknown. •  Seroprevalence—not well defined; false-positive results common with agglutination tests. •  Prevalence— 1–18% in United States, Japan; higher in rural United States; 25–30% in stray dogs in Mexico, Peru. GEOGRAPHIC DISTRIBUTION United States, Mexico, Japan, South America; Spain, Tunisia, China, Bulgaria; individual outbreaks in Germany, Czech Republic. SIGNALMENT Species

Dogs

Breed Predilections

•  No evidence of breed susceptibility,

reportedly high prevalence in beagles. •  Pure breeds in commercial kennels (“puppy mills”).

Mean Age and Range

•  Any age. •  Most common in sexually mature dogs.

Predominant Sex

Most common in females. SIGNS General Comments

Suspect with abortions, reproductive failures, or genital disease. Historical Findings

•  Animals may appear healthy or have vague signs of illness. •  Lethargy. •  Loss of libido. •  Swollen lymph nodes. •  Back or neck pain. •  Abortion—commonly 6–8 weeks after

conception, although pregnancy may terminate at any stage.

with strays in endemic areas.

­

  DIAGNOSIS

CBC/BIOCHEMISTRY/URINALYSIS

•  Normal in uncomplicated cases. •  Chronic

infection—hyperglobulinemia and hypo­ albuminemia. •  Cerebrospinal fluid— neutrophilic pleocytosis, elevated protein (meningoencephalitis); normal in discospondylitis. •  Urinalysis usually normal.

OTHER LABORATORY TESTS Serologic testing—most common diagnostic method; subject to error due to false-positive reactions to several species of bacteria common with tube agglutination tests; chronically infected dogs may test negative. Rapid 2-Mercaptoethanol Slide Agglutination Test (RSAT)

•  Simple, inexpensive, rapid. •  Detects

infected dogs 3–4 weeks after infection; accurate in identifying noninfected dogs. •  Screening test—sensitive, not specific; high rate (50%) of false-positive tests. •  Confirm results with other tests. Mercaptoethanol Tube Agglutination Test (2ME)

•  Semi-quantitative—similar information to

RSAT, but inactivates immunoglobulin (Ig) M. •  Good screening test (lacks specificity). •  If

positive RSAT and negative 2ME, retest in 2–4 weeks. Agar Gel Immunodiffusion (AGID) Test •  Soluble antigen test—recommended;

employs antigens highly specific for antibodies against Brucella spp. (including B. canis, B. abortus, and B. suis); reactive antibodies appear 4–12 weeks after infection and persist; may be positive after other tests become equivocal or negative. •  ELISA—using purified cytoplasmic antigens; not yet commercially available. •  PCR—available at some diagnostic laboratories; high sensitivity and specificity. •  Cell wall antigen test—not recommended; highly sensitive but not standardized; frequent false positives. IMAGING Discospondylitis—radiographic changes slow to develop, may not be seen even when spinal pain is present. DIAGNOSTIC PROCEDURES Isolation of Organism

•  Blood cultures—when clinical and serologic

findings suggest diagnosis, can be isolated from blood of infected dogs if they have not received antibiotics; onset of bacteremia 2–4 weeks after oral-nasal exposure, persists for 8 months to 5.5 years. Culture is preferred method for diagnosis in endemic situations or with known exposure (1–8 weeks ago); must specifically request Brucella culture. •  Culture or PCR of vaginal fluids or vaginal swab after abortion. •  Semen or urine—PCR more practical than culture. •  Tissue samples— culture or PCR of prostate, testicle, epididymis, lochia, or placenta. •  Contaminated samples—media that contain antibiotics (e.g., Thayer–Martin medium) have proven useful.

Semen Quality

•  Sperm motility, immature sperm, inflamm­ atory cells (neutrophils) with epididymitis. •  Abnormalities usually evident by 5–8 weeks post infection; conspicuous by 20 weeks. •  Azoospermia without inflammatory cells common with bilateral testicular atrophy.

Lymph Node Biopsy

•  Tissues (lymph node, uterus, testes) should

be sterilely obtained, cultured on appropriate media, and submitted for histopathology. •  Lymphoid hyperplasia—large numbers of plasma cells. •  Intracellular bacteria—may be observed in macrophages with special stains (e.g., Brown–Brenn stain). •  Histopathologic examination of testes—necrotizing vasculitis, inflammatory cells, granulomatous lesions. PATHOLOGIC FINDINGS

•  Gross findings—lymph node enlargement,

splenomegaly, enlarged and firm epididymides, scrotal edema, or atrophy of one or both testes; chronic infection: anterior uveitis and discospondylitis. •  Microscopic changes—



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Brucellosis

(continued)

diffuse lymphoreticular hyperplasia; chronic infection: lymph node sinusoids with plasma cells and macrophages that contain bacteria, diffuse lymphocytic infiltration and granulo­ matous lesions in all genitourinary organs (especially prostate, epididymis, uterus, and scrotum); inflammatory cell infiltration and necrosis of prostate parenchyma, seminiferous tubules. •  Ocular changes—granulomatous iridocyclitis; exudative retinitis; leukocytic exudates in anterior chamber.

­

CONTRAINDICATIONS Tetracyclines—do not use in immature animals. ALTERNATIVE DRUG(S) Gentamicin—6–15 mg/kg IM/SC q12h; limited success; insufficient data on efficacy combined with tetracycline.

 TREATMENT

APPROPRIATE HEALTH CARE Outpatient ACTIVITY Restricted CLIENT EDUCATION •  Goal is eradication of B. canis from animal (seronegative, no bacteremia for at least 3 months); sometimes result is persistent low antibody titers with no systemic infection. •  Antibiotic treatment is expensive, time consuming, and controversial (because outcomes are uncertain, and organism has potential to recrudesce). •  Euthanasia is strongly recommended for breeding or commercial kennels; treatment is only recommended for spayed or castrated dogs if the owner is willing to accept the ongoing zoonotic risk. •  Before treatment is attempted for an intact household pet or breeding dog, client must clearly agree that animal will be neutered and potentially euthanized if treatment fails. •  Zoonotic infection is a possibility; discuss proper sanitation and prevention of exposure. SURGICAL CONSIDERATIONS Neuter/spay plus treatment—when euthanasia is unacceptable to owner.

­

chlortetracycline, or minocycline: 25 mg/kg PO q8h for 4 weeks) or doxycycline (10 mg/ kg PO q12h for 4 weeks) and dihydrostrepto­ mycin (10 mg/kg IM q8h during weeks 1 and 4). •  Enrofloxacin (10–20 mg/kg PO q24h for 30 days)—not recommended: variable results.

  MEDICATIONS

DRUG(S) OF CHOICE •  Several therapeutic regimens have been evaluated, results have been equivocal; treat­ment duration longer than 30 days may be required. •  Most successful—combination of a tetracycline (tetracycline hydrochloride,

­

  FOLLOW-UP

PATIENT MONITORING •  Serologic tests—monthly at least 3 months after completion of treatment; continuous, persistent decline in antibodies to negative status indicates successful treatment. •  Recrudescent infections (rise in antibody levels, recurrence of bacteremia after therapy)— retreat, neuter and retreat, or euthanize. •  Blood cultures—negative for at least 3 months after completion of treatment. PREVENTION/AVOIDANCE

•  Vaccine—none. •  Testing—all females

before estrus if breeding is planned; breeding males at frequent intervals. •  Quarantine and test all new dogs twice at monthly intervals before entering breeding kennel; test all breeding animals yearly. POSSIBLE COMPLICATIONS

•  Owner reluctance to neuter or euthanize

valuable dogs, regardless of treatment failure. •  Remind owners of ethical considerations, obligation not to sell or distribute infected dogs. EXPECTED COURSE AND PROGNOSIS •  Prognosis guarded. •  Infected for T) was found only in Bernese mountain dogs. DM has been histopathologically confirmed in many purebred and mixed-breed dogs. Mean Age and Range

•  Mean—9 years of age in large dogs; mean

age at onset is 11 years in Pembroke Welsh corgi. •  Range—between 8 and 14 years. Predominant Sex

No known sex predilection.

CAUSES

•  Hereditary disease and genetic predi­-

sposition.

•  Other hypothesized causes include

immune-mediated, metabolic deficiencies, toxic, and oxidative stress. RISK FACTORS

•  Dogs homozygous for the mutant allele(s)

are at highest risk.

•  There may be other environmental factors

and modifying genes; studies underway.

C ­

  DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Type II intervertebral disc herniation. •  Intramedullary spinal cord neoplasia. •  Degenerative lumbosacral stenosis. •  Hip dysplasia. •  Other coexisting orthopedic disease. CBC/BIOCHEMISTRY/URINALYSIS

•  Usually normal. •  Performed to rule out other underlying

metabolic disease.

•  Urinalysis may identify secondary urinary

tract infection.

OTHER LABORATORY TESTS

•  Urine culture and sensitivity testing. •  Thyroid function testing. •  Electrodiagnostic testing results are normal

in early diagnosis of DM.

•  Genetic testing—test result of at-risk can

support a presumptive diagnosis of DM in light of typical clinical signs and normal findings on neuroimaging and cerebrospinal fluid analysis. IMAGING

•  Survey spinal radiography. •  Myelography evaluates for compressive

spinal cord disease.

•  Myelography combined with CT—more

sensitive technique to evaluate suspicious lesions. •  MRI—preferred technique to evaluate for extramedullary compressive and intramedullary lesions. DIAGNOSTIC PROCEDURES

•  CSF analysis evaluates for inflammatory

disease.

•  Definitive diagnosis is determined by

post-mortem histopathology of spinal cord. PATHOLOGIC FINDINGS

•  Spinal cord axons and myelin affected most

severely in dorsal and dorsal portion of lateral funiculi. •  Vacuolated axon cylinders/myelin sheaths most extensive in mid-thoracic spinal cord. •  Astroglial proliferation is prominent in severely affected areas of lesion distribution. •  Usually, lesion distribution is described as asymmetric and discontinuous; however, more recent evidence describes lesion distrib­ ution as symmetric and continuous in dogs that survive for long periods with DM. •  Neuronal cell body loss in ventral horn is evident at terminal or end-stage disease. •  Nerve specimens show fiber loss resulting from axonal degeneration and secondary demyelination. •  Muscle specimens show large and small groups of atrophic fibers typical of denervation.

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Canine Degenerative Myelopathy

(continued) •  Intervertebral Disc Disease, Thoracolumbar. •  Lumbosacral Stenosis and Cauda Equina

C ­

  TREATMENT

APPROPRIATE HEALTH CARE •  Supportive care. •  Breeds of small size may survive longer with DM because the pet owner is able to more easily give the appropriate care. NURSING CARE

•  When dog becomes nonambulatory, keep

on a well-padded surface to prevent decubitus ulceration over bony prominences. •  Keep hair trimmed, and skin clean and dry to prevent urine scald secondary to incontinence. •  Urine should be monitored for odor and color change, which may indicate urinary tract infection. •  Physical therapy using range-of-motion and active exercises may help maintain limb mobility and muscle strength. ACTIVITY

•  Exercise is encouraged to slow disuse

atrophy of pelvic limbs, but fatigue should be monitored and exercise intensity adjusted. •  Hydrotherapy can involve use of an underwater treadmill setup. •  A wheel cart may assist with patient mobility. DIET

•  Maintain balanced diet. •  Prevent weight gain.

CLIENT EDUCATION

•  Long-term prognosis is poor. •  Meticulous nursing care is crucial to

preventing secondary complications in a recumbent patient. SURGICAL CONSIDERATIONS None

­

  FOLLOW-UP

PATIENT MONITORING •  Repeat neurologic examinations. •  Urine retention. •  Urinalysis and urine culture to monitor for urinary tract infection. PREVENTION/AVOIDANCE

•  Decubitus ulceration. •  Urine retention. •  Dermatitis from urine scald. •  Weight gain.

POSSIBLE COMPLICATIONS

•  Urine retention may predispose to urinary

tract infections.

•  Local skin infections from decubitus ulceration.

EXPECTED COURSE AND PROGNOSIS •  Nonambulatory paraparesis occurs within 9–12 months from time of onset of signs. •  Tetraparesis may be evident within 3 years from time of onset of signs. •  Long-term prognosis is poor.

­

  MISCELLANEOUS

ASSOCIATED CONDITIONS •  Other neurologic diseases associated with old-age onset. •  Spinal cord neoplasia. •  Intervertebral disc disease. •  Orthopedic disease. AGE-RELATED FACTORS Older dogs commonly affected. ZOONOTIC POTENTIAL None PREGNANCY/FERTILITY/BREEDING N/A SYNONYMS

­

  MEDICATIONS

DRUG(S) OF CHOICE Clinical trials are underway to determine effectiveness in slowing or halting disease progression.

•  Canine ALS. •  DM. •  Degenerative radiculomyelopathy. •  German Shepherd dog myelopathy.

SEE ALSO

•  Intervertebral Disc Disease, Cervical.

Syndrome.

ABBREVIATIONS

•  ALS = amyotrophic lateral sclerosis. •  DM = degenerative myelopathy. •  SOD1 = superoxide dismutase 1.

INTERNET RESOURCES

•  www.caninegeneticdiseases.net/dm/

maindm.htm

•  www.ofa.org/diseases/dna-tested-diseases/dm

­Suggested Reading

Awano T, Johnson GS, Wade C, et al. Genome-wide association analysis reveals a SOD1 missense mutation canine degenerative myelopathy that resembles amyotrophic lateral sclerosis. Proc Natl Acad Sci USA 2009, 106:2794–2799. Coates JR, March PA, Ogelsbee M, et al. Clinical characterization of a familial degenerative myelopathy in Pembroke Welsh Corgi dogs. J Vet Intern Med 2007, 21:1323–1331. Coates JR, Wininger FA. Canine degenerative myelopathy. Vet Clin North Am Small Anim Pract 2010, 40:929–950. March PA, Coates JR, Abyad R, et al. Degenerative myelopathy in 18 Pembroke Welsh Corgi dogs. Vet Pathol 2009, 46:241–250. Ogawa M, Uchida K, Yamato O, et al. Neuronal loss and decreased GLT-1 expression observed in the spinal cord of Pembroke Welsh Corgi Dogs with canine degenerative myelopathy. Vet Pathol 2014, 51:591–602. Wininger FA, Zeng R, Johnson GS, et al. Degenerative myelopathy in a Bernese Mountain Dog with a novel SOD1 missense mutation. J Vet Intern Med 2011, 25:1166–1170. Zeng R, Coates JR, Johnson GC, et al. Breed distribution of SOD1 alleles previously associated with canine degenerative myelopathy. J Vet Intern Med 2014, 28:515–521. Author Joan R. Coates  Client Education Handout available online



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Canine and Feline, Seventh Edition

Canine Distemper ◦  Gray matter disease—affects cerebral

­

  BASICS

DEFINITION •  Acute to subacute, contagious, febrile, often fatal disease with respiratory, urogenital, gastrointestinal, ocular, and CNS manifestations. •  Caused by canine distemper virus (CDV), a Morbillivirus in the Paramyxoviridae family. •  Affects many Carnivora species; mortality rate varies greatly. PATHOPHYSIOLOGY •  Natural route of infection—airborne and droplet exposure; from nasal cavity, pharynx, and lungs, virus replication occurs in local lymph nodes; within 1 week, viral shedding occurs (mainly in respiratory exudates but also urine) and virtually all lymphatic tissues become infected; spreads via viremia to surface epithelium of respiratory, gastrointestinal, and urogenital tracts and to CNS. •  Disease progression depends on virus strain and host immune response: ◦  Strong cellular and humoral immune response—subclinical infection. ◦  Weak immune response—subacute infection; longer survival. ◦  Failed immune response—death within 2–4 weeks after infection; frequently due to CNS manifestations. •  Viral excretion can occur for up to 2–3 months. SYSTEMS AFFECTED

•  Multisystemic—all lymphatic tissues,

surface epithelium in respiratory, alimentary, and urogenital tracts, skin, endocrine and exocrine glands. •  CNS—brain and/or spinal cord. INCIDENCE/PREVALENCE •  Dogs—sporadic outbreaks. •  Wildlife (raccoons, skunks, fox, tigers)— fairly common. GEOGRAPHIC DISTRIBUTION Worldwide SIGNALMENT Species

Most species of the order Carnivora; has been reported in large exotic cats.

cortex, brainstem, and spinal cord and may cause a nonsuppurative meningitis, seizures, mentation change, and ataxia; dogs may die in 2–3 weeks; some dogs recover (associated with prompt humoral and cell-mediated immunity), others develop white matter disease. ◦  White matter disease—multifocal disease, commonly cerebellovestibular signs, paresis, ataxia, occasionally myoclonus; some dogs die 4–5 weeks after initial infection with noninflammatory, demyelinating disease; some dogs may recover with minimal CNS injury. •  Optic neuritis and retinal lesions may occur; anterior uveitis, keratoconjunctivitis sicca possible. •  Hardening of footpads (hyperkeratosis) and nose—some virus strains; uncommon. •  Enamel hypoplasia of teeth after neonatal infection. CAUSES

•  CDV exposure. •  Incompletely attenuated vaccines (rare).

RISK FACTORS Contact of nonimmunized animals with CDV-infected animals (dogs, wild carnivores).

IMAGING

•  Radiographs—evaluate pulmonary disease. •  CT and MRI—may or may not show

lesions; MRI sensitive for demyelination. DIAGNOSTIC PROCEDURES

•  Immunohistochemical detection in haired

skin, nasal mucosa, and footpad epithelium.

•  Viral antigen or viral inclusions—in buffy

coat cells, urine sediment, conjunctival or vaginal imprints, trans-tracheal wash (negative results do not rule out CDV). •  Reverse transcriptase polymerase chain reaction (RT-PCR)—on buffy coat, urine sediment cells, respiratory secretions, conjunctival swabs, CSF; false negatives possible, false positives with recent vaccination (uncommon). •  CSF—moderate mononuclear pleocytosis, elevated concentrations of CDV-specific antibody, interferon, and viral antigen early in disease course. PATHOLOGIC FINDINGS

­

  DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Diagnosis based on clinical suspicion; combination of respiratory and gastrointestinal, ± CNS disease, in unvaccinated dog. •  Respiratory signs—can mimic kennel cough. •  Enteric signs—differentiate from canine parvovirus, coronavirus, parasitism (giardiasis), bacterial infections, gastroenteritis from toxin ingestion, inflammatory bowel disease. •  CNS form—differentiate from auto­ immune meningoencephalitis (granulomatous meningoencephalomyelitis, necrotizing encephalitis, meningoencephalitis of unknown etiology), protozoal (e.g., toxoplasmosis, neosporosis), fungal (e.g., cryptococcosis), and rickettsial (e.g., ehrlichiosis, Rocky Mountain spotted fever) meningoencephalitis, rabies.

Young, especially unvaccinated animals are most susceptible.

CBC/BIOCHEMISTRY/URINALYSIS Lymphopenia in early infection; rare thrombocytopenia; intracytoplasmic inclusions in white and red blood cells.

SIGNS •  Fever—intermittent peaks starting 3–6 days after infection. •  Gastrointestinal and/or respiratory signs— nasal and ocular discharge, depression, anorexia, vomiting, diarrhea; often exacer­ bated by secondary bacterial infection. •  CNS—common; generally after systemic disease (depends on virus strain).

OTHER LABORATORY TESTS •  Serology—positive antibody tests do not differentiate between vaccination and exposure to virulent virus; patient may die from acute disease before neutralizing antibody is produced. Immunoglobulin (Ig) M responses may occur up to 3 months after exposure to virulent virus, up to 3 weeks after vaccination; rising IgG titers in unvaccinated

Mean Age and Range

dog are suggestive of infection; may be useful for risk assessment of clinically healthy dogs in shelter environment. •  CDV antibody in cerebrospinal fluid (CSF)—indicative of distemper encephalitis, false negatives possible.

Gross

•  Thymus—greatly reduced in size (young

animals); sometimes gelatinous.

•  Lungs—patchy consolidation. •  Footpads, nose—hyperkeratosis. •  Mucopurulent discharges—from eyes and

nose, bronchopneumonia, catarrhal enteritis, skin pustules (secondary bacterial infection).

Histologic

•  Intracytoplasmic eosinophilic inclusion

bodies—in epithelium of bronchi, stomach, urinary bladder; also in reticulum cells and leukocytes in lymphatic tissues. •  Inclusion bodies in glial cells and neurons— frequently intranuclear; also in cytoplasm. •  Immunofluorescence and/or immunocyto­ chemistry, virus isolation, and/or RT-PCR performed on tissues from lungs, stomach, urinary bladder, lymph nodes, brain.

­

  TREATMENT

APPROPRIATE HEALTH CARE Inpatient medical management to intensive care as indicated; isolate patient to prevent spread to other dogs. NURSING CARE •  Symptomatic. •  IV fluids—for hypovolemia, support. •  Oxygen therapy, nebulization, and coupage—for pneumonia. •  Clean ocular, nasal discharges.

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ACTIVITY Limited, to reduce spread. DIET Depends on extent of gastrointestinal involvement. CLIENT EDUCATION •  Inform client that mortality rate is about 50%. •  Inform client that dogs appearing to recover from early catarrhal signs may develop fatal CNS disease. •  Presenting neurologic abnormalities usually not reversible.

­

  MEDICATIONS

DRUG(S) OF CHOICE •  Antiviral drugs—none known to be effective. •  Broad-spectrum antibiotics—for secondary bacterial infection (CDV is immuno­ suppressive), beta-lactams or cephalosporins are good initial choices. •  Anticonvulsant therapy—phenobarbital, potassium bromide, levetiracetam. •  Myoclonus—no proven treatment; single case report describes use of botulinum toxin type A. CONTRAINDICATIONS Corticosteroids—use anti-inflammatory dosages with caution; may provide short-term control. Immunosuppressive dosages may enhance viral dissemination. PRECAUTIONS Tetracycline, fluoroquinolones—avoid in growing animals.

­

  FOLLOW-UP

PATIENT MONITORING •  Monitor for CNS abnormalities, partic­ ularly seizures. •  Monitor for respiratory distress or dehydration in acute phase. PREVENTION/AVOIDANCE

(continued) •  Modified live vaccine for CDV (MLV-CD)—

prevents infection and disease; two types available: ◦  Canine tissue culture-adapted vaccines (e.g., Rockborn strain)—induce complete immunity in virtually 100% of susceptible dogs; rarely, a postvaccinal fatal encephalitis develops 7–14 days after vaccination, especially in immunosuppressed animals. ◦  Chick embryo-adapted vaccines (e.g., Lederle strain)—safer; postvaccinal encephalitis does not occur; only about 80% of susceptible dogs seroconvert. ◦  Other species—chick embryo can safely be used in variety of wildlife species (e.g., gray fox); Rockborn type fatal in these animals. •  Killed vaccines—useful for species in which either type of MLV-CD is fatal (e.g., red panda, blackfooted ferret). •  Canarypox recombinant CDV vaccine. Maternal Antibody

•  Important. •  Most puppies lose protection from

maternal antibody at 6–12 weeks of age; 2–3 vaccinations should be given during this period. •  Heterotypic (measles virus) vaccination— recommended for puppies that have maternal antibody; induces protection from disease but not from infection. POSSIBLE COMPLICATIONS Possibility of CNS signs developing for 2–3 months after catarrhal signs have subsided. EXPECTED COURSE AND PROGNOSIS •  Depends on strain and individual host response—subclinical, acute, subacute, fatal, or nonfatal infection. •  Mild CNS signs—patient may recover; myoclonus may continue for several months or indefinitely. •  Death—2 weeks to 3 months after infection; mortality rate ~50%. •  Euthanasia—owner may elect if or when neurologic signs develop; indicated if uncontrollable seizures occur.

•  Vaccination. •  Isolate puppies to prevent infection from

wildlife (e.g., raccoons, foxes, skunks), CDV-infected dogs, ferrets. •  Recovered dogs may shed virus for up to 4 months; isolate for this time period or until multiple negative RT-PCR tests. Vaccines

•  Duration of immunity from most vaccines

is >3 years.

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  MISCELLANEOUS

ASSOCIATED CONDITIONS •  Persistent or latent Toxoplasma gondii infections—may be reactivated due to immunosuppressive state. •  Respiratory infections with Bordetella bronchiseptica (kennel cough).

AGE-RELATED FACTORS

•  Young puppies—more susceptible;

mortality rate is higher.

•  Nonimmunized old dogs—highly

susceptible to infection and disease.

ZOONOTIC POTENTIAL Possible that humans may become subclinically infected with CDV; immunization against measles virus also protects against CDV infection. PREGNANCY/FERTILITY/BREEDING In utero infection—occurs in antibody-negative bitches; rare; may lead to abortion or to persistent infection; infected neonates may develop fatal disease by 4–6 weeks of age. SYNONYMS

•  Canine distemper. •  Hard pad disease.

SEE ALSO Myoclonus ABBREVIATIONS

•  CDV = canine distemper virus. •  CSF = cerebrospinal fluid. •  Ig = immunoglobulin. •  MLV-CD = modified live virus of canine

distemper.

•  RT-PCR = reverse transcriptase polymerase

chain reaction.

INTERNET RESOURCES https://www.uwsheltermedicine.com/library/ resources/canine-distemper-cdv

­Suggested Reading

Greene CE, Vendevelde M. Canine distemper. In: Greene CE, ed., Infectious Diseases of the Dog and Cat, 4th ed. St. Louis, MO: Saunders Elsevier, 2012, pp. 25–42. Lempp C, Spitzbarth I, Puff C, et al. New aspects of pathogenesis of canine distemper leukoencephalitis. Viruses 2014, 6:2571–2601. Loots AK, Mitchell E, Dalton DL, et al. Advances in canine distemper virus pathogenesis research: a wildlife perspective. J Gen Virol 2017, 98:311–321. Pesavento PA, Murphy BG. Common and emerging infectious disease in the animal shelter. Vet Pathol 2014, 51:478–491. Author Michelle C. Tensley Consulting Editor Amie Koenig Acknowledgment The author and book editors acknowledge the prior contribution of Stephen C. Barr.  Client Education Handout available online



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Canine Infectious Diarrhea loss, hyporexia; no history of dietary indiscretion.

•  Hypoglycemia—parvoviral enteritis and

etiology and severity; may include dehydration, poor body condition, borborygmus, flatulence, hematochezia, melena, visualization of worms on rectal exam or peri-anal, signs of sepsis or systemic inflammatory response syndrome (SIRS).

•  Panhypoproteinemia and hypocholesterol­

•  Physical examination findings—depends on

­

  BASICS

DEFINITION •  Viral, enteropathogenic bacterial, protozoal, or parasitic etiologies; small, large, or mixedbowel diarrhea. •  Secondary systemic signs with canine parvovirus (CPV)-2 and salmonellosis. •  Presence of organisms on diagnostic screening does not indicate causation; patient factors (clinical signs, age, environmental exposure) should be considered before treatment. •  Some dogs will have self-resolution; diagnostic testing appropriate for more severely affected animals or if clinical signs are persistent having ruled out other causes of acute or chronic diarrhea. •  Puppies with acute diarrhea should be screened for CPV-2. PATHOPHYSIOLOGY •  Typically, fecal–oral route of infection. •  Diarrhea from enterotoxins, osmotic diarrhea, or invasion of epithelium resulting in inflammation. •  Up to 50% of dogs may have coinfections. SYSTEMS AFFECTED

•  Gastrointestinal (GI)—vomiting, diarrhea. •  Cardiovascular—fluid balance.

INCIDENCE/PREVALENCE

•  Prevalence of most pathogens similar in

dogs with or without diarrhea. ◦  Coronavirus more common in dogs with diarrhea. ◦  Dogs with diarrhea more likely to have >1 enteropathogen. •  Specific prevalence in dogs in United States: ◦  0–6%—CPV-2, Salmonella spp., Cystoisospora spp., Dipylidum caninum, Campylobacter spp., C. difficile toxin A and B, ascarids. ◦  7–20%—whipworms, Giardia spp., Cryptosporidium, circovirus. ◦  35–60%—C. perfringens enterotoxin A or alpha toxin gene, hookworm. GEOGRAPHIC DISTRIBUTION

•  Widespread. •  Prevalence of etiologies varies by location.

SIGNALMENT •  Species—dog. •  Breed predilections—none. •  Mean age and range—largely pediatric and young adult dogs; older animals if in high-risk environments. SIGNS

•  General comments—range from mild to

severely affected.

•  Historical findings—acute or chronic, small or

large bowel diarrhea; possibly vomiting, weight

CAUSES •  Viral—coronavirus, CPV-2, circovirus. •  Bacterial—Campylobacter spp., Clostridium perfringens enterotoxin, Clostridium difficile toxins, Salmonella spp. •  Parasitic—Toxocara spp., Ancylostoma spp.,Toxascaris leonine, Dipyldium caninum, Trichuris vulpis. •  Protozoal—Giardia spp. •  Coccidial—Cryptosporidium spp., Cystoisospora spp. RISK FACTORS

•  Pediatric and young adult dogs more

commonly affected, particularly for viral enteritis, Cryptosporidium spp., roundworm (Toxocara and Toxascaris), Cystoisospora spp., and Campylobacter spp. •  Administration of antimicrobials and immunosuppressive drugs increase risk for hospital-associated colonization of C. difficile. •  Crowding and poor sanitation. •  Lack of regular parasiticide administration. •  Dogs with environmental exposure to livestock or wildlife for Cryptosporidium spp., Campylobacter spp., Giardia spp.

­

  DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Acute diarrhea—dietary indiscretion, foreign body, pancreatitis, GI neoplasia; non-GI diseases: hepatotoxicity, renal disease, other systemic diseases (commonly other clinical signs such as hyporexia, vomiting, icterus). •  Chronic diarrhea—chronic enteropathy (dietary responsive, antibiotic responsive, or inflammatory bowel disease), chronic pancreatitis, primary GI neoplasia, and non-GI diseases of other organs. CBC/BIOCHEMISTRY/URINALYSIS

•  Eosinophilia—possible with intestinal

parasitism.

•  Anemia and/or microcytosis—GI hemor-

rhage or iron deficiency, particularly with high worm burden (e.g., T. vulpis) or GI mucosal shedding (e.g., CPV). •  Leukopenia—parvoviral enteritis (bacterial translocation or bone marrow suppression) or systemic salmonellosis. •  Hyponatremia and hyperkalemia with large bowel diarrhea—T. vulpis. •  Azotemia and electrolyte derangements with dehydration.

systemic salmonellosis.

emia if secondary protein-losing enteropathy or GI blood loss. IMAGING

•  Abdominal radiographs if no response to

symptomatic care to rule out other causes of diarrhea. •  Abdominal ultrasound recommended in nonpediatric patients with diarrhea that is nonresponsive to symptomatic care. DIAGNOSTIC PROCEDURES

•  Fecal flotation—for intestinal parasitism;

false negatives possible (ova are intermittently shed); dogs suspected to have intestinal parasitism should have multiple fecal flotations performed or be treated with anthelmintics. •  Fecal cytology—bacterial morphology (frequent spirochetes, spores) or presence of fungal or protozoal organisms. •  Giardia ELISA. •  Infectious diarrhea PCR panels detect a range of possible causes of diarrhea; however, caution should be used in interpretation of these assays, as a positive result does not necessarily indicate causation and falsenegative results are possible. PATHOLOGIC FINDINGS

•  Gross examination of intestinal mucosa

may demonstrate parasites attached to intestinal mucosa with multifocal hemorrhagic ulcerations, submucosal congestion or hemorrhage, intestinal wall thickening. •  Histopathology of intestine may show eosinophilic, neutrophilic, or lymphoplasmacytic enteritis with varying degrees of hemorrhage and necrosis, depending on etiology.

­

  TREATMENT

APPROPRIATE HEALTH CARE •  Mildly affected dogs—outpatient basis. •  Moderate to severely affected dogs may require IV administration of isotonic balanced electrolyte solution for dehydration. •  Electrolyte and acid-base imbalances should be corrected with fluid therapy and monitored closely. •  Dextrose should be supplemented parenterally in dogs with hypoglycemia. •  Packed red blood cell or plasma transfusions should be given as needed for severe anemia or coagulopathies from sepsis (rare). DIET

•  Easily digestible diets until clinical signs

have resolved, followed by slow transition (3–4 days) to maintenance diet. •  In anorexic pediatric patients, nasogastric tube feeding of liquid diet recommended if anorexia persists ≥48 hours.

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CLIENT EDUCATION •  For most infectious organisms, environmental decontamination prevents transmission to other pets/people and reinfection; isolation during hospitalization may be warranted depending on underlying cause. •  Appropriate vaccination and deworming schedules should be followed. •  Dogs with identified infectious causes of diarrhea should be isolated from other dogs if possible until clinical signs resolve. SURGICAL CONSIDERATIONS Viral and parasitic enterocolitis can result in intussusceptions, especially in puppies.

­

  MEDICATIONS

DRUG(S) OF CHOICE •  Many cases will self-resolve with supportive care and time. •  Empiric therapy pending diagnostics, if clinical signs persist—probiotics, or metronidazole (10 mg/kg PO q12h) and fenbendazole (50 mg/kg PO q24h for 5 days). •  Anthelmintics—fenbendazole (50 mg/kg PO q24h for 5 days), pyrantel pamoate (5–10 mg/kg PO for 3 days). •  Coccidiostatic—sulfadimethoxine (50–60 mg/kg PO q24h for 5–10 days), ponazuril (50 mg/kg PO once). •  Antiprotozoal drugs—fenbendazole (50 mg/kg PO q24h for 5 days). •  Campylobacteriosis with persistent clinical signs—erythromycin (10–15 mg/kg PO q8h) or azithromycin (5–10 mg/kg PO q24h). •  Probiotics may be of benefit for dogs with bacterial enteritis with acute or chronic signs; probiotics should be selected with evidence of efficacy (e.g., Visbiome®). •  Patients with systemic illness, leukopenia, or suspected GI mucosal barrier breakdown (evidenced by blood in the feces) should be treated with broad-spectrum antimicrobial agents and as indicated by specific etiology. •  Dogs with confirmed salmonella should not be treated with antibiotics unless systemically ill. PRECAUTIONS Metronidazole dose should be reduced in animals with hepatic insufficiency.

POSSIBLE INTERACTIONS

•  Metronidazole given at higher doses for

giardiasis or long-term use can lead to vestibular signs. •  Some dogs may be sensitive to sulfacontaining medications used for treatment of coccidiosis.

­

 FOLLOW-UP

PATIENT MONITORING •  Case-based, may include reassessment of anemia, leukopenia, or electrolyte derangements as appropriate. •  Persistent clinical signs after appropriate treatment is suggestive for alternative cause of diarrhea. •  Patients with recurrent clinical signs should be retested, particularly if environmental reinfection is possible (e.g., giardiasis, campylobacteriosis). PREVENTION/AVOIDANCE

•  Routine vaccination. •  Monthly flea/tick or heartworm preventa-

tive with combination anthelmintic therapy. •  Avoid subjecting poorly vaccinated or immunocompromised animals to high-traffic areas, including but not limited to pet supply stores, dog parks, or newly introduced poorly vaccinated pets. POSSIBLE COMPLICATIONS

•  Sepsis. •  Anemia. •  Electrolyte disturbances. •  Aspiration pneumonia if concurrent

vomiting (uncommon).

EXPECTED COURSE AND PROGNOSIS

•  Usually good to excellent; underlying

immunosuppressive conditions may increase susceptibility to infection and worsen prognosis. •  Parvoviral enteritis carries guarded to poor prognosis without treatment; appropriate supportive care provides full recovery rates of 90% or more.

­

  MISCELLANEOUS

AGE-RELATED FACTORS Puppies and young dogs affected.

(continued)

ZOONOTIC POTENTIAL

•  Giardiasis—low risk of transmission. •  Cryptosporidiosis. •  Salmonellosis. •  Campylobacter jejuni. •  Toxocara spp. (ascarids)—visceral larval

migrans in humans, most common in children. •  Ancylostoma (hookworms)—cutaneous larval migrans in humans, most common in children. PREGNANCY/FERTILITY/BREEDING If heavy endoparasite load, fenbendazole can be administered to pregnant bitches from 14th day of gestation through to 14th day of lactation. If risk of infection is high, all puppies (and mothers) should be treated with appropriate anthelmintics at 2, 4, 6, and 8 weeks of age. SEE ALSO

•  Acute Diarrhea. •  Campylobacteriosis. •  Canine Coronavirus Infections. •  Canine Parvovirus. •  Clostridial Enterotoxicosis. •  Coccidiosis. •  Diarrhea, Chronic—Dogs. •  Giardiasis. •  Hookworms (Ancylostomiasis). •  Roundworms (Ascariasis). •  Salmonellosis. •  Whipworms (Trichuriasis).

ABBREVIATIONS

•  CPV-2 = canine parvovirus. •  GI = gastrointestinal. •  SIRS = systemic inflammatory response

syndrome.

­Suggested Reading

Gookin JL. Infection, large intestine. In: Washabau RJ, Day MJ, eds., Canine & Feline Gastroenterology. St. Louis, MO: Saunders Elsevier, 2013, pp. 745–757. Lappin MR. Infection, small intestine. In: Washabau RJ, Day MJ, eds., Canine & Feline Gastroenterology. St. Louis, MO: Saunders Elsevier, 2013, pp. 683–695. Authors Kasey E. Mabry and Tracy Hill Consulting Editor Amie Koenig



Canine and Feline, Seventh Edition

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Canine Infectious Respiratory Disease Physical Examination Findings

•  Uncomplicated—cough readily induced with

­

 BASICS

DEFINITION A multifaceted disease whereby infectious disease and environment contribute to the genesis of cough and other respiratory signs in dogs. PATHOPHYSIOLOGY Initiated by injury to the respiratory epithelium by viral infection followed by invasion of damaged tissue by bacterial, mycoplasmal, or other virulent organisms, resulting in further damage and clinical signs. SYSTEMS AFFECTED Respiratory—upper and lower airways can be involved. Multisystemic—cases that develop sepsis. GENETICS None INCIDENCE/PREVALENCE Most common in areas of high density with immunologically naïve or immunosuppressed patients (i.e., training kennels, shelters, veterinary hospitals). GEOGRAPHIC DISTRIBUTION Worldwide SIGNALMENT Species

Dog

Breed Predilections

None

Mean Age and Range

•  Most severe in puppies 6 weeks–6 months old. •  Can develop in dogs of all ages, partic­-

ularly with preexisting airway disease.

Predominant Sex

None

minimal tracheal pressure; lung sounds often normal; systemically healthy. •  Complicated— low-grade or intermittent fever (39.4–40.0 °C; 103–104 °F); increased intensity of normal lung sounds, crackles or wheezes possible. CAUSES

•  Viral—canine distemper virus (CDV); canine

adenovirus (CAV-2); canine parainfluenza (CPIV); canine respiratory coronavirus (CRCoV), canine reovirus; canine herpesvirus-1 (CHV-1); canine influenza virus (CIV; H3N8 or H3N2); canine bocavirus, canine hepacivirus; canine pneumovirus (CnPnV). •  Most viral pathogens (except CHV and CDV) primarily infect epithelial and lymphoid tissue of the upper and lower respiratory tract; in severe cases, causing desquamation of the epithelium and aggregation of inflammatory cells in the lungs, leading to secondary bacterial coloni­ zation and infection; CRCoV infection leads to loss of cilia associated with the respiratory epithelium, increasing the severity and duration of secondary infections. •  Bacterial—Bordetella bronchiseptica, with no other respiratory pathogens, produces clinical signs indistinguishable from those of other bacterial causes; Streptococcus equi subsp. zooepidemicus is associated with a particularly virulent course that can progress to death; Pseudomonas, Escherichia coli, Klebsiella, Pasteurella, Streptococcus, Mycoplasma, and other species equally likely. RISK FACTORS •  Substandard hygienic conditions and overcrowding—encountered in some pet shops, shelters, research facilities, and boarding and training kennels. •  Coexisting subclinical airway disease—congenital anomalies; chronic bronchitis; bronchiectasis.

SIGNS General Comments

•  Related to the degree of respiratory tract damage and age of the affected dog and virulence of infectious organism. •  Can be subclinical, mild, or severe with pneumonia. •  Most viral, bacterial, and mycoplasmal agents spread rapidly from seemingly healthy dogs to others in the same environment; signs usually begin about 3–7 days after exposure to the infecting agent(s).

Historical Findings

•  Uncomplicated—acute-onset cough in an otherwise healthy animal; dry and hacking, soft and dry, moist and hacking, or paroxysmal, followed by gagging, retching, and expecto­ ration of mucus; excitement, exercise, and pressure on the trachea induce coughing spells. •  Complicated (severe)—inappetence to anorexia; cough is moist and productive; lethargy, difficulty breathing, hemoptysis, and exercise intolerance can occur.

­

 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  In systemically well dogs—parasitic bronchitis, irritant tracheobronchitis, airway foreign body, airway collapse. •  In a dog with systemic signs—fungal or bacterial (aspiration) pneumonia, primary or metastatic neoplasia, congestive heart failure, migrating foreign body. •  Provisional diagnosis of infectious tracheobronchitis is made in a dog with compelling clinical signs and a history of exposure to the implicated organisms. •  See Cough. CBC/BIOCHEMISTRY/URINALYSIS

•  Early, mild leukopenia (5,000–6,000 cells/

dL)—can be detected; suggests viral cause. •  Neutrophilic leukocytosis with a toxic left shift—frequently found with severe pneumonia.

OTHER LABORATORY TESTS Pulse oximetry and arterial blood gas analysis— can reveal hypoxemia in pneumonia. IMAGING

•  Uncomplicated disease—radiographs:

unremarkable; most useful for ruling out other differential diagnoses. •  Complicated disease—radiographs: interstitial and alveolar lung pattern with a cranioventral distribution typical of bacterial pneumonia; can see diffuse interstitial lung pattern typical of viral pneumonia; mixed lung pattern can be present. DIAGNOSTIC PROCEDURES •  In cases with severe disease—ideally perform bronchoalveolar lavage via bronchoscopy for cytology and microbial culture; tracheal wash sample acceptable, but increased likelihood for upper airway contamination. •  Antimicrobial sensitivity pattern of cultured bacteria—identification aids markedly in providing an effective treatment plan. •  PCR from bronchoalveolar lavage, nasal, ocular, or pharyngeal secretions can be used to detect virus, though there is difficulty in interpreting results as many healthy animals shed virus in the absence of clinical signs. PATHOLOGIC FINDINGS

•  CPIV—causes few to no clinical signs;

lungs of infected dogs 6–10 days after exposure may contain petechial hemorrhages that are evenly distributed over the surfaces; detected by immunofluorescence in columnar epithelial cells of the bronchi and bronchioles 6–10 days after aerosol exposure. •  CAV-2—lesions confined to the respiratory system; large intranuclear inclusion bodies found in bronchial epithelial cells and alveolar septal cells; clinical signs tend to be mild and shortlasting; lesions persist for at least a month after infection. •  CIV (H3N8, H3N2)— fulminant disease characterized by secondary Mycoplasma or bacterial infection and pulmonary hemorrhage. •  CRCoV— characterized by marked inflammation of the trachea and nares with cilia loss in the former; detected by immunohistochemistry of the trachea or bronchioles. •  Streptococcus equi subsp. zooepidemicus infection—acute, fibrinosuppurative pneumonia with large numbers of cocci found within the pulmonary parenchyma and, often, septic thomboemboli. •  Bordetellosis and severe bacterial infection—evidence of purulent bronchitis, tracheitis, and rhinitis with hyperemia and enlargement of the bronchial, mediastinal, and retropharyngeal lymph nodes; may see large numbers of Gram-positive or Gramnegative organisms in the mucus of the tracheal and bronchial epithelium.

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 TREATMENT

APPROPRIATE HEALTH CARE •  Outpatient—strongly recommended for uncomplicated disease. •  Inpatient—strongly recommended for complicated disease and/or pneumonia. NURSING CARE Fluid administration—indicated for complicated disease and/or pneumonia. ACTIVITY Enforced rest—14–21 days with uncomplicated disease; for at least the duration of radiographic evidence of pneumonia in severely affected dogs. DIET Good-quality commercial food. CLIENT EDUCATION •  Isolate patient from other animals; infected dogs can transmit the agent(s) before onset of clinical signs and afterward until immunity develops. •  Dogs with uncomplicated disease should respond to treatment in 10–14 days. •  Once infection spreads in a kennel, it can be controlled by evacuation for 1–2 weeks and disinfection with commonly used chemicals, such as sodium hypochlorite (1 : 30 dilution), chlorhexidine, and benzalkonium.

­

 MEDICATIONS

DRUG(S) OF CHOICE •  Amoxicillin/clavulanic acid (12.5–25 mg/kg PO q12h) or doxycycline (5 mg/kg PO q12h or 10 mg/kg PO q24h)—initial treatment of uncomplicated disease. •  Penicillin (ampicillin 10–20 mg/kg IV q6–8h or ticarcillin 40–50 mg/ kg IV q6–8h) with aminoglycoside (gentamicin 2–4 mg/kg IV/IM/SC q6–8h or amikacin 6.5 mg/kg IV/IM/SC q8h) or fluoroquinolone (enrofloxacin 5–10 mg/kg PO/IM/IV q24h)— usually effective for severe disease. •  Antimicrobial therapy—continue for at least 10 days beyond radiographic resolution. •  B. bronchiseptica and other resistant species—some antimicrobials may not reach adequate therapeutic concentrations in the lumen of the lower respiratory tract, so oral or parenteral administration may have limited effectiveness; nebulization with gentamicin (3–5 mg/kg) can decrease bacterial numbers when administered daily for 3–5 days; use in conjunction with systemic antibiotics in dogs with parenchymal disease. •  Butorphanol (0.55 mg/kg PO q8–12h) or hydrocodone bitartrate (0.22 mg/kg PO q6–8h)—effective suppression of dry, nonproductive cough not associated with bacterial infection. •  Bronchodilators (e.g., terbutaline 0.625–5 mg/dog q8–12h)—may be used to control bronchospasm and wheeze.

CONTRAINDICATIONS •  Do not use cough suppressants in patients with pneumonia. •  Employ glucocorticoids only in cases with significant inflammatory disease refractory to conventional supportive care.

(continued)

shortens the course. •  Typical course of severe disease—2–6 weeks; patients that die often develop severe pneumonia that affects multiple lung lobes and multiple organ dysfunction due to sepsis.

PRECAUTIONS None POSSIBLE INTERACTIONS Fluoroquinolones and theophylline derivatives—concurrent use causes high and possibly toxic plasma theophylline concentration. Dose reduce theophylline while concurrently administering fluoroquinolones.

­

 MISCELLANEOUS

ASSOCIATED CONDITIONS May accompany other respiratory tract anomalies.

ALTERNATIVE DRUG(S) None

AGE-RELATED FACTORS Most severe in puppies 6 weeks–6 months old and in puppies from commercial pet shops and humane society shelters.

­

ZOONOTIC POTENTIAL Potential zoonotic risk of Streptococcus equi subsp. zooepidemicus and B. bronchispetica reported in single case reports.

 FOLLOW-UP

PATIENT MONITORING •  Uncomplicated disease—should resolve spontaneously or respond to treatment in 10–14 days; if patient continues to cough 14 days or more after establishment of an adequate treat­ment plan, question the diagnosis of uncomplicated disease. •  Complicated disease— repeat thoracic radiography until at least 7 days beyond resolution of all clinical signs. PREVENTION/AVOIDANCE Shedding of the causative agent(s) of infectious respiratory disease in airway secretions of dogs undoubtedly accounts for the persistence of this problem in kennels, animal shelters, boarding facilities, and veterinary hospitals. Viral and Bacterial Vaccines

•  Modified live CDV and CAV-2 vaccines

provide reliable protection and are considered core vaccines for all puppies; can be admin­ istered at 6 weeks of age, every 2–4 weeks. •  B. bronchiseptica and CPIV vaccine—can vaccinate puppies mucosally or intranasally as early as 2–4 weeks of age without interference from maternal antibody and follow with annual revaccination; can vaccinate mature dogs with a one-dose intranasal vaccination (at the same time as their puppies or when they receive their annual vaccinations). •  Inactivated B. bronchiseptica parenteral vaccine—administered as two doses, 2–4 weeks apart; initial vaccination of puppies is recommended at or about 6–8 weeks of age; revaccinate at 4 months of age. •  Inactivated CIV vaccines (H3N2 and H3N8) available to reduce severity and duration of clinical signs but considered noncore; can be administered starting at 6 weeks as two doses, 2–4 weeks apart; results in seroconversion. POSSIBLE COMPLICATIONS N/A EXPECTED COURSE AND PROGNOSIS •  Natural course of uncomplicated disease, if untreated—10–14 days; simple restriction of exercise and prevention of excitement

PREGNANCY/FERTILITY/BREEDING High risk in dogs on extensive medical treatment; especially risky for dogs in overcrowded breeding facilities. SYNONYMS •  Kennel cough. •  Infectious tracheobronchitis—uncomplicated disease. ABBREVIATIONS •  CAV-2 = canine adenovírus. •  CDV = canine distemper vírus. •  CHV-1 = canine herpesvirus-1. •  CIV = canine influenza virus. •  CnPnV = canine pneumovirus. •  CPIV = canine parainfluenza. •  CRCoV = canine respiratory coronavirus. INTERNET RESOURCES https://www.cdc.gov/flu/other/canine-flu

­Suggested Reading

Bemis DA. Bordetella and Mycoplasma respiratory infection in dogs. Vet Clin North Am Small Anim Pract 1992, 22:1173–1186. Buonavoglia C, Martella V. Canine respiratory viruses. Vet Res 2007, 38(2):355–373. Chalker VJ, Owen WM, Paterson C, et al. Mycoplasmas associated with canine infectious respiratory disease. Microbiology 2004, 150(Pt 10):3491–3497. Erles K, Dubovi E, Brooks HW, Brownlie J. Longitudinal study of viruses associated with canine infectious respiratory disease. J Clin Micro 2004, 42:4524–4529. Priestnall SL, Mitchell JA, Walker CA, et al. New and emerging pathogens in canine infectious respiratory disease. Vet Path 2014, 51(2):492–504. Author Jonathan D. Dear Consulting Editor Elizabeth Rozanski  Client Education Handout available online



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Canine Parvovirus •  Higher fatality rates are seen in hounds,

•  Severely affected dogs exhibit severe

Mean Age and Range

•  Leukocytosis during recovery. •  Serum chemistry profiles help assess

gundogs, and nonsporting pedigree groups.

­

  BASICS

DEFINITION •  An acute systemic illness characterized by vomiting, hemorrhagic enteritis, and leukopenia. •  Myocardial form was observed in puppies in late 1970s, now rare. •  Most puppies protected against neonatal infection by maternal antibodies. •  Monoclonal antibodies have revealed antigenic changes in canine parvovirus (CPV)-2; CPV2a, b, and c strains have been identified. •  Original virus now virtually extinct in domestic dogs. •  CPV2c viruses are more virulent, and mortality rates higher. •  CPV-2 is closely related to feline panleuko­ penia virus (FPV). PATHOPHYSIOLOGY

•  Parvoviruses require actively dividing cells

for growth.

•  After ingestion of virus there is a 2–4-day

period of viremia. •  Early lymphatic infection is accompanied by lymphopenia and precedes intestinal infection and clinical signs. •  By postinfection (PI) day 3, rapidly dividing crypt cells of small intestine are infected. •  Viral shedding in feces starts ∼3–4 days PI, peaks with clinical signs. •  Virus ceases to be shed in detectable amounts by PI days 8–12. •  Absorption of bacterial endotoxins from damaged intestinal mucosa plays a role in CPV-2 disease. •  Intensity of illness related to viral dose and antigenic type. SYSTEMS AFFECTED

•  Cardiovascular—myocarditis (uncommon),

hypovolemia.

•  Gastrointestinal. •  Hemic/lymphatic/immune.

GENETICS Unknown INCIDENCE/PREVALENCE Common in breeding kennels, animal shelters, pet stores. GEOGRAPHIC DISTRIBUTION Worldwide SIGNALMENT Species

Dog

Breed Predilections

•  Certain breeds are at increased risk,

including Rottweiler, Doberman pinscher, American pit bull terrier, Labrador retriever, German shepherd dog, and Yorkshire terrier.

•  Illness occurs at any age. •  Most severe in dogs 6–24 weeks of age.

neutropenia with onset of intestinal damage.

Predominant Sex

electrolyte disturbances (especially hypokalemia), presence of azotemia, panhypoproteinemia, hypoglycemia.

SIGNS

•  Virus antigen detection in stool at onset of

None

OTHER LABORATORY TESTS

General Comments

Suspect CPV-2 infection whenever puppies have an enteric illness. Historical Findings

•  Sudden onset of bloody diarrhea, anorexia,

and vomiting.

•  Some dogs may collapse in a shock-like

state and die without enteric signs.

•  In breeding kennels, several littermates may

become ill simultaneously or within a short period. •  Occasionally, one or two puppies in a litter have minimal signs, followed by death of littermates, which may reflect degree of virus exposure. Physical Examination Findings

•  Hypovolemic shock—weak pulse, tachy­-

cardia, dull mentation.

•  Severe hemorrhagic diarrhea. •  Fluid-filled intestinal loops may be palpated. •  Dehydration, weight loss, abdominal

discomfort.

disease and for 2–4 days afterward; many commercial point-of-care ELISA assays available, also PCR and quantitative PCR methodologies. •  Serologic tests are not diagnostic because dogs often have high titers from vaccination and/or maternal antibodies. IMAGING

•  Abdominal radiographs—generalized small

intestinal ileus; exercise caution to prevent misdiagnosis of intestinal obstruction, but intussusception may cause obstructive pattern. •  Abdominal ultrasound—fluid-filled, atonic small and large intestines, duodenal and jejunal mucosal layer thinning with or without indistinct wall layers and irregular luminal-mucosal surfaces, extensive duodenal and/or jejunal hyperechoic mucosal speckling, and duodenal and/or jejunal corrugations; intussusceptions can be identified. DIAGNOSTIC PROCEDURES

•  May have fever or hypothermia.

•  Electron microscopy detects fecal virus

CAUSES CPV-2.

•  Samples for virus detection should be

RISK FACTORS •  Unvaccinated dogs. •  Dogs 0.2 μg/dL at 24 hours after admission is associated with 100% survival. An HDLcholesterol concentration >50.2 mg/dL at admission is associated with 100% survival.

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  FOLLOW-UP

PATIENT MONITORING There is an increased incidence of discospondylitis in puppies that had parvovirus infection. PREVENTION/AVOIDANCE •  Inactivated and live vaccines are available for prophylaxis, and vaccines differ in their capacity to immunize puppies with maternal antibodies. •  Vaccination with a modified live vaccine at 4 weeks of age in puppies with high maternally derived antibody concentrations resulted in seroconversion rates of up to 80%; this may lead to a decreased window of susceptibility to CPV infection and might be an adjunct control method in contaminated environments. •  Control of CPV-2 requires efficacious vaccines, isolation of puppies, and stringent hygiene. POSSIBLE COMPLICATIONS

•  Septicemia/endotoxemia. •  Bacterial pneumonia. •  Intussusception. •  Discospondylitis.

EXPECTED COURSE AND PROGNOSIS

•  Prognosis is guarded in severely affected

puppies. •  Prognosis is good for dogs that receive prompt initial treatment and survive initial crisis—approximately 80% survival rate. •  Poor prognosis if a patient is purebred, has a low bodyweight, and if the following biomarker levels are present after 24 hours of intensive therapy: severe persistent leuko- and lymphopenia, persistently elevated or rising serum cortisol concentration (>8.1 μg/dL), severe hypothyroxinemia (6 months old, and show the following biomarker values: total leukocyte count >4.5 × 103/μL, lymphocyte count >1 × 103/μL, and mature neutrophil count >3 × 103/μL. Additionally, a serum cortisol concentration 1 year of age, but can still occur, especially if unvaccinated. ZOONOTIC POTENTIAL Parvovirus per se is not zoonotic, but these puppies may harbor coinfections with Giardia, which can be zoonotic. PREGNANCY/FERTILITY/BREEDING Pregnant animals are likely to abort. SEE ALSO •  Acute Diarrhea. •  Acute Vomiting. •  Canine Coronavirus Infections. •  Gastroenteritis, Acute Hemorrhagic Diarrhea Syndrome. •  Sepsis and Bacteremia. •  Shock, Septic. ABBREVIATIONS

•  CPV = canine parvovirus. •  FPV = feline panleukopenia virus. •  PI = postinfection.

­Suggested Reading

Mohr AJ, Leisewitz AL, Jacobson LS, et al. Effect of early enteral nutrition on intestinal permeability, intestinal protein loss, and outcome in dogs with severe parvoviral enteritis. J Vet Intern Med 2003, 17:791–798. Schoeman JP, Goddard A, Herrtage ME. Serum cortisol and thyroxine concentrations as predictors of death in critically ill puppies with parvoviral diarrhea. J Am Vet Med Assoc 2007, 231:1534–1539. Venn EC, Preisner K, Boscan PL, et al. Evaluation of an outpatient protocol in the treatment of canine parvoviral enteritis. J Vet Emerg Crit Care 2017, 27:52–65. Author Johan P. Schoeman Consulting Editor Amie Koenig  Client Education Handout available online



Canine and Feline, Seventh Edition

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Canine Schistosomiasis (Heterobilharziasis)

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  BASICS

OVERVIEW •  Heterobilharzia americanum is a trematode of the genus Schistosoma that has fresh water lymnaeid snails as intermediate hosts and raccoons as the natural definitive host. •  Eggs passed in the feces of raccoons hatch to release miracidia that penetrate freshwater snail hosts. After a period of development and asexual multiplication, the snails release cercariae that infect the next host by skin penetration. After penetrating skin, larvae undergo a migration to the lung and then make their way to mesenteric veins, where separate males and females form pairs. Eggs laid by female worms are carried to the intestinal wall, where they erode their way through to the lumen to be passed in the feces. Other eggs are carried to the liver or other organs by the bloodstream, where they lodge and cause granulomatous disease. •  Dogs become infected in contact with freshwater containing cercariae. •  Endemic in raccoons in southeastern United States; canine cases reported from Arkansas, Indiana, Florida, Georgia, Kansas, Louisiana, North Carolina, Oklahoma, and Texas. SIGNALMENT Dogs, typically adult, that have access to swampy areas or bayous. SIGNS •  Lethargy (most common sign), weight loss, and decreased appetite. •  Other signs include vomiting, diarrhea, anorexia, polyuria/polydipsia; more rarely melena, borborygmus, ascites. CAUSES & RISK FACTORS Swimming in freshwater in areas contaminated with cercariae from miracidia.

­

  DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Coccidiosis. •  Bacterial diarrhea. •  Viral enteritis. •  Hepatopathies. CBC/BIOCHEMISTRY/URINALYSIS •  CBC—anemia, lymphopenia, eosinopenia or eosinophilia, thrombocytopenia. •  Biochemistry—elevated liver enzyme activities, azotemia, hypercalcemia, hyper­ natremia, hyperglobulinemia, hypoalbuminemia. •  Urinalysis—proteinuria.

OTHER LABORATORY TESTS •  Elevated parathyroid hormone-related protein (PTH-rp) reported in dogs with hypercalcemia. •  PCR on feces (Texas A&M Gastrointestinal Laboratory). IMAGING Contrast radiographs and ultrasound may reveal thickened bowel walls; calcified eggs disseminated into tissues may give the false impression of soft tissue mineralization. DIAGNOSTIC PROCEDURES •  Eggs with miracidia can be identified in feces, but feces must be kept in saline (not water) or miracidia will spontaneously hatch, making diagnosis impossible. •  Fecal direct or sedimentation methods are preferred to fecal flotation; routine fecal flotation will not detect these heavy eggs; if used, requires flotation with sugar solution with specific gravity of 1.3. •  Histopathology—trematode eggs in multiple organs (especially liver, intestine, pancreas, lymph nodes); lymphoplasmacytic, histiocytic, and eosinophilic to granuloma­ tous enteritis, hepatitis with possible peri-portal fibrosis, dystrophic mineralization of multiple tissues.

­

  TREATMENT

­

  MEDICATIONS

Inpatient care for the first few days of treat­ment may be warranted, as the response to worm kill may require supportive care.

DRUG(S) OF CHOICE •  Praziquantel—25 mg/kg PO q8h for 2–3 days. •  Fenbendazole—50 mg/kg PO q24h for 10 days; clinical improvement without parasite elimination has been reported with fenbendazole.

­

 FOLLOW-UP

•  Check feces after treatment to ensure that it

does not contain eggs.

•  Reinfection from environment is possible.

­

  MISCELLANEOUS

In Japan and other countries with endemic Schistosoma japonicum, dogs can be infected with this human and zoonotic species.

ZOONOTIC POTENTIAL Stages in the dog pose no threat to people; with shared waterway exposure, cercariae can cause skin lesions in people. SYNONYMS

•  Schistosomiasis. •  Swimmer’s itch (human, skin penetration of

cercariae).

ABBREVIATIONS

•  PTH-rp = parathyroid hormone-related

protein.

­Suggested Reading

Fabrick C, Bugbee A, Fosgate G. Clinical features and outcome of Heterobilharzia americana infection in dogs. J Vet Intern Med 2010, 24:140–144. Flowers JR, Hammerberg B, Wood SL, et al. Heterobilharzia americana infection in a dog. J Am Vet Med Assoc 2002, 220:193–196. Stone RH, Frontera-Acevedo K, Saba CF, et al. Lymphosarcoma associated with Heterobilharzia americana infection in a dog. J Vet Diag Invest 2011, 23:1065–1070. Author Dwight D. Bowman Consulting Editor Amie Koenig

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Car Ride Anxiety—Dogs and Cats CAUSES & RISK FACTORS

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•  Behavioral causes include unruliness,

­

  BASICS

DEFINITION Excessive or disruptive distress, fear, or panic associated with vehicle travel. Anxiety exhibited during travel can be mistaken for excitement. PATHOPHYSIOLOGY Unknown or not definitively determined. Lack of car ride experience, generalized anxiety disorder, nausea, previous negative experience with car rides; fear, anxiety, or arousal related to visual or auditory stimuli. SYSTEMS AFFECTED •  Behavioral. •  Gastrointestinal. •  Neuromuscular. GENETICS May be genetic component, but experiential learning may be more significant. INCIDENCE/PREVALENCE Reported in over 50% of cats and over 20% of dogs. SIGNALMENT Dog and cat. Breed Predilections

None

Mean Age and Range

Any. Young or ill animals may be predisposed to motion sickness. Predominant Sex

None

inadequate or poor prior experience traveling; insufficient adaptation to carriers, leashes, or restraint devices; fear and reactivity to visual stimuli such as people, animals, bikes, or cars; and generalized anxiety. •  Prior stressful or uncomfortable experiences following car rides such as veterinary visits, boarding, or shelter relinquishment. •  Traumatic events such as sudden stops or car accidents. •  Medical conditions may exacerbate or manifest as anxiety—motion sickness, musculoskeletal pain or discomfort, dental disease or pain, gastrointestinal upset, sensory hypersensitivity.

•  May include pacing, restlessness,

inappetence, vigilance, excitability, and vocalization including whining or highpitched barking in dogs and growling, hissing, meowing, or yowling in cats. •  Locomotion varies between individuals— some may pace while others remain immobile; fear that manifests as freezing or hiding may be underrecognized and underreported. •  Pet-related panic, vocalization, and pacing may impair owner’s ability to drive safely. •  Travel-related anxiety may prevent owners from taking pets to destinations (e.g., veterinary visits, grooming, social events, training). Physiologic and Physical Signs

May include panting, rapid heart rate, drooling, urination, vomiting, defecation. Physical Examination

Normal unless underlying medical problems.

to prevent exacerbating established fears; for example, when carrying a pet in a carrier, consider their viewpoint and the unsettling motion that may be experienced. •  Avoid reprimands or scolding. •  Avoid forcing pets that are unfamiliar or do not get along to be in close proximity. Management and Safety

•  Provide stable footing and secure resting

locations.

•  Consider crating if pet acclimated to crate

confinement; pet seat belts, barriers, and seat slings can also be beneficial. •  A nondriver should accompany highly distressed pets. Anxiety Reduction

•  Multimodal comforting and anxiolytic

support provides the best outcome.

­

  DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Fear and anxiety-related behavior. •  Manifestation of pain, nausea, or physical discomfort. •  Acute onset or abrupt change in car ride anxiety warrants ruling out contributory medical conditions. CBC/BIOCHEMISTRY/URINALYSIS If indicated by clinical signs and prior to drug therapy. OTHER LABORATORY TESTS If indicated by clinical signs. IMAGING If indicated by clinical signs.

•  Window shades, covered crates, solid wall

carriers, or products for dogs such as Doggles® or Thundercap® may alleviate anxiety related to visual stimuli. •  Classical music or psychoacoustically designed music for dogs or cats may help to calm; music or white noise may mute perception of fear-evoking sounds. •  Comforting pressure wraps may alleviate anxiety. •  Synthetic pheromone analogues (Adaptil®, Feliway®) sprayed into carriers, onto bedding, or on a bandana (for dogs) may reduce anxiety. •  Anxiety-reducing supplements or medications should be considered. Behavior Modification

•  Rehearse settle and relax positions when not

traveling.

•  Teach the dog to get in and out of the car

SIGNS Historical Findings

•  Anticipate and avoid evoking the pet’s fears

­

  TREATMENT

ACTIVITY Normal. Recommend adequate exercise and play before car ride. DIET •  Normal. •  Providing highly palatable food during car travel may distract, reduce stress, and promote a positive association with car travel. •  If the pet has experienced nausea or vomiting in association with car travel, fasting is recommended. CLIENT EDUCATION A complete behavior program includes empathy, environmental management, and behavior modification together with supplements or medication where indicated. Compassion

•  Give thoughtful preparation and consid­

eration for the pet’s perspective before traveling; allow time for travel and be patient.

by positive reinforcement (e.g., food or toy reward). •  Teach cats and small dogs to go in and out of carriers willingly; they should be acclimated to the motion of being in a carrier that is being carried. •  Practice training when travel is not imminent; use positive reinforcement training and avoid reprimand or intimidation training; animals should never receive corrections from shock, prong, or choke collars. •  During travel, provide comforting activities such as toys, food chews, or feeding puzzles that may distract the pet, reduce anxiety, or counter-condition the pet to car rides.

­

  MEDICATIONS

DRUG(S) OF CHOICE General Comments

•  Psychotropic medication, supplements, or

pheromones may be beneficial or necessary



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Car Ride Anxiety—Dogs and Cats

(continued)

Table 1 

C

Benzodiazepine doses

Alprazolam Clonazepam Diazepam Lorazepam Oxazepam

as an adjunct to the behavior program; short-acting anxiolytics are appropriate for pets traveling occasionally; administer anxiolytics so that optimal effect precedes onset of anxiety; the effect of anxiolytics may be overcome by severe anxiety or distress; high or repeated doses, extreme anxiety, and other medical conditions increase the risk for profound sedation and drug reactions. •  Drugs should be trial dosed in advance to determine effects, side effects, optimal dose, and duration. •  Address concurrent behavioral conditions (e.g., separation anxiety, fears, phobias, anxiety, reactivity) that may warrant ongoing anxiolytics (e.g., tricyclic anti­ depressants [TCAs] or selective serotonin reuptake inhibitors [SSRIs]) in conjunction with the treatment of travel-related anxiety. Benzodiazepines

•  Anxiolytic; see Table 1 for drug options and

dosing information.

•  Give 30–60 minutes prior to travel. •  Side effects—incoordination, hyperphagia,

paradoxical excitability, muscle relaxation, possible amnesic effect that might interfere with learning. •  Hyperphagia may be advantageous for pets with stress anorexia. •  Oxazepam and lorazepam have no active intermediate metabolites and may be safer if hepatic function compromised; injectable midazolam may be useful if administered in the veterinary hospital before home travel. Maropitant

•  May be indicated for nausea related to

travel and prior to opioid sedation. •  Dog—1–2 mg/kg PO 2h before travel; for motion sickness 8 mg/kg given with a small amount of food 1–2h before travel. •  Cat—1 mg/kg SC daily. Trazodone

•  Dog—2–5 mg/kg; titrate up to 5–10 mg/kg

based on effect; higher doses may be utilized by experienced clinicians; may be started twice daily 12–48h in advance.

Canine

Feline

0.02–0.1 mg/kg PO q6–12h 0.1–1.0 mg/kg PO q8–12h 0.5–2 mg/kg PO PRN (e.g., q6h) 0.025–0.2 mg/kg PO q24h to PRN 0.2–1 mg/kg PO q12–24h

0.025–0.1 mg/kg PO q8–24h 0.02–0.2 mg/kg PO q12–24h 0.025–0.05 mg/kg PO 12–24h 0.2–0.5 mg/kg PO 12–24h

•  Cat—25–50 mg/cat for car travel. •  Side effects—sedation, lethargy,

incoordination, cardiac conduction disturbances, agitation.

Gabapentin

•  Cat—20 mg/kg (50–150 mg/cat) 2–3h

before travel.

•  Dog—10–30 mg/kg PRN to BID; may be

started twice daily 12–48h in advance.

•  Side effects—sedation, ataxia.

Clonidine

•  Dog—0.01–0.05 mg/kg PO; begin at low

dose and titrate to most effective dose; maximum effect may take up to 2h with faster absorption on an empty stomach; may be started twice daily 12–48h in advance. •  Side effects—transient hyperglycemia, anticholinergic, hypotension, collapse, bradycardia, agitation; use with caution in cardiac disease or compromised renal or liver function. Dexmedetomidine Oromucosal Gel

•  Dogs—125 μg/m2 onto oral mucosa 30–60

min prior to travel; can be repeated in 2h. •  Licensed for use in dogs with noise aversion. •  Side effects—sedation, paradoxical excite­ ment, pale mucous membranes, emesis. Acepromazine

•  Dog and cat—0.5–2.2 mg/kg PO. •  Not for sole use; may be combined with

anxiolytic medication for added sedation.

•  Side effects—ataxia, inhibits thermoregulation,

peripheral vasodilation, muscle tremor or spasm, altered noise reactivity.

•  Lavender essential oils may have a calming

effect in dogs, but avoid in cats since floral scents may be aversive.

CONTRAINDICATIONS Avoid use or use with caution in combination with any drug that enhances serotonin transmission (e.g., trazodone, SSRIs, TCAs) and that may pose an increased risk for serotonin syndrome. PRECAUTIONS All listed medications are extra-label or off-label (except maropitant). Use with informed consent.

­

  FOLLOW-UP

PATIENT MONITORING Ask about travel-related distress as part of wellness assessment, and recommend early intervention and prevention. Travel-related difficulties pose a barrier for bringing pets to the veterinary hospital. PREVENTION/AVOIDANCE •  Provide preventive guidance on making travel positive and carrier training at first puppy or kitten visit. •  Avoid travel for severely affected pets. •  Use appropriate medication when travel required. EXPECTED COURSE AND PROGNOSIS Likely to worsen if untreated.

Pheromone

F3 cheek gland pheromone or dog-appeasing pheromone given 30–60 min before travel. Natural Supplements

•  For mild to moderate anxiety or adjunctive

therapy—alpha-casosopene alone or in a diet in combination with l-tryptophan; l-theanine alone or in combination products containing whey protein, Phellodendron amurense, and Magnolia officinalis; melatonin; Souroubea and Plantanus; or a calming probiotic supplement.

­

  MISCELLANEOUS

ASSOCIATED CONDITIONS •  Generalized anxiety disorder, noise-related fears and phobias, separation anxiety; hyper­attac­hment. •  Dental disease or pain. AGE-RELATED FACTORS Cognitive decline may exacerbate anxiety.

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Car Ride Anxiety—Dogs and Cats C

ZOONOTIC POTENTIAL A distressed pet may cause distraction and put drivers at risk for accidents.

•  Fears, Phobias, and Anxieties—Cats. •  Fears, Phobias, and Anxieties—Dogs.

PREGNANCY/FERTILITY/BREEDING Drug use in breeding, pregnant, or lactating animals should be avoided.

•  SSRI = selective serotonin reuptake inhibitor. •  TCA = tricyclic antidepressant.

SEE ALSO •  Fear and Aggression in Veterinary Visits—Cats. •  Fear and Aggression in Veterinary Visits—Dogs.

ABBREVIATIONS

INTERNET RESOURCES www.catalystcouncil.org/resources/video

­Suggested Reading

Crowell-Davis SL, Murray T, Dantas L. Veterinary Psychopharmacology, 2nd ed. Hoboken, NJ: Wiley, 2019.

(continued)

Horwitz D, ed. Blackwell’s 5 Minute Consult Clinical Companion: Canine and Feline Behavior, 2nd ed. Hoboken, NJ: Wiley, 2018, pp. 873–884. Author Theresa L. DePorter Consulting Editor Gary M. Landsberg



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Carbon Monoxide Toxicosis •  Smoke inhalation, primary neurologic

C

disease, and severe metabolic disease.

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  BASICS

OVERVIEW •  Carbon monoxide (CO)—odorless, colorless, nonirritating gas produced by inefficient combustion of carbon fuels. •  Common sources are fires, automotive exhaust, leaking coal, oil, or natural gas/ propane furnaces, gas appliances or fireplaces, and some paint strippers and sprays. •  CO is absorbed into the blood, forming carboxyhemoglobin (COHb). •  Affinity of CO for hemoglobin is approx­ imately 240 times that of oxygen. •  COHb cannot bind oxygen and impairs oxyhemoglobin from releasing oxygen to the tissues. •  Major effect is acute cellular hypoxia, leading to death. •  Survivors may have cardiac damage, acute and delayed neurotoxicity. •  Lethal concentration is approximately 1,000 ppm (0.1%) for 1 hour. SIGNALMENT Dogs and cats equally affected. SIGNS Acute Exposure

CBC/BIOCHEMISTRY/URINALYSIS Biochemistry—may see liver and kidney value elevations secondary to hypoxia. OTHER LABORATORY TESTS •  Carboxyhemoglobin can be measured via co-oximetry; may return to normal within hours after removal from CO source. Available at human hospital or veterinary specialty/diagnostic lab. •  Blood gas—metabolic acidosis due to lactic acidosis; arterial blood gas may have normal partial pressure of oxygen (PaO2). IMAGING Thoracic radiographs—evaluate for pulmonary injury and rule out other causes of respiratory signs. DIAGNOSTIC PROCEDURES •  Pulse oximetry may overestimate hemo­ globin saturation (SpO2); COHb and oxyhemoglobin absorb light at the same wavelength. •  ECG—sinus tachycardia or cardiac dysrhythmia, ST-T depression with myocardial hypoxia/anoxia. •  Blood pressure—hypotension common in shock.

•  Acute signs progress within minutes to hours. •  Neurologic signs—lethargy or agitation,

weakness, ataxia, depressed mentation, deafness, coma, seizures. •  Respiratory—tachypnea and dyspnea. •  Cardiovascular—tachycardia, dysrhythmias, hypotension. •  Hyperemic skin and mucous membranes are rarely apparent in animals. Chronic Exposure

•  Nausea, vomiting, decreased activity, and

cough; may mimic other diseases. •  Disturbance of postural and position reflexes and gait.

­

  TREATMENT

•  Supplemental oxygen (flow-by, mask, nasal,

oxygen cage, or intubation ± mechanical ventilation)—improves oxygen delivery to vital organs, especially brain and heart; decreases half-life of COHb. •  Hyperbaric oxygen therapy use is controversial and not readily available in veterinary medicine, but will further reduce half-life of COHb. •  IV fluid therapy for hydration and perfusion and to correct metabolic acidosis.

CAUSES & RISK FACTORS

•  Housed in areas with blocked exhaust vents,

furnaces, appliances, or chimneys; exposure to automobile exhaust or kerosene heaters in closed spaces with poor ventilation. •  Trapped in house or kennel fires. •  Animals with impaired cardiac or pulmonary function.

­

  DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Sedatives, ethanol, ethylene glycol, petroleum hydrocarbons, lead poisoning; cyanide or hydrogen sulfide gas toxicosis.

­

  MEDICATIONS

DRUG(S) OF CHOICE •  Sedatives and anxiolytics may be needed to allow oxygen supplementation—diazepam 0.1–0.5 mg/kg IV q6–8h. •  Short-acting opioids such as fentanyl (2–5 μg/kg IV followed by CRI 2–5 μg/kg/h) can be used for pain and sedation. CONTRAINDICATIONS/POSSIBLE INTERACTIONS Limit 100% oxygen to 8–9 years of age. •  Cat—rare, generally >7–8 years of age.

SIGNS Clinical signs depend on the location of the primary tumor or metastases and may include anorexia, vomiting, dyschezia, melena, collapse, ascites, weight loss, and signs of hepatic failure or gall bladder obstruction.

­

  DIAGNOSIS

DIFFERENTIAL DIAGNOSIS Differentials include primary gastrointestinal diseases—neoplasia, infection, inflammation, parasites, foreign body, dietary indiscretion, or hepatic/biliary disease. CBC/BIOCHEMISTRY/URINALYSIS •  Normal, possible mild nonregenerative anemia. •  Electrolyte abnormalities, elevated liver enzyme activities, and hyperbilirubinemia can be present.

IMAGING •  Radiography and ultrasound can identify primary tumors and metastases. •  CT scan and MRI may also be useful. •  In humans, more sensitive molecular imaging includes radiolabeled somatostatin receptor scintigraphy (OctreoScan); radioiodinated metaiodobenzylguanidine (MIBG) imaging; and PET scans.

reported in a dog with a completely excised nonmetastatic jejunal carcinoid.

  FOLLOW-UP

Abdominal ultrasound and thoracic radiographs should be performed regularly to identify metastasis. EXPECTED COURSE AND PROGNOSIS •  Limited survival data exists (few reported cases). •  Survival of 18 months seen in dog with intestinal carcinoid treated with surgery and carboplatin. •  Survival of 12 months reported in cats with extrahepatic carcinoids.

DIAGNOSTIC PROCEDURES

•  Biopsy often confirms diagnosis. •  If histopathologic results are equivocal,

­

electron microscopy and/or immunohistochemistry (looking for chromogranin A and/ or synaptophysin expression) may be used to confirm a carcinoid tumor.

ABBREVIATIONS •  APUD = amine precursor uptake and decarboxylation. •  MIBG = metaiodobenzylguanidine.

PATHOLOGIC FINDINGS Tumors have a fine fibrovascular stroma with minimal to moderate cellular pleomorphism. Cytoplasm is eosinophilic and usually contains secretory granules that stain argyrophilic and/ or argentaffin-positive (silver stains).

INTERNET RESOURCES https://www.carcinoid.com

­

  TREATMENT

­

  MEDICATIONS

In some cases, surgical excision can be curative, especially if no metastasis. Debulking can decrease hormone secretion in humans, and it may relieve tumor-related gastrointestinal obstruction.

DRUG(S) OF CHOICE •  Octreotide, a somatostatin analogue that inhibits hormone secretion from the tumor cells, is used in humans for palliative therapy; as carcinoid syndrome has not been reliably reported in animals with carcinoid tumors, octreotide may be of little benefit. •  High-dose radioiodinated MIBG is used in humans with nonresectable or metastatic carcinoid. •  Interferons have demonstrated limited success in humans with carcinoid tumors. •  Chemotherapy and radiotherapy have minimal efficacy in humans with carcinoid tumors.

  MISCELLANEOUS

­Suggested Reading

Corrigan A, Bechtel S. APUDomas: diagnosis, supportive care, and definitive treatment. Proceedings of the American College of Veterinary Internal Medicine Forum, Indianapolis, Indiana, 2015. Rossmeisl JH Jr., Forrester SD, Robertson JL, Cook WT. Chronic vomiting associated with a gastric carcinoid in a cat. J Am Anim Hosp Assoc 2002, 38(1):61–66. Author Virginia L. Gill Consulting Editor Patty A. Lathan



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Cardiac Glycoside Plant Toxicosis

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  BASICS

OVERVIEW •  Same toxic profile as digoxin, in particular cardiovascular (CV) and gastrointestinal (GI) signs. •  All plant parts, fresh or dry, are considered toxic, but the concentration varies depending on specific plant and plant part. •  Plants are best identified by scientific name. •  Common plants include Adenium obesum (desert rose); Apocynum cannabinum (dogbane); Asclepias spp. (milkweed); Calatropis spp. (giant milkweed); Convallaria majalis (lily of the valley); Digitalis lanata (wooly foxglove); Digitalis purpurea (common or purple foxglove); Kalanchoe spp. (mother of millions); Nerium oleander (oleander); Ornithogalum umbellatum (star of Bethlehem); Thevetia peruviana (yellow oleander). SIGNALMENT •  Cats are more sensitive to some of the plant toxins than dogs. •  Dogs with the ABCB1-1Δ gene mutation may be more sensitive to toxins. SIGNS •  CV—bradycardia (rarely tachycardia), atrioventricular (AV) block, all forms of arrhythmias, death from asystole. •  GI (most frequent)—hypersalivation, vomiting ± blood, diarrhea ± blood. •  Neuromuscular—coma, tremors, seizures (rarely); may be related to decreased cardiac output. CAUSES & RISK FACTORS

•  Cardiac glycoside–containing plants inhibit

the ATPase sodium/potassium pump, resulting in an increase in intracellular sodium and a decrease in intracellular potassium; increased intracellular (myocyte) calcium results in increased cardiac contractions. •  Animals with a prior history of cardiac or renal disease and receiving digoxin or other cardiac glycoside drugs are at risk.

­

  DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Beta blocker or calcium channel blocker toxicosis. •  Cardiac disease in general. •  Digoxin/digitoxin toxicosis. •  Ingestion of medications with known cardiac effects. •  Ingestion of other plants with known cardiac effects such as Taxus spp. (yew), Rhododendron spp. (azalea, rhododendron), Kalmia spp. (mountain laurel, lambkill), and Pieris japonica (Japanese pieris).

CBC/BIOCHEMISTRY/URINALYSIS Serum chemistry—hyperkalemia early and severe, may switch to hypokalemia. OTHER LABORATORY TESTS Serum digoxin levels may be useful in some ingestions. DIAGNOSTIC PROCEDURES

•  Presence of plant pieces in vomit or stool. •  ECG monitoring for cardiac arrhythmias.

PATHOLOGIC FINDINGS Sudden death is common. Plant pieces are often found in the stomach and small intestine. Clotted blood may be present in the ventricles with a mottled appearance to the epicardium. Histopathology findings are similar to digoxin toxicosis.

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  TREATMENT

•  Emesis quickly after ingestion. •  Activated charcoal (1–2 g/kg) with a

cathartic × 1, followed by activated charcoal without a cathartic every 6–8 hours × 2 doses. •  Asymptomatic animals—hospitalize and monitor for 12 hours. •  Symptomatic animals—hospitalize and monitor with an ECG for 24 hours; administer appropriate IV fluids (dependent on serum potassium) to maintain blood pressure but not overload the CV system; monitor blood pressure closely, as hypotension may be persistent.

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  FOLLOW-UP

PATIENT MONITORING •  ECG and blood pressure monitoring for first 24 hours, then PRN. •  Strict attention to serum electrolytes. PREVENTION/AVOIDANCE

•  Identify and recognize plants. •  Oleander grows seemingly everywhere in

parts of the SW United States and off-leash dogs and cats should be monitored closely. POSSIBLE COMPLICATIONS Sudden death. EXPECTED COURSE AND PROGNOSIS

•  Good nursing care for 5–7 days. •  Prognosis is good with early and

appropriate care.

•  Cardiac arrhythmias prolong treatment and

hospitalization.

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  MISCELLANEOUS

ABBREVIATIONS •  AV = atrioventricular. •  CV = cardiovascular. •  Fab = fragment antigen binding. •  GI = gastrointestinal. INTERNET RESOURCES

•  http://www.petpoisonhelpline.com/poisons •  http://www.aspca.org/pet-care/animal-

poison-control/toxic-and-non-toxic-plants

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  MEDICATIONS

DRUG(S) OF CHOICE •  Digoxin-specific fragment antigen binding (Fab; Digibind®) may be useful in some cases, especially oleander toxicosis. •  Antiemetics if vomiting is severe or persistent— maropitant 1 mg/kg SC/IV/PO q24h in dogs and cats; ondansetron 0.5–1 mg/kg IV, SC, PO q8–12h in dogs and cats. •  Bradycardia—atropine 0.02–0.04 mg/kg IV/IM/SC in dogs and cats; repeat q4–6h as needed. •  Antiarrhythmics may be necessary in patients with ventricular dysrhythmias, evidence of poor perfusion, or who remain tachycardic despite IV fluid therapy— lidocaine: dogs, 2–4 mg/kg IV to effect. •  GI protectants as needed—H2 blockers such as famotidine (0.5–1 mg/kg PO/SC/IM/ IV q12h); omeprazole (0.5 mg/kg PO daily); or sucralfate (0.25–1 g PO q8h). CONTRAINDICATIONS/POSSIBLE INTERACTIONS Beta blockers and calcium channel blockers may have an additive effect on AV conduction and cause complete heart block.

­Suggested Reading

Eucher J. Cardiac glycosides. In: Hovda LR, Brutlag A, Poppenga RH, Peterson K, eds. Blackwell’s Five-Minute Veterinary Consult Clinical Companion: Small Animal Toxicology. Ames, IA: Wiley-Blackwell, 2016, pp. 760–769. Author Lynn R. Hovda Consulting Editor Lynn R. Hovda  Client Education Handout available online

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Cardiomyopathy, Arrhythmogenic Right Ventricular—Cats C ­

  BASICS

OVERVIEW Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare primary cardiomyopathy characterized by progressive atrophy of the right ventricular (RV) and/or right atrial (RA) myocardium, with replacement by fatty or fibrofatty tissue that may act as an arrhythmogenic substrate. The condition in cats typically manifests as signs of right-sided congestive heart failure (CHF) due to progressive RV dysfunction. A variety of arrhythmias have been observed in cats with ARVC; however, sudden death does not appear to be well recognized in this species. SIGNALMENT •  Cats. •  One study reported mean age at present­ ation of 7.3 years (range: 1–20 years). •  Breed or sex predilections unknown. SIGNS General Comments

Compared to dogs and humans, sudden death does not appear to be as well recognized in cats with ARVC, despite the wide variety of arrhythmias documented with this condition. Historical Findings

•  Lethargy. •  Anorexia. •  Dyspnea. •  Tachypnea. •  Abdominal distention may be noted.

Physical Examination Findings

•  Signs consistent with right-sided CHF. •  Dyspnea. •  Tachypnea. •  Jugular venous distention. •  Ascites. •  Heart and/or lung sounds may be muffled. •  Weak femoral pulses. •  Hepatosplenomegaly. •  Thoracic percussion may reveal presence of

pleural effusion. •  May auscult arrhythmia.

CAUSES & RISK FACTORS

•  Unknown. •  A genetic mutation in the striatin (desmosomal

protein) gene is associated with ARVC in some dogs. Genetic mutations are identified in approx­imately 60% of humans with ARVC, with mutations identified in at least 13 genes. Genetic studies in feline ARVC are lacking.

absence of myocardium in the RV free wall. Histopathology is required to distinguish this from ARVC and demonstrates apposing endocardial and epicardial surfaces, without any interposed adipose tissue or any evidence of inflammation or necrosis.

•  Focal or multifocal myocarditis. •  Apoptotic cardiomyocytes.

CBC/BIOCHEMISTRY/URINALYSIS Alanine aminotransferase may be elevated secondary to hepatic congestion.

the mainstay of treatment for clinically affected cats with ARVC. •  Anti-arrhythmic therapy is not routinely required, but in cases with hemodynamically significant arrhythmias, anti-arrhythmic drugs should be selected based on the suspected underlying mechanism of the arrhythmia.

IMAGING Radiographic Findings

•  Cardiomegaly, typically in regions of right

atrium and right ventricle; left atrial enlarge­ment may also be noted. •  Pleural effusion. •  Ascites. •  Pericardial effusion. •  Caudal vena caval dilation.

 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS Uhl’s anomaly—a congenital abnormality characterized by partial or complete

  TREATMENT

•  Medical management of right-sided CHF is

­

  MEDICATIONS

­

  FOLLOW-UP

See Congestive Heart Failure, Right-Sided.

Echocardiographic Findings

•  Severe RA and RV dilation. •  RV systolic dysfunction/hypoknesis. •  Tricuspid regurgitation. •  Paradoxical septal motion. •  Focal aneurysms may be observed in the

RV wall, often toward the apex.

•  Left atrial enlargement sometimes seen.

DIAGNOSTIC PROCEDURES ECG

•  A variety of various arrhythmias have been

observed in cats with ARVC.

•  Ventricular premature complexes (right-

sided or left-sided in origin).

•  Ventricular tachycardia. •  Atrial fibrillation. •  Supraventricular tachycardia. •  Ventricular premature complexes. •  Right bundle branch block. •  First-degree atrioventricular block. •  Third-degree atrioventricular block. •  RA and RV enlargement (tall P wave, deep

S waves in lead II), right axis deviation.

Paracentesis and Fluid Analysis

Fluid analysis of pleural or abdominal effusions typically reveals modified transudate consistent with right-sided CHF. PATHOLOGIC FINDINGS

PATIENT MONITORING Recheck when decompensation or other clinical signs develop. EXPECTED COURSE AND PROGNOSIS Prognosis appears to be very poor in cats identified with ARVC. Reported median survival time after development of clinical signs of approximately 1 month (range: 2 days to 4 months). Most cats die or are euthanized due to signs of right-sided CHF or thromboembolic complications.

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  MISCELLANEOUS

SEE ALSO •  Cardiomyopathy, Arrhythmogenic Right Ventricular—Dogs. •  Congestive Heart Failure, Right-Sided. ABBREVIATIONS

•  ARVC = arrhythmogenic right ventricular

cardiomyopathy.

Gross Pathology

•  CHF = congestive heart failure. •  RA = right atrial. •  RV = right ventricular.

are easily trans-illuminated.

­Suggested Reading

•  Moderate-to-severe RA and RV dilation. •  Severe thinning of RA and RV walls, which •  Left atrial dilation and rarely left ventricular

dilation may be seen in some cats.

•  Thrombi sometimes identified.

Histopathology

­

­

•  RV myocardial atrophy with replacement

by fatty or fibrofatty tissue.

•  Fibrosis may also be observed in right

atrium, left ventricular free wall, and interventricular septum.

Fox P, Maron B, Basso C, et al. Spontaneously occurring arrhythmogenic right ventricular cardiomyopathy in the domestic cat: a new animal model similar to the human disease. Circulation 2000, 102(15):1863–1870. Author Michael Aherne Consulting Editor Michael Aherne



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Cardiomyopathy, Arrhythmogenic Right Ventricular—Dogs •  Uncommon forms of acquired cardiac

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disease (neoplasia, endocarditis).

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  BASICS

OVERVIEW A myocardial disease commonly character­ ized by ventricular tachyarrhythmias that can be accompanied by syncope or sudden death. A small percentage (10 years of age. SIGNS •  Usually one of three presentations: ◦  Asymptomatic dog with ventricular premature complexes (VPCs) detected on routine examination. ◦  Syncope with VPCs detected on ECG or Holter monitor. ◦  Signs of left heart failure (e.g., tachypnea, coughing) or biventricular failure (e.g., ascites, tachypnea, coughing) with VPCs; this presentation is least common. •  Sudden death may occur before develop­ ment of obvious clinical signs. CAUSES & RISK FACTORS •  Adult onset, inherited (autosomal dominant). •  A genetic mutation (deletion) in a cardiac desmosomal gene (striatin) is associated with the development of the disease. Dogs that are homozygous for the striatin deletion appear to be more likely to be more severely affected with a higher number of VPCs, and are more likely to have cardiac dilation and myocardial dysfunction. Sudden death is more common. It is not yet known if this is the only genetic cause or if additional genetic mutations will be identified. •  At least one family of boxers with VPCs, ventricular dilation, and systolic dysfunction was found to have decreased myocardial l-carnitine levels and demonstrated some clinical improvement when supplemented with l-carnitine. The cause and effect of this relationship is unclear, and response to this supplementation does not occur in all dogs with myocardial dysfunction.

­

  DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Aortic stenosis—moderate and severe forms can be associated with VPCs.

•  Abdominal disease (especially splenic

disease) can be associated with VPCs.

•  Echocardiography and abdominal

ultrasonography can be used to differentiate other causes of cardiac and abdominal disease. OTHER LABORATORY TESTS •  Genetic testing can now be performed to screen for the genetic mutation (https://cvm. ncsu.edu/genetics) associated with arrhythmo­ genic right ventricular cardiomyopathy. Submission samples can be either a blood sample in an EDTA tube or a buccal swab of the oral mucosal surface. •  Plasma l-carnitine levels may be evaluated in boxers with ventricular dilation and systolic dysfunction. However, plasma levels are not always reflective of myocardial levels. If plasma levels are not low, it is still possible to have low myocardial levels, and supplementation with l-carnitine might be considered. IMAGING Thoracic Radiography

•  Normal in most affected dogs. •  Dogs with ventricular dilation and systolic

dysfunction may have cardiac enlargement and evidence of heart failure (e.g., pulmonary edema).

Echocardiography

•  Normal in most affected dogs. •  A small percentage of dogs have ventricular

dilation and systolic dysfunction, particularly if they are homozygous for the deletion mutation. DIAGNOSTIC PROCEDURES

ECG

•  Many dogs will not have VPCs on an ECG

of brief duration since the arrhythmia can be intermittent. However, some dogs will have one or more upright VPCs on a brief lead II ECG. •  In either case, if suspicion of disease is present, Holter monitoring is recommended to determine the severity and complexity of the arrhythmia and to have a baseline for comparison once treatment is started. If Holter monitoring is not available and the dog is symptomatic with upright VPCs on an ECG, therapy should be considered.

­

  TREATMENT

•  The goals of therapy include reduction of

the number of VPCs, reduction of clinical signs, and reduction of the risk of sudden cardiac death. Unfortunately, there is no evidence that therapy can reduce the risk of sudden death. The decision to start therapy in the asymptomatic boxer with VPCs is controversial, since all antiarrhythmics have the potential to make the arrhythmia worse. However, dogs with as few as 300 VPCs/24 hours have been observed to die suddenly. In general, initiate antiarrhythmic drugs if there are >1,000 VPCs/24 hours and/or significant runs of ventricular tachycardia or other signs of arrhythmia complexity (e.g., bigeminy, couplets), or clinical signs (syncope, exercise intolerance) related to the VPCs. •  Syncope and sudden cardiac death may be more frequently associated with stress and excitement. Reduce stress and effort when possible. There is no direct relationship between exercise restriction and survivability. Some dogs die while asleep. Thus, strict exercise restriction is not recommended.

­

 MEDICATIONS

DRUG(S) OF CHOICE •  The two best choices for treating the ventricular arrhythmia are sotalol (1.5– 2.0 mg/kg PO q12h) or mexiletine (5–6 mg/kg PO q8h). Some cases continue to have significant ventricular ectopy after treatment with one of these; such cases seem to respond well to the combination of sotalol and mexiletine. These drugs have different mechanisms and appear to work in a safe and complementary fashion. •  In dogs with systolic dysfunction and heart failure, consider treatment with furosemide, enalapril, pimobendan, spironolactone, and l-carnitine. CONTRAINDICATIONS/POSSIBLE INTERACTIONS Any antiarrhythmic drug has the potential to make an arrhythmia worse.

PATHOLOGIC FINDINGS

•  Gross pathology is nonspecific in most

cases. In a small percentage of cases, left and right ventricular dilation may be observed. •  Histopathologic abnormalities include a fatty and fibrous infiltrate into the right ventricular (and sometimes interven­ tricular and left ventricular) free wall.

­

  FOLLOW-UP

•  If possible, repeat the Holter monitor 2–3

weeks after starting therapy to evaluate for a response. Affected dogs can have an 85% day-to-day variability in VPC number before medications; therefore, a good response to therapy would be an 85% reduction in VPC number. It is also anticipated that the complexity of the arrhythmia (bigeminy,

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Cardiomyopathy, Arrhythmogenic Right Ventricular—Dogs (continued)

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trigeminy, couplets, triplets, runs of ventricular tachycardia) will be reduced once on therapy. It may not always be possible to achieve an 85% reduction in VPC number; in those cases an improvement in arrhythmia complexity and clinical signs would be reasonable goals. •  Annual Holter monitoring and echocardio­ graphy are suggested, since in some cases the disease can be progressive. •  Advise owners that dogs are always at risk of sudden death. However, the majority of affected dogs can be maintained on antiarrhy­

thmics for years with good quality of life. Dogs with systolic dysfunction and dilation have the worst prognosis, although some of these dogs do show improvement and a decreased rate of progression on l-carnitine supplementation.

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  MISCELLANEOUS

SYNONYMS Boxer cardiomyopathy.

SEE ALSO

•  Ventricular Premature Complexes. •  Ventricular Tachycardia.

ABBREVIATIONS

•  VPC = ventricular premature complex.

Author Kathryn M. Meurs Consulting Editor Michael Aherne



Canine and Feline, Seventh Edition

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Cardiomyopathy, Dilated—Cats

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  BASICS

DEFINITION •  Dilated cardiomyopathy (DCM) is a disease of the heart muscle characterized by systolic myocardial failure and a dilated, volumeoverloaded heart that leads to signs of congestive heart failure (CHF) or low cardiac output. •  Before 1987, DCM was the second most commonly diagnosed heart disease in cats. Most cats had a secondary DCM as a result of taurine deficiency. Primary idiopathic DCM is now an uncommon cause of heart disease in cats. PATHOPHYSIOLOGY

•  Histopathologically, the myocardium of

cats with idiopathic DCM has evidence of myocytolysis, fibrosis, myofibril fragmen­ tation, and vacuolization. Gross examination reveals global eccentric enlargement of all four cardiac chambers. •  These anatomic changes are associated with progressive myocardial systolic failure, decreased contractility, decreased compliance, and secondary mitral valve regurgitation due to mitral valve annular dilation. These changes are typically identified by echocardiography. •  Eventually, the chronic myocardial dysfunction leads to CHF and clinical signs. SYSTEMS AFFECTED •  Cardiovascular—DCM is a primary myocardial disease and primarily affects the heart and its ability to maintain an adequate cardiac output to maintain the body’s needs. •  Musculoskeletal—cats with DCM can present with aortic thromboembolism (ATE), which causes acute paraparesis or monoparesis. •  Renal/urologic—cats with DCM and CHF often have poor renal perfusion and commonly have prerenal azotemia. •  Respiratory—cats usually present with tachypnea or dyspnea due to CHF with DCM. These cats can develop both pulmonary edema and pleural effusion. GENETICS Because of the human experience with DCM, it is likely that feline DCM also has a genetic basis, either inherited or de novo, as the cause of the disease. No definitive mutation has been identified in the cat to date; however, a quantitative genetic evaluation of a large cattery suggested an inherited factor in the development of DCM. INCIDENCE/PREVALENCE Idiopathic feline DCM is relatively uncommon now that taurine is adequately supplemented in cat foods. A retrospective survey of 106 cats with feline myocardial disease from 1994 to 2001 from Europe revealed that DCM was diagnosed in approximately 10% of the cases

in this series. In the author’s experience, the prevalence of feline idiopathic DCM may be less than 10%. SIGNALMENT Species

Cat

Breed Predilections

Because the prevalence is low, breed predilections are not clearly defined. That said, the Burmese cat may have an increased incidence. Mean Age and Range

9 years (5–13 years). Predominant Sex

None. (One study cites a male predisposition, while another states a female overrepresentation.) SIGNS General Comments

•  Cats with idiopathic DCM usually present

for signs of CHF.

•  They are rarely diagnosed prior to onset of

clinical signs.

Historical Findings

•  Signs related to low cardiac output—

anorexia, weakness, depression.

•  Signs related to CHF—dyspnea, tachypnea. •  Signs related to ATE—sudden-onset pain

and paraparesis.

Physical Examination Findings

•  Heart rate can be fast, normal, or slow. •  Soft systolic heart murmur. •  Weak left cardiac impulse. •  Gallop sound. •  Possible arrhythmia. •  Hypothermia. •  Prolonged capillary refill time. •  Tachypnea. •  Quiet lung sounds (pleural effusion). •  Crackles (pulmonary edema). •  Ascites. •  Hypokinetic femoral pulses. •  Possibly, posterior paresis and pain as a

result of ATE.

CAUSES The underlying etiology of idiopathic DCM remains unknown, although a genetic predisposition has been identified in some families of cats. Taurine deficiency was a common cause of secondary myocardial failure before 1987.

­

  DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Taurine deficiency DCM; because primary idiopathic DCM and taurine deficiency have similar clinical presentations, cats with myocardial failure should be assumed to have

taurine deficiency until shown to be unresponsive to taurine. •  Myocardial failure secondary to long­ standing congenital or acquired left ventricular volume overload diseases. •  End-staged remodeled hypertrophic cardiomyopathy may manifest with a dilated hypocontractile heart. •  Arrhythmogenic right ventricular cardiomyopathy. CBC/BIOCHEMISTRY/URINALYSIS Many cats will have prerenal azotemia related to low cardiac output. OTHER LABORATORY TESTS

•  Ensure that thyroid concentrations are normal. •  Plasma taurine concentrations less than

40 nmol/L or whole blood taurine concentrations less than 250 nmol/L, are subnormal and suggestive of taurine deficiency DCM. Taurine assays are performed at a limited number of institutions and require special handling. •  Cardiac biomarkers such as plasma amine terminal B-type natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI) concentrations would be elevated in a cat with CHF due to idiopathic DCM. IMAGING Radiography

•  Radiography often shows pleural effusion

or pulmonary edema.

•  Generalized cardiomegaly.

Echocardiography

•  Diagnostic modality of choice. •  Characteristic findings include thin ventricular

walls, enlarged left ventricular end-systolic and end-diastolic dimensions, left atrial enlargement, and low fractional shortening. •  Pleural and pericardial effusion may be visualized. •  Spontaneous echocardiographic contrast or a thrombus may be visualized. DIAGNOSTIC PROCEDURES ECG

•  ECG may be normal or may show left atrial

or ventricular enlargement patterns.

•  Both ventricular and supraventricular

arrhythmias can be seen.

Pleural Effusion Analysis

•  Pleural effusion typically is a modified

transudate with total protein 2.5 mg/dL. •  Digoxin is optionally recommended to strengthen contractility and for its positive neurohumoral effects at a dose of 0.03 mg/ cat (one-fourth of a 0.125 mg tablet) or 0.01 mg/kg PO q48h. Digoxin can be given concurrently with pimobendan. However, digoxin is often omitted when pimobendan is given because of the difficulties in giving a cat several pills and digoxin’s side-effect profile. •  Dobutamine at extremely low dosages can be given to a patient with severe signs of CHF and low cardiac output that cannot take oral medications. Dose varies 0.25–5 μg/kg/ minute IV CRI. ECG monitoring is recommended. •  Because ATE is a concern, an antithrom­ botic agent is also recommended. Clopidogrel given at a dose of 18.75 mg (one-fourth of a 75 mg tablet) PO q24h is generally the author’s preferred antithrombotic agent. Other options include aspirin 81 mg PO q72h (with food) or low molecular weight heparin (e.g., dalteparin 100–150 units/kg SC q8–24h or enoxaparin 1 mg/kg SC q12–24h). •  Antiarrhythmic drugs may also be needed to control supraventricular or ventricular arrhythmias. If hemodynamically significant supraventricular tachycardia or rapid atrial fibrillation is present, diltiazem is recomm­ ended. Usually, diltiazem is given orally in either a non-sustained-release formulation (7.5 mg/cat PO q8h) or a sustained-release oral formulation (Cardizem CD® at 10 mg/kg PO q24h or Dilacor XR® 30 mg/cat [or 1/2 of an inner 60 mg tablet] PO q12h). Diltiazem is also available in an injectable formulation for urgent control of a supraventricular arrhythmia in a cat that cannot take oral medications (0.05–0.1 mg/kg slow IV, repeated PRN up to 0.25 mg/kg). If rapid and sustained ventricular tachycardia, lidocaine slow IV 0.2–0.5 mg/kg (repeat once or twice max) or sotalol PO 2 mg/kg q12h is recommended. •  Beta blockers, such as atenolol, may be useful in the chronic management of both

(continued)

supraventricular and ventricular arrhythmias. Beta blockers are used in the long-term management of DCM in humans because of their positive myocardial effects and survival benefit. Clinical experience is limited in feline DCM and they must be used cautiously, as they acutely decrease contractility and could worsen CHF. Recommended dose ranges from 3.125 to 6.25 mg PO q12–24h. Start low and titrate up based on heart rate and clinical signs. PRECAUTIONS

•  Unless needed for acute cardiac rhythm

control, drugs such as calcium channel blockers (diltiazem) or beta-adrenergic blockers may reduce contractility and lower cardiac output. Use cautiously. •  Overzealous diuretic and vasodilation therapy may cause azotemia and electrolyte disturbances. •  Digoxin should not be used if renal insufficiency is documented or suspected. •  Enalapril or benazepril should be used with caution and possibly withheld if serum creatinine is >2.5 mg/dL. •  Dobutamine may cause seizures and cardiac tachyarrhythmias.

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  FOLLOW-UP

PATIENT MONITORING •  Repeat examination with ideally blood pressure, diagnostic imaging (either a thoracic radiograph or focused thoracic ultrasound for fluid assessment), and chemistry panel within 1 week to determine response of therapy. •  Home resting respiratory rate monitoring is helpful to determine need for diuretic dose adjustment or thoracocentesis. •  Periodically monitor electrolyte and renal parameters. Periodically monitor for CHF fluid accumulation with diagnostic imaging. •  If using digoxin, serum blood concen­ trations should be measured approximately 10–14 days after initiating therapy. Therapeutic range is 0.5–1.5 ng/dL 8–12 hours post-pill. •  Repeat diagnostic echocardiogram in 2–3 months after initiating taurine supplemen­ tation to determine echocardiographic response to therapy. Although echocardio­ graphic response may take 2–3 months to assess, one should see dramatic clinical response within 2 weeks of initiating taurine therapy if cat has taurine-responsive DCM. PREVENTION/AVOIDANCE Ensure that cats eat a high-protein diet with sufficient dietary taurine. No vegetarian diets.



Canine and Feline, Seventh Edition



Cardiomyopathy, Dilated—Cats

(continued)

POSSIBLE COMPLICATIONS ATE is the most feared complication of any feline myocardial disease. EXPECTED COURSE AND PROGNOSIS •  These cats have a poor prognosis despite intensive therapy. If cat is not taurine responsive, survival is usually weeks to months. •  CHF can be medically refractory and recurrent despite appropriate medical therapy. •  Repeated thoracocentesis may be necessary.

SYNONYMS Cardiomyopathy SEE ALSO •  Aortic Thromboembolism. •  Congestive Heart Failure, Left-Sided. •  Congestive Heart Failure, Right-Sided. ABBREVIATIONS

•  ATE = aortic thromboembolism. •  CHF = congestive heart failure. •  cTnI = cardiac troponin I. •  DCM = dilated cardiomyopathy.

­Suggested Reading

­

  MISCELLANEOUS

ASSOCIATED CONDITIONS •  CHF. •  ATE. •  Pleural effusion. •  Cardiac arrhythmias.

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Ferasin L, Sturgess CP, Cannon MJ, et al. Feline idiopathic cardiomyopathy: a retrospective study of 106 cats (1994–2001). J Feline Med Surg 2003; 5:151–159. Hambrook LE, Bennett PF. Effect of pimobendan on the clinical outcome and survival of cats with non-taurine responsive dilated cardiomyopathy. J Feline Med Surg 2012; 14:233–239.

Kittleson MD. Feline myocardial disease. In: Ettinger SJ, Feldman EC, eds. Textbook of Veterinary Internal Medicine, 6th ed. St. Louis, MO: Elsevier, 2005, pp. 1082–1103. Lawler DF, Templeton AJ, Monti KL. Evidence of genetic involvement in feline dilated cardio­ myopathy. J Vet Intern Med 1993; 7:383–387. Pion PD, Kittleson MD, Rogers QR, et al. Myocardial failure in cats associated with low plasma taurine: a reversible cardiomyopathy. Science 1987; 237:764–768. Author Teresa C. DeFrancesco Consulting Editor Michael Aherne

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Cardiomyopathy, Dilated—Dogs SIGNALMENT

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Species

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  BASICS

DEFINITION Dilated cardiomyopathy (DCM) character­ ized by left- and right-sided dilation, normal coronary arteries, anatomically normal although commonly insufficient atrioventricular valves, significantly decreased inotropic state, and myocardial dysfunction occurring primarily during systole; however, progressive diastolic dysfunction with restrictive physiology may also be present and is a negative predictor of survival. PATHOPHYSIOLOGY •  Myocardial failure leads to reduced cardiac output and congestive heart failure (CHF). •  Atrioventricular (AV) annulus dilation and altered papillary muscle function promote valvular insufficiency. •  Although left-sided signs commonly predominate, evidence of severe right-sided disease can occur and infrequently is the dominant clinical scenario. SYSTEMS AFFECTED •  Cardiovascular. •  Renal/urologic—prerenal azotemia. •  Respiratory—pulmonary edema, infrequently pulmonary hypertension. •  All organ systems are affected by reductions in cardiac output. GENETICS

•  Genetic cause or heritable susceptibility

strongly suspected in most breeds and documented in some (Portuguese water dog, boxer, and Doberman pinscher) with variable forms of inheritance. •  A genetic test is commercially available for causative mutations in boxer dogs (striatin) and Doberman pinscher (NCSU DCM 1— pyruvate dehydrogenase kinase; NCSU DCM 2—titin). •  These mutations are not causative in other predisposed breeds in which they have been evaluated. •  Correlations between genotype and phenotype have shown that Doberman pinschers with both mutations have, on average, an earlier onset of clinical disease with a predisposition to sudden death; boxers homozygous for the mutation are more likely to develop the DCM phenotype. INCIDENCE/PREVALENCE Estimated at 0.5–1.1% in predisposed breeds and perhaps higher in specific geographic regions. GEOGRAPHIC DISTRIBUTION None with the exception of Chagas’ cardio­ myopathy, which is limited to the southern United States (Gulf Coast) and both Central and South America.

Dog

Breed Predilections

•  Doberman pinscher, boxer. •  Giant breeds—Scottish deerhound, Irish

wolfhound, Great Dane, St. Bernard, Newfoundland. •  Cocker spaniel, Portuguese water dog (juvenile). Mean Age and Range

4–10 years.

Newfoundland, and cocker spaniel; dietassociated DCM, which may be associated with taurine deficiency, commonly secondary to boutique, exotic-ingredient, or grain free (BEG) diets, is increasing recognized and potentially reversible. •  Viral, protozoal, and immune-mediated mechanisms have been proposed but not proven. •  Doxorubicin toxicity. •  Hypothyroidism and persistent tachy­ arrhythmias (sometimes associated with congenital tricuspid valve malformation) may cause reversible myocardial failure.

Predominant Sex

Males > females in most but not all breeds (minor predisposition). SIGNS Historical Findings

•  Respiratory—tachypnea, dyspnea,

coughing.

•  Weight loss, typically of lean muscle mass. •  Weakness, lethargy, anorexia. •  Abdominal distention. •  Syncope, usually associated with

arrhythmias (atrial fibrillation; ventricular tachycardia). •  Some dogs are asymptomatic, having what is termed preclinical DCM, the diagnosis of which in specific breeds is well described. •  Breed-specific echocardiographic parameters coupled with cardiac biomarkers (NT-proBNP; cardiac troponin I [cTnI]) may help identify dogs with preclinical DCM. Physical Examination Findings

•  May be completely normal with preclinical

DCM.

•  Weakness, possibly cardiogenic shock. •  Hypokinetic femoral pulse from low cardiac

output.

•  Pulse deficits with atrial fibrillation,

ventricular or supraventricular premature contractions, and paroxysmal ventricular tachycardia. •  Jugular pulses from tricuspid regurgitation, arrhythmias, or right-sided CHF. •  Breath sounds—muffled with pleural effusion; crackles with pulmonary edema. •  S3 or summation gallop sounds. •  Mitral and/or tricuspid regurgitation murmurs are common but usually focal and soft. •  Auscultatory evidence of cardiac arrhythmia is common. •  Slow capillary refill time, infrequent cyanosis. •  Hepatomegaly with or without ascites. CAUSES

•  Majority of cases represent familial

abnormalities of structural, energetic, or contractile cardiac proteins, some of which have been identified. •  Nutritional deficiencies (taurine and/or carnitine) have been documented in several breeds including golden retriever, boxer,

­

  DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Myxomatous valvular degeneration. •  Congenital heart disease. •  Heartworm disease. •  Bacterial endocarditis. •  Cardiac tumors and pericardial effusion. •  Airway obstruction—foreign body, neoplasm, laryngeal paralysis. •  Primary pulmonary disease—bronchial disease, pneumonia, neoplasia, aspiration, vascular disease (e.g., heartworms). •  Noncardiogenic pleural effusions (e.g., pyothorax, hemothorax, chylothorax). •  Trauma resulting in diaphragmatic hernia, pulmonary hemorrhage, hemothorax, pneumothorax. CBC/BIOCHEMISTRY/URINALYSIS Routine hematologic tests and urinalysis are usually normal unless altered by severe reductions in cardiac output or severe elevations in venous pressures (e.g., prerenal azotemia, high alanine aminotransferase, hyponatremia), therapy for heart failure (e.g., hyponatremia, hypokalemia, hypo­ chloremia, azotemia, and metabolic alkalosis from diuresis), or concurrent disease. OTHER LABORATORY TESTS Cardiac biomarkers including NT-proBNP and cTnI are elevated in both the preclinical and clinical stages of the disease. Clinical studies investigating use of these markers for diagnosis, prognosis, and optimization of therapy are ongoing. IMAGING Radiography

•  Typically normal in the preclinical phase. •  Generalized cardiomegaly and signs of

CHF are common.

•  Left ventricular (LV) enlargement and left

atrial enlargement may be most evident in early cases. •  In some cases, the degree of cardiomegaly may be less than expected for the severity of clinical signs; it is also often substantially less than would be expected in a dog with



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Cardiomyopathy, Dilated—Dogs

(continued)

primary valvular heart disease and comparable clinical signs. •  Pleural effusion, hepatomegaly, ascites. Echocardiography

•  Gold standard for diagnosis. •  LV dilation often precedes overt reductions

in indices of systolic function.

•  Ventricular and atrial dilation. •  Indices of myocardial systolic function

(fractional shortening [FS%]), ejection fraction, area shortening, and mitral annular motion by tissue Doppler imaging may be reduced. •  Spectral Doppler studies may confirm decreased velocity and/or acceleration of trans-aortic flow as well as mitral regurgitation and/or tricuspid regurgitation. •  Doppler evidence of restrictive LV filling is associated with decreased survival. DIAGNOSTIC TESTS ECG

DIET

•  During initial therapy for clinical signs,

simply maintaining adequate caloric intake is paramount. •  Goal—reduce dietary sodium intake to 0.06 second), possible increased voltages (R >3 mV lead II), suggesting LV enlargement. •  May have “sloppy” R wave descent with ST-T coving, suggesting myocardial disease or LV ischemia. •  May have low voltages (pleural or pericardial effusion, concurrent hypothyroidism).

DRUG(S) OF CHOICE First identify patient problems—CHF (left or right-sided), arrhythmia, hypothermia, renal failure, shock.

PATHOLOGIC FINDINGS •  Dilation of all chambers with or without thinning of chamber walls. •  Slightly thickened endocardium with pale areas within myocardium (necrosis, fibrosis). •  Two histologically distinct forms—fatty infiltration: degenerative type seen in boxers and Doberman pinschers; and attenuated wavy fiber type: seen in many giant-, large-, and medium-sized breeds, including some boxers and Doberman pinschers.

Initial Stabilization

­

  TREATMENT

APPROPRIATE HEALTH CARE With the exception of severely affected dogs (life-threatening arrhythmias, severe pulmonary edema, cardiogenic shock), most therapy can be administered on an outpatient basis. ACTIVITY Allow the dog to choose its own level of activity.

233

Preclinical Disease

•  There is clinical evidence (PROTECT Trial)

that early intervention with pimobendan monotherapy substantially changes the course of preclinical disease in Doberman pinschers. •  These results are routinely extrapolated to other breeds, but have not been proven. •  Critical evaluation suggests that early intervention with monotherapy using an angiotensin-converting enzyme (ACE) inhibitor is of minimal or no survival benefit in preclinical disease. •  Treat hypoxemia with oxygen adminis­

tration; prevent heat loss if hypothermic (warm environment). •  If pulmonary edema—furosemide (1–4 mg/kg IM/IV, then 1–2 mg/kg q6–12h for first 1–3 days), or CRI 1–2 mg/kg/h (author’s preference). •  2% topical nitroglycerin for first 24–48h for severe pulmonary edema—apply 1 inch–2 inches q8h (beware of hypotension in both patients and staff ). •  If significant pleural effusion—drain each hemithorax. •  If severe heart failure and cardiogenic shock—dobutamine may be indicated; this drug may exacerbate arrhythmias, particularly in hypoxic dogs; oral pimobendan (see dosing below) may have important acute (2–4h) hemodynamic benefit as well; IV pimobendan (0.15 mg/kg) is available in select countries. •  Dobutamine 5–15 μg/kg/min infused for 24–72h with care (start low and gradually up-titrate based on response).

•  If paroxysmal ventricular tachycardia is

present—administer lidocaine slowly in 2 mg/kg boluses (up to 8 mg/kg total over 30 min) to convert to sinus rhythm; follow with lidocaine infusion (50–100 μg/kg/min). •  If lidocaine is ineffective—administer procainamide slowly at dose of 2–5 mg/kg (up to 15 mg/kg) IV to convert to sinus rhythm; follow with 25–50 μg/kg/min CRI (beware of proarrhythmia and infrequently hypotension). Maintenance Therapy

•  ACE inhibitors (enalapril, benazepril,

lisinopril) are considered cornerstone of therapy for DCM. •  Enalapril (0.25–0.5 mg/kg PO q12h), benazepril (0.5 mg/kg PO q12–24h), or lisinopril (0.5 mg/kg PO q 12–24h) should be initiated early in the therapeutic regimen. •  Furosemide (1–4 mg/kg PO q8–12h) is used to control signs of congestion. •  Torsemide (0.1–0.4 mg/kg PO q8–12h) is commonly employed as an alternative to furosemide, particularly in later-stage disease. •  Spironolactone (1–2 mg/kg PO q12h) may impart an independent survival benefit by blocking aldosterone; higher doses can be used for refractory heart failure (2–4 mg/kg PO q12h). •  Hydrochlorthiazide (1–2 mg/kg PO q12h) may be beneficial as a third diuretic. •  Beta blockers can be used cautiously once heart failure is controlled with other drugs (see Precautions); if tolerated, they may improve myocardial function with chronic use; carvedilol (0.25–1.25 mg/kg PO q12h) is an alpha and beta blocker with antioxidant activity: start at the low end of the dose range and gradually up-titrate over a 6-week period if tolerated; consult with a cardiologist before using beta blockers in clinical DCM patients as can result in rapid and profound clinical deterioration. •  Pimobendan (0.25–0.3 mg/kg PO q12h) is a calcium-sensitizing drug and a vasodilating, positive inotrope (inodilator) that, when added to furosemide, ACE inhibitors, and spironolactone improves functional heart failure class and in Doberman pinschers increases survival time; the author has administered pimobendan 0.5 mg/kg PO q8h in refractory cases with perceived clinical benefit. •  The role of carnitine and taurine in therapy of DCM remains controversial; however, American cocker spaniels with DCM generally respond favorably to taurine and l-carnitine supplementation, but still require additional cardiac medications. Arrhythmias

•  In atrial fibrillation, slowing of ventricular

rate response typically achieved with chronic administration of extended-release diltiazem

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(Dilacor®) 2–7 mg/kg PO q12h, or atenolol 0.75–1.5 mg/kg PO q12h (never start in patient with active CHF), occasionally combined with digitalis at dose of 0.005 mg/ kg PO q12h; therapeutic drug monitoring recommended when administering digoxin. •  Therapeutic goal is obtaining resting ventricular rate of 100–140 bpm. •  At-home monitoring with AliveCor Kardia device. •  This therapy merely controls ventricular rate, by depressing atrioventricular nodal conduction; generally does not convert rhythm from atrial fibrillation to sinus rhythm. •  Amiodarone (10–15 mg/kg PO q24h for 7–10 days followed by 5–10 mg/kg PO q24h) may either control ventricular response rate or in some cases result in conversion to normal sinus rhythm. •  Chronic oral therapy for ventricular tachycardia includes sotalol (1–2 mg/kg PO q12h), mexiletine (5–10 mg/kg PO q8h), or amiodarone (5–10 mg/kg PO q24h). •  Mexiletine can be combined with sotalol if necessary. CONTRAINDICATIONS Digoxin should be avoided in severe uncontrolled paroxysmal ventricular tachycardia, in animals with compromised renal function, and in animals with important hypokalemia. PRECAUTIONS

•  Calcium channel blockers and notably beta

blockers are negative inotropes and may have acute adverse effect on myocardial function; numerous human studies, however, have suggested that chronic administration of beta blockers may be of benefit in DCM. •  Combination of diuretics and ACE inhibitors may result in azotemia, especially in patients with severe heart failure or preexisting renal dysfunction, and must be closely monitored.

POSSIBLE INTERACTIONS

•  Quinidine, amiodarone, and diltiazem may

increase serum digoxin levels and predispose to digitalis intoxication. •  Renal dysfunction, hypothyroidism, and hypokalemia predispose to digitalis intoxication. ALTERNATIVE DRUG(S) •  Other vasodilators, including hydralazine and amlodipine, may be used instead of or in addition to ACE inhibitors (beware of hypotension). •  Role of co-enzyme Q10, fish oil, and arginine remains to be determined.

­

  FOLLOW-UP

PATIENT MONITORING •  Serial clinical examinations, thoracic radiographs, blood pressure measurements, routine serum biochemical evaluations (including electrolytes), and electrocardio­ graphy are most helpful. •  Repeat echocardiography is rarely informative or indicated. •  Serial evaluation of serum digoxin levels (therapeutic range: 0.5–1 ng/mL) taken 6–8 hours post-pill and serum biochemistries may help prevent iatrogenic problems. POSSIBLE COMPLICATIONS

•  Sudden death due most commonly to

arrhythmias.

•  Iatrogenic problems associated with medical

management (see above).

EXPECTED COURSE AND PROGNOSIS

•  Always fatal unless associated with

nutritional deficiencies.

(continued)

survival following identification in preclinical phase averages over 700 days. •  Atrial fibrillation, paroxysmal ventricular tachycardia, Doppler evidence of restrictive LV filling, markedly decreased FS%, homo­­ zygosity for known mutations (boxer), or presence of multiple mutations (Doberman pinschers) are believed to be markers for shortened survival and increased risk for sudden arrhythmogenic death.

­

  MISCELLANEOUS

ASSOCIATED CONDITIONS Prevalence increases with age. SYNONYMS •  Congestive cardiomyopathy. •  Giant-breed cardiomyopathy. SEE ALSO

•  Atrial Fibrillation and Atrial Flutter. •  Ventricular Tachycardia.

ABBREVIATIONS

•  ACE = angiotensin-converting enzyme. •  AV = atrioventricular. •  BEG = boutique, exotic-ingredient, or grain

free.

•  CHF = congestive heart failure. •  cTnI = cardiac troponin I. •  DCM = dilated cardiomyopathy. •  FS% = percent fractional shortening. •  LV = left ventricular.

INTERNET RESOURCES https://cardiaceducationgroup.org Author Matthew W. Miller Consulting Editor Michael Aherne

•  Death usually occurs 6–24 months

following diagnosis.

•  Dobermans typically have worst prognosis;

however, with addition of pimobendan,

 Client Education Handout available online



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Cardiomyopathy, Hypertrophic—Cats Breed Predilections

­

  BASICS

DEFINITION Inappropriate concentric hypertrophy of the ventricular free wall and/or the interventricular septum of the nondilated left ventricle. The disease occurs independently of other cardiac or systemic disorders. PATHOPHYSIOLOGY •  Diastolic dysfunction results from a thickened, less compliant left ventricle. •  High left ventricular filling pressure develops, causing left atrial (LA) enlarge­ment. •  Pulmonary venous hypertension causes pulmonary edema. Some cats develop biventricular failure (i.e., pulmonary edema, pleural effusion, small volume pericardial effusion without tamponade, and infrequently ascites). •  Stasis of blood in the large left atrium predisposes the patient to aortic thrombo­ embolism (ATE). •  Dynamic aortic outflow obstruction and systolic anterior mitral motion (SAM) with secondary mitral insufficiency may occur, but unlike in humans, appears not to affect prognosis. •  Recent evidence suggests that some cats with apparent hypertrophic cardiomyopathy (HCM) and congestive heart failure (CHF) actually have transient myocardial thickening, often associated with high serum troponin I concentrations. These cats are younger than average for HCM, with on average less severe left ventricular (LV) hypertrophy, and they can experience resolution of both CHF and LV hypertrophy. SYSTEMS AFFECTED •  Cardiovascular—CHF, ATE, and arrhythmias. •  Pulmonary—dyspnea if CHF develops. •  Renal/urologic—prerenal azotemia. GENETICS Some families of cats have been identified with a high prevalence of the disease, and the disease appears to be an autosomal dominant trait in Maine coon cats and ragdoll cats, due to a mutation in the myosin-binding protein C (MyBPC) gene. The genetics have not been definitively determined in other breeds; however, the Maine coon and ragdoll mutations have not been identified in affected Sphynx, Norwegian forest cats, Bengals, Siberians, or British shorthair cats. INCIDENCE/PREVALENCE Unknown, but relatively common. May be as high as 15% of the population. SIGNALMENT Species

Cat

Maine coon cats, ragdolls, Sphynx, British and American shorthairs, and Persians. Mean Age and Range

C ­

  DIAGNOSIS

•  5–7 years, with reported ages of 3 months–

DIFFERENTIAL DIAGNOSIS •  Other forms of cardiomyopathy. •  Hyperthyroidism. •  Aortic stenosis. •  Systemic hypertension. •  Acromegaly. •  Noncardiac causes of pleural effusion.

Predominant Sex

•  Results usually normal. •  Prerenal azotemia in some animals.

17 years. Some breeds of cats including ragdolls and Sphynx may develop the disease at a younger age (average of 2 years). •  HCM is most often a disease of young to middle-aged cats; unexplained murmurs in geriatric cats are more likely associated with hyperthyroidism or hypertension. Male

SIGNS Historical Findings

•  Dyspnea, tachypnea. •  Anorexia. •  Exercise intolerance. •  Vomiting. •  Collapse. •  Sudden death. •  Coughing is uncommon in cats with HCM

and suggests primary pulmonary disease.

Physical Examination Findings

•  Gallop rhythm (S3 or S4). •  Systolic murmur in approximately half of

affected cats.

•  Apex heartbeat may be exaggerated. •  Muffled heart sounds, lack of chest

compliance, and dyspnea characterized by rapid shallow respirations may be associated with pleural effusion. •  Dyspnea and crackles if pulmonary edema is present. •  Weak femoral pulse. •  Acute pelvic limb paralysis with cyanotic pads and nailbeds, cold limbs, and absence of femoral pulse in animals with ATE; emboli rarely affect thoracic limbs. •  Arrhythmia in some animals. •  May have no clinical signs. CAUSES

•  Usually unknown—multiple causes exist. •  MyBPC mutations in some cats with HCM.

Possible Causes

•  Abnormalities of contractile protein myosin

or other sarcomeric proteins (e.g., troponin, myosin-binding proteins, tropomyosin). •  Abnormality affecting catecholamineinfluenced excitation contraction coupling. •  Abnormal myocardial calcium metabolism. •  Collagen or other intercellular matrix abnormality. •  Growth hormone excess. •  Dynamic LV outflow obstruction may contribute to secondary LV hypertrophy. RISK FACTORS Offspring of animals with familial mutations of MyBPC.

CBC/BIOCHEMISTRY/URINALYSIS

OTHER LABORATORY TESTS

•  MyBPC assay; mutation differs for Maine

coon cats and ragdoll cats.

•  In cats >6 years old, check thyroid hormone

concentration; hyperthyroidism causes myocardial hypertrophy that might be confused with HCM. •  Serum NT-proBNP concentrations higher in cats with HCM than in normal cats, and higher still in cats with symptomatic HCM. SNAP NT-proBNP point-of-care testing is also available to help differentiate symptomatic cats with HCM from those that are sympto­matic from other causes. Send-out serum NT-proBNP testing is useful in identifying cats with suspicion of HCM from asymptomatic cats with abnormal physical exam findings (e.g., murmur). Follow-up echocardiography indicated in cats with serum NT-proBNP concentrations in “equivocal” or “high” range, or positive SNAP results. IMAGING Radiography

•  Dorsoventral radiographs often reveal a

valentine-appearing heart because of atrial enlargement and a left ventricle that comes to a point. •  Pulmonary edema, pleural effusion, or both in some animals. •  Radiographs may be normal in asymptomatic cats. •  Different forms of cardiomyopathy cannot be reliably differentiated by radiography. Echocardiography

•  Hypertrophy of interventricular septum

(IVS) or LV posterior wall (diastolic wall thickness >6 mm). •  Hypertrophy may be symmetric (affecting IVS and posterior wall) or asymmetric (affecting IVS or posterior wall, but not both). •  Hypertrophy of papillary muscles. •  Normal or high fractional shortening. •  Normal or reduced LV lumen. •  LA enlargement. •  Systolic anterior motion of mitral valve (some animals). •  LV outflow obstruction (some animals); specialized Doppler studies performed by

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experienced sonographers often reveal LV relaxation abnormalities (e.g., mitral inflow E : A wave reversal). •  Thrombus in left atrium (rare). •  Note: there is some overlap between normal cats (especially ketaminized or dehydrated) and cats with mild HCM. Correlate echo findings with physical findings. Presence of LA enlargement favors HCM.

DRUG(S) OF CHOICE

DIAGNOSTIC PROCEDURES

Furosemide

ECG

•  Sinus tachycardia (heart rate >240) common

clopidogrel and any of those medications, minimize potential for trauma and subsequent hemorrhage.

­

  MEDICATIONS

•  Dosage—1–2 mg/kg PO/IM/IV q8–24h. •  Critically dyspneic animals often require

with heart failure; however, some cats with severe heart failure and hypothermia are bradycardic. •  Atrial and ventricular premature complexes seen more often in cats with cardiomyopathy, but also occasionally seen in normal cats. •  Atrial fibrillation seen in some advanced cases. •  Left axis deviation often seen. •  Prolongation of QT interval and QTc (QT interval corrected for heart rate) often seen with LV hypertrophy. •  Cannot differentiate different forms of cardiomyopathy; may be normal.

high dosage (4 mg/kg IV); this dose can be repeated in 1 hour if cat still severely dyspneic; indicated to treat pulmonary edema, pleural effusion, and ascites. •  Cats are sensitive to furosemide and prone to dehydration, prerenal azotemia, and hypokalemia. •  Once pulmonary edema resolves, taper to lowest effective dose.

Systemic Blood Pressure

CHF (e.g., pulmonary edema or pleural effusion) in cats with HCM, possibly by enhancing diastolic function and LA fractional shortening; not used in management of asymptomatic HCM at this time. •  Not currently licensed for use in cats.

•  Normotensive or hypotensive. •  Evaluate blood pressure in all patients with

myocardial hypertrophy to rule out systemic hypertension as cause of hypertrophy.

PATHOLOGIC FINDINGS •  Nondilated left ventricle with hypertrophy of IVS or LV free wall. •  Hypertrophy of papillary muscles. •  LA enlargement. •  Mitral valve thickening. •  Myocardial hypertrophy with disorganized alignment of myocytes (myofiber disarray). •  Interstitial fibrosis. •  Myocardial scarring. •  Hypertrophy and luminal narrowing of intramural coronary arteries.

­

  TREATMENT

APPROPRIATE HEALTH CARE Cats with CHF should be hospitalized. NURSING CARE •  Minimize stress. •  Oxygen if dyspneic. •  Warm environment if hypothermic. ACTIVITY Restricted with CHF. DIET Modest to moderate sodium restriction in animals with CHF. CLIENT EDUCATION

•  Many cats diagnosed while asymptomatic

eventually develop CHF and may develop ATE and die suddenly. •  If cat is receiving warfarin, dalteparin, enoxaparin (Lovenox®), or combination of

Pimobendan

•  Dosage—0.25–0.3 mg/kg PO q12h. •  Appears to be useful in management of

Angiotensin-Converting Enzyme (ACE) Inhibitors •  Dosage—enalapril or benazepril 0.25–

0.5 mg/kg PO q24h.

•  Indications in cats with HCM not well

defined—authors currently use for CHF.

(continued) •  Depresses platelet aggregation, hopefully

minimizing risk of thromboembolism.

•  Warn owners that thrombi can still

develop despite aspirin administration; aspirin appears to be not as effective as clopidogrel (1/4 of 75 mg tablet PO q24h) in prevention of ATE, at least in cats with previous embolic episode.

Nitroglycerin Ointment

•  Dosage—one-fourth inch/cat topically

applied q6–8h or 2.5 mg/24h patch.

•  Often used in acute stabilization of cats with

severe pulmonary edema or pleural effusion.

•  When used intermittently, may be useful

for long-term management of refractory cases. CONTRAINDICATIONS Avoid beta blockers in cats with emboli; these agents cause peripheral vasoconstriction. If beta blockers must be used in this setting for arrhythmia control, choose beta-1 selective blocker such as atenolol. PRECAUTIONS Use ACE inhibitors cautiously in azotemic animals. ALTERNATIVE DRUG(S)

Torsemide

•  Dosage—0.1–0.5 mg/kg q24h, sometimes

with dose escalation to q12h.

•  Used as substitute for furosemide in

refractory pulmonary edema or pleural effusion in cats with apparently normal (or at least stable) renal function. •  Monitor renal function closely in first days after switching to torsemide. Spironolactone

•  Dosage—atenolol (6.25–12.5 mg/cat PO

•  Dosage—1 mg/kg q12–24h. •  Used in conjunction with furosemide in

•  Beneficial effects may include slowing of

•  May cause facial pruritis.

Beta Blockers

q12h).

sinus rate, correcting atrial and ventricular arrhythmias, platelet inhibition. •  More effective than diltiazem in controlling dynamic outflow tract obstruction. •  Role in asymptomatic patients unresolved, but many clinicians use if dynamic outflow obstruction and hyper­ trophy present. •  Contraindicated in presence of CHF. Diltiazem

•  Dosage—7.5–15 mg/cat PO q8h or 10 mg/kg PO q24h (Cardizem® CD) or 30 mg/cat q12h (Dilacor XR®). •  Beneficial effects may include slower sinus rate, resolution of supraventricular arrhythmias, improved diastolic relaxation, coronary and peripheral vasodilation, platelet inhibition. •  May reduce hypertrophy and LA dimensions in some cats. •  Role in asymptomatic patients unresolved.

Aspirin

•  Dosage—81 mg/cat q2–3 days if severe

atrial enlargement.

cats with CHF, especially refractory effusions.

Warfarin and Low Molecular Weight Heparin

•  Used sometimes in cats at high risk for

thromboembolism.

•  See Aortic Thromboembolism.

Clopidogrel

•  Dosage—18.75 mg/cat/day. •  Platelet function inhibitor, superior to

aspirin in cats with previous ATE.

Beta Blocker plus Diltiazem

•  Cats that remain tachycardic on a single

agent can be treated cautiously with a combination of a beta blocker and diltiazem. •  Monitor for bradycardia and hypotension.

­

  FOLLOW-UP

PATIENT MONITORING •  Observe closely for dyspnea, lethargy, weakness, anorexia, and painful posterior paralysis or paresis.



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(continued)  •  If treating with warfarin, monitor prothrom­bin time. •  If treating with ACE inhibitor or spirono­ lactone, monitor renal function and electrolytes. •  Repeat echocardiogram in 6 months to assess efficacy of treatment for hypertrophy. If beta blocker or diltiazem was prescribed in asymptomatic animal and there is evidence of progressive hypertrophy/LA enlargement, consider switching to another class of medications (or adding an ACE inhibitor) and recheck 4–6 months later. •  Echocardiographic evaluations that reveal LA diameters >2 cm or loss of LV systolic function should prompt more aggressive prophylaxis against ATE (e.g., clopidogrel with low molecular weight heparin).

PREVENTION/AVOIDANCE Avoid stressful situations that might precipitate CHF. POSSIBLE COMPLICATIONS •  Heart failure. •  ATE and paralysis. •  Cardiac arrhythmias/sudden death. EXPECTED COURSE AND PROGNOSIS

•  Animals homozygous for MyBPC mutations

more likely to develop severe HCM and at earlier age than heterozygous animals. •  Prognosis varies considerably, probably because there are multiple causes. In one study of cats with HCM living at least 24 hours following presentation:

∘∘ Asymptomatic cats—median survival

563 days (range: 2–3,778 days). ∘∘ Cats with syncope—median survival 654 days (range: 28–1,505 days). ∘∘ Cats with CHF—median survival 563 days (range: 2–4,418 days). ∘∘ Cats with ATE—median survival 184 days (range: 2–2,278 days). ∘∘ Older age and larger left atria predicted shorter survival.

­

  MISCELLANEOUS

ASSOCIATED CONDITIONS Aortic thromboembolism. PREGNANCY/FERTILITY/BREEDING •  High risk of complications. •  Avoid aspirin. SEE ALSO

•  Aortic Thromboembolism. •  Congestive Heart Failure, Left-Sided. •  Hypersomatotropism/Acromegaly in Cats. •  Hypertension, Systemic Arterial. •  Hyperthyroidism. •  Murmurs, Heart.

ABBREVIATIONS

•  ACE = angiotensin-converting enzyme. •  ATE = aortic thromboembolism. •  CHF = congestive heart failure. •  HCM = hypertrophic cardiomyopathy. •  IVS = interventricular septum.

•  LA = left atrial. •  LV = left ventricular. •  MyBPC = myosin-binding protein C. •  QTc = QT interval corrected for heart rate. •  SAM = systolic anterior mitral motion.

­Suggested Reading

Fox PR, Keene BW, Lamb K, et al. International collaborative study to assess cardiovascular risk and evaluate long-term health in cats with preclinical hypertrophic cardiomyopathy and apparently healthy cats: the REVEAL study. J Vet Intern Med 2018, 32(3):930–943. McDonald K. Feline cardiomyopathy. In: Smith FWK, Tilley LP, Oyama MA, Sleeper MM, eds. Manual of Canine and Feline Cardiology, 5th ed. St. Louis, MO: Saunders Elsevier, 2016, pp. 153–180. Novo Matos J, Pereira N, Glaus T, et al. Transient myocardial thickening in cats associated with heart failure. J Vet Intern Med 2018, 32(1):48–56. Romito G, Guglielmini C, Mazzarella MO, et al. Diagnostic and prognostic utility of surface electrocardiography in cats with left ventricular hypertrophy. J Vet Cardiol 2018, 20(5):364–375. Authors Francis W.K. Smith, Jr., Bruce W. Keene, and Kathryn M. Meurs Consulting Editor Michael Aherne  Client Education Handout available online

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Cardiomyopathy, Hypertrophic—Dogs •  Thyrotoxicosis. •  Mitral dysplasia.

C ­

  BASICS

OVERVIEW Hypertrophic cardiomyopathy (HCM) is defined as inappropriate myocardial hypertrophy of a nondilated left ventricle, occurring in the absence of an identifiable stimulus. HCM is rare in dogs, and is characterized by left ventricular (LV) concentric hypertrophy (increased wall thickness). The primary disease process is confined to the heart and only affects other organ systems when congestive heart failure (CHF) is present. Increased LV wall thickness leads to impaired ventricular filling (due to lack of compliance and abnormal relaxation), with resultant increases in LV end-diastolic pressure and left atrial (LA) pressure. LA enlargement is usually in response to increased LV end-diastolic pressure. Mitral insufficiency and/or dynamic LV outflow tract obstruction commonly occur secondary to structural and/or functional changes of the mitral valve apparatus caused by papillary muscle malalignment due to hyper­trophy. SIGNALMENT

•  The incidence of HCM in dogs is very low,

thus accurate accounts of signalment are lacking. •  Young ( dogs). • Bacterial infection— common; retrograde duct bacterial invasion from intestines or hematogenous dispersal from splanchnic circulation. • Toxoplasmosis and biliary coccidiosis—rare causes. • Necrotizing cholecystitis (dogs)—ruptured GB (common, often secondary to cholelithiasis or hypermature GBM); E. coli and Enterococcus spp.: common isolates. • Emphysematous cholecystitis/choledochitis— rare, associated with diabetes mellitus, traumatic GB ischemia, acute cholecystitis (with or without cholelithiasis); common gas-forming organisms: Clostridia spp. and E. coli.

­

DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  EHBDO. • GBM. • Cholelithiasis. • Cholangitis/cholangiohepatitis. • Pancreatitis. • Focal or diffuse peritonitis. • Bile peritonitis. • Gastroenteritis with biliary involvement. • Hepatic necrosis or abscessation. • Septicemia. CBC/BIOCHEMISTRY/URINALYSIS

•  Variable leukocytosis with toxic neutrophils

and inconsistent left shift if necrosis or sepsis. • High bilirubin and bilirubinuria common. • High alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and γ-glutamyl transferase (GGT) activity. • Low albumin with peritonitis. • High cholesterol and bilirubin if EHBDO. • Hypercholesterolemia and/or hypertriglyceridemia—breed related, endocrine related, pancreatitis, nephrotic syndrome, EHBDO, GBM. OTHER LABORATORY TESTS

•  Abdominocentesis—inflammatory effusion

(see Bile Peritonitis). • Bile culture (dogs and cats)—E. coli, Enterococcus spp., Klebsiella spp., Pseudomonas spp., Clostridium spp., many others. • Coagulation tests—abnormal if chronic EHBDO (vitamin K deficiency) or disseminated intravascular coagulation (DIC) in severe conditions with sepsis; cats display coagulopathy with EHBDO early.

(“kiwi sign”) in mature GBM; GB rupture implicated by discontinuous GB wall, pericholecystic fluid, or generalized effusion, and hyperechogenicity of pericholicystic tissue; failure to image GB: may implicate rupture or agenesis; mineralized GB wall may indicate dystrophic mineralization (limey or porcelain GB) due to chronic cholecystis often associated with sacculated GB or bile ducts in DPM: Caroli’s phenotype; intrahepatic bile ducts may be difficult to visualize or be thick and prominent: ascending cholangitis or EHBDO (dilated ducts, “too many tubes signs” defined with color-flow Doppler); pericholecystic fluid: necrotizing cholecystitis and surgical emergency. • Choledochitis involving common bile duct (CBD)—thick wall, intraluminal debris, extends into hepatic ducts. PATHOLOGIC FINDINGS

•  Gross appearance—erythematous GB; may

appear green-black if necrotizing lesion; tenacious “inspissated” biliary material common with GBM; pigmented choleliths if infection; dark black or frank blood if hemobilia; CBD with thick wall, variable intraductal debris (e.g., biliary particulates, cholelithiasis, suppurative inflammation). • Microscopic features of GBM without cholecystitis are benign, with wall thinning, mucosal cystic hyperplasia, elongated mucosal fronds extending from flattened mucosa, without granulation response in GB wall; if chronic GBM may involve arterial thrombi and/or transformation to chronic cholecystitis. • Microscopic features of cholecystitis include inflammatory infiltrates in lamina propria (lymphoplasmacytic or suppurative with macrophages, rarely eosinophilic, occasional lymphoid follicular hyperplasia), intraluminal suppurative/necrotic debris; if chronic cholecystitis—submucosal ­granulation tissue with variable ulcerative/ necrotic mucosa, occasional hemobilia, occasional arterial thrombi; if cholelithiasis— hyperplastic mucosa with dense elongated mucosal fronds and glands contrasting with flattened appearance of GBM.

IMAGING

•  Abdominal radiography—may reveal loss of

cranial abdominal detail with focal or diffuse peritonitis or effusion; ileus; radiodense choleliths; gas in biliary structures; radiodense GB (dystrophic mineralization due to chronic inflammation; porcelain GB is rare). • Ultrasonography—diffusely thick GB wall, segmental hyperechogenicity and/or laminated wall or double-rimmed GB wall observed with necrotizing cholecystitis; double-rimmed GB wall also observed with acute cholecystitis, hepatitis, cholangiohepatitis; GB lumen filled with amorphous echogenic stellate or finely striated pattern, resembling sliced kiwi fruit

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TREATMENT

•  Inpatient—provision of critical care during

diagnostic/presurgical evaluations or if septic. • Place IV catheter in peripheral vein for polyionic fluids and blood component therapy as needed. • Restore fluid and electrolyte balance; monitor electrolytes frequently. • Vitamin K—if jaundiced; give parenterally (see Medications) before surgical interventions, cystocentesis, jugular venipuncture, other iatrogenic trauma. • Plasma—preferred colloid; indicated if hypoalbuminemia and coagulopathy or if anticipated surgical

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interventions and complicating coagulopathy uncorrected. • Whole blood or fresh frozen plasma—for surgical cases with bleeding tendencies; if septic, artificial colloids may delay recovery; if bleeding, some artificial colloids impair platelet aggregation. • Monitor urine output. • Remain vigilant for vasovagal reflex (abrupt bradycardia, hypotension, cardiac arrest) during biliary tree manipulation or cholecystocentesis; be prepared with anticholinergics (atropine) and pressor drugs. • Remain vigilant for cholangiovenous reflux—systemic dispersal of endotoxin or bacteria while handling septic biliary tree: give IV antibiotics promptly (but after culture collection). • GB resection advised for cholecystis, best based on surgical evaluations, ultrasound images, bedside cytology of bile—bacterial infection mandates cholecystec­tomy.

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MEDICATIONS

DRUG(S) OF CHOICE •  Antibiotics—before surgery; broad spectrum; surgical manipulations may cause bacteremia; select antibiotics for Enterococcus spp., enteric Gram-negative and anaerobic flora; refine treatment using culture and sensitivity results; good initial choice is triad combination of metronidazole, ticarcillin (or clavamox), and a fluorinated quinolone; reduce standard dose for metronidazole by 50% if cholestatic jaundice. • Ursodeoxycholic acid—10–15 mg/ kg PO daily divided BID with food; requires decompression of EHBDO prior to treatment. • Antioxidants—vitamin E (α-tocopherol acetate): 10 IU/kg (see Bile Duct Obstruction (Extrahepatic); use water-soluble form if EHBDO); S-adenosylmethionine (SAMe): use enteric-coated bioavailable product; on empty stomach: used as glutathione (GSH) donor (20 mg/kg PO q24h), 2h before

feeding; nonbile acid-dependent (GSH) choleresis (40 mg/kg PO q24h); n-acetylcysteine (NAC) IV if oral administration of antioxidants not possible; loading dose 140 mg/kg IV over 20 min, follow by 70 mg/ kg over 20 min q6–8h. • Vitamin K1—0.5– 1.5 mg/kg SC/IM q12h for 3 doses; caution: never administer IV (anaphylactoid reaction); treat early to allow response before surgical manipulations. CONTRAINDICATIONS/POSSIBLE INTERACTIONS Ursodeoxycholic acid—contraindicated in uncorrected EHBDO or bile peritonitis.

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FOLLOW-UP

PATIENT MONITORING •  After critical crisis resolution and surgery— physical examination and pertinent diagnostic testing: repeat every 1–2 weeks until abnorm­alities resolve. • If septic—continue anti­ biotics until enzymes, hyperbilirubinemia, leukocytosis, left shift, and fever resolve. POSSIBLE COMPLICATIONS Anticipate protracted clinical course with ruptured biliary tract or peritonitis; postoperative pancreatitis.

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MISCELLANEOUS

ASSOCIATED CONDITIONS •  Cholelithiasis. • DPM. • EHBDO. • GBM. • Bile peritonitis. AGE-RELATED FACTORS Congenital malformations of biliary structures do not predispose patients to cholecystitis, but do predispose to choledochitis and cholelithiasis that lead to GB disease and infection.

(continued)

ZOONOTIC POTENTIAL Campylobacter and Salmonella may cause cholecystitis in dogs; advise owner if diagnosed. SEE ALSO

•  Bile Peritonitis. •  Gallbladder Mucocele.

ABBREVIATIONS

•  ALP = alkaline phosphatase. •  ALT = alanine aminotransferase. •  AST = aspartate aminotransferase. •  CBD = common bile duct. •  DIC = disseminated intravascular

coagulation. •  DPM = ductal plate malformation. •  EHBDO = extrahepatic bile duct obstruction. •  GB = gallbladder. •  GBM = gallbladder mucocele. •  GGT = γ-glutamyltransferase. •  GSH = glutathione. •  NAC = n-acetylcysteine. •  SAMe = S-adenosylmethionine.

­Suggested Reading

Center SA. Diseases of the gallbladder and biliary tree. Vet Clin North Am Small Anim Pract 2009, 39(3):543–598. Lawrence YA, Ruaux CG, Nemanic S, et al. Characterization, treatment, and outcome of bacterial cholecystitis and bactibilia in dogs. J Am Vet Med Assoc 2015, 246:982–989. Tamborini A, Jahns H, McAllister H, et al. Bacterial cholangitis, cholecystitis, or both in dogs. J Vet Intern Med 2016, 30:1046–1055. Author Sharon A. Center Consulting Editor Kate Holan



267

Canine and Feline, Seventh Edition

Cholelithiasis •  Fused feline pancreatic and bile duct

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BASICS

OVERVIEW •  Radiopaque or radiolucent calculi in common bile ducts (CBD), gallbladder (GB), or less commonly in intrahepatic bile ducts (hepatolithiasis); gallbladder mucocele (GBM) qualifies as a form of cholelithiasis (see Gallbladder Mucocele). •  May be asymptomatic. •  Symptomatic—signs reflect sludging of bile, extrahepatic bile duct obstruction (EHBDO), cholecystitis, cholangiohepatitis, or bile peritonitis. •  Primary constituents of choleliths—mucin, glycoprotein, calcium carbonate, and bilirubin pigments; while dog bile is less lithogenic than human bile (lower cholesterol saturation), dog bile forms calcium bilirubinate sludge upon fasting. •  50% feline choleliths are mineralized; may be radiographically visible (calcium carbonate). •  Surgical treatment—not recommended without clinical signs or clinicopathologic abnormalities (current or historical), with the exception of preemptive GBM removal. SIGNALMENT

•  Cat and dog. •  Small-breed dogs may be predisposed;

animals with ductal plate malformations (DPM) predisposed: particularly Caroli DPM phenotypes (i.e., malformative dilated large ducts causing bile stasis in sacculated ducts); microhepatolithiasis encountered more often in DPM. •  Hyperlipidemic and hypercholesterolemic dogs—predisposed to GBM; may relate to endocrine disorders, idiopathic condition, or other disorders (see Gallbladder Mucocele). SIGNS

•  May be asymptomatic. •  When accompanied by infection or causing

intermittent or complete EHBDO (with or without peritonitis)—vomiting; meal-related discomfort, vague abdominal pain; fever; ± jaundice. •  Episodic vague peri- or postprandial abdominal pain or behavior seeking position of relief. CAUSES & RISK FACTORS

•  Predisposing factors—stasis of bile flow:

GB dysmotility, choledochal cysts (cat especially, form of DPM); lith nidus may evolve from inflammatory debris, infection, epithelial irregularity/exfoliation, neoplasia, residual suture material; bile supersaturation: heme-bilirubin pigments, hemobilia, calcium-bilirubinate, enhanced mucin production (inflammation, prostaglandins), cholesterol.

predisposes to concurrent biliary/pancreatic cholelithiasis, choledochitis, and bile stasis progressing to EHBDO as well as cholelithinitiated pancreatitis or signs mistaken for pancreatitis. •  Bile sludge associated with GB distention— may enhance mucin production and coalescence of bile particulates increasing risk for choleliths; but EHBDO does not cause choleliths. •  Inflammatory mediators and bacterial enzymes associated with cholecystitis— increase risk for stone precipitation. •  Hemobilia—bleeding into GB or bile ducts or chronic hemolysis can lead to heme-­ initiated cholelith formation. •  Low-methionine and high-cholesterol experimental diet in dogs is proven lithogenic.

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DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  EHBDO—inflammatory, infectious, or neoplastic conditions involving liver, CBD, or extrahepatic tissues adjacent to porta hepatis; suggested by marked increases in alkaline phosphatase (ALP), γ-glutamyltransferase (GGT), bilirubin, and gradual increase in cholesterol. •  Cholangiohepatitis. •  Cholecystitis/choledochitis. •  Bile peritonitis. •  GBM. •  Consequence of DPM. •  Chronic hypercalcemia may increase risk. CBC/BIOCHEMISTRY/URINALYSIS •  May have no clinicopathologic abnormalities—asymptomatic cholelithiasis. •  CBC—may be normal; may reflect bacterial infection, endotoxemia, biliary obstruction, or other underlying causal factors; inflammatory leukogram in some cases. •  Biochemistry—if symptomatic: variable hyperbilirubinemia, increase ALP, GGT, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) activities; also see Bile Duct Obstruction (Extrahepatic). OTHER LABORATORY TESTS

•  Bacterial culture—bile: aerobic and

anaerobic bacteria often confirmed in symptomatic patients if crushed cholelith, sludged bile, ± GB wall (if cholecystectomy) submitted for cultures. •  Cholelith nidus—may house associated bacterial infection. •  Coagulation profile—bleeding associated with prolonged clotting times may develop with EHBDO of >7–10 days; see Bile Duct Obstruction (Extrahepatic); responsive to parenteral vitamin K1 administration.

•  Cholelith analysis—infrequently done;

submit to laboratory equipped for cholelith analyses. IMAGING

•  Abdominal radiography—limited value in

delineating GB structure/content; choleliths often small, may be radiolucent; rarely mistaken for dystrophic biliary mineralization in animals with chronic cholangitis or Caroli DPM phenotype. •  Ultrasonography—can detect: choleliths ≥2 mm diameter, thickened GB wall, distended biliary tract, increased hepatic parenchymal echogenicity and extrahepatic ductal involvement; may facilitate specimen collection for culture, cytology, and histopathology; may detect evidence of EHBDO within 72h; caution: distended GB with bile “sludge” is common in anorectic or fasted patients; do not mistake for GB obstruction. Hepatolithiasis usually casts acoustic shadows. Imaging of choleliths within extrahepatic ducts may be difficult owing to enteric gas obstructing imaging “window”; confirmation of distended intrahepatic bile duct done with color-flow Doppler. DIAGNOSTIC PROCEDURES Histopathologic evaluation of liver necessary in patients undergoing surgical cholelith removal to detect comorbid conditions influencing treatment and prognosis, i.e., suppurative cholangitis, nonsuppurative cholangitis, DPM, neoplasia.

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TREATMENT

•  Controversial whether choleresis with

ursodeoxycholate (UDCA) is beneficial in animals lacking clinical or clinicopathologic signs; can resolve cholesterol choleliths in humans, but these are rare in dogs or cats; choleresis with UDCA may help move sludged biliary debris. •  Supportive fluids—if hospitalized, according to hydration, electrolyte, and acid-base status. •  If hyperlipidemia coexistent—prescribe fat-restricted diet, identify and manage endocrinopathies; if failure to control hyperlipidemia, may require additional medical management. •  Control predisposing conditions, especially biliary tree infection (with antimicrobials) and GB dysmotility (by GB removal). •  Exploratory surgery, choledochotomy, cholecystotomy, and possibly cholecystectomy or biliary-enteric anastomosis—indicated in symptomatic cases according to circumstances. •  Warn client that cholelithiasis is chronic problem and that stones may reform even after surgical removal despite chronic medical treatment; choleliths in GB is strong

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indication for cholecystectomy unless GB needed for biliary enteric anastomosis in certain conditions.

­M EDICATIONS DRUG(S) OF CHOICE •  Antibiotics—based on culture of bile, tissue, and cholelith nidus, cytology and Gram staining of biliary debris or crushed lith if cultures negative; if culture negative then directed against enteric microbial opportunists; initial treatment with Timentin or Clavamox with metronidazole, combined ® with a fluoroquinolone, usually successful. •  Ursodeoxycholic acid—10–15 mg/kg/day PO, divided BID, given with food to increase bioavailability; provides choleretic, hepatoprotectant, anti-endotoxic, antifibrotic effects, and may facilitate cholesterol stone dissolution; therapy often continued lifelong if no cause for cholelithiasis identified to augment choleresis thwarting bile stasis. •  Vitamin K1—parenterally; 0.5–1.5 mg/kg to max 3 doses in 24–36h in jaundiced patients; do not administer IV (anaphylaxis). Antioxidants

•  Vitamin E (α-tocopherol acetate)—10 IU/kg

per day for patients with high liver enzymes or confirmed hepatobiliary inflammation; use water-soluble form if EHBDO. •  S-adenosylmethionine (SAMe; use form with proven bioavailability and efficacy)— glutathione (GSH) donor (important hepatic antioxidant, GSH also provides driving force for non-bile acid–dependent

(continued)

choleresis) and thus is potential choleretic for patients with high liver enzymes or confirmed hepatobiliary inflammation; 20–40 mg/kg using enteric-coated tablet PO q24h, administer 2h before feeding; higher dose recommended for choleresis; also provides antifibrotic and antiinflammatory benefits. CONTRAINDICATIONS/POSSIBLE INTERACTIONS Ursodeoxycholic acid—contraindicated with EHBDO before biliary decompression.

­

FOLLOW-UP

PATIENT MONITORING •  Physical examination and pertinent diagnostic testing q2–4 weeks postoperatively until clinical signs and clinicopathologic abnormalities resolve. •  Periodic ultrasonography—assess cholelith status, integrity/distention of biliary tract, hepatic parenchymal changes. POSSIBLE COMPLICATIONS Sudden onset of fever, abdominal pain, and malaise—may signify bile peritonitis and/or sepsis from breakdown in bile containment, or recurrent cholelith lodged in sphincter of Oddi (duodenal papilla) or obstructing pancreatic duct (cats only). EXPECTED COURSE AND PROGNOSIS

•  May be asymptomatic. •  Symptomatic disease—reflects existing

infection, EHBDO, cholecystitis, DPM, or bile peritonitis.

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MISCELLANEOUS

SEE ALSO •  Bile Duct Obstruction (Extrahepatic). •  Cholecystitis and Choledochitis. •  Ductal Plate Malformation (Congenital Hepatic Fibrosis). •  Gallbladder Mucocele. ABBREVIATIONS

•  ALP = alkaline phosphatase. •  ALT = alanine aminotransferase. •  AST = aspartate aminotransferase. •  CBD = common bile duct. •  DPM = ductal plate malformation. •  EHBDO = extrahepatic bile duct

obstruction.

•  GB = gallbladder. •  GBM = gallbladder mucocele. •  GGT = γ-glutamyltransferase. •  GSH = glutathione. •  SAMe = S-adenosylmethionine. •  UDCA = ursodeoxycholate.

­Suggested Reading

Center SA. Diseases of the gallbladder and biliary tree. Vet Clin North Am Small Anim Pract 2009, 39:543–598. van Geffen C, Savary-Bataille K, Chiers K, et al. Bilirubin cholelithiasis and haemosiderosis in an anaemic pyruvate kinasedeficient Somali cat. J Small Anim Pract 2008, 49:479–482. Author Sharon A. Center Consulting Editor Kate Holan



269

Canine and Feline, Seventh Edition

Chondrosarcoma, Bone CBC/BIOCHEMISTRY/URINALYSIS Usually normal.

­

BASICS

OVERVIEW •  Chondrosarcoma (CSA) is a malignant mesenchymal tumor arising from cartilage and characterized by production of chondroid and fibrillar matrix. • CSA is the second most common primary bone tumor in dogs and accounts for 5–10% of all primary bone tumors; primary bone tumors are uncommon in cats, and CSA is third in incidence behind osteosarcoma and fibrosarcoma. • Dogs—majority of CSAs arise from flat bones (axial skeleton); approximately 30% occur in nasal cavity and 20% of CSAs arise from ribs; 20% of CSAs in dogs arise from appendicular skeleton; sites are generally similar to where osteosarcoma typically occurs. • Cats: 66% of CSAs arise in appendicular skeleton, with 33% occurring in the axial skeleton. • Rarely, CSA can arise in soft tissue (extraskeletal) sites. SIGNALMENT

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IMAGING

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of aggressive bone lesion (cortical lysis, nonhomogenous reactive bone formation, ill-defined zone of transition). • Thoracic radiographs recommended to screen for pulmonary metastasis. • CT recommended for axial tumors to more accurately stage local disease and plan for surgery and/or radiation therapy; concurrent CT imaging of thorax recommended as more sensitive way to screen for pulmonary metastasis. • MRI, alone or in combination with CT, may be recommended for treatment planning for vertebral CSA.

PATIENT MONITORING Physical examination every 2–3 months and thoracic radiographs every 3–4 months to monitor for local tumor control and distant metastases, respectively.

•  Radiographs of affected area show features

DIAGNOSTIC PROCEDURES • Histopathology needed for definitive diagnosis. • Fine-needle aspirate bone cytology may provide supportive diagnosis; differentiation of CSA from other sarcomas may be challenging if sample contains sparse amounts of matrix.

FOLLOW-UP

EXPECTED COURSE AND PROGNOSIS •  Overall, 15–30% of dogs will develop metastatic disease, with lungs being most commonly affected site; metastatic rates approach 50% for high-grade canine tumors; development of metastasis rare for cats with CSA. • With curative-intent surgery, median survival >3 years; depending on tumor location and completeness of excision, up to 40% will develop local recurrence. • With palliative care alone, survival times of >1 year still possible.

•  Dogs—medium- to large-breed dogs, with

mixed-breed dogs, golden retrievers, boxers, and German shepherd dogs overrepresented; median age is 8 years (range: 1–15 years). • Cats—median age is 9 years (range: 2–18 years), with males twice as likely to be affected. SIGNS

Historical Findings

•  Patients often present with a visible mass at

the affected site. • History of lameness if involvement of weight-bearing bone. • Rarely, CSA of the rib may be associated with respiratory signs. • Additional clinical signs vary with site of involvement.

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TREATMENT

•  Amputation recommended for appendicu-

lar tumors. • For axial tumors, wide surgical excision recommended whenever possible. • Stereotactic radiation therapy provides effective local control for canine osteosarcoma and might be alternative to surgery for patients with CSA. • Palliative therapy recommended for patients with nonresectable local disease or gross metastasis, or when definitive therapy is declined; palliative care focuses on pain control.

Physical Examination Findings

•  Findings depend on anatomic location.

• A firm to hard mass often is palpable, with variable degrees of pain elicited on palpation. • CSA of the rib occurs most commonly at the costochondral junction; dyspnea is rare and associated with space-occupying effect.

CAUSES & RISK FACTORS •  Etiology largely unknown. • Osteochondromatosis (multiple cartilaginous exostosis) lesions can transform into CSA.

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MEDICATIONS

DRUG(S) OF CHOICE Pain Management

•  Nonsteroidal anti-inflammatory drugs

(NSAIDs). • Tramadol. • Gabapentin. • IV aminobisphosphonates (e.g., pamidronate, zoledronate) might alleviate bone pain and slow pathologic bone resorption.

Chemotherapy

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DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Other primary bone tumors (osteosarcoma, fibrosarcoma, hemangiosarcoma). • Metastatic bone tumors (transitional cell, prostatic, mammary, thyroid, apocrine gland, anal sac carcinomas). • Tumors that locally invade adjacent bone (especially oral, nasal, digital, and joint tumors). • Fungal osteomyelitis.

Role of chemotherapy has not been defined in veterinary oncology, but does not improve outcome in humans. CONTRAINDICATIONS/POSSIBLE INTERACTIONS •  Use NSAIDs cautiously in all cats and in dogs with renal insufficiency. • Do not combine NSAIDs with corticosteroids.

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MISCELLANEOUS

SEE ALSO •  Chondrosarcoma, Nasal and Paranasal Sinus. •  Chondrosarcoma, Oral. •  Fibrosarcoma, Bone. •  Osteosarcoma. ABBREVIATIONS

•  CSA = chondrosarcoma. •  NSAID = nonsteroidal anti-inflammatory

drug.

­Suggested Reading

Durham AC, Popovitch CA, Goldschmidt MH. Feline chondrosarcoma: a retrospective study of 67 cats (1987–2005). J Am Anim Hosp Assoc 2008, 44(3):124–130. Farese JP, Kirpensteijn J, Kik M, et al. Biologic behavior and clinical outcome of 25 dogs with canine appendicular chondrosarcoma treated by amputation: a Veterinary Society of Surgical Oncology retrospective study. Vet Surg 2009, 38:914–919. Author Jenna H. Burton Consulting Editor Timothy M. Fan Acknowledgment The author and book editors acknowledge the prior contribution of Dennis B. Bailey.

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•  Thoracic radiographs to screen for

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BASICS

OVERVIEW •  Chondrosarcoma (CSA) is a malignant mesenchymal tumor arising from cartilage and characterized by production of chondroid and fibrillar matrix. •  Nasal CSA arises most commonly from the nasal turbinates. •  In dogs, CSA accounts for 15% of all nasal tumors. SIGNALMENT •  Mixed-breed dogs, Labrador retrievers, golden retrievers, boxers, and German shepherd dogs are overrepresented. •  Median age is 7 years (range: 2–13 years). •  CSA tends to develop at a younger age than other nasal tumors. •  Rare in cats, with no obvious breed or sex predilections. SIGNS Historical Findings

•  Intermittent unilateral epistaxis and/or

mucopurulent discharge, may progress to bilateral involvement. •  Sneezing, stertorous breathing, and/or facial deformity. •  Decreased appetite and/or halitosis secondary to oral cavity invasion. •  Seizures, behavior changes, and/or obtundation secondary to cranial invasion. Physical Examination Findings

•  Epistaxis and/or nasal discharge, initially

unilateral but can progress to bilateral. •  Decreased nasal air flow (unilateral or bilateral). •  Pain on nasal or paranasal sinus palpation or percussion. •  Facial deformity, decreased ocular retropulsion, exophthalmia, or epiphora. •  Visible mass effect protruding through the palate into the oral cavity. CAUSES & RISK FACTORS Unknown

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DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Other nasal tumors—adenocarcinoma, squamous cell carcinoma, osteosarcoma, fibrosarcoma, lymphoma, transmissible venereal tumor (dogs), nasopharyngeal polyp (cats). •  Fungal rhinitis—aspergillosis and penicilliosis (dogs), cryptococcus (cats), sporotrichosis (both). •  Rhinosporidiosis (dogs). •  Foreign body. •  Thrombocytopenia or other coagulopathy. •  Tooth root abscess. •  Oronasal fistula. CBC/BIOCHEMISTRY/URINALYSIS Usually normal—evaluate for thrombocytopenia if signs of epistaxis. OTHER LABORATORY TESTS •  Nasal flush for cytology and culture—rarely helpful. •  Coagulation profile. •  Buccal mucosal bleeding time.

pulmonary metastasis (uncommon). •  CT for detecting soft tissue opacity within nasal cavity and surrounding sinuses, bony destruction, and extension through cribriform plate into brain. •  If CT scan is not accessible, skull radiographs can be performed to assess for soft tissue opacity in nasal cavity and/or frontal sinuses. DIAGNOSTIC PROCEDURES

•  Blood pressure, to rule out systemic hyper­-

tension as cause for epistaxis. •  Mandibular lymph node cytology to screen for possible metastasis. •  Rhinoscopy is helpful for visualization of mass or fungal plaque and guiding subsequent tissue biopsy. •  Tissue biopsy and histopathology needed for definitive diagnosis; biopsy instrument should not pass caudal to level of medial canthus of eye to avoid penetrating cribriform plate. •  Intranasal approach to obtaining tissue biopsy preferable if treatment radiation therapy planned.

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TREATMENT

•  Radiation therapy is treatment of choice.

•  Conventional linear accelerator used most commonly; however, if available, stereotactic radiation therapy can reduce number of radiation treatments and reduce adverse effects. •  Palliative radiation protocols (fewer treatments and lower total radiation dose) might be preferable for dogs with very advanced disease.

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MEDICATIONS

DRUG(S) OF CHOICE •  Nonsteroidal anti-inflammatory drugs (NSAIDs) for pain control. •  Prednisone (0.5–1 mg/kg PO q24h) to help relieve nasal congestion. •  Phenylephrine nasal spray can be used intermittently to help with epistaxis. •  Empiric antibiotic therapy can be considered for secondary bacterial infections. CONTRAINDICATIONS/POSSIBLE INTERACTIONS •  Use NSAIDs cautiously in all cats and in dogs with renal insufficiency. •  Do not combine NSAIDs with corticosteroids.

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FOLLOW-UP

PATIENT MONITORING •  Physical examinations every 2–3 months and thoracic radiographs every 3–4 months.

•  CT of skull can be considered when clinical signs recur or progress. EXPECTED COURSE AND PROGNOSIS

•  3 months. This definition includes all cases previously described by the terms renal insufficiency or renal failure, as well as less advanced forms of kidney disease. Patients are categorized into stages along a continuum of progressive CKD (IRIS CKD stages 1–4; www.iris-kidney.com) based on >2 serum creatinine values obtained over several weeks when the patient is fasted and well hydrated. The IRIS system uses the term “kidney” rather than “renal” because it is more universally recognized by pet owners. PATHOPHYSIOLOGY More than ~67–75% reduction in renal function results in impaired urineconcentrating ability (leading to polyuria/ polydipsia [PU/PD]) and retention of nitrogenous waste products of protein catabolism (azotemia). CKD is progressive; more advanced CKD results in uremia. Decreased renal erythropoietin and calcitriol production results in hypoproliferative anemia and renal secondary hyperpara­ thyroidism, respectively. SYSTEMS AFFECTED •  Cardiovascular—hypertension; uremic pericarditis. •  Endocrine/metabolic—renal secondary hyperparathyroidism, activation of reninangiotensin-aldosterone system, erythropoietin deficiency. •  Gastrointestinal—uremic stomatitis and halitosis, nausea, vomiting, anorexia, gastrointestinal bleeding, diarrhea. •  Hemic/lymphatic/immune—anemia; hemorrhagic diathesis. •  Musculoskeletal—renal osteodystrophy; sarcopenia. •  Neuromuscular—seizures and other neurologic signs, muscle tremors, muscle wasting. •  Ophthalmic—retinal detachment, hemorrhage, or edema due to hypertension. •  Reproductive—impaired reproductive capacity. •  Respiratory—uremic pneumonitis. GENETICS •  Inherited in these breeds (mode of inheritance indicated in parentheses)— Abyssinian cat (dominant with incomplete penetrance); Persian cat (dominant); bull terrier (dominant); Cairn terrier (recessive); German shepherd (dominant); Samoyed

(X-linked dominant); English cocker spaniel (recessive). •  Renal dysplasia—shih tzu, Lhasa apso, golden retriever, Norwegian elkhound, chow chow, standard poodle, soft-coated wheaten terrier, Alaskan Malamute, miniature schnauzer, Dutch kooiker, and many other breeds.

•  Uremic halitosis. •  Hypertensive retinopathy. •  Renal osteodystrophy may manifest as bone

INCIDENCE/PREVALENCE •  9 cases per 1,000 dogs and 16 cases per 1,000 cats examined. •  Prevalence increases with age—age >15 years, reportedly 57 cases per 1,000 dogs and 153 cases per 1,000 cats examined.

•  Familial and congenital renal disease,

GEOGRAPHIC DISTRIBUTION Worldwide SIGNALMENT Species

Dog and cat.

pain, particularly in skull.

•  Reduced body temperature with uremia.

CAUSES

•  Unknown in most cases due to late

diagnosis.

nephrotoxins, hypercalcemia, hypokalemic nephropathy, glomerulopathies, amyloidosis, pyelonephritis, polycystic kidney disease, nephroliths, chronic urinary obstruction, drugs, lymphoma, leptospirosis (following acute kidney injury [AKI]), feline infectious peritonitis. RISK FACTORS Age, proteinuria, hypercalcemia, hypokalemia, hypertension, urinary tract infection (UTI).

Breed Predilections

See Genetics.

Mean Age and Range

Mean age at diagnosis is 7 years in dogs and 9 years in cats. Animals of any age can be affected; prevalence increases with age. Predominant Sex

None

SIGNS General Comments

•  Clinical signs related to stage of CKD and

complications such as proteinuria and hyper­tension. •  CKD stages 1 and 2 may be asymptomatic; overt clinical signs typically become apparent in stages 3 and 4. •  Animals with stable CKD (particularly stages 3 and 4) may decompensate, resulting in uremic crisis. Historical Findings

•  PU/PD. •  Anorexia. •  Lethargy. •  Vomiting. •  Weight loss. •  Nocturia. •  Constipation. •  Diarrhea. •  Acute blindness. •  Seizures or coma. •  Cats may have ptyalism and muscle

weakness with cervical ventroflexion.

Physical Examination Findings

•  Kidneys may be small, irregular, enlarged

(secondary to polycystic kidney disease or lymphoma), or normal. •  Dehydration. •  Cachexia. •  Weakness. •  Mucous membrane pallor. •  Oral ulceration.

­D IAGNOSIS DIFFERENTIAL DIAGNOSIS •  See Polyuria and Polydipsia for differential diagnosis. •  Azotemia—includes causes of prerenal and postrenal azotemia, AKI, and hypoadreno­corticism. •  Prerenal azotemia—azotemia with urine specific gravity (USG) >1.030 in dogs and >1.035 in cats; rapid reduction in azotemia after correcting hypoperfusion indicates prerenal azotemia; prerenal azotemia commonly occurs concurrent with primary renal azotemia when gastrointestinal signs of uremia are present. •  Postrenal azotemia—obstruction or rupture of excretory system; rapid correction of azotemia following elimination of obstruction or resolution of leakage from urinary tract supports postrenal azotemia. •  AKI—differentiated by normal to large renal size, cylindruria, lack of indications of chronicity, and history of recent nephrotoxin exposure or hypotensive episode; AKI can also occur in patients with CKD where rapid developing increase in serum creatinine concentration and uremic signs suggests acute-onset CKD. •  Hypoadrenocorticism—characterized by hyponatremia and hyperkalemia with hypo­cortisolemia. CBC/BIOCHEMISTRY/URINALYSIS

•  Hypoproliferative anemia. •  High blood urea nitrogen (BUN), creatinine,

and symmetric dimethylarginine (SDMA). •  Hyperphosphatemia. •  Metabolic acidosis (normal or high anion gap). •  Hypokalemia or hyperkalemia. •  Hypercalcemia or hypocalcemia.





Chronic Kidney Disease

(continued)

•  USG patient tolerance. •  Hepatic iron accumulation—

supplementation.

•  Chronic hepatobiliary inflammation. •  Chronic EHBDO. •  Chronic phenobarbital administration (dogs). •  NSAIDS—dogs, especially carprofen.

retrievers—no sex predilection.

•  DPM—no gender predilection.

SIGNS General Comments

•  Initially—vague and nonspecific. •  Later—relate to complications of portal

hypertension (e.g., HE, ascites, gastroduodenal bleeding) and impaired hepatic function. Historical Findings

•  Chronic intermittent lethargy, anorexia,

reduced body condition.

•  GI signs—vomiting, diarrhea or constipa-

tion. Melena—late stage or as APSS develop.

•  PU/PD. •  Late onset—ascites, bleeding, HE.

­

DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Chronic hepatitis—common in dogs. •  Cholangiohepatitis—common in cats. •  Noncirrhotic portal hypertension—dogs. •  Chronic EHBDO. •  Chronic IBD or pancreatitis. •  Hepatic neoplasia. •  Metastatic neoplasia or carcinomatosis. •  Congenital portosystemic vascular anomaly (shunt). •  Congenital portal atresia—intrahepatic or extrahepatic. •  Right-sided heart failure, pericardial disease.

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•  Cats—hepatic lipidosis, feline infectious

peritonitis, toxoplasmosis. •  Hemolytic anemia (jaundice differential). CBC/BIOCHEMISTRY/URINALYSIS CBC

•  Microcytic RBCs: APSS; mild anemia:

small RBCs with normal cell count; anemia of chronic disease; microangiopathic shearing: sinusoidal fibrosis, APSS. •  Mild thrombocytopenia variable. •  Leukogram variable. Biochemistry

•  Bilirubin variable. •  Liver enzyme activities—high (alanine

transaminase [ALT] > alkaline phosphatase [ALP]) noted before clinical signs or liver dysfunction; at end-stage enzymes may decline. •  Normal to hypoalbuminemia. •  Normal to hyperglobulinemia. •  Hypocholesterolemia—reflects APSS. •  Low blood urea nitrogen (BUN)—reduced urea cycle activity, APSS, protein-restricted diet, PU/PD. •  Hypoglycemia—rare. •  Hypokalemia—may predispose to HE. •  Hyponatremia—fluid imbalance with ascites. Urinalysis

•  Isosthenuria—with PU/PD. •  Ammonium biurate crystalluria. •  Bilirubinuria, bilirubin crystalluria.

OTHER LABORATORY TESTS

•  Ascitic fluid—pure or modified transudate. •  Coagulation tests—inconsistently prolonged

prothrombin time (PT), activated partial thromboplastin time, buccal mucosal bleeding time (BMBT). •  Low protein C and antithrombin activity— reflects APSS, synthetic failure, or disseminated intravascular coagulation (DIC). •  Serum bile acids—high; reflects APSS or cholestasis in cirrhosis. •  Hyperammonemia—inferred from ammonium biurate crystalluria. IMAGING Radiography

Abdominal—small to normal-sized liver; ascites may obscure details; urate calculi radiolucent unless calcium complexed. Ultrasonography

•  Abdominal—hyperechoic or mixed

echogenic liver parenchyma; ± nodularity; often small with cirrhosis; abdominal effusion (ascites); APSS (color-flow Doppler); enlarged portal lymph nodes; no parenchymal change in some cases. •  Doppler interrogation of portal vasculature— may confirm hepatofugal flow or nests of APSS, esp. near left kidney or splenic vessels. DIAGNOSTIC PROCEDURES

•  Fine-needle aspiration cytology—helps rule

out neoplasia; rule in bacterial infection; cannot define fibrosis or nonsuppurative inflammation.

•  Liver biopsy—for definitive diagnosis; accuracy increased by multiple biopsy samples. •  Ultrasound guided—14–16G. •  Laparoscopy/laparotomy—best methods, permits gross visualization, documents APSS, biopsy access to multiple liver lobes and focal lesions.

PATHOLOGIC FINDINGS Gross

•  Fibrosis—small, firm irregular to finely

nodular liver; DPM-CHF may not be small; fibrotic liver may display APSS, ± ascites. •  Cirrhosis—firm irregular liver; prominent micro- or macronodules, APSS, ± ascites. Histopathology

•  Immune-mediated hepatitis—periportal,

lobular, or centrilobular lymphoplasmacytic infiltrates, hepatic cord disorganization, sinusoidal fibrosis, biliary hyperplasia. •  CuAH—initially centrilobular, may evolve immune-mediated hepatitis; single necrotic hepatocytes; significant fibrotic tissue may falsely decrease quantitative Cu concentration measurements in biopsy samples. •  DPM—bridging partitions with proliferative nonfunctional embryonic bile ducts embedded in ECM interconnecting portal regions. •  Postnecrotic fibrosis—fibrosis marks regen­erative repair, disorganized wide hepatic cords; engorged lymphatics reflect sinusoidal hypertension. •  Cirrhosis—diffuse lesion; fibrosis, nodular regeneration distorting lobular architecture, periportal or sinusoidal fibrosis depending on zone of chronic injury, engorged lymphatics; single hepatocyte necrosis if active disease.

­

TREATMENT

APPROPRIATE HEALTH CARE •  Outpatient—minimally symptomatic patients. •  Inpatient—diagnostic tests; treatment for dehydration, severe HE, enteric bleeding, tense ascites. NURSING CARE •  Fluids—avoid lactate if hepatic failure; avoid sodium loading if ascites. •  B complex vitamins (esp. cats)—2 mL/L fluid advised. •  Vitamin K1—0.5–1.5 mg/kg SC q12h for 3 doses initially; titrate with proteins invoked by vitamin K absence or antagonism (PIVKA; if available) or PT. •  Glucose—if hypoglycemia; 2.5–5% dextrose in polyionic solution; titrate to response. •  Potassium chloride—in fluids, as needed. •  Avoid alkalosis—worsens HE. •  Therapeutic large-volume abdominocentesis if tense ascites nonresponsive to medical treatment; caution: PHS—hypotensive crisis and acute renal failure.

(continued)

ACTIVITY Limit DIET

•  Withhold oral food in acute severe HE if

stupor, coma, or vomiting associated with enteric bleeding or pancreatitis. •  Consider partial parenteral nutrition or total parenteral nutrition. •  If HE—restrict protein intake, use soy or dairy protein sources (dogs) with medical interventions to increase nitrogen tolerance (see Hepatic Encephalopathy). •  Supplement water-soluble vitamins. CLIENT EDUCATION

•  Treatment palliative and symptomatic. •  Fibrosis diminished by control of inflam-

mation and provocative diseases.

•  Attenuate factors provoking HE—

azotemia, dehydration; infection; catabolism; high-protein meals, hypokalemia; alkalemia; constipation, endoparasitism; enteric bleeding; certain drugs. SURGICAL CONSIDERATIONS

•  Cirrhosis—high anesthetic risk; gas

anesthesia preferred: isoflurane or sevoflurane. •  Coagulopathy—predisposes to bleeding; BMBT may better assess risk for bleeding. •  Postoperative intensive care—avoid HE, maintain hydration, euglycemia, electrolytes, acid-base balance (avoid alkalemia). •  Predisposed to enteric bacterial translocation—judiciously administer antibiotics, esp. if surgical procedures involve alimentary canal or biliary structures.

­

MEDICATIONS

DRUG(S) OF CHOICE •  Treatments for specific etiologies—chelate Cu if CuAH; withdraw potentially hepatotoxic drugs, herbal or natural remedies. •  No clinical trials prove efficacy of specific regimens in animals. Immune Modulation

•  Prednisolone/prednisone—1–2 mg/kg q24h

PO; taper to 0.5 mg/kg q48h; do not exceed 40 mg/day/dog. •  Azathioprine—2 mg/kg (or 50 mg/m2) q24h for 14 days, then q48h; contraindicated in cats (toxic); dogs: with prednisone, anti­oxidants, antifibrotics, and polyenylphosphatidylcholine (PPC). •  Cyclosporine—5 mg/kg BID tapered to q24h; has been successful as single agent or with corticosteroids. •  Mycophenolate—10–15 mg/kg BID; has been successful as first- or second-line treat­ment with corticosteroids. Antifibrotics

•  Immunomodulation, S-adenosylmethionine

(SAMe), silybin, vitamin E—considered antifibrotics as well as hepatoprotectants.



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(continued)

•  Ursodiol—7.5 mg/kg/day PO q12h with

food; use indefinitely. •  Polyunsaturated phosphatidylcholine with dilinolylphosphatidylcholine (PhosChol®)— 25 mg/kg/q24h, mix with food. •  Colchicine—0.025–0.03 mg/kg q24–48h; no evidence of chronic benefit; side effects complicate use; no longer recommended. •  Losartan and telmisartan—losartan: 0.5 mg/ kg/q24h; telmisartan: 0.5–1 mg/kg q24h initial dose; closely monitor blood pressure, renal function, and potassium, reducing dose if hypotension or hyperkalemia; angiotensin receptor blockers used in humans as antihypertensives and have been shown to be nephroprotective, to protect against some forms of drug-induced hepatotoxicity, and to inconsistently limit hepatic fibrosis.

PRECAUTIONS

•  Diuretics—dehydration, hypokalemia,

alkalemia worsen HE. •  Glucocorticoids—increase susceptibility to infection, enteric bleeding, sodium and water retention, ascites, protein catabolism, HE. •  Avoid drugs or reduce dose if first-pass hepatic extraction, if require hepatic conjugation or biotransformation (e.g., metronidazole—reduce conventional dose to 7.5 mg/kg PO q12h, as used for HE). ALTERNATIVE DRUG(S)

•  Dexamethasone—if ascites, replace

prednisone/prednisolone to avoid mineralocorticoid effect); divide dose by 7–10, administer q3–4 days; taper dose to efficacy.

Antioxidants

•  Necroinflammatory disorders. •  SAMe—20 mg/kg q24h PO, empty stomach. •  Vitamin E mixed tocopherols—10 U/kg

q24h PO with food.

Hepatoprotectants

•  Necroinflammatory disorders. •  Ursodeoxycholate, vitamin E, SAMe. •  Silibinin—efficacy unclear, use PPC

complexed form (bioavailable), 2–5 mg/kg q24h PO. •  Elemental zinc—1.5–3 mg PO q24h (if low liver zinc confirmed); adjust dose with plasma zinc measurements; avoid ≥800 μg/dL; contraindicated with concurrent d-penicillamine administration. Gastroprotectants

•  Gastric acid inhibitors—if enteric bleeding

(see Hepatitis, Chronic).

•  Eliminate endoparasitism.

Ascites

•  Restrict activity and sodium intake

combined with diuretic therapy.

•  Dietary sodium restriction (0.2% dry

matter basis or 80% of healthy dogs and 43–63% of normal cats. •  Fecal endospore cultures are not useful, as sporulation of enterotoxigenic strains of CP occurs in dogs with and without diarrhea.

Enterotoxin Assay

•  Fecal ELISA for identification of CPE in

patients with diarrhea suspected to be due to CP is the current recommendation; since CPE is present in the feces of 5–14% of clinically normal dogs, this may or may not be clinically useful. •  Fecal ELISA should be run in conjunction with PCR to detect enterotoxigenic strains. •  Real-time polymerase chain reaction (RT-PCR) for detection of the CPE gene and the alpha toxin gene is available; the CPE gene has been found in up to 33.7% of healthy dogs, therefore its presence in a dog with GI disease does not confirm that CP is the cause.

Fecal Cytology

•  CP endospores, characterized by “safety-

pin” appearance with oval form and dense body at one end of spore wall, can be seen on microscopic evaluation of heat-fixed thin fecal smear stained with Romanowsky-type stain (e.g., Diff-Quik®), Wright’s stain, or new methylene blue. •  High numbers of CP endospores on fecal cytology correlates poorly with clinical disease or fecal CPE activity. •  High numbers of fecal endospores can be found in feces of healthy dogs. DIAGNOSTIC PROCEDURES

•  Abdominal ultrasound can help rule out

other causes of GI disease. •  Colonoscopy and endoscopy with biopsy can be used to confirm presence of acute mucosal necrosis and neutrophilic infiltration, as well as adherence of rod-shaped bacteria to these necrotic areas, and can rule out other causes of GI disease. PATHOLOGIC FINDINGS

•  Grossly hyperemic or ulcerated mucosa. •  Acute

intestinal mucosal destruction and neutrophilic infiltration. •  Immunohistochemical staining of bacterial plaques on necrotic areas may be clostridial antigen positive.

­

TREATMENT

APPROPRIATE HEALTH CARE •  There are no research-based recommendations for optimal treatment of patients with CP-associated illness. •  If vomiting or diarrhea is not severe, animals may be treated as outpatients with antiemetics and subcutaneous fluids. •  If more severe diarrhea, vomiting, dehydration, or evidence of hypovolemia, hospitalization with IV replacement crystalloids and antiemetics is recommended. DIET

•  Diet change plays a role in treatment and

management of cases with chronic recurring disease; diets high in either soluble (fermentable) or insoluble fiber often result in clinical improvement by reducing enteric CP





Clostridial Enterotoxicosis

(continued)

number, possibly through acidification of the distal intestine, which limits CP sporulation and enterotoxin production. •  Commercial diets can be supplemented with psyllium (1/2–2 tsp/day) as a source of soluble fiber. •  Diets low in fiber should be supplemented with fiber (coarse bran 1–3 tbs/day) as a source of insoluble fiber or psyllium added as a source of soluble fiber. •  Probiotics might help restore the normal intestinal microbiota, thereby reducing risk of recurrent CPassociated diarrhea. CLIENT EDUCATION

•  Acute disease is often self-limiting. •  There

have been no documented reports of trans­mission of CP from animals to humans; however, if there are immunosuppressed members in the household, strict hygiene protocols should be followed.

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MEDICATIONS

DRUG(S) OF CHOICE Antiemetics

probiotics than with no treatment. •  Diet change can be instituted following resolution of clinical signs.

­

FOLLOW-UP

PATIENT MONITORING •  Ensure adequate hydration and intravascular volume, with replacement fluid administration as needed. •  Monitor PCV, total plasma protein, acid-base balance, and electrolyte concentrations. PREVENTION/AVOIDANCE

•  Regular use of high-fiber diets or probiot-

ics. •  Avoiding or anticipating stressful events (e.g., kenneling) and using anxiolytics. EXPECTED COURSE AND PROGNOSIS

•  Overall excellent prognosis; many animals

will have resolution of clinical signs without in-hospital treatment. •  Acute hemorrhagic diarrheal events should be addressed with aggressive resuscitation and hospitalization; if the animal responds to therapy, the prognosis is good.

•  Maropitant—1 mg/kg IV/SC q 24h.

•  Ondansetron—0.5–1 mg/kg IV/PO q24h.

Antibiotics

•  Antibiotics are unnecessary in animals with

mild disease as the infection is typically self-limiting. •  If signs of systemic disease or sepsis are present, antibiotics should be administered. •  Antibiotics that are recommended are ampicillin: 22 mg/kg IV q8h; amoxicillin: 22 mg/kg PO q8h; metronidazole: 10–25 mg/kg IV/PO q12h for 5–7 days; tylosin: 5–10 mg/kg PO q24h. •  Tetracyclines are no longer recommended due to resistance of CP isolates.

­

MISCELLANEOUS

ASSOCIATED CONDITIONS •  CP enterotoxicosis can be associated with AHDS. •  The connection to chronic enteropathies is less well understood. ZOONOTIC POTENTIAL Unknown PREGNANCY/FERTILITY/BREEDING Antibiotic therapy may be contraindicated. SEE ALSO

ALTERNATIVE DRUGS(S)

•  Colitis and Proctitis. •  Small Intestinal Dysbiosis.

intestinal microbiota, reducing likelihood of recurrences. •  One study reported faster resolution of clinical signs with use of

ABBREVIATIONS •  AHDS = acute hemorrhagic diarrhea syndrome.

•  Probiotics (e.g., lactobacillus) may alter the

•  ALT = alanine aminotransferase. •  AST = aspartate aminotransferase. •  BUN = blood urea nitrogen. •  CP = Clostridium perfringens. •  CPE = Clostridium perfringens enterotoxin. •  GI = gastrointestinal. •  HGE = hemorrhagic gastroenteritis. •  PCV = packed cell volume. •  RT-PCR = real-time polymerase chain

reaction.

­Suggested Reading

Albini S, Brodard I, Jaussi A. Real-time multiplex PCR assays for reliable detection of Clostridium perfringens toxin genes in animal isolates. Vet Microbiol 2008, 127:179–185. Marks SL, Rankin SC, Byrne BA, et al. ACVIM Consensus Statement: enteropathogenic bacteria in dogs and cats: diagnosis, epidemiology, treatment, and control. J Vet Intern Med 2011, 25:1195–1208. Minamoto Y, Dhanani N, Markel ME, et al. Prevalence of Clostridium perfringens, Clostridium perfringens enterotoxin and dysbiosis in fecal samples of dogs with diarrhea. Vet Microbiol 2014, 174:463–473. Weese SJ, Staempfli HR, Prescott JF, et al. The roles of Clostridium difficile and enterotoxigenic Clostridium perfringens in diarrhea in dogs. JVIM 2001, 15:374–378. Ziese AL, Suchodolski JS, Hartmann K, et al. Effect of probiotic treatment on the clinical course, intestinal microbiome, and toxigenic Clostridium perfringens in dogs with acute hemorrhagic diarrhea. Plos One 2018, 13(9):e0204691. Author Jennifer Good Consulting Editor Amie Koenig Acknowledgment The author and book editors acknowledge the prior contribution of Stanley L. Marks. Client Education Handout available online

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Coagulation Factor Deficiency C ­

  BASICS

DEFINITION Hemostatic defects characterized by a lack of one or more procoagulant proteins (coagulation factors). PATHOPHYSIOLOGY •  Coagulation involves a complex series of enzymatic reactions that generate a burst of thrombin (factor IIa) at sites of blood vessel injury; thrombin then cleaves plasma fibrinogen into fibrin monomers that subsequently polymerize and cross-link to form an insoluble fibrin clot. •  Functional and/or quantitative coagulation factor deficiencies cause a failure of fibrin clot formation. •  The liver is the sole or primary site of synthesis of most coagulation factors; after synthesis, factors II, VII, IX, and X require a vitamin K– dependent modification to become fully active. SYSTEMS AFFECTED •  Coagulation factor deficiency can cause spontaneous hemorrhage, prolonged posttraumatic hemorrhage, and ultimately blood loss anemia. •  Spontaneous hemorrhage—often develops in body cavities or potential spaces (i.e., hemothorax, hemoperitoneum, hemarthrosis, subcutaneous, or intramuscular hematoma). GENETICS

•  Hemophilia A and B (factor VIII and IX

deficiencies)—X-linked recessive traits.

•  All other factor deficiencies are autosomal

traits.

•  Specific defects are more likely to be

propagated within a single breed, but all breeds are at risk for developing new mutations. SIGNALMENT •  Dog and cat. •  Hereditary factor deficiencies—severe defects manifest by 3–6 months of age, milder hemostatic defects manifest after surgery or trauma. •  For X-linked recessive traits, males express the bleeding tendency, female carriers are clinically normal. •  For autosomal traits, males and females express signs with equal frequency. •  Hemophilia A is a common hereditary factor deficiency and may be seen in all breeds and mixed-breed dogs and cats. •  Factor XII deficiency is common in cats, but does not cause a clinical bleeding tendency. •  Acquired factor deficiencies—depends on underlying disease process. SIGNS •  Hematoma formation. •  Intracavitary hemorrhage. •  Prolonged hemorrhage after surgery or trauma. •  Blood loss anemia.

CAUSES •  Acquired—synthetic failure (liver disease); vitamin K deficiency (cholestasis, anticoagulant rodenticide toxicity, malabsorption, long-term antibiotics, coumadin); factor inhibition (anticoagulant overdose, envenomation, auto- or alloantibodies); factor consumption and depletion (disseminated intravascular coagulopathy [DIC]); factor dilution (high-volume transfusion, crystalloid, or colloid fluid therapy); hyperfibrinolysis (secondary fibrinogen depletion). •  Hereditary—distinct mutations in coagulation factor genes.

­

  DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Thrombocytopenia should be the first rule-out for any patient with abnormal hemorrhage; thrombocytopathies may also cause bleeding (see Thrombocytopenia, Thrombocytopathies). •  Hereditary coagulation factor deficiencies cause prolongation of coagulation screening tests, whereas vonWillebrand disease (vWD) does not. •  Hyperfibrinolysis may cause hemorrhage in patients with hypovolemic shock, acute blood loss, or trauma, but generally does not cause prolongation of activated partial thromboplastin time (APTT) or prothrombin time (PT) tests; a breed predisposition for hyperfibrinolysis may exist in sighthounds. •  Acquired coagulopathies often develop because of liver disease, anticoagulant rodenticide ingestion, or DIC. •  Liver disease is accompanied by changes in the chemistry profile (see Coagulopathy of Liver Disease). •  Anticoagulant rodenticide toxicity prolongs the PT and/or APTT, but does not affect thrombin clotting time (TCT) or fibrinogen concentration. •  DIC always develops secondary to systemic disease (especially sepsis, neoplasia, other inflammatory conditions) and is often accompanied by low or falling platelet count. •  Massive transfusion (>1 blood volume) with stored blood products may dilute functional factors, fibrinogen, and platelets below hemostatic levels; hypocalcemia may also result. •  Contamination of blood samples (e.g., with heparin flush) or delayed processing can generate spurious PT and APTT abnormalities. CBC/BIOCHEMISTRY/URINALYSIS

•  Regenerative anemia develops over the

course of days after blood loss.

•  Platelet count is normal unless the patient

has DIC or massive bleeding.

•  Resorption of blood from a large hematoma

may cause hyperbilirubinemia.

OTHER LABORATORY TESTS

•  Coagulation screening tests (activated

clotting time [ACT], APTT, PT, TCT) are functional tests that measure the time for in vitro clot formation; coagulation factor and fibrinogen deficiencies prolong clotting time (see Figure 1). •  ACT is a point-of-care screening test that detects severe deficiencies of all factors (except factor VII); ACT may be influenced by anemia, thrombocytopenia, and changes in blood viscosity. •  APTT is a screening test of the contact pathway (prekallikrein, high molecular weight kininogen, factor XII), intrinsic system (factors XI, IX, VIII), common system (factors X, V, II), and severe fibrinogen deficiency. •  PT is a screening test of factor VII, common system, and severe fibrinogen deficiency. •  The TCT is a screening test of functional fibrinogen and is sensitive to the presence of fibrinogen inhibitors. •  Acquired coagulation factor deficiencies generally cause prolongation of more than one screening test; the most common hereditary factor deficiencies (hemophilia and factor XII deficiency) specifically prolong APTT. •  Individual factor assays can be performed for definitive diagnosis of hereditary or complex coagulopathies. Drugs That May Alter Laboratory Results

Therapeutic dosages of unfractionated heparin, coumadin, and plasma expanders (dextran, hetastarch) prolong coagulation screening tests. Disorders That May Alter Laboratory Results

•  Improper sample collection (poor venipuncture technique, partially or overfilled citrate collection tubes, use of heparin or clot activator tubes) will invalidate coagulation test results. •  Extreme lipemia, hemoglobinemia, or icterus may interfere with clot detection by photo-optical coagulation analyzers. •  Because of factor lability, samples should be assayed on site or plasma separated and sent on ice to the laboratory.

Valid if Run in Human Laboratory?

•  Interpretation of coagulation assay results requires same-species reference intervals and controls; for example, human APTT values are generally twice those of dogs and cats. •  The laboratory should confirm crossreactivity of antigenic assays and optimization of functional tests for animal species.

DIAGNOSTIC PROCEDURES Buccal mucosal bleeding time (BMBT) is prolonged in patients with severe thrombocyto­ penia, platelet dysfunction, vWD, and fibrinogen deficiency, but BMBT is insensitive to coagulation factor deficiencies.



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(continued) 

COAGULATION SCREENING TESTS: APTT, PT, TCT APTT: LONG PT, TCT: NORMAL

PT: LONG APTT, TCT: NORMAL

APTT& PT: LONG TCT NORMAL

INTRINSIC FACTOR DEFECTS

EXTRINSIC FACTOR DEFECTS

COMMON PATHWAY OR COMBINED DEFECTS

Factor VIII (Hemophilia A) Factor IX (Hemophilia B)

ALL TESTS LONG

FIBRINOGEN AND COMBINED DEFECTS

Factor VII deficiency

Fibrinogen Severe deficiency High concentration inhibitors

Common Pathway Factor II (Thrombin) Factor V Factor X

Contact Deficiencies Factor XI Factor XII (Hageman trait) Prekallikrein HMW Kininogen

C

Combined Deficiency Deficiency of fibrinogen and intrinsic, extrinsic, and common pathway factors

Combined Deficiency Vitamin K dependent factors: Factor II, VII, IX, X

Figure 1. Diagnostic algorithm for coagulation factor deficiencies

•  Intravenous administration of vitamin K is

­

  TREATMENT

•  Transfusion of fresh whole blood, fresh

plasma, and fresh frozen plasma will supply all coagulation factors. •  Cryoprecipitate is a specific source of factor VIII, fibrinogen, and von Willebrand factor; cryo-supernatant plasma supplies all other factors. •  Component therapy is preferred for surgical prophylaxis and nonanemic patients to prevent red cell sensitization and volume overload. •  Patients with severe acquired or hereditary factor deficiencies may require repeated transfusion (q8–12h) to control or prevent hemorrhage.

­

  MEDICATIONS

DRUG(S) OF CHOICE Vitamin K1 (1.0 to 2.0 mg/kg SQ using a small needle, or preferably PO q24h) is an effective treatment for patients with anti­coagulant rodenticide poisoning and other causes of vitamin K deficiency. CONTRAINDICATIONS Nonsteroidal anti-inflammatory drugs (NSAIDs), anticoagulants, and plasma expanders should be avoided to prevent further compromise of hemostasis. PRECAUTIONS

•  IM injections and jugular venipuncture

should be avoided, when possible, because of the risk of inducing additional bleeding.

not recommended because of the risk of anaphylaxis.

ALTERNATIVE DRUG(S) Antifibrinolytic drugs (aminocaproic acid and tranexamic acid) help correct coagulopathy due to acute trauma and reduce transfusion requirements for orthopedic procedures in humans, and have shown benefit to prevent postoperative bleeding in greyhounds. These drugs may also be used topically (e.g., bleeding from tooth extraction).

­

  FOLLOW-UP

PATIENT MONITORING •  PT or factor VII assays can be used to monitor effectiveness of vitamin K admin­ istration in animals with anticoagulant toxicity; test results should normalize after 24–48 hours of initiating therapy. •  ACT is a less specific but reasonable substitute for monitoring response to vitamin K. •  Hereditary defects can be monitored by cessation of bleeding, stabilization of hematocrit, resolution of hematoma, and, if needed, specific factor analyses. POSSIBLE COMPLICATIONS Transfusion poses a risk of immune and nonimmune reactions (see Blood Transfusion Reactions).

­

  MISCELLANEOUS

PREGNANCY/FERTILITY/BREEDING Patients with hereditary factor deficiencies should not be bred. SYNONYMS •  Coagulation defects. •  Coagulopathies. SEE ALSO

•  Coagulopathy of Liver Disease. •  Disseminated Intravascular Coagulation. •  Thrombocytopathies. •  Thrombocytopenia. •  Von Willebrand Disease.

ABBREVIATIONS

•  ACT = activated clotting time. •  APTT = activated partial thromboplastin time. •  BMBT = buccal mucosal bleeding time. •  DIC = disseminated intravascular coagulation. •  NSAID = nonsteroidal anti-inflammatory drug. •  PT = prothrombin time. •  TCT = thrombin clotting time. •  vWD = von Willebrand disease.

INTERNET RESOURCES http://eclinpath.com/hemostasis

­Suggested Reading

Brooks MB and DeLaforcade A. Acquired coagulopathies. In: Weiss DJ, Wardrop KJ, eds., Schalm’s Veterinary Hematology, 6th ed. Ames, IA: Wiley-Blackwell, 2010, pp. 654–660. Author Marjory B. Brooks Consulting Editor Melinda S. Camus

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Coagulopathy of Liver Disease •  Abdominal trauma, gastrointestinal

C

infiltrative disorders.

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BASICS

OVERVIEW •  The liver is the sole/primary site of synthesis of procoagulant, anticoagulant, and fibrinolytic proteins, except factors V, VIII, von Willebrand factor (vWF), tissue plasmin­ogen activator (TPA). •  Some patients develop prolonged in vitro clotting times, but few exhibit spontaneous bleeding. •  Causes of hemostatic imbalance: ◦ reduced synthesis or activation of procoagulant proteins; ◦  vitamin K deficiency; ◦  dysfibrinogenemia due to abnormal fibrin polymerization; ◦  reduced clearance of fibrin/fibrinogen degradation products (FDP); ◦  thrombocytopenia or thrombocytopathy; ◦  enhanced fibrinolysis. •  Vitamin K deficiency—linked to severe intra- or extrahepatic cholestasis, steatorrhea, or prolonged oral antibiotic administration.

CBC/BIOCHEMISTRY/URINALYSIS

­

microcytosis; thrombocytopenia.

DRUG(S) OF CHOICE •  Based on cause of hepatic abnormality. •  Vitamin K deficiency—parenteral vitamin K1 (0.5–1.5 mg/kg q12h SC up to 3 doses in 24h interval initially); vitamin K1 PO (Mephyton , 1 mg/kg q24h) if normal enteric bile ®acid uptake. •  DIC—correct primary disease; consider heparin for overt thrombosis (unfractionated heparin [UFH]: 200 U/kg q6–12h; or low molecular weight heparin [enoxaparin]: 1 mg/ kg q12–24h), dose titration based on clinical status and laboratory monitoring (ACT, APTT [UFH], heparin anti-Xa activity [all heparins]). •  Blood products—fresh whole blood: 12–20 mL/kg q24h; fresh frozen plasma: 10–20 mL/kg q12h; plasma cryosupernatant (albumin, vitamin K–dependent factors): 10–20 mL/kg q12h; cryoprecipitate (fibrinogen, vWF, factor VIII): 1 U/10 kg or dose to effect. •  Desmopressin acetate (DDAVP)— 0.5–1 μg/kg IV in saline; may increase coagulation factors, shortens bleeding times, reduces bleeding tendencies; empirically used for biopsy-induced bleeding. •  Antifibrinolytics—epsilon aminocaproic acid (EACA): 100 mg/kg loading, 30 mg/ kg/h up to 8h; tranexamic acid: 25 mg/kg q8h; if evidence of hyperfibrinolysis.

•  CBC—normal or regenerative anemia; •  Biochemistry—high liver enzymes;

bilirubinemia; low albumin; hypoglobulin­ emia; low cholesterol. •  Urinalysis—hematuria; bilirubinuria. OTHER LABORATORY TESTS Hemostatic tests—thrombocytopenia; prolonged APTT (activated clotting time [ACT]), prothrombin time (PT), thrombin clotting time (TCT), and proteins induced by vitamin K absence (PIVKA); low fibrinogen and coagulation factors; low anticoagulant factors (antithrombin [AT], protein C); high FDP and D-dimer. IMAGING Abdominal Ultrasonography

•  Effusion (ascites, hemorrhage). •  Liver changes—variable. •  Abnormal enteric motility, thickening in

area of bleeding.

SIGNALMENT Dog and cat of any age, breed, or sex. SIGNS

•  Often minor or absent. •  Melena, hematemesis, hematochezia, hematuria. •  Prolonged bleeding if provoked—venipunc-

ture, cystocentesis, biopsy, surgical wounds.

•  Spontaneous bruising/hematomas—rare

unless severe vitamin K deficiency or fulminant disseminated intravascular coagulation (DIC). CAUSES & RISK FACTORS

•  Severe hepatic failure of any etiology. •  Acute viral liver disease. •  Extrahepatic bile duct obstruction

(EHBDO).

•  Chronic liver disease—especially cirrhosis. •  Concurrent small bowel disease (e.g., cats

with cholangiohepatitis or hepatic lipidosis) predisposing to vitamin K deficiency. •  High central venous pressure (CVP) and portal hypertension. •  Portosystemic vascular anomaly (PSVA)— asymptomatic factor deficiency common; overt bleeding uncommon.

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DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Toxicities—see Hepatotoxins. •  Hereditary hemostatic defects. •  Thrombocytopenia. •  DIC—any cause. •  Hepatic amyloidosis.

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TREATMENT

•  Not necessary unless invasive procedures

planned or spontaneous hemorrhage noted.

•  Fresh whole blood—provides replacement

of red cells, coagulation factors, functional platelets. •  Fresh frozen plasma—provides coagulation factors, other hemostatic proteins, and reduces risk of red cell sensitization or volume overload. •  Cryoprecipitate—for severe hypofibrinogenemia or bleeding with coexistent von Willebrand’s disease (vWD). •  Platelet-rich plasma—rarely indicated. •  Avoid synthetic colloids if bleeding tendencies observed. Biopsy

•  High risk for bleeding—PIVKA, PT,

APTT, or ACT prolonged by >50%; thrombocytopenia 5 years. •  Large- to giant-breed dogs may present

injury. •  Osteochondritis dissecans of femoral condyle. •  Neoplasia (e.g., synovial sarcoma, osteosarcoma, chondrosarcoma). •  Traumatic fractures or avulsions. •  Caudal cruciate ligament rupture—uncommon and generally only seen with significant trauma.

Predominant Sex

CBC/BIOCHEMISTRY/URINALYSIS N/A

SIGNS

OTHER LABORATORY TESTS N/A

General Comments

IMAGING

Mean Age and Range

earlier in life; approx. 2 years of age.

Female—neutered.

Severity of lameness—related to degree of rupture (partial vs. complete), mode of rupture (acute vs. chronic), occurrence of meniscal injury, and severity of inflammation and DJD. Condition and therefore lameness may be bilateral. Historical Findings

•  Athletic or traumatic events—generally precede acute injuries. •  Normal activity

resulting in acute lameness—suggests degenerative rupture. •  Subtle to marked intermittent lameness (for weeks to months)— consistent with partial tears that are progressing to complete rupture.

Physical Examination Findings

•  Varying degrees of lameness and joint

effusion, pain, and/or crepitus; affected limb generally held in partial flexion while standing. •  Cranial drawer test—diagnostic for rupture; test in flexion, normal standing angle, and extension. •  Tibial compression test—cranial movement of tibia relative to femur when tightening gastrocnemius by flexing hock. •  Medial periarticular thickening (medial buttress). •  Presence of click or pop—63% accurate in detecting meniscal injury. •  Hind limb muscle atrophy—especially quadriceps muscle group. •  Falsenegative drawer or compression tests with chronic or partial tears and in painful or anxious patients that are not sedated or anesthetized. •  Earliest sign of partial rupture is pain on hyperextension of stifle.

CAUSES •  Trauma. •  Repetitive microinjury; excessive stifle loading. •  Progressive degeneration. RISK FACTORS

•  Obesity. •  Patella luxation. •  Conformati­ onal abnormalities. •  Excessive caudal slope of tibial plateau. •  Narrowed intercondylar

notch.

SIGNALMENT SPECIES Dog and cat. Breed Predilections

•  All susceptible. •  Rottweiler and Labrador

retriever—increased incidence when 1 year; DJD is progressive; not generally recommended. NURSING CARE Postsurgery—restricted activity with physical rehabilitation (e.g., ice packing, range-ofmotion exercises, massage, and muscle electrical stimulation); important for improving mobility and strength. ACTIVITY Restricted—duration depends on method of treatment and progress of patient.



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Cruciate Ligament Disease, Cranial

(continued)

DIET •  Weight control—important for decreasing load and thus stress on stifle joint. •  Joint-health diets rich in omega-3 fatty acids and chondroprotectants may support overall joint health. CLIENT EDUCATION •  Regardless of treatment, DJD is common and progressive. •  Return to full athletic function is possible, but requires early surgical intervention and rehabilitation. •  Rupture of contralateral CrCL can occur in 37–48% of patients. SURGICAL CONSIDERATIONS

•  No one technique has proven consistently superior, clinically or radiographically. •  Recent

force plate studies show slight differences between common techniques; dogs with tibial plateau leveling osteotomy (TPLO) procedure achieve normal limb loading faster than with extracapsular procedure.

Extra-articular Methods

•  Wide variety of techniques that use an

implant to mimic CrCL and restore stability; these techniques rely on periarticular fibrosis for long-term stability. •  Alternative method includes fibular head transposition to realign and tension lateral collateral ligament in order to restrict internal rotation and cranial drawer.

Intra-articular Methods

Designed to replace CrCL anatomically with autografts (patellar ligament, fascia), allografts, xenografts, and synthetic materials. Osteotomy Procedures

Cranial Tibial Closing Wedge Osteotomy •  Levels TPA by removing cranially based

wedge of bone from proximal tibia and eliminates cranial thrust. •  Held in place with bone plate and screws. •  Can potentially shorten tibia and alter stifle biomechanics.

TPLO

•  Rotational osteotomy of proximal tibia to level TPA and neutralize cranial tibial thrust. •  Held in place with bone plate and screws. •  Can accomplish correction for angular and torsional deformities.

Tibial Tuberosity Advancement

•  Tibial crest osteotomy; crest is held in

advanced position with cage and plate; bone graft fills defect. •  Active control of cranial tibial displacement improved, which helps stabilize stifle. •  Can combine technique with lateral transposition of tibial tuberosity to correct concurrent medial luxating patella.

PREGNANCY/FERTILITY/BREEDING N/A

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 MEDICATIONS

DRUG(S) OF CHOICE NSAIDs—minimize pain; decrease inflammation. CONTRAINDICATIONS Avoid concurrent use of corticosteroids with NSAIDs. PRECAUTIONS NSAIDs—gastrointestinal irritation or renal/ hepatic toxicity may preclude use in some patients. POSSIBLE INTERACTIONS N/A ALTERNATIVE DRUG(S) •  Chondroprotective drugs (polysulfated glycosaminoglycans, glucosamine, and chondroitin sulfate) may help reduce cartilage damage and improve regeneration. •  Omega-3 fatty acid supplementation to reduce inflammation is recommended.

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 FOLLOW-UP

PATIENT MONITORING Most techniques require 2–4 months of rehabilitation. PREVENTION/AVOIDANCE Avoid breeding animals with conformational abnormalities. POSSIBLE COMPLICATIONS •  Subsequent meniscal injury can occur in 6–22% of patients. •  Incisional and/or implant-related infection. •  Tibial tuberosity avulsion and/or fractures. •  Patellar luxation. •  Delayed bone healing (osteotomy procedures). •  Pivot shift—unknown clinical significance 1.040 in cats)—consider prerenal disorders such as dehydration. •  Cylindruria with azotemia and inadequately concentrated urine—consider renal failure. •  Cylindruria with leukocytosis—consider pyelonephritis or other infectious and inflammatory disorders. •  Cylindruria with glucosuria and proteinuria— consider renal tubular necrosis. •  Transient hyaline and/or granular casts can be seen after strenuous exercise. CBC/BIOCHEMISTRY/URINALYSIS

•  Casts classified by appearance and

quantified per low power field. •  Granular casts (fine or coarse) associated with tubular degeneration, inflammation, or necrosis. •  Hyaline casts can be seen with proteinuria,

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 TREATMENT

•  Manage as outpatient unless patient is

dehydrated or has decompensated kidney failure. •  Acute kidney injury and chronic kidney disease should be managed according to standard recommendations. •  If patient cannot maintain hydration, administer parenteral fluid therapy. •  Consider dialysis if toxin exposure or leptospirosis infection.

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 MEDICATIONS

CONTRAINDICATIONS/POSSIBLE INTERACTIONS Avoid nephrotoxic drugs.

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 FOLLOW-UP

PATIENT MONITORING •  Physical examination including patient’s weight to assess hydration status. •  Blood pressure monitoring. •  CBC/chemistry/ urinalysis monitoring. PREVENTION/AVOIDANCE Avoid or correct risk factors (e.g., exposure to toxins, infectious disease prevention, etc.). POSSIBLE COMPLICATIONS Irreversible renal disease, depending on underlying cause of cylindruria.

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 MISCELLANEOUS

ZOONOTIC POTENTIAL Possible in patients with leptospirosis. Use safety precautions when handing urine. SEE ALSO Nephrotoxicity, Drug-Induced. ABBREVIATIONS •  RBC = red blood cell. •  WBC = white blood cell.

­Suggested Reading

Latimer K. Duncan and Prasse’s Veterinary Laboratory Medicine Clinical Pathology, 5th ed. Ames, IA: Wiley-Blackwell, 2011, pp. 264–272. Sink C, Weinstein N. Practical Veterinary Urinalysis. Ames, IA: Wiley-Blackwell, 2012, pp. 69–84. Stockham S, Scott M. Fundamentals of Veterinary Clinical Pathology, 2nd ed. Ames, IA: Wiley-Blackwell, 2008, pp. 472–473. Author Tracie D. Romsland Consulting Editor J.D. Foster Acknowledgment The authors and book editors acknowledge the prior contributions of Allyson C. Berent and Cathy E. Langston.

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Cytauxzoonosis •  Moderate hyperbilirubinemia and

C

bilirubinuria.

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 BASICS

OVERVIEW •  Infection with the protozoan Cytauxzoon felis. •  Affects vascular system of lungs, liver, spleen, kidneys, and brain; bone marrow and developmental stages of red blood cells (RBCs) affected as well. •  Uncommon in most regions, but common during the spring and summer in endemic regions. •  Affects feral and domestic cats in southcentral, southeastern, and mid-Atlantic United States; range appears to be expanding towards eastern and northeastern United States. •  Related Cytauxzoon spp. have been identified in Europe and Asia, but have not been associated with classic Cytauxzoonosis (see Signs) as seen in North America. SIGNALMENT •  Domestic cats of all ages. •  Wild felids are also at risk. •  No breed or sex predilection, although most cases are diagnosed in young cats that have access to outdoors. SIGNS

•  Most cats have severe illness at presentation. •  Pale mucous membranes. •  Depression. •  Anorexia. •  Dehydration. •  High fever. •  Icterus. •  Splenomegaly. •  Hepatomegaly. •  Some cats may be infected but

•  Mild hyperglycemia. •  If present, anemia is believed to be

secondary to hemolysis.

OTHER LABORATORY TESTS

•  Fresh blood smear—Cytauxzoon erythro-

cytic form; 1–3 μm in diameter; shape of signet ring or safety pin. •  Schizont-infected monocyte/macrophages may be observed on feathered edge of thin blood smears. •  Splenic, lymph node, liver, or bone marrow aspirate—best suited to demonstrate extraerythrocytic schizont forms. •  PCR assay is commercially available. •  Blood type in all cats prior to transfusion. IMAGING Radiographs or ultrasound may assist in identifying pleural effusion or pulmonary edema.

CAUSES & RISK FACTORS

americanum or Dermacentor variabilis). •  Roaming in areas shared by reservoir hosts (bobcats). •  Living in same household/region as cat diagnosed with cytauxzoonosis.

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Other causes of pancytopenia such as sepsis and panleukopenia. •  Other causes of fever and jaundice such as pancreatitis, hepatitis, and cholangitis. CBC/BIOCHEMISTRY/URINALYSIS •  Bicytopenia or pancytopenia are the most common findings; thrombocytopenia is almost always present.

 FOLLOW-UP

EXPECTED COURSE AND PROGNOSIS •  With aggressive supportive care and treatment, expect 3–7 days of hospitalization with severe illness. •  Some cats develop pleural effusion and require thoracocentesis. •  Cats that survive will return to normal within 2–4 weeks of discharge and appear immune to reinfection. •  Some cats remain persistently infected with the intraerythrocytic form without overt signs. •  Without treatment, most cats with acute cytauxzoonosis have died within 5 days of presentation.

DIAGNOSTIC PROCEDURES N/A

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PATHOLOGIC FINDINGS Organisms inside myeloid cells in bone marrow aspirate and in dramatically enlarged myeloid cells in vessels of multiple organs including lung, liver, spleen, kidney, and brain.

•  RBC = red blood cell.

 MISCELLANEOUS

ZOONOTIC POTENTIAL •  No known risk to humans. •  Cannot be directly transmitted to another cat except by blood or tissue inoculation. ABBREVIATIONS

­Suggested Reading

­

 TREATMENT

•  Inpatient with aggressive supportive therapy

including supplemental oxygen.

•  Blood transfusion. •  Feeding tube for medication and nutri-

tional support.

asymptomatic.

•  Bite of infected tick (primarily Amblyomma

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­

 MEDICATIONS

DRUG(S) OF CHOICE •  Combination of atovaquone (15 mg/kg PO q8h with a fatty meal) and ­azithromycin (10 mg/kg PO q24h) and supportive care is associated with survival rates of 60%. •  Imidocarb dipropionate—5 mg IM two injections 14 days apart has been recommended, but is associated with survival rates of approximately 27%. •  Heparin (100–300 U/kg SC q8h or 300–900 U/kg/day as IV CRI) until time of discharge (longer if significant thrombosis such as pulmonary thromoboembolism is present). CONTRAINDICATIONS/POSSIBLE INTERACTIONS N/A

Cohn LA, Birkenheuer AJ, Brunker JD, et al. Efficacy of atovaquone and azithromycin or imidocarb dipropionate in cats with acute cytauxzoonosis. J Vet Intern Med 2011, 25(1):55–60. Reichard MV, Thomas JE, Arther RG, et al. Efficacy of an imidacloprid 10%/flumethrin 4.5% collar (Seresto®, Bayer) for preventing the transmission of Cytauxzoon felis to domestic cats by Amblyomma americanum. Parasitol Res 2013, 112(Suppl. 1):11–20. Author Adam J. Birkenheuer Consulting Editor Amie Koenig



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Canine and Feline, Seventh Edition

Deafness

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 BASICS

DEFINITION •  Partial or complete hearing loss. •  Two forms: ◦  Sensorineural deafness—caused by damage to receptors in cochlea, cochlear nerve, or auditory pathways in CNS. ◦  Conduction deafness—caused by inability to conduct sound vibration through external to inner-ear structures. PATHOPHYSIOLOGY Sensorineural Deafness

•  Hereditary—breed-related cochlear

degeneration closely associated with the recessive alleles of the piebald locus and the dominant allele of the merle locus in dogs and with the dominant allele of the white locus in cats. These genes alter the ability of neural crest melanocytes to populate regions of the body including skin, hair, iris, ocular tapetum, and portions of the cochlea. The absence of melanocytes in the stria vascularis of the cochlea is associated with early postnatal degeneration of this structure. Can also be non-pigment-associated and in some cases also affect the vestibular system, such as in Doberman pinschers (associated with a mutation in the PTPRQ gene). •  Acquired—cochlear degeneration due to chronic infection, ototoxicity, neoplasia, chronic exposure to loud noises, anesthesiaassociated, or age-related loss of hair cells and spiral ganglion cells (presbycusis). Conduction Deafness

•  Congenital defects in external ear canal,

tympanic membrane, or ossicles that transmit vibration in middle ear are rare. Hereditary predisposition in primary secretory otitis media in the cavalier King Charles spaniel. •  Acquired defects resulting in stenosis/ obstruction of external ear canal, rupture of tympanic membrane, or fusion of bony ossicles; most commonly associated with chronic otitis or middle ear polyps. SYSTEMS AFFECTED Nervous—inner ear. GENETICS Genetics of congenital deafness not fully understood, although strong association with the piebald and the merle locus in dogs and dominant white locus in cats (pigment-associated genes related to coat color). INCIDENCE/PREVALENCE Prevalence of congenital deafness in one or both ears available for the following breeds— Dalmatian: 30% in United States, 18% in UK, 17% in Switzerland, 20% in Germany; Jack Russell terrier: 4% in United States; Australian cattle dog: 15% in United States, 10% in Australia; English bull terrier: 11%

(20% if white) in UK; English setter: 8% in United States; English cocker spaniel: 7% in United States; border collie: 2–3% in UK; purebred white cats: 20% in United States and Germany; non-purebred white cats: 50% in UK and United States. GEOGRAPHIC DISTRIBUTION Prevalence for different breeds varies between countries. SIGNALMENT •  Breed-related congenital cochlear degeneration described in >90 breeds of dogs. Most breeds have a large amount of white pigmen­tation associated with merle or piebald genes, except for Doberman pinscher, puli, Shropshire terrier. Congenital sensorineural deafness present by 6 weeks of age, although has late onset in border collie (5 years) and Rhodesian ridgeback (4–12 months). •  No association with gender. Dogs with blue iris color have a higher incidence of congenital deafness. •  Mixed-breed cats with white hair coat and blue irises—high incidence of deafness. Purebred white cats that carry the Siamese gene for blue eyes have a lower incidence of congenital deafness. •  Acquired deafness may occur in any breed or age of dog and cat. SIGNS

•  Unilateral deafness often goes unnoticed.

Rarely, dogs have difficulty localizing sound.

•  With bilateral disease, animals do not

respond to auditory cues such as calling their name or rattling food dish. Often they are easily startled. Commonly have heightened response to vibration and visual cues. CAUSES

Sensorineural Deafness

•  Genetic etiology likely in neonates. •  Acquired cochlea and cochlear nerve

damage—infectious (otitis interna), neoplasia of bony labyrinth or nerve, trauma (physical or noise), systemic or topically applied drugs or toxins (antibiotics: aminoglycosides, polymyxin, erythromycin, vancomycin, chloramphenicol; antiseptics: ethanol, chlorhexidine, cetrimide; antineoplastics: cisplatin, carboplatin; diuretics: furosemide; heavy metals: arsenic, lead, mercury; miscellaneous: ceruminolytic agents, propylene glycol, salicylates), presbycusis, anesthesia-induced.

Conduction Deafness

•  Otitis externa and other external ear canal

disease (e.g., stenosis of canal, foreign bodies, neoplasia, or ruptured tympanum). •  Otitis media, middle-ear polyps, primary secretory otitis media. RISK FACTORS •  Merle, piebald gene, or white coat color; blue eye color.

•  Chronic otitis externa, media, or interna. •  Use of ototoxic drugs. •  General anesthesia.

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Early age of onset—suggests congenital causes in predisposed breeds. •  Use of ototoxic drugs, recent anesthesia, or chronic ear disease—suggests acquired causes. •  Evaluate for brain disease. CBC/BIOCHEMISTRY/URINALYSIS Usually normal. OTHER LABORATORY TESTS • Bacterial culture and sensitivity of ear canal if otitis externa. • Myringotomy with culture of aspirates if otitis media. IMAGING

•  Tympanic bullae and skull radiographs—

may show soft tissue opacity and bone remodeling of tympanic bulla; often unremarkable in cases with otitis media/interna. •  Ultrasound of tympanic bullae—may show anechoic content in cases with otitis media/ interna, but low sensitivity. •  CT/MRI—higher sensitivity for middle– inner ear disease and intracranial pathology. DIAGNOSTIC PROCEDURES

•  Brainstem auditory evoked response

(BAER)—gold standard test for evaluation of hearing. Measures electrical response of cochlea and auditory pathways in the brain to an auditory stimulus; reliable to identify dogs with unilateral disease or partial hearing loss. Bone conduction stimulation can be useful to distinguish sensorineural from conduction deafness. Can be used to determine the hearing threshold. •  Otoacoustic emissions (OAEs)—low-level sounds produced by inner ear as part of the normal hearing process that can be measured by placing a probe containing a microphone in the external ear canal. Two forms have been used in dogs for assessment of sensorineural deafness—transient evoked OAEs (TEOAEs) and distortion product OAEs (DPOAEs). OAE is best suited for cases with congenital deafness, as it tests outer hair cell function and is not affected by inner hair cell, synapse, or cochlear nerve deficiencies. DPOAEs may show benefits in assessing age-related and noise-induced hearing loss and may reduce cost and testing times in congenital sensorineural deafness compared to BAER. PATHOLOGIC FINDINGS

•  Congenital deafness—degeneration of the

stria vascularis with subsequent collapse of membranous labyrinth structures. Bony labyrinth remains intact.

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Deafness •  Acquired deafness—related to primary

D

disease such as otitis or neoplasia. •  Ototoxicity—degeneration of otic hair cells, cochlear nerve degeneration, and loss of stria vascularis.

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 TREATMENT

CLIENT EDUCATION Deaf animals may be functional pets, but require patience, specialized training, and extra protection from traffic. SURGICAL CONSIDERATIONS •  Directed toward acquired causes; congenital deafness irreversible. •  Otitis externa, media, or interna—medical or surgical approaches depend on culture and sensitivity test results, response to antibiotics, and imaging findings. Conduction may improve as otitis externa or media resolves.

(continued) •  Cochlear implants can be used in dogs with

moderate to profound deafness, but only preliminary data available and very expensive.

POSSIBLE COMPLICATIONS Deaf dogs need protected environments and training to be functional pets.

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 MEDICATIONS

DRUG(S) OF CHOICE •  None for congenital deafness. •  Treat otitis based on culture and sensitivity results. PRECAUTIONS •  Aminoglycosides or other ototoxic drugs— use with caution. •  Topical treatment of external ear canal— avoid if tympanic membrane is ruptured.

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 FOLLOW-UP

PATIENT MONITORING As needed for management of otitis.

 MISCELLANEOUS

PREGNANCY/FERTILITY/BREEDING Dogs homozygous for recessive merle gene can be blind and sterile. ABBREVIATIONS •  BAER = brainstem auditory evoked response. •  DPOAE = distortion product OAE. •  OAE = otoacoustic emission. •  TEOAE = transient evoked OAE. Author Rita Gonçalves   C  lient Education Handout available online



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Canine and Feline, Seventh Edition

Deciduous Teeth, Persistent (Retained) CAUSES & RISK FACTORS

a genetic basis. •  Small-breed dogs are predisposed.

erupted in an abnormal position, full root extraction of the deciduous tooth is necessary. •  If the deciduous root has undergone resorption, it may not need to be extracted.

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­

•  Cause is unknown, but is suspected to have

­

 BASICS

OVERVIEW •  A persistent (retained) deciduous tooth is one that is still present when the permanent tooth begins to erupt or has fully erupted. • Numerous factors influence the exfoliation of deciduous teeth—lack of a permanent successor; ankylosis of the deciduous crown or root to the alveolus; failure of the developing permanent crown to contact the deciduous root, preventing resorption of the deciduous root during eruption. SIGNALMENT

•  More common in dogs than cats. • More

common in small-breed dogs (e.g., Maltese, poodle, Yorkshire terrier, Pomeranian, etc.). • Occurs during permanent tooth eruption phase, which begins at 3 months of age for incisors and 5–7 months of age for canine teeth and molars. • Persistent deciduous teeth may not be detected or diagnosed until later in life. • No sex predilection. SIGNS

General Comments

•  Persistent deciduous teeth can cause the

permanent teeth to erupt in an abnormal position resulting in a malocclusion; early recognition and intervention are essential. •  Maxillary canine teeth erupt mesial (rostral) to the persistent deciduous canine teeth; this can result in a diastema (space) between the maxillary canine tooth and the third incisor that is too narrow to accommodate the crown zcanine position is referred to as mesioversion. •  Mandibular canine teeth erupt lingual to the persistent deciduous teeth; this can result in a narrow space between the lower canines resulting in impingement on the soft tissue of the hard palate. The mandibular canine position is referred to as linguoversion. •  All permanent incisors erupt lingual to the persistent deciduous incisors; this can result in a rostral crossbite.

Physical Examination Findings

•  Presence of a deciduous tooth with the permanent tooth erupting or fully erupted. •  Abnormal position of the permanent tooth due to persistence of the deciduous tooth. •  Oral malodor from accumulation of debris and plaque due to crowding of the permanent tooth and the persistent deciduous tooth. •  Local gingivitis and periodontal disease due to plaque accumulation from crowding. •  Oronasal fistula from linguoversion of the permanent mandibular canine teeth. •  Deciduous tooth crown is usually smaller than the permanent tooth. •  Deciduous tooth might not have an underlying permanent tooth, and will often remain intact and vital.

 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Supernumerary teeth. •  Gemination of the crown. CBC/BIOCHEMISTRY/URINALYSIS N/A IMAGING Intraoral Radiography

 MEDICATIONS

DRUG(S) OF CHOICE •  Topical oral antimicrobial rinse prior to extraction. •  Pain management prior to, during, and following extraction. CONTRAINDICATIONS/POSSIBLE INTERACTIONS N/A

•  Distinguish between permanent tooth and

deciduous tooth. •  Provide evidence or extent of root resorption of the deciduous tooth. •  Identify dental abnormalities prior to extraction, including persistent deciduous tooth with no permanent successor, retained root with crown missing, and unerupted permanent tooth. •  Identify relationship of deciduous root and permanent crown prior to extraction. DIAGNOSTIC PROCEDURES

•  Complete oral examination—chart oral

cavity to indicate presence of persistent deciduous teeth, malpositioned teeth, missing teeth, soft tissue trauma, and other oral abnormalities. •  Appropriate preoperative diagnostics prior to procedure to include intraoral radiography.

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 FOLLOW-UP

PATIENT MONITORING •  After surgery, restrict activity for the rest of the day. •  Analgesia (nonsteroidal anti-inflammatory drug [NSAID]) for 24–36 hours postop. •  Soft diet for 3 days—canned food or moistened dry kibble. •  No chew toys for 3 days; no “tug of war” for 1 week. •  Oral chlorhexidine rinse for 3–5 days. •  Continue daily tooth brushing after 24 hours. PREVENTION/AVOIDANCE May be prevalent in certain breeds and lines—avoid similar breeding.

PATHOLOGIC FINDINGS N/A

POSSIBLE COMPLICATIONS •  Malocclusion that results after full eruption of permanent teeth may require treatment. •  Linguoversion of one or both mandibular canine teeth. •  Mesioversion of one or both maxillary canine teeth.

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•  Once extracted, there should be no further

 TREATMENT

Client Education

•  Persistent deciduous teeth may be prevalent

in certain breeds. •  Start looking at teeth from the first puppy or kitten visit. •  Inform owners that you will be evaluating for exfoliation of deciduous teeth as well as for proper eruption of permanent teeth.

Surgical Considerations

•  Extract the deciduous tooth as soon as the

permanent tooth has erupted through the gingiva. •  Pain management - local/regional and systemic. •  Intraoral radiographs. •  General anesthesia with endotracheal tube in place and cuff inflated. •  Elevation of deciduous tooth. •  Careful, gentle elevation is critical; excessive force or pressure can damage the developing permanent tooth (and other underlying structures). •  A fractured or retained root may need to be removed with a gingival flap. •  If a permanent tooth has

EXPECTED COURSE AND PROGNOSIS problems. •  Resulting malocclusion needs further evaluation. •  Gingiva generally heals uneventfully.

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 MISCELLANEOUS

SEE ALSO Malocclusions—Skeletal and Dental. ABBREVIATIONS •  NSAID = nonsteroidal anti-inflammatory drug. INTERNET RESOURCES http://www.avdc.org/avdc-nomenclature

­Suggested Reading

Lobprise HB, Dodd JR eds. Wiggs’s Veterinary Dentistry: Principles and Practice, 2nd. Hoboken, NJ, Wiley-Blackwell; 2019. Author Randi Brannan Consulting Editor Heidi B. Lobprise

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Deep Cutaneous Mycoses SIGNALMENT

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Cryptococcosis

 BASICS

DEFINITION •  Fungal infections that may secondarily disseminate by hematogenous route to the skin. •  Most often caused by cryptococcosis, blastomycosis, and coccidioidomycosis.

•  Young dogs and cats; more common in

cats. •  Siamese, Birman, and ragdoll cats •  Doberman pinscher, German shepherd dogs, and cocker spaniels. Blastomycosis

PATHOPHYSIOLOGY

•  Young dogs (1–3 years); rare in cats. •  Doberman pinscher. •  Increased incidence in male dogs

Cryptococcosis

Coccidioidomycosis

Main route of infection is inhalation and colonization of nasal mucosa, followed by hematogenous spread to lymph nodes, skin, bones, and CNS. Blastomycosis

•  Infection by inhalation of spores produced from mycelial growth in the environment. •  Spores settle in airways, transform into yeast forms, and establish a primary infection of the lungs, followed by dissemination via blood and lymphatic vessels. •  Colonize lymph nodes, skin, eyes, bones, CNS, and testes.

Coccidioidomycosis

•  Infection by inhalation of arthroconidia. •  In the lungs, arthroconidia transform into

spherules filled with endospores, which disseminate by hematogenous routes to bones, skin, eyes, heart, testes, CNS, liver, and kidneys, among others.

•  Young dogs; rare in cats. •  Boxer and Doberman pinscher predisposed. •  Increased incidence in males.

•  Nonspecific clinical signs (asthenia, weakness, anorexia, weight loss), respiratory signs, or the appearance of skin lesions in the animal. •  Upper respiratory signs—cryptococcosis and blastomycosis. •  Lameness—coccidioidomycosis.

Physical Examination Findings (Skin)

Cryptococcosis

•  Cat—multiple papules, nodules, abscesses,

and ulcers; bridge of nose/dorsal muzzle (primary site) or any skin ara; lesions may drain a serous exudate. •  Dog—papules, dermal-subcutaneous nodules or ulcers; located on any portion of the integument, lips, tongue, or claw beds.

Blastomycosis

GENETICS N/A

Dog—dermal nodules that progress to abscesses and ulcers, or draining tracts over sites of infected bone; Coccidioides infection may also be asymptomatic.

INCIDENCE/PREVALENCE

can be very high (e.g., coccidioidomycosis in areas of Arizona). GEOGRAPHIC DISTRIBUTION

Cryptococcosis

•  C. neoformans worldwide distribution. •  C. gattii associated with tropical and

subtropical climates.

•  Recognized also in North America and

British Columbia (Vancouver Island).

Blastomycosis

Areas of the United States and Canada surrounding the Ohio and Mississippi River valleys, the Great Lakes, and the Saint Lawrence River. Coccidioidomycosis

Southwestern United States, Mexico, and areas of Central and South America.

disseminated infection.

Coccidioidomycosis

•  Dimorphic saprophytic fungi. •  Found in sandy, alkaline soils with high

environmental temperature.

•  Main infectious species Coccidioides immitis

and C. posadasi.

RISK FACTORS

•  Immunosuppressed hosts are more predis­-

posed to develop cryptococcosis caused by C. neoformans. •  Living in or visiting endemic areas increases risk of cryptococcosis (C. gattii), blasto­ mycosis, and coccidioidomycosis.

SIGNS Historical Findings

SYSTEMS AFFECTED Systemic infections via inhalation with hematogenous dissemination to multiple organs—skin, lymph nodes, eyes, bones, CNS, testes.

•  Uncommon diseases, •  Incidence depends on geographic location;

•  Yeast form in the mammal host causes

Dog—draining tracts and abscesses in one-third of cases; Planum nasale, face, and claw bed most frequent locations.

Coccidioidomycosis

CAUSES Cryptococcosis

•  Dimorphic fungi. •  Filamentous form in the environment. •  Yeast phase in mammalian tissues. •  Genus Cryptococcus includes 40 species—

most infections in dogs and cats caused by C. neoformans and C. gattii. •  C. neoformans often found in soils associated with bird excrement. •  C. gattii found in soils, especially in those covered with leaves of some tree species (eucalyptus), and in the bark of some trees (oak, maple, cedar). Blastomycosis

•  Dimorphic fungus. •  Mycelial form lives in moist soil and in

decomposing organic matter such as wood and leaves.

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Deep staphylococcal pyoderma. •  Nocardiosis. •  Actinomycosis. •  Mycobacterial infections. •  Pseudomycetoma (cat). •  Chromoblastomycosis. •  Pheohyphomycosis. •  Hyalohyphomycosis. •  Leishmaniasis. •  Sterile nodular panniculitis. •  Sterile pyogranuloma syndrome. •  Eosinophilic granuloma. CBC/BIOCHEMISTRY/URINALYSIS

•  Generally nonspecific—nonregenerative

anemia, leukocytosis, monocytosis, eosinophilia. •  Serum biochemical profile may reflect specific organ involvement; hypoalbuminemia and hyperglobulinemia common. OTHER LABORATORY TESTS Cryptococcosis

•  Detection of cryptococcal polysaccharide

capsular antigen in serum using a latex agglutination technique. •  Organism can be cultured in Sabouraud agar from skin lesions. Blastomycosis

Measuring antibodies in serum (agar gel immunodiffusion [AGID], ELISA) assists in diagnosis of blastomycosis when organisms cannot be specifically identified in cytologic or histologic specimens. Coccidioidomycosis

•  Conclusively diagnosed by cytologic or

histologic visualization of the organism.

•  Detection of antibodies (AGID, ELISA)

commonly used when the organism cannot be demonstrated in cytology or biopsy samples. •  Coccidioides grows in common culture media.



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Deep Cutaneous Mycoses

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•  Exposure to mycelial growth in cultures a

potential hazard to humans—organism should not be cultured outside of qualified laboratories with proper warning of the differential diagnosis.

IMAGING •  Radiographs-- evaluate for the presence of lesions in the upper airways, lungs, and bones. •  Ultrasound imaging—to evaluate for the presence of lesions in the abdominal cavity. DIAGNOSTIC PROCEDURES •  Cytologic evaluation of all cutaneous lesions (papules, nodules, abscesses) by fine-needle aspirate of solid lesions or impression smears of exudates. •  Cytologic preparations usually reveal a pyogranulomatous exudate with the presence of the causal organism. •  Cryptococcosis—number of organisms is very high and they are easily detected. •  Blastomycosis and coccidioidomycosis— detection of the fungal elements more difficult. If cytologic preparations are inconclusive, a skin biopsy for histopathologic examination should be obtained. •  Histologically, these diseases are characterized by a nodular to diffuse pyogranulomatous dermatitis and panniculitis, with the presence of the causal organisms. PATHOLOGIC FINDINGS Chronic pyogranulomatous reaction with the presence of organisms in tissues.

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 MEDICATIONS

DRUG(S) OF CHOICE Cryptococcosis

•  Itraconazole (5 mg/kg PO q12–24h). •  Fluconazole (10 mg/kg PO q12–24h). •  Treatment maintained for 6–18 months—

until resolution of clinical disease.

•  Some authors recommend continued

 TREATMENT

APPROPRIATE HEALTH CARE Outpatient medical management, unless severe internal lesions (meningoencephalitis, severe kidney disease). NURSING CARE N/A ACTIVITY Normal activity. DIET N/A CLIENT EDUCATION Owners should be informed of the risk involved in visiting areas where these infections are endemic. SURGICAL CONSIDERATIONS Surgical excision of large tissue masses infected with Cryptococcus (skin nodules, lymph nodes, nasopharyngeal masses) when possible.

POSSIBLE COMPLICATIONS N/A EXPECTED COURSE AND PROGNOSIS

•  Prognosis is guarded; depends on the

affected organs.

•  Poor prognosis with CNS involvement in

cryptococcosis.

antifungal therapy until the cryptococcal antigen is zero.

Blastomycosis

•  Itraconazole (5 mg/kg PO q12–24h). •  Fluconazole (10 mg/kg PO q12–24h). •  Treatment continued for at least 60 days

and at least 1 month after all signs of disease have resolved.

Coccidioidomycosis

•  Fluconazole (10 mg/kg PO q12–24h). •  Itraconazole (5 mg/kg PO q12–24h). •  Treatment is prolonged—treat for at least

1 year and/or until resolution of clinical disease. PRECAUTIONS N/A

POSSIBLE INTERACTIONS Azole antifungals, especially ketoconazole, are inhibitors of cytochrome P450 (CYP) and can increase serum levels of other drugs that are metabolized by this route (e.g., cyclosporine). ALTERNATIVE DRUG(S) Cryptococcosis

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PREVENTION/AVOIDANCE Avoid visiting areas where these infections are endemic.

Amphotericin B and flucytosine for CNS and/or resistant infection. Blastomycosis

Amphotericin B for resistant infection. Coccidioidomycosis

•  Ketoconazole (5–10 mg/kg PO q12– 24h)—if fluconazole or itraconazole is not available. •  Side effects more common and more severe with ketoconazole than with the other two azoles in cats.

CONTRAINDICATIONS

•  Ketoconazole is hepatotoxic and should not

be prescribed to patients with liver damage. •  Amphotericin B is nephrotoxic and is contraindicated in patients with kidney damage.

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 FOLLOW-UP

PATIENT MONITORING The frequency of monitoring depends on the severity and location of the lesions.

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 MISCELLANEOUS

ASSOCIATED CONDITIONS N/A ZOONOTIC POTENTIAL •  Cryptococcosis, blastomycosis, and coccidioidomycosis are not considered zoonoses. •  Infected dogs and cats pose no public health threat because infective forms are not produced in tissues. •  Handling mycelial cultures of the organism in the laboratory is dangerous. PREGNANCY/FERTILITY/ BREEDING •  Vertical transmission of cryptococcosis and blastomycosis has been reported in humans— considered extremely rare and not reported in dogs and cats. •  Intrauterine transmission of coccidioidomycosis not likely to occur because of the large size of the spherules. SYNONYMS

•  Cryptococcosis—torulosis, European

blastomycosis.

•  Blastomycosis—Gilchrist disease, Chicago

disease.

•  Coccidioidomycosis—valley fever, San

Joaquín Valley fever. ABBREVIATIONS

•  AGID = agar gel immunodiffusion.

INTERNET RESOURCES https://www.cdc.gov/fungal

­Suggested Reading

Greene CG. Infectious Diseases of the Dog and Cat, 4th ed. St. Louis, MO: Elsevier, 2012. Helton Rhodes KA, Werner A. Blackwell’s Five-Minute Veterinary Consult Clinical Companion: Small Animal Dermatology, 3rd ed. Hoboken, NJ: Wiley-Blackwell, 2018. Author Lluís Ferrer Consulting Editor Alexander H. Werner Resnick

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Demodicosis

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 BASICS

DEFINITION An inflammatory parasitic disease of dogs and cats characterized by an increased number of demodectic mites in the hair follicles and on the epidermis. PATHOPHYSIOLOGY Dogs

•  Three species of mites identified in the dog: ◦  Demodex canis—follicular mite; part of the

normal fauna of the skin; typically present in small numbers; resides in the hair follicles and sebaceous glands of the skin, transmitted from the mother to the neonate during the first 2–3 days of nursing. ◦  Demodex injai—large, long-bodied mite found in the pilosebaceous unit, mode of transmission unknown; only associated with adult-onset disease, with highest incidence noted in the terrier breeds often along the dorsal midline (West Highland white terrier and wirehaired fox terrier).◦  Demodex cornei—lives in the stratum corneum of the epidermis; mode of transmission unknown; most likely a morphologic variant of D. canis. •  Proliferation of mites may be the result of immunologic disorder, either genetic or iatrogenic. •  Pruritus occurs when a secondary bacterial infection is present. Cats

•  Two species of mites identified in the cat: ◦  Demodex gatoi—contagious; can be asympto­-

matic, but most commonly is associated with pruritic dermatitis leading to self-trauma, alopecia, and barbering. ◦  Demodex cati— often associated with immunosuppressive and metabolic disease; these mites cause folliculitis and alopecia, but are rarely pruritic. SYSTEMS AFFECTED Skin/exocrine. GENETICS Initial proliferation of mites may be the result of a genetic disorder. INCIDENCE/PREVALENCE •  Dogs—D. canis is very common. •  Cats— depending on geographic location, D. gatoi may be common or rare; D. cati is rare. SIGNALMENT Species

Dogs and cats. Breed Predilections

30 to depigmented and sun-exposed areas of skin. •  Uveodermatologic syndrome—management by veterinary ophthalmologist recommended. •  Appropriate antibiotics—pyoderma. •  Appropriate antifungals— dermatophytosis.

gus), neoplastic lymphocytes (epitheliotropic lymphoma). •  Joint tap—evidence of polyarthritis in SLE. •  Ocular examination—uveitis in uveodermatologic syndrome. •  Direct immunofluorescence— deposition of immunoglobulin at the basement membrane zone with DLE, SLE, and PE, and in the intercellular spaces of the epidermis with PF and PE. •  Skin biopsy. •  Genetic testing for oculocutaneous albinism. PATHOLOGIC FINDINGS Histopathologic Examination of the Skin •  Interface dermatitis—DLE, SLE, uveodermatologic syndrome. •  Pigmentary incontinence—DLE, PE. •  Intraepidermal

pustules with acantholysis—PF and PE. •  Hypomelanosis—vitiligo, uveodermatologic syndrome, seasonal nasal hypopigmentation, and Auriotrichosis. •  Apoptosis (individual cell necrosis of keratinocytes)— drug reaction and EM. •  Proliferation of spindle cells of dermal arteries and arterioles—proliferative arteritis. •  Infiltration of neoplastic lymphocytes— epitheliotropic lymphoma.

­

 MEDICATIONS

DRUG(S) OF CHOICE •  Auto-immune dermatoses—immuno­ suppressive therapy with prednisolone or dexamethasone and azathioprine (dogs) or chlorambucil (cats); see specific diseases. •  Topical corticosteroids—PE, DLE. •  Vitiligo and nasal depigmentation—no treatment. •  Epitheliotropic lymphoma— multiple treatment protocols. CONTRAINDICATIONS Azathioprine therapy—not recommended in cats; may cause fatal leukopenia or thrombocytopenia. ADVERSE REACTIONS Ketoconazole may cause lightening of the hair coat, elevated alkaline phosphatase, and gastro­intestinal distress. ALTERNATIVE DRUG(S)

•  Cyclosporine, modified—5 mg/kg/day for auto-immune disorders. •  Tacrolimus—0.1%

gel applied daily to lesions in combination with or to replace corticosteroids; may sting; avoid licking; wear latex gloves to apply. •  Pimecrolimus—1% cream applied daily to lesions in combination with or to replace corticosteroids; may sting; avoid licking; wear latex gloves to apply.

 TREATMENT

•  Outpatient, except for SLE, EM, and

cutaneous lymphoma with systemic involvement. •  Reduce exposure to sunlight—DLE, SLE, and PE. •  Immunosuppressive therapy— SLE, PF, and PE. •  Avoid contact with topical drugs. •  Contact dermatitis—avoid irritant; replace plastic or rubber dishes: particularly if

POSSIBLE COMPLICATIONS

•  Sunburn in areas of depigmentation. •  Squamous cell carcinoma—in cases of solar

damage and actinic keratosis of depigmented areas. •  SLE—associated scarring with ulcerative dermatitis.

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DIAGNOSTIC PROCEDURES

•  Cytology—acantholytic cells (pemphi-

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 FOLLOW-UP

PATIENT MONITORING •  Varies with specific disease and treatment prescribed. •  Postinflammatory depigmentation should resolve when the cause of inflammation is treated.

 MISCELLANEOUS

ZOONOTIC POTENTIAL Dermatophytosis—can cause infection in humans. SEE ALSO •  Cutaneous Drug Eruptions. •  Lupus Erythematosus, Cutaneous (Discoid). •  Lupus Erythematosus, Systemic (SLE). •  Lymphoma, Cutaneous Epitheliotropic. •  Pemphigus. •  Uveodermatologic Syndrome (VKH). ABBREVIATIONS

•  ANA = antinuclear antibody. •  DLE = discoid lupus erythematosus. •  EM = erythema multiforme. •  PE = pemphigus erythematosus. •  PF = pemphigus foliaceus. •  SLE = systemic lupus erythematosus.

­Suggested Reading

Mealey KL. Pharmacotherapeutics for Veterinary Dispensing. Ames, IA: WileyBlackwell, 2019. Miller W, Griffin C, Campbell, K. Muller and Kirk’s Small Animal Dermatology, 7th ed. St. Louis, MO: Elsevier, 2013. Morris DO, Kennis RA. Clinical dermatology, special issue. Vet Clin Small Anim Pract 2013, 43(1). Torres SMF, Roudebush P, eds., Advances in Veterinary Dermatology, Vol. 8. Hoboken, NJ: Wiley, 2017. Author Guillermina Manigot Consulting Editor Alexander H. Werner Resnick   Client Education Handout available online

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Dermatoses, Erosive or Ulcerative

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 BASICS

DEFINITION A heterogenous group of skin disorders characterized by disruption of the epidermis (erosions) or, if the basement membrane is compromised, the epidermis and dermis (ulcers). PATHOPHYSIOLOGY Varies widely, depending on the cause; may include congenital or developmental disorders that compromise tissue cohesion; cell-mediated (inflammatory or neoplastic) injury; anoxic injury; antigen-specific auto-immune disorders; and necrosis due to trauma, toxins, contactants (irritants), microbial organisms, or parasitic migration. SYSTEMS AFFECTED Skin/exocrine. GENETICS Some diseases are likely heritable due to breed predilections; however, there are no genetic screening tests available for any of the diseases listed. INCIDENCE/PREVALENCE Rare to common, depending on the cause. SIGNALMENT Species

Dogs and cats. Breed Predilections

Some specific causes (see below) have strong breed predilections, e.g., lupoid disorders, familial dermatomyositis, and zinc-responsive dermatosis. Mean Age and Range

•  Highly variable according to etiology.

• Canine juvenile cellulitis and several congenital diseases (see below) are diagnosed in very young animals.

Predominant Sex

Sex predispositions may vary according to the disease in question. SIGNS

Historical Findings

•  Pruritus may result in ulcers or erosions

due to self-trauma; especially ectoparasitism, superficial pyoderma, and Malassezia dermatitis. •  Exposure to caustic chemicals, burns, cold stress, venomous reptiles and insects, etc. •  Some infectious diseases (e.g., pythiosis, coccidioidomycosis, feline cow pox) have very restricted ranges. • Previous or concurrent systemic signs or illness.

Physical Examination Findings

•  Lesions may be heterogenous in gross

appearance; some diseases result in erythematous erosions with minimal crust or scale, while others cause scale or crusting that (when removed) results in erosion. •  Ulcers may be shallow/

superficial or deep; deep ulceration can present as sinuses with draining tracts, cavitated lesions with well-demarcated borders, or exudative crusted lesions. •  Some specific diseases are typically accompanied by fever and malaise, especially auto-immune disorders and infectious etiologies. •  May be associated with extracutaneous disease (e.g., superficial necrolytic dermatitis and hyper­eosinophilic syndrome of cats). CAUSES Autoimmune

•  Pemphigus foliaceus—crusting with erosion.

•  Pemphigus vulgaris—superficial ulcerative. • Bullous pemphigoid and epidermolysis bullosa acquisita—superficial ulcerative. • Discoid lupus erythematosus and muco­ cutaneous lupus erythematosus—erosive or superficial ulcerative. •  Exfoliative lupus (German shorthaired pointers)—scaling with erosion. • Vesicular lupus (rough collies and Shetland sheepdogs)—superficial ulcerative. • Cold agglutinin disease—deep ulcerative. Immune-Mediated

•  Erythema multiforme, Stevens–Johnson syndrome, and toxic epidermal necrolysis (may be drug induced)—erosive to superficial ulcerative. •  Vasculitis—superficial to deep ulcerative (may be cavitated). •  Idiopathic panniculitis—deep ulcerative (usually exudative with crusting). •  Canine eosinophilic furunculosis of the face (may be insect related)—ulcerative and crusting. •  Canine juvenile cellulitis (puppy strangles)—erosive to superficial or deep ulcerative. •  Feline indolent ulcer (rodent ulcer)—erosive to superficial or deep ulcerative.

Infectious

•  Surface pyoderma—acute moist pyotraumatic dermatitis: erosive. •  Superficial staphylococcal folliculitis—erosive to superficial ulcerative. •  Bacterial folliculitis/furunculosis—deep ulcerative. •  Superficial fungal (Malassezia dermatitis, dermatophytosis)—erosive to superficial ulcerative. •  Deep fungal (sporotrichosis, cryptococcosis, histoplasmosis, blastomycosis, coccidioidomycosis)—deep ulcerative with or without sinuses and draining tracts. •  Opportunistic mycobacteriosis—deep ulcerative nodules with sinuses and draining tracts. • Actinomycetic bacteria (Nocardia spp., Actinomyces spp., Streptomyces spp.)—deep ulcerative nodules with sinuses and draining tracts. •  Pythiosis/lagenidiosis and protothecosis— ulcerative, proliferative with or without draining tracts. •  Leishmaniasis—erosive to superficial or deep ulcerative. • Feline cow pox—deep ulcerative. •  Feline immunodeficiency virus (FIV)/feline leukemia virus (FeLV) related—erosive to superficial ulcerative. •  Feline herpesvirus-associated dermatosis—ulcerative with crusting.

Parasitic

•  Demodicosis—ulcerative with crusting

(especially with secondary bacterial folliculitis). •  Sarcoptic/notoedric mange—erosive with crusting. •  Flea bite allergy—erosive to ulcerative. •  Feline mosquito bite hypersensitivity—erosive to superficial or deep ulcerative. •  Pelodera and hookworm migration—deep ulcerative.

Congenital/Hereditary

•  Canine familial dermatomyositis (predomi-

nantly in collies and Shetland sheepdogs)— erosive. •  Epidermolysis bullosa—superficial ulcerative. • Cutaneous asthenia (Ehlers– Danlos syndrome)—skin tears easily.

Metabolic

•  Superficial necrolytic dermatitis (usually associated with advanced hepatic disease or pancreatic glucagonoma)—crusting with erosion. •  Hyperadrenocorticism—erosive to ulcerative when complicated by secondary infections or calcinosis cutis. •  Uremia (mucous membranes)—superficial ulcerative.

Neoplastic

•  Squamous cell carcinoma—erosive to

ulcerative with scale or crust. •  Feline squamous cell carcinoma in situ (Bowenoid in situ carcinoma)—erosive with scale or crust. •  Mast cell tumors—superficial to deep ulcerative. •  Epitheliotropic lymphoma (mycosis fungoides)—erosive to superficial ulcerative. • Feline thymoma-associated exfoliative dermatosis—scaling with erosion. •  Feline paraneoplastic alopecia—erosive.

Nutritional

Zinc-responsive dermatosis—crusting with erosion. Physical/Conformational Dermatoses

•  Pressure point ulcers—deep ulcerative.

• Intertrigo (skinfold pyoderma)—erosive.

Idiopathic

•  Feline dorsal neck ulcer—deep ulcerative

with crusting. •  Canine and feline acne— erosive to ulcerative. •  Feline plasma cell pododermatitis—superficial to deep ulcerative.

Miscellaneous

Thermal (heat/cold), electrical, solar, or chemical irritant/burns—depth of lesions depends on severity of insult.

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS Depends upon presentation. CBC/BIOCHEMISTRY/URINALYSIS May be abnormal with metabolic or systemic disease.



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Dermatoses, Erosive or Ulcerative

(continued)

IMAGING •  Rarely indicated. •  Thoracic radiographs—deep/systemic fungal diseases, feline thymoma-associated exfoliative dermatitis, or systemic neoplasia. •  Abdominal ultrasound—superficial necrolytic dermatitis (dogs) or paraneoplastic alopecia (cats). DIAGNOSTIC PROCEDURES •  Skin scraping—ectoparasitism. •  Direct impression cytology—bacteria, yeast, or acantholytic keratinocytes in pemphigus. •  Fine-needle aspirate with cytology— indurated or nodular lesions. •  Culture: bacterial (aerobic and anaerobic), mycobacterial, and/or fungal—suspected infectious disease. •  Fungal serology and serology for pythiosis and lagenidiosis may be indicated on a case-bycase basis and depending upon geographic location. •  PCR and immunohistochemistry are adjuncts to the histologic diagnosis of feline herpesvirus-associated dermatitis. PATHOLOGIC FINDINGS Skin Biopsy

•  For cavitated lesions, the leading edge (elliptical full-thickness biopsy) should be harvested with a scalpel blade if the defect is too large to be excised in total. •  Punch biopsy sufficient for diffuse erosive lesions; should take normal skin near a lesion and lesions that are both early and late in development.

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 TREATMENT

APPROPRIATE HEALTH CARE •  Outpatient for most diseases. •  Varies widely according to the cause. DIET

•  Nutritional support may be necessary in

debilitated animals, especially those with superficial necrolytic dermatitis. •  Correcting dietary deficiencies is the only treatment for generic dog-food dermatosis. •  Supplementation of zinc is necessary for zincresponsive dermatosis. CLIENT EDUCATION Variable by diagnosis; most important with suspected or confirmed zoonotic disease. SURGICAL CONSIDERATIONS

•  Indicated as curative treatment for feline

thymoma-associated exfoliative dermatitis. •  May be curative for nonmetastatic pancreatic or hepatobiliary tumors causing paraneoplastic alopecia. •  Radical surgical excision of nodules and draining tracts may be an adjunct to antimicrobial therapy of infections caused by rapid-growing Mycobacteria spp. and Nocardia spp. in cats and pythiosis or lagenidiosis in dogs.

immune-mediated, and infectious diseases listed may be teratogens.

­

 MEDICATIONS

DRUG(S) OF CHOICE Variable by cause. PRECAUTIONS Side effects—associated with many antimicrobial, immunosuppressive, and antineoplastic drugs. POSSIBLE INTERACTIONS Dependent on medications administered.

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 FOLLOW-UP

PATIENT MONITORING Dependent on disease process, concurrent systemic disease(s), drugs used, and potential side effects expected. PREVENTION/AVOIDANCE •  Incidence of many feline infectious diseases can be minimized by restricting outdoor activity. •  Some autoimmune diseases (lupus and pemphigus) are aggravated by ultraviolet light exposure; patients should be restricted from sun exposure during peak hours of the day. POSSIBLE COMPLICATIONS •  Determined by cause. •  Some diseases are potentially life-threatening. •  Some diseases have zoonotic potential. •  Infections and drug side effects are possible in cases requiring immunosuppression. EXPECTED COURSE AND PROGNOSIS •  Some infectious diseases (nocardiosis, atypical mycobacteriosis) may be controlled with chronic antimicrobial therapy, but are generally not curable if lesion progression is extensive by the time of diagnosis. •  Pythiosis/lagenidiosis— prognosis is extremely poor for response to therapy and survival when lesions are extensive.

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 MISCELLANEOUS

ZOONOTIC POTENTIAL •  Sarcoptic acariasis. •  Dermatophytosis. •  Sporotrichosis. •  Mycelial phase of some fungi (e.g., Coccidioides immitis, Blastomyces dermatitidis), when grown on culture media, can be infectious to humans through inhalation. In-clinic fungal culturing (other than for dermatophytes) is not advised. PREGNANCY/FERTILITY/BREEDING

•  Due to the potential severity of clinical

signs and syndromes, any patient diagnosed with an erosive/ulcerative disease that occurs with moderate to strong breed predilections should not be used for breeding. •  Many drugs used to treat the auto-immune,

SYNONYMS Superficial necrolytic dermatitis = necrolytic migratory erythema, metabolic epidermal necrosis, hepatocutaneous syndrome. SEE ALSO

•  Acne—Cats. •  Acne—Dogs. •  Actinomycosis & Nocardia. •  Azotemia and Uremia. •  Blastomycosis. •  Coccidioidomycosis. •  Cold Agglutinin Disease. •  Cryptococcosis. •  Demodicosis. •  Dermatophytosis. •  Feline Herpesvirus Infection. •  Feline Immunodeficiency Virus (FIV)

Infection.

•  Feline Leukemia Virus (FeLV) Infection. •  Feline Paraneoplastic Alopecia. •  Flea Bite Hypersensitivity and Flea Control. •  Histoplasmosis. •  Hookworms (Ancylostomiasis). •  Hyperadrenocorticism (Cushing’s Syndrome—

Dogs. •  Hyperadrenocorticism (Cushing’s Syndrome— Cats. •  Leishmaniosis, Cutaneous. •  Lupus Erythematosus, Cutaneous (Discoid). •  Lymphoma, Cutaneous Epitheliotropic. •  Malassezia Dermatitis. •  Mast Cell Tumors. •  Mycobacterial Infections. •  Notoedric Mange. •  Panniculitis/Steatitis. •  Pemphigus. •  Pododermatitis. •  Protothecosis. •  Puppy Strangles (Juvenile Cellulitis). •  Pyoderma. •  Pythiosis. •  Sarcoptic Mange. •  Sporotrichosis. •  Squamous Cell Carcinoma, Skin. •  Superficial Necrolytic Dermatitis. •  Vasculitis, Cutaneous. ABBREVIATIONS

•  FeLV = feline leukemia virus. •  FIV = feline immunodeficiency virus.

­Suggested Reading

Mason IS. Erosions and ulcerations. In: Ettinger SH, Feldman EC, eds., Textbook of Veterinary Internal Medicine, 7th ed. St. Louis, MO: Saunders Elsevier, 2010, pp. 79–83. Author Daniel O. Morris Consulting Editor Alexander H. Werner Resnick  Client Education Handout available online

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Dermatoses, Exfoliative

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 BASICS

DEFINITION Excessive or abnormal shedding of epidermal cells resulting in the clinical presentation of cutaneous scaling. PATHOPHYSIOLOGY •  An increase in the production, an increase in the desquamation, or a decrease in the cohesion of keratinocytes results in abnormal shedding of epidermal cells individually (fine scale) or in sheets (coarse scale). •  Primary exfoliative disorders—keratinization defects: genetic control of epidermal cell proliferation and maturation is abnormal. •  Secondary exfoliative disorders—disease alters the normal maturation and proliferation of epidermal cells. •  Anomalies in sebaceous or apocrine gland function may be present or causative. SYSTEMS AFFECTED Skin/exocrine. SIGNALMENT •  Dog and cat. •  Primary—apparent by 2 years of age; characteristic in affected breeds. •  Secondary—any age; any breed of dog or cat. SIGNS Physical Examination Findings

•  Dry or greasy collections of fine or coarse

scale located diffusely throughout the hair coat or focally in keratinaceous plaques. •  Oily skin and hair. •  Malodor. •  Comedones. •  Follicular casts. •  Candle wax–like deposits on hair. •  Silver scales, mostly affecting nose, face, and ears. •  Alopecia. •  Pruritus. •  Secondary bacterial folliculitis and/or Malassezia dermatitis. CAUSES Primary

•  Primary idiopathic seborrhea (primary keratinization disorder)—primary cellular defect; accelerated epidermopoiesis and hyperproliferation of the epidermis, follicular infundibulum, and sebaceous gland; cocker and springer spaniel, West Highland white terrier, basset hound, Doberman pinscher, Irish setter, and Labrador retriever. •  Vitamin A–responsive dermatosis—young cocker spaniels; clinically similar to severe idiopathic seborrhea; identified by response to oral vitamin A supplementation. •  Zinc-responsive dermatosis—alopecia, dry

scaling, crusting, and erythema around the eyes, ears, feet, lips, and external orifices; two syndromes: young adult dogs (mainly Siberian husky and Alaskan Malamute) and rapidly growing large-breed puppies; nutritionally responsive. •  Ectodermal defects—follicular dysplasias; color mutant or dilution alopecia; represent anomalies in melanization of the hair shaft and structural hair growth; keratinization defects theorized as causative for several syndromes; Doberman pinscher, Irish setter, dachshund, chow chow, Yorkshire terrier, poodle, Great Dane, whippet, saluki, and Italian greyhound; failure to regrow blue or fawn hair with normal “point” hair growth, excessive scaliness, comedone formation, secondary pyoderma. •  Idiopathic nasodigital hyperkeratosis— excessive build-up of scale and crusts on the nasal planum and footpad margins; possibly a senile change; generally asymptomatic; spaniels and retrievers; cracking and secondary bacterial infection can cause pain. •  Sebaceous adenitis—inflammatory disease targeting sebaceous glands and ducts causing patchy or diffuse hair loss and excessive scaling; tightly adherent follicular casts; standard poodle, Akita, Samoyed, German shepherd, Havanese, Bernese Mountain dog, and vizsla. •  Ichthyosis—rare and severe congenital disorder of keratinization; West Highland white terrier, golden retriever, cavalier King Charles spaniel, and Norfolk terrier; generalized accumulations of scale and crusts at an early age; secondary infections (bacterial and yeast) common. •  Primary seborrhea in Persian kittens. Secondary

•  Cutaneous hypersensitivity—with pruritus,

secondary skin trauma, and irritation.

•  Ectoparasitism—scabies, demodicosis, and

cheyletiellosis; with inflammation and exfoliation. •  Bacterial folliculitis—bacterial enzymatic disadhesion with increased exfoliation of keratinocytes. •  Dermatophytosis—increased exfoliation as a skin mechanism in resolving infection. •  Cutaneous Leishmaniasis in endemic regions of the world; systemic signs might be present. •  Endocrinopathy—hypothyroidism: abnormalities in keratinization, failure to regrow hair, and excessive sebum production; hyperadrenocorticism: abnormal keratinization and decreased follicular activity; excessive scaling and secondary pyoderma common in both syndromes; other hormonal abnormalities may also be associated with excessive scaling. •  Age—dull, brittle, and scaly hair coat due to alterations caused by natural changes in epidermal metabolism associated with age; no specific defect identified.

•  Nutritional disorders—malnutrition and

generic dog food dermatosis; auto-immune dermatoses—pemphigus complex: may appear exfoliative; vesicles become scaly and crusty; cutaneous and systemic lupus erythematosus: cutaneous signs often appear as areas of alopecia and scaling. •  Neoplasia—primary epidermal neoplasia (epitheliotropic lymphoma): with alopecia and scaling as epidermal structures are damaged by infiltrating lymphocytes; preneoplastic conditions (actinic keratosis): initially appear exfoliative. •  Miscellaneous—any disease process may result in excessive scale formation due to a metabolic disorder or to cutaneous inflammation. •  Exfoliative disorders—rare in cats: tail gland hyperplasia, feline thymoma-associated exfoliative dermatitis.

­

 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS Based on signalment and history (breed-associated vs. age of onset), presence/absence of pruritus (hypersensitivity vs. secondary infection), and concurrent signs (endocrinopathy). CBC/BIOCHEMISTRY/URINALYSIS •  Normal with primary keratinization disorders. •  Mild, nonregenerative anemia and hypercholesteremia are consistent with hypothyroidism. •  Neutrophilia, monocytosis, eosinopenia, lymphopenia, elevated serum alkaline phosphatase, hypercholesterolemia, and hyposthenuria suggest hyperadrenocorticism. OTHER LABORATORY TESTS Thyroid hormone levels and adrenal function tests if an endocrinopathy is suspected; see specific chapters for test recommendations. Serology, PCR, cytology, and histopathology for Leishmaniasis; see specific chapter. IMAGING Thoracic radiographs—feline thymomaassociated exfoliative dermatitis. DIAGNOSTIC PROCEDURES

•  Skin scraping. •  Skin biopsy—rule out particular differential

diagnoses; strongly recommended for most cases. •  Intradermal allergy test. •  Restricted ingredient food trial. •  Cytology of skin surface. •  Microscopic examination of plucked hairs—macromelanosomes and structural anomalies in follicular dysplasia and color dilution alopecia.





Dermatoses, Exfoliative

(continued)

•  Systemic antibiotics—secondary pyoderma. •  Retinoids—varied success for idiopathic or

­

 TREATMENT

•  Frequent and adequate topical therapy. •  Diagnose and control treatable primary and

secondary diseases. •  Recurrence of secondary infections may require repeated therapy and further diagnostics. •  Maintaining control is often lifelong. •  Prioritize restoration of epidermal barrier integrity and function.

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 MEDICATIONS

DRUG(S) OF CHOICE Shampoos

•  Contact time—5–15 minutes required; >15

minutes discouraged, may result in epidermal maceration, loss of barrier function, and excessive epidermal drying and irritation. •  Relative keratolytic activity—hypoallergenic < sulfur/salicylic acid < benzoyl peroxide. •  Ethyl lactate—less keratolytic/less drying; useful for moderate bacterial folliculitis and dry scale. •  Chlorhexidine—antimicrobial; mildly drying; useful for moderate bacterial folliculitis and Malassezia dermatitis. •  Tar—keratolytic, keratoplastic, and antipruritic; useful for moderate scale associated with pruritus. Moisturizers/Barrier Restoration

•  Restore skin hydration and increases

effectiveness of subsequent shampoos.

•  Humectants—enhance hydration of the

stratum corneum by attracting water from the dermis; at high concentrations may be keratolytic. •  Propylene glycol spray (50–75% dilution with water) applied frequently. •  Microencapsulation—may improve residual activity of moisturizers by allowing sustained release after bathing. •  Emollients—coat the skin; smooth the roughened surfaces produced by excessive scaling; usually combined with occlusives to promote hydration of the epidermis. •  Barrier restoration—phytosphingosines, ceramides. Systemic Therapy

•  Specific disease (e.g., thyroxine replacement

for hypothyroidism).

primary seborrhea; reports of individual response in refractory cases; isotretinoin (1 mg/kg PO q12–24h); if response is seen, taper dosage (1 mg/kg q48h or 0.5 mg/kg q24h); difficult to dispense due to strict prescription procedures. •  Cyclosporine (modified) 5 mg/kg/day until controlled, then decreased to minimal effective maintenance dosage for individual cases of keratinization disorder associated with hypersensitivity, sebaceous adenitis, epidermal dysplasia, ichthyosis, and/or Malassezia dermatitis. PRECAUTIONS

•  Corticosteroids—use judiciously to

control the inflammation resulting from exfoliative disorders; may mask signs of pyoderma and prevent accurate diagnosis of primary disease. •  Vitamin A and D analogues—side effects can be severe; patients should be referred to a dermatologist before being treated with these drugs; teratogenic.

ZOONOTIC POTENTIAL

•  Dermatophytosis and several ectoparasites

have zoonotic potential.

•  Leishmaniasis is a reportable disease.

PREGNANCY/FERTILITY/BREEDING Systemic retinoids and vitamin A in therapeutic dosages—extreme teratogen; do not use in intact females because of severe and predictable teratogenicity and extremely long withdrawal period; women of childbearing age should not handle these medications. SYNONYMS

•  Keratinization disorder, seborrhea,

idiopathic seborrhea, keratinization defect, dyskeratinization. •  Eczema, psoriasis, dandruff—incorrect human terms. •  Sebopsoriasis—correct term to describe similarities between some human and canine keratinization defects. SEE ALSO

•  Atopic Dermatitis. •  Demodicosis. •  Hyperadrenocorticism (Cushing’s

Syndrome)—Cats.

•  Hyperadrenocorticism (Cushing’s

Syndrome)—Dogs.

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 FOLLOW-UP

PATIENT MONITORING •  Antibiotics and topical therapy—monitor response every 3 weeks; patients may respond differently to the various topical therapies. •  Development of additional diseases and recurrence of pyoderma—reevaluation critical to determine if new factors are involved and if changes in therapy are necessary. •  Endocrinopathy—specific laboratory testing for disease management. •  Selective autoimmune disorders—clinical evaluation and laboratory monitoring frequent initially; based on diagnosis and treatment protocols. •  Retinoid drugs—serum chemistries, including triglycerides, and Schirmer tear tests.

•  Hypothyroidism. •  Leishmaniosis •  Malassezia Dermatitis. •  Pyoderma. •  Sarcoptic Mange.

­Suggested Reading

Gross TL, Ihrke PJ, Walder EJ, Affolter V. Skin Diseases of the Dog and Cat: Clinical and Histopathologic Diagnosis, 2nd ed. Oxford: Blackwell Science, 2005. Miller W, Griffin C, Campbell, K. Muller and Kirk’s Small Animal Dermatology, 7th ed. St. Louis, MO: Elsevier, 2013. Torres SMF, Roudebush P, eds., Advances in Veterinary Dermatology, Vol. 8. Hoboken, NJ: Wiley, 2017. Author Guillermina Manigot Consulting Editor Alexander H. Werner Resnick  Client Education Handout

­

 MISCELLANEOUS

AGE-RELATED FACTORS Skin aging might be related to increase in exfoliative disorders or relapses.

available online

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Dermatoses, Neoplastic •  The most frequently reported cutaneous or

D ­

 BASICS

DEFINITION •  Neoplastic proliferation of cells derived from the skin or migrating to the skin. •  Epidermal tumors include those arising from keratinocytes, melanocytes, Merkel cells, and Langerhans cells, and epitheliotropic lymphoma. •  Adnexal tumors include those arising from hair follicles, sebaceous glands, and sweat glands. •  Dermal and subcutaneous skin tumors include those of mesenchymal origin and tumors of round cell origin. •  Secondary or metastatic skin tumors result from the proliferation of cells from primary neoplasms of other organs in the skin. PATHOPHYSIOLOGY •  Neoplasia develops as a result of changes in genes controlling cell proliferation and homeostasis. •  More than 100 cancer-related genes have been identified. •  Oncogenes encode proteins that promote cell growth; tumor-suppressor genes encode proteins that restrict cell proliferation and differentiation. •  Mutations in p53, a tumor-suppressor gene, are found in approximately 50% of cancers in humans and have also been found in many tumors affecting dogs and cats. •  Ultraviolet light promotes tumor development by damaging DNA and suppressing the immune system. •  Many viruses promote tumor growth through stimulating cell proliferation and/or suppressing the immune system. •  Reports of specific cutaneous neoplasia associated with medications and/or vaccinations. SYSTEMS AFFECTED Skin/exocrine. GENETICS •  Breed predispositions have been reported for specific tumors, but the mode of inheritance in these breeds has not been determined. Mutations in oncogenes and/or tumor-suppressor genes (e.g., p53) are present in many types of skin tumors. INCIDENCE/PREVALENCE

•  The combined incidence rate for skin

tumors has been reported as 728/100,000 (0.728%) for dogs and 84/100,000 (0.084%) for cats. •  The skin is the most common site of occurrence of neoplasia in the dog (30% of total tumors) and the second most common site in the cat (20% of total tumors). •  Canine skin tumors are approximately 55% mesenchymal, 40% epithelial, and 5% melanocytic. •  The most frequently reported cutaneous or subcutaneous tumors in descending order for dogs are lipoma, sebaceous gland adenoma, mast cell tumor, papilloma, and histiocytoma. •  Feline skin tumors are approximately 50% epithelial, 48% mesenchymal, and 2% melanocytic.

subcutaneous tumors in cats are basal cell tumor, squamous cell carcinoma, mast cell tumor, and fibrosarcoma. •  Skin tumors in cats are more frequently malignant; skin tumors in dogs are more frequently benign.

GEOGRAPHIC DISTRIBUTION Geographic regions near the equator, with high altitude, or with sand or other reflective surfaces, have a higher incidence of solarinduced neoplastic dermatoses.

SIGNS General Comments

Most common clinical sign is a cutaneous or subcutaneous nodule; some tumors have an ulcerated surface; others may result in excessive scaling or in the formation of cutaneous plaques. Historical Findings

•  Tumors are most often slow growing; the

SIGNALMENT

owner may find them during petting, bathing, or grooming of the pet. •  Tumors may be rapidly growing and appear (or increase in size) quickly (e.g., histiocytoma).

Species

Physical Examination Findings

Dogs and cats. Breed Predilections

•  Canine breeds with the highest overall

incidence of skin tumors include boxer, Scottish terrier, bullmastiff, basset hound, Weimaraner, Kerry blue terrier, and Norwegian elkhound. •  Feline breeds with the highest overall incidence of skin tumors include Siamese and Persian. •  Certain breeds are predisposed to specific types of tumors (see Suggested Reading). •  Dog— breeds associated with the most common cutaneous neoplasms: ◦  Lipoma—cocker spaniel, dachshund, Doberman pinscher, Labrador retriever, miniature schnauzer, Weimaraner. ◦  Sebaceous gland tumor— beagle, cocker spaniel, dachshund, Irish setter, Lhasa apso, Malamute, miniature schnauzer, poodle, shih tzu, Siberian husky. ◦  Mast cell tumor—American Staffordshire terrier, beagle, Boston terrier, boxer, bull terrier, dachshund, English bulldog, fox terrier, golden retriever, Labrador retriever, pug, shar-pei, Weimaraner. ◦  Histiocytoma— American Staffordshire terrier, Boston terrier, boxer, cocker spaniel, dachshund, Doberman pinscher, English springer spaniel, Great Dane, Labrador retriever, miniature schnauzer, Rottweiler, Scottish terrier, shar-pei, Shetland sheepdog, West Highland white terrier. ◦  Papilloma—cocker spaniel, Kerry blue terrier. •  Cat—breeds associated with the most common cutaneous neoplasms: ◦  Basal cell tumor—Persian, Himalayan (basal cell carcinoma—Siamese). ◦  Squamous cell carcinoma—no predisposed breed reported. ◦  Mast cell tumor—Siamese. ◦  Fibrosarcoma—no predisposed breed reported. Mean Age and Range

•  The median age for cutaneous neoplasia is 10.5 years in dogs and 12 years in cats. •  The

peak age period for cutaneous neoplasia in dogs and cats is 6–14 years.

Predominant Sex

•  Females have a higher incidence of tumors in dogs (56%). •  Males have a higher

incidence of tumors in cats (56%).

•  Nodules—cutaneous or subcutaneous. •  Cutaneous ulcers. •  Excessive scaling. •  Cutaneous papillomas. •  Cutaneous

plaques.

CAUSES •  Genetic (gene mutations). •  Environmental (e.g., ultraviolet light, radiation exposure). •  Viruses (e.g., papillomaviruses, feline leukemia virus, feline immunodeficiency virus). •  Toxins (e.g., tars). •  Drugs (e.g., immuno­ suppressive agents, chemotherapeutic agents). ◦  Epidermal neoplasms: ◦  Keratinocytes— papillomas, squamous cell carcinoma, basal cell carcinoma, basosquamous carcinoma. ◦  Melanocytes—melanoma. ◦  Merkel cells—Merkel cell carcinoma. ◦  Langerhans cells—histiocytoma and malignant histiocytosis. ◦  Epitheliotropic lymphoma— T lymphocytes. •  Adnexal neoplasms: ◦  Hair follicles—trichofolliculoma, trichoepithelioma, infundibular keratinizing acanthoma, tricholemmoma, pilomatrixoma, trichoblastoma. ◦  Sebaceous glands—sebaceous adenoma, sebaceous epithelioma, sebaceous adenocarcinoma, perianal gland epithelioma, perianal gland carcinoma. ◦  Sweat glands— apocrine cystadenoma, apocrine secretory adenoma/adenocarcinoma, apocrine ductal adenoma/carcinoma, eccrine carcinoma. •  Dermal and subcutaneous neoplasms: ◦  Mesenchymal origin—soft tissue sarcoma: fibroma/fibrosarcoma, myxoma/ myxosarcoma, hemangiopericytoma, lymphangioma/lymphangiosarcoma, hemangioma/hemangiosarcoma, lipoma/ liposarcoma, neurofibrosarcoma, leiomyoma/ leiomyosarcoma, synovioma/synovial sarcoma, rhabdomyoma/rhabdomyosarcoma. ◦  Round cell origin—transmissible venereal tumor, mast cell tumor, plasmacytoma, lymphoma, histocytoma, and histocytic tumors. •  Secondary or metastatic skin tumors result from the metastasis or primary neoplasms in other organs to the skin. RISK FACTORS

•  Hair coat color and length (e.g., hairless

breeds, white hair coat, lightly pigmented skin—increased risk for squamous cell carcinoma). •  Age (e.g., young animals



Canine and Feline, Seventh Edition



Dermatoses, Neoplastic

(continued)

highest risk for viral infections, older animals at highest risk for environmentassociated neoplasia). •  Sunlight exposure (e.g., dogs and cats that sunbathe or spend time outdoors on reflective surfaces have higher risk of ultraviolet light–induced skin tumors). •  Genetics—certain breeds have higher risk of developing specific types of tumors (see above and Suggested Reading).

ACTIVITY Varies with tumor type and location.

AGE-RELATED FACTORS Vary with tumor type and location.

DIET Diets high in omega-3 fatty acids, arginine, and protein may be beneficial in boosting the immune response and preventing cancerassociated cachexia.

ZOONOTIC POTENTIAL None

CLIENT EDUCATION Varies with tumor type and location.

SYNONYMS N/A

SURGICAL CONSIDERATIONS

•  Vary with tumor type and location—wide

­

 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Cyst. •  Abscess. •  Inflammatory nodule/ granuloma/plaque—sterile granulomatous and pyogranulomatous disease, sterile panniculitis, fungal infection, mycobacterial infection, foreign body. •  Trauma/self-induced skin ulceration. •  Hamartoma/nevus.

379

margins may be needed to prevent reoccurrence of infiltrative tumors. •  Pretreatment with antihistamines approp­ riate when excising mast cell tumors.

­

 MEDICATIONS

PREGNANCY/FERTILITY/BREEDING Varies with tumor type; some may have a genetic predisposition.

SEE ALSO

•  Adenocarcinoma, Skin (Sweat Gland,

Sebaceous). •  Basal Cell Tumor. •  Fibrosarcoma, Bone. •  Lipoma, Infiltrative. •  Malignant Fibrous Histiocytoma. •  Mast Cell Tumors. •  Papillomatosis. •  Squamous Cell Carcinoma, Skin. INTERNET RESOURCES

DRUG(S) OF CHOICE Vary with tumor type—chemotherapy protocols are useful in some cases.

•  http://www.oncolink.org/types/section.

OTHER LABORATORY TESTS

CONTRAINDICATIONS Vary with tumor type and presence of concurrent disease.

­Suggested Reading

staging).

PRECAUTIONS Vary with tumor type and location.

CBC/BIOCHEMISTRY/URINALYSIS N/A •  Cytology (fine-needle aspirate or impression smear). •  Regional lymph node aspirate (for

IMAGING Thoracic radiographs and abdominal ultrasonography useful for staging (evaluate for metastatic disease or underlying primary neoplasia). DIAGNOSTIC PROCEDURES

POSSIBLE INTERACTIONS Vary with tumor type and location. ALTERNATIVE DRUG(S) Vary with tumor type and location.

•  Cytology. •  Biopsy with histopathologic examination. •  Immunohistochemistry (useful

in confirming certain types of tumors).

PATHOLOGIC FINDINGS Varies with tumor type; see specific tumors for additional information.

­

 TREATMENT

APPROPRIATE HEALTH CARE •  Varies with tumor type. •  Observation is appropriate for some benign tumors. •  Surgical excision, cryosurgery, radiation therapy, and/or tumor-specific chemotherapy or immunotherapy may be curative or palliative.

­

 FOLLOW-UP

PATIENT MONITORING Varies with tumor type and location. PREVENTION/AVOIDANCE •  Varies with tumor type and location. •  Minimize exposure to ultraviolet light to help prevent some types of tumors. POSSIBLE COMPLICATIONS Vary with tumor type and location. EXPECTED COURSE AND PROGNOSIS Vary with tumor type and location.

NURSING CARE

­

tumors may become secondarily infected.

ASSOCIATED CONDITIONS Vary with tumor type and location.

•  Varies with tumor type and location. •  Traumatized

 MISCELLANEOUS

cfm?c=22&s=69

•  http://www.vetcancersociety.org

Campbell KL, ed. Small Animal Dermatology Secrets. Philadelphia, PA: Hanley & Belfus, 2004, pp. 385–458. Goldschmidt MH, Shofer FS. Skin Tumors of the Dog and Cat. Oxford: Butterworth Heinemann, 1992. Gross TL, Ihrke PJ, Walder EJ, et al. Skin Diseases of the Dog and Cat: Clinical and Histopathologic Diagnosis, 2nd ed. Oxford: Blackwell, 2005, pp. 561–893. Martin PD, Argyle DJ. Advances in the management of skin cancer. Vet Dermatol 2013, 24:173–180. Miller WH, Griffin CE, Campbell KL, eds. Muller & Kirk’s Small Animal Dermatology, 7th ed. Philadelphia, PA: Elsevier, 2013, pp. 774–843. Shearer D, Dobson J. An approach to nodules and draining sinuses. In: Foster A, Foil C, BSAVA Manual of Small Animal Dermatology, 2nd ed. Gloucester: BSAVA, pp. 55–65. Author Karen L. Campbell Consulting Editor Alexander H. Werner Resnick

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Dermatoses, Papulonodular •  Metabolic—cutaneous xanthomatosis,

D ­

 BASICS

DEFINITION •  Diseases whose primary lesions manifest as papules and nodules. •  Papule—solid, elevated lesion of the skin less than 1 cm in diameter. •  Nodule—solid, elevated lesion of the skin more than 1 cm in diameter that extends into deeper layers of the skin. PATHOPHYSIOLOGY •  Papules—usually the result of tissue infiltration by inflammatory cells; accompanying intraepidermal edema or epidermal hyperplasia and dermal edema. •  Nodules—usually the result of a massive infiltration of inflammatory or neoplastic cells into the dermis or subcutis. SYSTEMS AFFECTED Skin/exocrine. GENETICS Determined by cause; specific diseases may be more commonly seen in certain breeds. INCIDENCE/PREVALENCE Determined by cause. GEOGRAPHIC DISTRIBUTION Determined by cause. SIGNALMENT Species

Dogs and cats. Breed Predilection

Determined by cause. Mean Age and Range

Determined by cause. Predominant Sex

Determined by cause. SIGNS •  Papules and/or nodules with distribution characteristic of the cause. •  Accompanying crusting, inflammation, pigmentation changes, and hair coat changes often noted; also characteristic of the cause. CAUSES •  Superficial and deep bacterial folliculitis (e.g., Staphylococcus). •  Other bacterial—mycobacterial, actinomy­ cosis, nocardiosis, abscess. •  Fungal—dermatophytosis (including pseudomycetoma/kerion), histoplasmosis, cryptococcosis, coccidiomycosis, sporo­ trichosis, blastomycosis, phaeohyphomycosis. •  Sebaceous adenitis, granulomatous. •  Canine and feline acne. •  Parasitic—demodicosis, Leishmaniasis, flea bite hypersensitivity, sarcoptic mange, pelodera dermatitis. •  Sterile nodular—sterile pyogranulomatous dermatitis and panniculitis, reactive histiocytosis.

calcinosis circumscripta. •  Hypersensitivity—feline eosinophilic dermatitis. •  Neoplasia. RISK FACTORS

•  Bacterial folliculitis, dermatophytosis, and

demodicosis—any disease or medication that causes immune compromise or interferes with the barrier function of the skin. •  Pelodera dermatitis—may be associated with contact with decaying organic debris (straw or hay) containing Pelodera strongyloides.

­

 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS Determined by cause. CBC/BIOCHEMISTRY/URINALYSIS Usually normal—determined by cause. OTHER LABORATORY TESTS Determined by cause. IMAGING N/A DIAGNOSTIC PROCEDURES •  Skin scraping—parasites. •  Dermatophyte cultures—dermatophytes. •  Pustule (if present) impression smear cytology—bacteria and degenerative neutrophils compatible with bacterial folliculitis; eosinophils can be compatible with hypersensitivity and/or with rupturing folliculitis or furunculosis; acantholytic keratinocytes consistent with an inflamma­ tory folliculitis or pemphigus disease. •  Culture from tissue (fungal, bacterial, myco­bacterial)—identify deep/systemic infection; possible susceptibility report for treatment. •  Aspirate and cytology from nodule—identify cellular infiltrate; presence of organisms. •  Skin biopsy— determine definitive diagnosis; especially if baseline diagnostic procedures are normal and/or initial empiric treatment is ineffective. PATHOLOGIC FINDINGS Depends upon underlying disease process.

­

 TREATMENT

APPROPRIATE HEALTH CARE •  Outpatient for nearly all causes (except some cases of neoplasia). •  Generalized demodicosis with secondary sepsis requires hospitalization. NURSING CARE Depends upon underlying issue.

ACTIVITY No specific alteration of activity recommended. DIET No specific alteration of diet recommended. CLIENT EDUCATION

•  For fungal infections, treatment may be

expensive and prognosis can be guarded for deep/systemic fungal infections. •  For immune-mediated processes, treatment may be for the duration of the patient’s life. SURGICAL CONSIDERATIONS Rarely necessary unless neoplasia is diagnosed.

­

 MEDICATIONS

DRUG(S) OF CHOICE Bacterial Folliculitis

•  Superficial pyoderma—appropriate

antibiotics based on bacterial culture and susceptibility testing for at least 3–4 weeks, or 1 week beyond resolution of clinical signs. •  Deep pyoderma—appropriate antibiotics based on bacterial culture and susceptibility testing for at least 6–8 weeks, or 2 weeks beyond resolution of clinical signs. •  Identify and control underlying cause to prevent recurrence. •  See Pyoderma for additional recomm­endations. Sebaceous Adenitis

•  Appropriate antibiotics if secondary

bacterial infection present.

•  Propylene glycol and water (50–75%

dilution) once daily as a spray to affected areas helpful in mild cases. •  Essential fatty acid dietary supplements (omega-3 and omega-6 PO). •  Topical therapy—antiseborrheic shampoos, emollient rinses (baby oil), and humectants. •  Cyclosporine, modified (5 mg/kg PO q24h). •  Vitamin A (10,000–30,000 IU PO daily or 1000 IU/kg PO daily). •  Refractory cases—isotretinoin (1 mg/kg PO q12–24h); if response is seen, taper dosage (1 mg/kg q48h or 0.5 mg/kg q24h); the synthetic retinoids have become difficult to dispense due to strict prescrip­ tion procedures. •  Most cases are refractory to corticosteroids. •  See Sebaceous Adenitis, Granulomatous for additional recommendations. Canine and Feline Acne

•  May resolve without therapy in mild cases. •  Warm water soaks or Epsom salt solution

(2 T/quart or 30 m/L of water) for 5–10 min.

•  Chlorhexidine-based pads, or acetic acid/

boric acid pads/wipes, or benzoyl peroxide gels used daily or alternated daily; topical ceramide/EFA preparations may be helpful.



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Dermatoses, Papulonodular

(continued)

•  Topical creams/ointments—mupirocin 2%

ointment: topical antibiotic; apply q24h; should not be used in cats with deep lesions; metronidazole, 0.05% Vitamin A acid cream, clindamycin are alternative options. •  Secondary bacterial infection—systemic antibiotics. •  Underlying cause(s) should be determined and treated accordingly. •  Refractory cases—isotretinoin (1–2 mg/kg PO q24h); oral synthetic retinoids have become difficult to dispense due to strict prescription procedures; prednisolone PO (1–2 mg/kg/day for 10–14 days and taper) may reduce scar tissue formation. •  See Acne—Cats and Acne—Dogs for additional recommendations. Pelodera Dermatitis

•  Remove and destroy bedding. •  Wash kennels, beds, and cages and treat

with a premise insecticide or flea spray.

•  Bathe affected animal and remove crusts. •  Parasiticidal dip or ivermectin as recom­

mended for sarcoptic mange.

•  Corticosteroids as needed for inflammation. •  Severe infection—may require use of

antibiotics.

Sterile Nodular Dermatoses

•  Attempt to identify underlying cause. •  Cyclosporine, modified 5 mg/kg PO q24h. •  Tetracycline (250 mg 10 kg q8–12h), doxycycline (10 mg/kg q24h), or minocycline (5 mg/kg q12h) with niacinamide (250 mg 10 kg q8–12h). •  Corticosteroids at immunosuppressive doses and taper according to response. •  Chemotherapeutic drugs (chlorambucil or azathioprine or mycophenolate mofetil). Other

PRECAUTIONS

•  Side effects more common and more severe

with ketoconazole than with other azoles in cats. •  Cats can be sensitive to the irritant effects of benzoyl peroxide. •  Fatty acids—use with caution in dogs with inflammatory bowel disease or recurrent pancreatitis. •  Isotretinoin—may cause keratoconjunctivi­ tis sicca, hyperactivity, pinnal pruritus, erythematous mucocutaneous junctions, swollen tongue, lethargy with anorexia or vomiting, abdominal distension, or collapse; CBC and chemistry screen abnormalities include high platelet count, hypertriglyceri­ demia, hypercholesterolemia, and high alanine transaminase; teratogen. •  Cyclosporine—may cause vomiting and diarrhea, gingival hyperplasia, B lymphocyte hyperplasia, hirsutism, papillomatous skin eruptions, and increased incidence of infection; decreased glucose homeostasis; potential toxic reactions rare and include nephrotoxicity and hepatotoxicity. •  Azathioprine, mycophenolate mofetil, and chlorambucil—potential for bone marrow suppression, gastrointestinal upset; azathioprine can cause hepatotoxicity and possibly pancreatitis. POSSIBLE INTERACTIONS

•  Cyclosporine and corticosteroids interact

with several medications; an appropriate drug formulary should be consulted prior to usage. •  Referral to a veterinary dermatologist should be considered if the etiology remains undetermined and/or prior to prescribing unfamiliar medications. ALTERNATIVE DRUG(S) N/A

•  Dermatophytosis—itraconazole,

ketoconazole, or terbinafine; see Dermatophytosis. •  Kerion—see Dermatophytosis. •  Demodicosis/sarcoptic mange—see Demodicosis, Sarcoptic Mange. •  Other bacterial infection—antibiotics dependent upon culture and sensitivity results. •  Deep/systemic fungal infection. •  Feline eosinophilic dermatitis—look for underlying cause. •  Neoplasia—see Dermatoses, Neoplastic. CONTRAINDICATIONS Corticosteroids and immunosuppressive medications should be avoided with folliculitis, dermatophytosis, kerion, and demodicosis.

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 FOLLOW-UP

PATIENT MONITORING •  CBC, chemistry screen, urinalysis, and urine cultures—monitor periodically in patients receiving immunosuppressive medications; monitoring will depend upon medication and dosage. •  CBC, chemistry screen, and urinalysis— monitor monthly for 4–6 months in patients receiving synthetic retinoid therapy. •  Tear production—monitor monthly for 4–6 months, then every 6 months in patients receiving synthetic retinoid therapy or sulfonamide-containing antibiotics. •  Skin scraping—monitor therapy in patients with Demodicosis (see Demodicosis).

•  Repeat fungal culture—monitor therapy in

patients with dermatophytosis (see Dermatophytosis). •  Resolution of lesions—monitor progress of sebaceous adenitis, actinic conditions, and all other diseases. POSSIBLE COMPLICATIONS Dependent upon specific disease.

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 MISCELLANEOUS

ASSOCIATED CONDITIONS N/A AGE-RELATED FACTORS N/A ZOONOTIC POTENTIAL •  Dermatophytosis—incidence in humans reported in 30–50% of cases of Microsporum canis, but possible with all dermatophytosis cases. •  Fungal infections—potential depends upon organism. •  Sarcoptic mange. PREGNANCY/FERTILITY/BREEDING

•  Synthetic retinoids—teratogens; do not use in

pregnant animals, animals intended for reproduction, or intact female animals; should not be handled by women of childbearing age. •  Corticosteroids—avoid use in pregnant animals. •  Cyclosporine—avoid during pregnancy unless necessary; dosages two to five times normal have been fetotoxic and embryotoxic in rats and rabbits. •  Antifungal agents should be avoided in pregnant animals. •  All drugs should be used with caution in pregnant and breeding animals. SEE ALSO

•  Acne—Cats. •  Acne—Dogs. •  Demodicosis. •  Dermatophytosis. •  Pyoderma. •  Sebaceous Adenitis, Granulomatous.

­Suggested Reading

Helton Rhodes KA, Werner A. Blackwell’s Five-Minute Veterinary Consult Clinical Companion: Small Animal Dermatology, 3rd ed. Hoboken, NJ: Wiley-Blackwell, 2018. Author Karen A. Kuhl Consulting Editor Alexander H. Werner Resnick  Client Education Handout available online

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Dermatoses, Sterile Nodular/Granulomatous •  Cutaneous xanthoma—high-fat treats or

diet, diabetes mellitus, hyperlipidemia.

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 BASICS

DEFINITION Sterile diseases with primary lesions of nodules and/or plaques. PATHOPHYSIOLOGY •  Nodules/plaques—usually result from an infiltration of inflammatory cells into the dermis and subcutis; may be secondary to endogenous or exogenous stimuli. •  Inflammation is typically, but not always, granulomatous to pyogranulomatous. SYSTEMS AFFECTED Skin/exocrine. GENETICS Oligogenic transmission is proposed for histiocytic sarcoma for Bernese mountain dogs. SIGNALMENT

•  Collagenous nevi—German shepherd dogs

3–5 years old.

•  Calcinosis circumscripta—German

shepherd dogs 18 mEq/L, along with minimal ketonuria, are criteria in humans. PATHOPHYSIOLOGY •  Hyperglycemia is due to insulin deficiency from DM; insulinopenia reduces tissue glucose utilization and increases hepatic glucose production, leading to increased extracellular glucose concentrations; the magnitude of hyperglycemia in HHS is usually greater than in DKA. •  Hyperosmolarity develops secondary to hyperglycemia and is exacerbated by dehydration and reduced extracellular fluid volume; the contribution of glucose to total plasma osmolarity is significant in HHS. •  Dehydration and volume deficit are typically severe and are caused by several factors, including reduced water intake and volume losses via gastrointestinal and renal systems. •  Reduced plasma volume decreases glomerular filtration rate and urine production, leading to azotemia; in HHS, severe volume contraction with reduced urinary glucose excretion results in severe hyperglycemia and plasma hyperosmolarity. •  Hyperketonemia and ketonuria are not major features of HHS; lactic acidosis secondary to volume depletion, tissue hypoperfusion, and impaired glucose metabolism is the major cause of acidosis in patients with HHS. SYSTEMS AFFECTED •  Endocrine. •  Renal/urologic—prerenal azotemia due to decreased extracellular fluid volume; urine production usually maintained by glucose-induced diuresis unless volume deficit is severe or acute kidney injury is present. •  Cardiovascular—hypovolemia; metabolic acidosis and electrolyte abnormalities may contribute to hypotension and poor myocardial contractility. •  Nervous— hyperosmolarity promotes intracellular dehydration and neuronal dysfunction. GENETICS N/A INCIDENCE/PREVALENCE Uncommon GEOGRAPHIC DISTRIBUTION N/A

•  Myxedema coma—manifestation of severe

Breed Predilections

hypothyroidism with similar clinical signs without hyperosmolarity or hyperglycemia; low total thyroxine and elevated thyroidstimulating hormone present.

Mean Age and Range

•  Hyperglycemia—blood glucose concen­

Species

Dog and cat (more frequent). N/A

Most common in middle-aged dogs (mean 9 years) and cats (mean 12 years). Predominant Sex

N/A

SIGNS Historical Findings

•  All patients have DM; in some, diagnosis of DM occurs prior to HHS. •  Some patients have concurrent chronic illness. •  Signs

caused by DM—may not be appreciated after HHS onset: ◦ Polydipsia. ◦ Polyuria. ◦ Polyphagia. ◦  Weight loss. •  Signs caused by HHS: ◦ Weakness/lethargy. ◦ Vomiting. ◦  Reduced appetite. ◦  Neurologic complaints— abnormal responsiveness, coma. Physical Examination Findings

•  Findings associated with dehydration and hypovolemia: ◦  Decreased skin turgor. ◦  Prolonged capillary refill time. ◦ Reduced pulse pressure. ◦ Tachycardia. ◦ Hypothermia. •  Findings associated with hyperosmolarity: ◦  Lethargy, depressed mentation, stupor, or coma. ◦ Seizure. •  Findings associated with DM: ◦  Low body condition score. ◦  Cataracts (dogs).

CAUSES •  Develops in patients with DM and severe dehydration/volume loss. •  Reduced water intake may precede onset of HHS. •  Comorbid conditions common. RISK FACTORS Risk for HHS may be higher in diabetic animals with concurrent disorders, including heart disease, renal insufficiency, hyperadrenocorticism, acute pancreatitis, and neoplasia.

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  DM—may be uncomplicated to complicated, including DKA and HHS; all have similar clinical signs and laboratory findings, but can be subcategorized based on magnitude of hyperglycemia and hyperketonemia. •  Hypernatremia—severe hypernatremia produces CNS signs similar to HHS, but with sodium as major osmole; polyuria and polydipsia may be present, particularly if hypernatremia develops secondary to diabetes insipidus. •  Hyperosmolarity of any cause— may produce similar CNS abnormalities; toxins (e.g., ethylene glycol or alcohol) or CNS lesions (e.g., causing adipsia) may cause hyperosmolarity. •  CNS disease—primary CNS disorders may produce clinical signs of HHS; marked fluid deficits are not expected.

CBC/BIOCHEMISTRY/URINALYSIS

tration frequently exceeds 600 mg/dL and severe hyperglycemia (1500–2000+ mg/dL) exists in some patients. •  Azotemia—elevated blood urea nitrogen (BUN) and serum creatinine concentrations are common, usually prerenal, but renal azotemia occurs in some patients. •  Sodium—hypo- or hypernatremia may be observed; hyperosmolarity is most severe with concurrent hyperglycemia and hypernatremia. •  Potassium—hypokalemia is common; hyperkalemia is associated with acute kidney injury or reduced urine output. •  Acidosis—metabolic acidosis is less severe than DKA; hypobicarbonemia and hyperlactatemia occur secondary to hypovolemia or renal failure. •  Glucosuria— present; mild ketonuria possible. •  Urine specific gravity (USG) variable; may be misleading due to glucosuria, which increases USG. OTHER LABORATORY TESTS

•  Blood and urine osmolarity—serum

osmolarity >320 mosm/L consistent with HHS; urine osmolality elevated due to glucosuria. •  Serum osmolarity can be estimated from routine serum chemistry results: 2 ([Na+]+[K+]) + [BUN]/2.8 + [Glucose]/18; if results are in IU, equation is modified: 2 ([Na+]+[K+]) + [BUN] + [Glucose]. IMAGING N/A DIAGNOSTIC PROCEDURES N/A PATHOLOGIC FINDINGS

•  Pancreas—consistent with DM: islet

atrophy and loss (dogs and cats) and islet amyloid (cats). •  Brain—changes not specific for HHS; evidence of CNS edema.

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 TREATMENT

APPROPRIATE HEALTH CARE Life-threatening medical emergency requiring inpatient treatment. After HHS resolution, patients require treatment and follow-up for DM. NURSING CARE •  Correction of fluid deficits—major treatment goal, begin prior to insulin replacement; IV fluid replacement indicated for ill patients; enteral water can assist with free water replacement in patients that tolerate oral intake. •  Fluid type and rate depend on patient’s hydration and volume status and magnitude of metabolic derangements; fluid

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deficit is estimated using the equation: %volume depletion * body weight(kg) = fluid deficit (L). •  Hypo- and normonatremic patients—isotonic crystalloid solution is appropriate for initial volume replacement; replacement of volume deficit should occur over 12–24h; patients with hypotension or shock due to hypovolemia should receive fluid bolus of 20–25% of estimated blood volume (dog: 80 mL/kg; cat: 50 ml/kg), which can be repeated until blood pressure is adequate; once blood pressure is restored, the remaining deficit is replaced over 12–24h. •  Hypernatremic patients—hypernatremia implies a free water deficit and its occurrence with hyperglycemia in HHS may result in life-threatening hyper­osmolarity; isotonic (0.9%) saline solution appropriate for initial volume replacement in hypernatremic patients with hypovolemic hypotension; if hypernatremia persists after blood pressure and urine output are restored, use of hypotonic (0.45%) saline solution indicated to replace free water and reduce sodium, unless oral water intake possible; recommended that serum sodium concentration reduction should not exceed 12 mEq/day (see Hypernatremia). •  Electrolyte replacement—potassium deficiency is expected, and should be replaced unless hyperkalemia is present; dosage based on magnitude of hypokalemia; potassium replacement by IV infusion should not exceed 0.5 mEq K+/kg/h and fluids with supplemented K+ should be avoided during rapid volume infusion; supplementation of other electrolytes (e.g., magnesium, phosphorous) may also be necessary. •  Glucose supplementation—some protocols recommend using dextrose infusion to prevent hypoglycemia during insulin therapy; 2.5–5% dextrose CRI used as needed to maintain blood glucose concentrations between 150 and 250 mg/dL.

kg/24h (some protocols recommend 1.1 U/ kg/24h dose in cats) added to 250 mL of 0.9% NaCl; prior to beginning CRI, 50 mL of solution should pass through plastic administration tubing and be discarded (insulin binds to some plastics); CRI started at 5 mL/h (cat) or 10 mL/h (dog) and infusion rate adjusted as needed to reduce hyperglycemia at desired rate and maintain target glucose concentration. •  Once HHS is resolved and patient stable, discontinue insulin CRI and transition to longer-acting insulin to be used for chronic DM management.

ACTIVITY N/A

PATIENT MONITORING •  Volume and hydration status—monitor heart rate, pulse quality, capillary refill time, blood pressure, bodyweight, and urine output. •  Blood glucose—monitor q1–2h to guide insulin therapy; aim for gradual reduction of serum glucose (50–100 mg/ dL/h) to 150–250 mg/dL without hypo­ glycemia. •  Monitor serum Na+ and K+ concentrations, especially during correction of hypernatremia or K+ supplementation; magnesium and phosphorous should be monitored, especially after start of insulin therapy. •  After stabilization, long-term monitoring appropriate for DM is indicated.

DIET N/A CLIENT EDUCATION

•  Patients frequently have a serious concurrent disorder(s) that affects prognosis. •  Permanent

DM is expected and survivors will require lifelong treatment for DM. SURGICAL CONSIDERATIONS N/A

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 MEDICATIONS

DRUG(S) OF CHOICE •  CRI of regular insulin is recommended for initial glucose control; insulin therapy should be started 2–6h after starting fluid therapy so initial decrease in serum glucose is not extreme. •  CRI preparation—regular insulin at 2.2 U/

CONTRAINDICATIONS N/A PRECAUTIONS

•  Brain edema may occur when hyperosmolarity

is corrected too rapidly; patients with edema develop worsening neurologic status during treatment; minimizing rapid decreases in glucose and sodium during treatment lowers edema risk. •  Insulin administration can result in hypokalemia; electrolytes should be monitored frequently (q4–6h) until stable. POSSIBLE INTERACTIONS N/A ALTERNATIVE DRUG(S)

•  Ultrashort-acting insulins (insulin aspart or

insulin lispro) may be substituted for regular insulin in CRI protocols. •  Protocol for intermittent IM use of regular insulin (when CRI not available)—0.2 U/kg IM initially, followed by 0.1 U/kg IM q1h until glucose 250 mg/dL.

•  High liver enzyme activity. •  Hypercholesterolemia and lipemia. •  Azotemia. •  Hypochloremia. •  Hypokalemia. •  Hyponatremia. •  Hypophosphatemia. •  Hypomagnesemia. •  High anion gap—anion gap = (sodium +

potassium) – (chloride + bicarbonate); normal is 16 ± 4. •  Glucosuria and ketonuria. •  Variable urinary specific gravity with active or inactive sediment. •  Hyperproteinemia. •  Heinz body anemia (cats). OTHER LABORATORY TESTS •  Metabolic acidosis—HCO3– 330 mOsm/kg). •  Bacterial culture of urine and blood. DIAGNOSTIC PROCEDURES

•  Abdominal and thoracic radiography and

ultrasound may be necessary to identify comorbid diseases.

cardiac output and tissue perfusion and to maintain vascular volume; also reduce blood glucose concentration. •  IV administration of isotonic crystalloid supplemented with potassium is initial fluid of choice; volume and rate determined by fluid replacement needs plus maintenance requirements; replace over 24–48h. ACTIVITY N/A DIET Following stabilization, diet should be adjusted to account for patient’s diabetes, concurrent disease, and body condition. High-fiber diets are not recommended in underweight pets. CLIENT EDUCATION Serious medical condition requiring lifelong insulin administration in most patients. Confirm that client is prepared to inject twice daily insulin prior to treatment of DKA.

SURGICAL CONSIDERATIONS N/A

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 MEDICATIONS

DRUG(S) OF CHOICE Insulin

•  Regular insulin is the insulin of choice until eating; lispro insulin may also be considered. •  Initial dosage—0.2 U/kg IM (or SC if hydration normal). •  Subsequent dosage 0.1–0.2 U/kg IM given 3–6h later—may be given hourly if patient is closely monitored; response to previous insulin dosage should be considered when calculating

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subsequent dosages; ideally, glucose concentration should drop by 50–100 mg/dL/h. •  Regular insulin can also be administered as CRI via designated catheter. Dogs: 2.2 units/kg in 250 mL of 0.9% NaCl; Cats: 1.1 units/kg in 250 mL 0.9% NaCl. Then, allow 50 mL of dilute insulin to flow through IV tubing and discard. If blood glucose >250 mg/dL, administer at 10 mL/h; if blood glucose 200–250 mg/dL, administer at 7 mL/h; if blood glucose 150–200 mg/dL, administer at 5 mL/h; if blood glucose 100–150 mg/dL, administer at 5 mL/h and add 2.5% dextrose to IV crystalloid fluids; if blood glucose 350 μmol/L—confirms

persistence of hyperglycemia.

ACTIVITY Strenuous activity may lower insulin require­ments; consistent daily activity level is helpful. DIET Ultra-low-carbohydrate (40% metabolizable energy) canned diets may improve glycemic control, and increase the likelihood of diabetic remission in newly diagnosed diabetic cats. CLIENT EDUCATION

•  Discuss maintaining a consistent daily

feeding and medication schedule, home glucose monitoring, signs of hypoglycemia and what to do, and when to seek veterinary assistance. •  Clients are encouraged to chart pertinent daily information about the pet, such as any home-obtained glucose readings or patterns of exhibited clinical signs (e.g., PU/PD or appetite). SURGICAL CONSIDERATIONS Intact females should have ovariohysterectomy when stable; progesterone secreted during diestrus makes management of DM difficult.

•  Feline pancreas-specific lipase >3.50 μg/L—

identifies presence of pancreatitis. •  Urine culture—positive in 10–15% of newly diagnosed DM. IMAGING

•  Thoracic and abdominal radiography— to

evaluate for concurrent or underlying disease (e.g., neoplasia, cystic or renal calculi, emphysematous cystitis, or cholecystitis). •  Abdominal ultrasonography—in selected patients, particularly those with jaundice, to evaluate for hepatic lipidosis, cholangio­ hepatitis, and pancreatitis.

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 MEDICATIONS

DRUG(S) OF CHOICE •  Insulin is treatment of choice and should be initiated at 1–2 units per cat SC q12h; based on routine monitoring, some cats may eventually be reduced to once-daily dosing. •  Two U-40 insulin formulations are FDAapproved for use in cats—protamine zinc (PZI) and porcine zinc lente insulin suspension.

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the use of PZI or glargine (U-100) as first-choice insulin therapy for cats.

PRECAUTIONS Glucocorticoids, megestrol acetate, and progesterone cause insulin resistance. If steroid therapy is necessary, use oral methylprednisolone. Avoid injectable steroids. POSSIBLE INTERACTIONS

•  Drugs that may increase insulin sensitivity—

angiotensin-converting enzyme inhibitors, sulfonamides, tetracycline, beta blockers, monoamine oxidase inhibitors, salicylates. •  Drugs that increase insulin resistance— glucocorticoids, estrogen supplements, furosemide, thiazide diuretics, and calcium channel blockers. •  Always consult a new medication’s product insert. ALTERNATIVE DRUG(S)

•  Oral sulfonylureas (e.g., glipizide)—only

are normal and weight stable to increasing, disease is likely to be regulated. •  Glucose curves—ideally generated by the owner at home. Perform 5–14 days after starting insulin or after any dose adjustments until controlled, then again at 1 month, and every 3–6 months thereafter. •  Fructosamine—maintain 80 mg/dL and 4 times/ day); often hematochezia and mucus; tenesmus, urgency, dyschezia; flatulence and borborygmus: variable; vomiting: variable.

Physical Examination Findings

•  Hepatobiliary disease—lack of bile salts needed for intraluminal digestion. •  Exocrine

pancreatic insufficiency (EPI).

Dietary

•  Dietary intolerance (food-responsive diarrhea). •  Food allergy.

Metabolic Disorders

•  Hyperthyroidism. •  Cobalamin deficiency—

typically secondary to underlying IBD or lymphoma. •  Renal disease. •  Hepatobiliary disease. •  Adverse drug reactions. Congenital Anomalies

•  Short colon. •  Portosystemic shunt. •  Persistent pancreaticomesojejunal ligament.

RISK FACTORS Dietary changes, feeding poorly digestible or high-fat diets.

Small Bowel

•  Poor body condition associated with malab­-

sorption, maldigestion, and protein-losing enteropathy (PLE). •  Variable dehydration. •  Abdominal palpation may reveal segmental or diffusely thickened small bowel loops associated with infiltrative disease, abdominal effusion, foreign body, neoplastic mass, intussusception,

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS First localize the origin of the diarrhea to the small or large bowel (or both) on the basis of historical signs.

CBC/BIOCHEMISTRY/URINALYSIS

•  Eosinophilia in some cats with parasitism,

eosinophilic enterocolitis, hypereosinophilic syndrome, or neoplasia. •  Macrocytosis in some cats with hyperthyroidism or FeLV infection. •  Anemia that is variably regenerative and may show microcytosis suggests chronic GI bleeding and iron deficiency. •  Leukopenia in some cats with FeLV or FIV infection. •  Panhypoproteinemia caused by PLE is uncommon in cats with intestinal disease, but can occur; hypoalbuminemia can be seen. •  Biochemical profiles and urinalysis abnormalities may suggest renal disease, hypoproteinemia, hepatobiliary disease, or endocrinopathy. OTHER LABORATORY TESTS Fecal and/or Rectal Scraping Exam

•  Direct wet prep, routine centrifugation fecal flotation, fecal ELISA testing may indicate GI parasites. •  Cytologic examination of rectal scrapings may reveal specific organisms, such as Histoplasma, Prototheca, or Tritrichomas. •  PCR fecal testing should be interpreted with caution, because positive results for toxin genes or infectious agents may or may not correlate with clinical disease; interpret PCR results in light of patient signalment, history, clinical presentation, vaccination history, and other laboratory data. •  PCR for Tritrichomonas—most sensitive test; be certain to send fresh fecal sample, colonic lavage fluid, or loop scraping for testing. •  Culture feces if Salmonella is suspected— special media required.

Thyroid Function Tests

•  High total T4 or free T4 concentration indicates hyperthyroidism. •  If hyper­

thyroidism is suspected but T4 is normal, perform a T3 suppression test, repeat the T4 a few months later, or perform a technetium scan of the thyroid glands. Serologic Testing

Test for FeLV and FIV—especially if hematologic abnormalities are present. Test for Exocrine Pancreatic Function

Feline-specific trypsin-like immunoreactivity—test of choice for diagnosis of EPI. IMAGING •  Survey abdominal radiography may indicate abnormal intestinal pattern, organomegaly, mass, foreign body, pancreatic disease, hepatobiliary disease, urinary disease, or abdominal effusion; low yield in most cats with chronic diarrhea. •  Contrast radio­ graphy (upper GI series or barium enema) may indicate bowel wall thickening, intestinal ulcers, mucosal irregularities, mass, radiolucent foreign body, or stricture; procedure performed infrequently in cats in light of advantages of abdominal ultrasonography. •  Abdominal ultrasonography may demonstrate bowel wall thickening, abnormal bowel wall layering, GI or extra-GI masses, intussusception, foreign body, ileus, abdominal effusion, hepatobiliary

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Diarrhea, Chronic—Cats disease, pancreatitis, renal disease, or mesenteric or mesocolic lymphadenopathy.

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DIAGNOSTIC PROCEDURES If maldigestive (EPI), metabolic, parasitic, dietary, and infectious causes have been excluded, consider empiric dietary therapy, utilizing an elimination diet for 2 weeks before performing endoscopy and biopsy or a laparotomy for definitive diagnosis. Endoscopy/Laparoscopy

•  Upper GI flexible endoscopy allows exam­-

ination and biopsy of gastric and duodenal mucosa; always obtain multiple (8–10) mucosal specimens from each segment/area. •  Flexible colonoscopy allows examination of entire rectum, colon, cecum, and ileum; always obtain multiple mucosal specimens (8–10) from each segment. •  Visual impressions of GI mucosal detail may not reflect histopathologic changes; always take biopsies. •  Endoscopic biopsies rely upon infiltrative and inflammatory diseases being represented in first two layers of the intestinal wall, and segments biopsied being representative of disease process. •  Full-thickness biopsies can be obtained via laparoscopy from one or more segments of small intestine (not large intestine) via exteriorization of the segment(s), but are not typically necessary as most diseases can be diagnosed endoscopically. Surgical Biopsy

Surgical approach beneficial if biopsies of multiple organs (small intestine, lymph nodes, stomach, pancreas, liver) are desired. Ultrasound-Guided GI Aspiration or Biopsy

•  Can perform ultrasound-guided fine-needle aspiration on some GI mass lesions, but cytologic interpretation accuracy is subject to sample quality, expertise, and limitations of technique; small cell alimentary lymphoma cannot be diagnosed by cytology, as cells will be small lymphocytes. •  Paracentesis of peritoneal fluid for fluid analysis, culture, and cytology is recommended. •  Concern has been expressed for risk of translocation of cancer cells or infective organisms with these procedures.

PATHOLOGIC FINDINGS Vary with underlying disease.

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DIET

•  Feeding elimination diet (intact novel

protein source or hydrolyzed protein) will resolve diarrhea in 40–60% of cats with chronic enteropathy; response should be detected within 2–3 weeks following dietary implementation. •  Repeated changes of diet made in order to maintain a symptom-free situation suggest that further testing needed.

NURSING CARE •  Give fluid therapy with balanced electrolyte solution as needed. •  Correct electrolyte and acid-base imbalances. ACTIVITY No restriction.

POSSIBLE COMPLICATIONS

•  Dehydration. •  Lowered body condition. •  Abdominal effusions as related to specific

cause of chronic diarrhea.

EXPECTED COURSE AND PROGNOSIS Vary with underlying disease.

CLIENT EDUCATION Complete resolution of signs is not always possible in cats with IBD, neoplasia, or fungal disease despite proper treatment.

­

SURGICAL CONSIDERATIONS Pursue exploratory laparotomy and surgical biopsy if evidence of obstruction, intestinal mass, or mid-small bowel disease unreachable via endoscopic procedure.

AGE-RELATED FACTORS N/A

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 MEDICATIONS

DRUG(S) OF CHOICE •  Disease specific. •  Prednisolone (1–2 mg/ kg BID) for management of IBD; chlorambucil (2 mg/cat q48–72h) should be considered together with prednisolone in severe IBD cases that are refractory to steroids alone or for management of small cell intestinal lymphoma. •  Supplementation with cyanocobalamin at 250 ug SC per cat on a weekly basis for 6 consecutive weeks, followed by every 3 weeks for the indefinite future. •  Probiotics can be beneficial in some patients with chronic nonspecific diarrhea. CONTRAINDICATIONS Anticholinergics exacerbate most types of chronic diarrhea and should not be used for empirical treatment. PRECAUTIONS Opiate antidiarrheals such as diphenoxylate and loperamide can cause hyperactivity and respiratory depression in cats and should not be used for more than 3 days. POSSIBLE INTERACTIONS N/A ALTERNATIVE DRUG(S) N/A

 TREATMENT

APPROPRIATE HEALTH CARE •  Outpatient medical management most common. •  Treat underlying cause.

(continued)

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 FOLLOW-UP

PATIENT MONITORING •  Assess changes in frequency and severity of diarrhea and bodyweight. •  Resolution usually occurs within 2–3 weeks following successful implementation of dietary therapy; consider reevaluating diagnosis if diarrhea does not resolve. PREVENTION/AVOIDANCE N/A

 MISCELLANEOUS

ASSOCIATED CONDITIONS N/A

ZOONOTIC POTENTIAL •  Toxoplasmosis. •  Giardiasis (low zoonotic potential). •  Cryptosporidiosis. •  Salmonellosis. •  Campylobacter jejuni. PREGNANCY/FERTILITY/BREEDING N/A SYNONYMS None SEE ALSO

•  Cobalamin Deficiency. •  Diarrhea, Antibiotic Responsive. •  Exocrine Pancreatic Insufficiency. •  Food Reactions (Gastrointestinal), Adverse. •  Inflammatory Bowel Disease. •  Small

Intestinal Dysbiosis. ABBREVIATIONS

•  EPI = exocrine pancreatic insufficiency. •  FeLV = feline leukemia virus. •  FIV = feline immunodeficiency virus. •  GI = gastrointestinal. •  IBD = inflammatory bowel disease. •  PLE

= protein-losing enteropathy.

­Suggested Reading

Evans SE, Bonczynski JJ, Broussard JD, et al. Comparison of endoscopic and full-thickness biopsy specimens for diagnosis of inflammatory bowel disease and alimentary tract lymphoma in cats. J Am Vet Med Assoc 2006, 229(9):1447–1450. Sabattini S, Bottero E, Turba ME, et al. Differentiating feline inflammatory bowel disease from alimentary lymphoma in duodenal endoscopic biopsies. J Small Anim Pract 2016, 57(8):396–401. doi: 10.1111/jsap.12494 Tolbert MK, Gookin JL. Tritrichomonas foetus: a new agent of feline diarrhea. Compend Contin Educ Pract Vet 2009, 31(8):374–381. Willard MD, Mansell J, Fosgate GT, et al. Effect of sample quality on the sensitivity of endoscopic biopsy for detecting gastric and duodenal lesions in dogs and cats. J Vet Intern Med 2008, 22(5):1084–1089. Author Karin Allenspach Consulting Editor Mark P. Rondeau Acknowledgment The author and book editors acknowledge the prior contribution of Mark E. Hitt.  Client Education Handout available online



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Diarrhea, Chronic—Dogs

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 BASICS

DEFINITION •  A change in the frequency, consistency, and volume of feces for more than 3 weeks. •  Can be small bowel, large bowel, or mixed. PATHOPHYSIOLOGY •  Secretory diarrhea. •  Osmotic diarrhea. •  Increased permeability. •  Abnormal gastrointestinal (GI) motility. •  Many cases involve combinations of these pathophysio­ logic mechanisms. SYSTEMS AFFECTED

•  Endocrine/metabolic. •  Exocrine. •  Cardiovascular (fluid balance). •  GI. •  Lymphatic.

GENETICS N/A INCIDENCE/PREVALENCE Unknown GEOGRAPHIC DISTRIBUTION Pythiosis occurs often in young, large-breed dogs living in rural areas, with a higher incidence in states bordering the Gulf of Mexico. SIGNALMENT Species

Dog

Breed Predilections

•  Yorkshire terrier, West Highland white

terrier, Rottweiler, soft-coated wheaten terrier—lymphangiectasia secondary to inflammatory bowel disease (IBD). •  Boxer and French bulldog—granulomatous colitis.

Mean Age and Range

enteropathy (PLE). •  Variable dehydration. •  Abdominal palpation may reveal thickened small bowel loops (diffuse or segmental) associated with infiltrative disease, abdominal effusion, foreign body, neoplastic mass, intussusception, or enlarged mesenteric lymph nodes. •  Rectal palpation typically unremarkable.

Large Bowel

•  Body condition more typically normal. •  Dehydration—uncommon. •  Abdominal

palpation may reveal thickened large bowel, foreign body, neoplastic mass, intussusception, or enlarged mesocolic lymph nodes. •  Rectal palpation may reveal irregularity of colorectal mucosa, intraluminal or extraluminal rectal masses, rectal stricture, or sublumbar lymphadenopathy. Small Bowel

Primary Small Intestinal Disease

•  Inflammatory bowel disease (e.g., lympho­ plasmacytic enteritis, eosinophilic enteritis, granulomatous enteritis, immunoproliferative enteropathy of Basenjis). •  Primary or secondary lymphangiectasia. •  Neoplasia. •  Bacterial (Campylobacter jejuni, Salmonella spp., invasive adherent or enterotoxic Escherichia coli, other enterobacteriaceae species). •  Mycotic (e.g., histoplasmosis). •  Algal (e.g., protothecosis, pythiosis). •  Parasites (e.g., Giardia, Toxocara spp., Ancylostoma, Toxascaris leonina, Cryptosporidium spp., Cystoisospora spp.). •  Partial obstruction (e.g., foreign body, intussusception, neoplasia). •  Antibioticresponsive diarrhea (ARD; intestinal microbial dysbiosis). •  Short bowel syndrome.

Maldigestion

Any age.

Predominant Sex

Dietary

SIGNS General Comments

•  Disease processes determine extent of clinical signs. •  2–3% increase of water

content of stool results in gross description of diarrhea. •  Classification of small, large, and mixed bowel types of diarrhea may have overlap of descriptive findings.

Historical Findings

•  Small bowel diarrhea can include—normal to

increased volume; normal to moderately increased (2–4 times/day) defecation frequency; weight loss; polyphagia; melena; flatulence and borborygmus; vomiting—variable. •  Large bowel diarrhea can include—smaller volume; frequency of defecation increased (>4 times/ day); often hematochezia and mucus; tenesmus, urgency, dyschezia; flatulence and borborygmus— variable; vomiting—variable. Physical Examination Findings

Small Bowel

•  Poor body condition associated with

malabsorption, maldigestion, and protein-losing

•  Large-breed, younger, and less severely

affected dogs have higher risk of foodresponsive diarrhea. •  Yorkshire terrier, West Highland white terrier, Rottweiler, soft-coated wheaten terrier predisposed to lymphang­ iectasia secondary to IBD.

Large Bowel

•  Dietary changes or indiscretion, stress, and

psychological factors may play a role.

•  Granulomatous colitis (invasive adherent E.

coli–associated)—boxer, French bulldog 80% of patients. •  Any disc space may be affected; lumbo­sacral space is most commonly involved. •  Paresis or paralysis, especially in chronic, untreated cases. •  Fever in ~30% of patients. •  Lameness.

•  Organisms other than Staphylococcus

•  Focal or multifocal areas of spinal pain in

­

 BASICS

DEFINITION A bacterial, fungal, and rarely algal infection of the intervertebral end plates, discs, and adjacent vertebral bodies. PATHOPHYSIOLOGY •  Hematogenous spread of bacterial or fungal organisms—most common cause. •  Seeding secondary to migrating foreign body (grass awn) is also reported. •  Neurologic dysfunction—may occur; usually the result of spinal cord compression caused by proliferation of bone and fibrous tissue; less commonly owing to luxation or pathologic fracture of the spine, epidural abscess, or extension of infection to the meninges and spinal cord. SYSTEMS AFFECTED

•  Musculoskeletal—infection and

inflammation of the spine.

•  Nervous—compression and/or infection of

the spinal cord.

GENETICS •  No definite predisposition identified. •  An inherited immunodeficiency has been detected in a few cases. INCIDENCE/PREVALENCE Approximately 0.1–0.8% of dog hospital admissions. GEOGRAPHIC DISTRIBUTION

•  More common in the southeastern United

States. •  Grass awn migration and coccidiomycosis— more common in certain regions. SIGNALMENT Species

Dog; rare in cat. Breed Predilections

Large and giant breeds, especially German shepherd and Great Dane. Mean Age and Range

•  Mean age—4–5 years. •  Range—5 months–12 years.

Predominant Sex

Males outnumber females by ~2 : 1. SIGNS Historical Findings

•  Onset usually relatively acute; however, some patients may have mild signs for several months before presenting for examination. •  Pain—difficulty rising, reluctance to jump, and stilted gait are most common signs. •  Ataxia or paresis. •  Weight loss and anorexia. •  Lameness.

CAUSES •  Bacterial—Staphylococcus pseudintermedius is most common. Others include Streptococcus, Brucella canis, and Escherichia coli, but virtually any bacteria can be causative. •  Fungal—Aspergillus, Paecilomyces, Scedosporium apiospermum, and Coccidioides immitis. •  Grass awn migration is often associated with mixed infections, especially Actinomyces; tends to affect the L2–L4 disc spaces and vertebrae. •  Other causes—surgery, bite wounds. RISK FACTORS

•  Urinary tract infection; reproductive tract

infection. •  Periodontal disease. •  Bacterial endocarditis. •  Pyoderma. •  Immunodeficiency. •  Recent steroid administration. •  Intact male status.

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Intervertebral disc protrusion—may cause similar clinical signs; differentiated on the basis of radiography and myelography. •  Vertebral fracture or luxation—detected on radiographs. •  Vertebral neoplasia—usually does not affect adjacent vertebral end plates. •  Spondylosis deformans—rarely causes clinical signs; has similar radiographic features, including sclerosis, ventral spur formation, and collapse of the disc space; rarely causes lysis of the vertebral end plates. •  Focal meningomyelitis—often identified by cerebrospinal fluid (CSF) analysis. CBC/BIOCHEMISTRY/URINALYSIS

•  Hemogram—often normal; may see

leukocytosis. •  Urinalysis—may reveal pyuria and/or bacteriuria with concurrent urinary tract infections. OTHER LABORATORY TESTS •  Aerobic, anaerobic, and fungal blood cultures identify the causative organism in about 35% of cases; obtain if available. •  Sensitivity testing—indicated if cultures are positive.

30% of patients.

spp.—may not be the cause. •  Serologic testing for Brucella canis— indicated as this presents zoonotic potential. IMAGING

•  Spinal radiography—usually reveals lysis of

vertebral end plates adjacent to the affected disc, collapse of the disc space, and varying degrees of sclerosis of the end plates and ventral spur formation; may not see lesions until 3–4 weeks after infection (therefore normal radiographs do not rule out). •  Myelography—indicated with substantial neurologic deficits; determine location and degree of spinal cord compression, especially if considering decompressive surgery; spinal cord compression caused by discospondylitis typically displays an extradural pattern. •  CT or MRI—more sensitive than radio­graphy; indicated when radiographs are normal or inconclusive. DIAGNOSTIC PROCEDURES

•  CSF analysis—occasionally indicated to

rule out meningomyelitis; usually normal or reveals mildly high protein. •  Bone scintigraphy—occasionally useful for detecting early lesions; helps clarify if radiographic changes are infectious or degenerative (spondylosis deformans). •  Fluoroscopically guided fine-needle aspiration of the disc—valuable for obtaining tissue for culture when blood and urine cultures are negative and there is no improvement with empiric antibiotic therapy. PATHOLOGIC FINDINGS

•  Gross—loss of normal disc space; bony

proliferation of adjacent vertebrae.

•  Microscopic—fibrosing pyogranulomatous

destruction of the disc and vertebral bodies.

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 TREATMENT

APPROPRIATE HEALTH CARE •  Outpatient—mild pain managed with medication. •  Inpatient—severe pain or progressive neurologic deficits require intensive care and monitoring. NURSING CARE Nonambulatory patients—keep on clean, dry, well-padded surface to prevent decubital ulceration. ACTIVITY Restricted CLIENT EDUCATION

•  Explain that observation of response to

treatment is very important in determining the need for further diagnostic or therapeutic procedures.

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Discospondylitis •  Instruct the client to immediately contact

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the veterinarian if clinical signs progress or recur or if neurologic deficits develop.

SURGICAL CONSIDERATIONS •  Curettage of a single affected disc space— occasionally necessary for patients that are refractory to antibiotic therapy. •  Goals—remove infected tissue; obtain tissue for culture and histologic evaluation. •  Decompression of the spinal cord by hemilaminectomy or dorsal laminectomy— indicated for substantial neurologic deficits and spinal cord compression evident on MRI or myelography when there is no improvement with antibiotic therapy; also perform curettage of the infected disc space; it may be necessary to perform surgical stabilization if more than one articular facet is removed from a disc site.

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 MEDICATIONS

DRUG(S) OF CHOICE Antibiotics

•  Selection based on results of blood cultures

and serology or end plate aspirate culture and sensitivity. •  Negative culture and serology—assume causative organism is Staphylococcus spp.; treat with a cephalosporin (e.g., cephalexin 22 mg/kg PO q8h) for 8–12 weeks. •  Acutely progressive signs or substantial neurologic deficits—initially treated with parenteral antibiotics (e.g., cefazolin; dogs and cats: 22 mg/kg IV q8h). •  Brucellosis—treated with tetracycline (dogs: 15 mg/kg PO q8h) and streptomycin (dogs: 3.4 mg/kg IM q24h) or enrofloxacin (dogs: 10 mg/kg PO q24h). •  One study suggested that antibiosis be continued until radiographic signs were resolved (range of 40–80 weeks). The roll of imaging in definitively determining length of treatment has not been proven, however. Analgesics

•  Signs of severe pain—treated with an

analgesic (e.g., oxymorphone; dogs: 0.05– 0.2 mg/kg IV/IM/SC q4–6h). •  Taper dosage after 3–5 days to gauge effectiveness of antibiotic therapy. CONTRAINDICATIONS Glucocorticoids PRECAUTIONS Use nonsteroidal anti-inflammatory drugs (NSAIDs) and other analgesics cautiously— may cause temporary resolution of clinical signs even when infection is progressing; when used, discontinue after 3–5 days to assess efficacy of antibiotic therapy. POSSIBLE INTERACTIONS None

(continued)

ALTERNATIVE DRUG(S)

•  Initial therapy—cephradine (dogs: 20 mg/kg

PO q8h); amoxicillin trihydrate/clavulanate potassium (dogs: 13.75–22 mg/kg PO q12h). •  Refractory patients—clindamycin (dogs and cats: 10 mg/kg PO q12h), enrofloxacin (dogs: 10 mg/kg PO q24h; cats: 5 mg/kg PO q24h), orbifloxacin (dogs and cats: 2.5– 7.5 mg/kg PO q24h).

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 FOLLOW-UP

PATIENT MONITORING •  Reevaluate after 5 days of therapy. •  No improvement in pain, fever, or appetite—reassess therapy; consider a different antibiotic, percutaneous aspiration of the affected disc space, or surgery. •  Improvement—evaluate clinically and radiographically every 4 weeks. PREVENTION/AVOIDANCE Early identification of predisposing causes and prompt diagnosis and treatment—help reduce progression of clinical symptoms and neurologic deterioration. POSSIBLE COMPLICATIONS

•  Spinal cord compression owing to

proliferative bony and fibrous tissue.

•  Vertebral fracture or luxation. •  Meningitis or meningomyelitis. •  Epidural abscess.

EXPECTED COURSE AND PROGNOSIS •  Recurrence is common if antibiotic therapy is stopped prematurely (before 8–12 weeks of treatment). •  Some patients require prolonged therapy (1 year or more). •  Prognosis—depends on causative organism and degree of spinal cord damage. •  Mild or no neurologic dysfunction (dogs)—usually respond within 5 days of starting antibiotic therapy. •  Substantial paresis or paralysis (dogs)— prognosis guarded; may note gradual resolution of neurologic dysfunction after several weeks of therapy; treatment warranted. •  Brucella canis—signs usually resolve with therapy; infection may not be eradicated; recurrence common.

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 MISCELLANEOUS

ASSOCIATED CONDITIONS See Risk Factors. AGE-RELATED FACTORS N/A

ZOONOTIC POTENTIAL Brucella canis—human infection uncommon but may occur. PREGNANCY/FERTILITY/BREEDING N/A SYNONYMS

•  Diskitis. •  Intervertebral disc infection. •  Intradiskal osteomyelitis. •  Vertebral osteomyelitis.

SEE ALSO Brucellosis ABBREVIATIONS

•  CSF = cerebrospinal fluid. •  NSAID = nonsteroidal anti-inflammatory

drug.

­Suggested Reading

Ameel L, Martlè V, Gielen I, et al. Discospondylitis in the dog: a retrospective study of 18 cases. Vlaams Diergeneeskundig Tijdschrift 2009, 78(5):347–353. Bagley RS. Diskospondylitis. Fundam Clin Neuro 2005, 172–173(283–285):346. Braund KG, Sharp NJH. Discospondylitis. In: Vite C, ed., Braund’s Clinical Neurology in Small Animals: Localisation, Diagnosis and Treatment. Ithaca, NY: IVIS, 2003. https:// www.ivis.org/library/braunds-clinicalneurology-small-animals-localizationdiagnosis-and-treatment/degenerative Burkert BA, Kerwin SC, Hosgood GL, et al. Signalment and clinical features of diskospondylitis in dogs: 513 cases (1980–2001). J Am Vet Med Assoc 2005, 227(2):268–275. Fischer A, Mahaffey MB, Oliver JE. Fluoroscopically guided percutaneous disk aspiration in 10 dogs with diskospondylitis. J Vet Intern Med 1997, 11:284–287. Johnson RG, Prata RG. Intradiskal osteomyelitis: a conservative approach. JAAHA 1983, 19:743–750. Kerwin SC, Lewis DD, Hribernik TN, et al. Diskospondylitis associated with Brucella canis infection in dogs: 14 cases (1989– 1991). J Am Vet Med Assoc 1992, 201:1253–1257. Kornegay JN. Diskospondylitis. In: Kirk RW, ed., Current Veterinary Therapy IX. Philadelphia, PA: Saunders, 1986, pp. 810–814. Ruoff CM, Kerwin SC, Taylor AR. Diagnostic imaging of discospondylitis. Vet Clin North Am Small Anim Pract 2018, 48:85–94. Thomas WB. Diskospondylitis and other vertebral infections. Vet Clin North Am Small Anim Pract 2000, 30:169–182. Author Mathieu M. Glassman Consulting Editor Mathieu M. Glassman  Client Education Handout available online



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Disseminated Intravascular Coagulation

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 BASICS

DEFINITION An acquired complex hemostatic defect arising from a variety of inciting causes that leads to intravascular activation of coagulation and consumption of clotting factors. It results in widespread formation of microthrombi with clinical manifestations of thrombosis and/or hemorrhage. Non-overt disseminated intravascular coagulation (DIC) is the early, compensated form of DIC that features consumption of coagulation factors and generation of microthrombi without clear clinical signs. Overt (decompensated) DIC refers to the classic phenotype associated with hemorrhage, thrombosis, and organ failure. PATHOPHYSIOLOGY •  DIC represents a complication of a variety of primary conditions. It begins with a hypercoagulable state that leads to production or embolization of microthrombi in small vessels. •  The primary conditions act through increased exposure/production of tissue factor (TF) that activates the extrinsic coagulation pathway. •  TF is normally restricted from intravascular exposure. Increased TF exposure occurs through widespread endothelial injury and/or inflammation. •  Inflammation activates endothelial cells, platelets, and monocytes leading to membrane expression of TF. Inflammatory cytokines also induce vesiculation of these membranes, releasing large quantities of microparticles into circulation that are enriched with both TF and phosphatidylserine (PS) and facilitate initiation of coagulation. Some neoplastic cells constitutively produce membrane TF and also release microparticles. •  Microparticles provide a suitable membrane surface for amplifying intrinsic and common pathway coagulation, potentially leading to uncontrolled production of thrombin that overwhelms endogenous coagulation inhibitors. Fibrin clots generated by thrombin can cause vascular occlusion and lead to organ dysfunction. •  Widespread microthrombus formation consumes coagulation factors and platelets while initiating fibrinolysis. By-products of fibrinolysis (fibrin degradation products [FDPs]) have anticoagulant properties and inhibit platelet function. Hemorrhage at a variety of sites can follow. •  Uncontrolled progression leads to widespread tissue hypoxia, multiorgan dysfunction, and death. SYSTEMS AFFECTED Multisystemic syndrome.

INCIDENCE/PREVALENCE Associated with severe systemic inflammatory disease. SIGNALMENT Species

Dogs and cats; diagnosed more in dogs. Breed Predilections

None

Mean Age and Range

Depends on the primary disease. Predominant Sex

None

SIGNS •  Vary with the primary disease and with DIC-associated organ dysfunction. •  Petechiae. •  Bleeding from venipuncture sites, mucosa, or into body cavities. •  Bleeding is infrequent in cats, possibly leading to underdiagnosis. CAUSES

•  Gastric dilatation-volvulus. •  Heart failure. •  Heartworm disease. •  Heat stroke. •  Hemolysis, especially immune mediated. •  Hemorrhagic gastroenteritis. •  Infectious diseases, systemic (especially

endotoxemia).

•  Inflammation, severe—regardless of

underlying cause.

•  Liver disease, severe. •  Malignancies, especially hemangiosarcoma,

mammary carcinoma, and pulmonary adenocarcinoma in dogs and lymphoma in cats. •  Pancreatitis. •  Protein-losing nephropathy. •  Shock, hypoxia, acidosis. •  Thrombocytopenia, especially immunemediated. •  Transfusion incompatibility. •  Trauma. •  Envenomation. RISK FACTORS Vary with cause.

­

 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Key differentials—immune-mediated thrombocytopenia, anticoagulant toxicity, coagulation factor deficiency, paraproteinemia. •  Highly variable diagnostic pattern includes thrombocytopenia, prolonged clotting times (prothrombin time [PT], activated partial thromboplastin time [APTT]), decreased fibrinogen, decreased antithrombin (AT), and increased products of fibrinolysis (FDPs, D-dimers).

•  Suspect DIC any time thrombocytopenia

and prolonged clotting tests are seen together. •  Patients showing predisposing conditions should have laboratory monitoring every 24–48 hours. A sudden drop in platelet count and a 20–30% prolongation in APTT is suspicious for non-overt DIC. This is a critical stage for intervention to prevent progression to overt DIC. •  Hepatic insufficiency may mimic DIC. Decreased production of clotting factors is common. Decreased clearance of normal fibrin(ogen)olytic by-products may increase FDP values. Mild idiopathic thrombocyto­ penia may also be seen. Spontaneous bleeding is uncommon unless DIC is present. CBC/BIOCHEMISTRY/URINALYSIS

•  Inflammatory leukogram, often with a

stress component.

•  Mild to moderate thrombocytopenia

(40–100 × 103/μL); less reliable in cats. •  Anemia is possible. Red blood cell (RBC) fragmentation is a supportive finding. •  Biochemical changes reflect affected organs; acute kidney injury may result in isosthenuria, oligo-anuria, or the identification of casts in urine sediment. OTHER LABORATORY TESTS

•  Prolonged clotting tests (PT, APTT);

APTT is prolonged first, PT becomes prolonged with transition to overt DIC. •  Hypofibrinogenemia, although inflammatory increase may mask consumption. •  Increased FDPs and D-dimers. D-dimers are very sensitive and specific. DIC is unlikely if D-dimers are low/negative. Neither test is specific enough alone to diagnose DIC. •  Decreased AT; may be a positive acute phase reactant in cats, masking consumption. •  Thromboelastography may provide evidence of hypocoagulability or fibrinolysis. DIAGNOSTIC PROCEDURES Diagnostic procedures should be focused on identifying the inciting cause of inflammation, and may include imaging, tissue biopsy, or surgery as dictated by clinical signs. PATHOLOGIC FINDINGS •  Usually related to the primary disease or DIC-affected organs. •  Petechiae common.

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 TREATMENT

APPROPRIATE HEALTH CARE •  Requires intensive inpatient treatment. •  Aggressive treatment of the primary disease is essential (e.g., antimicrobials for sepsis).

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Disseminated Intravascular Coagulation

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NURSING CARE •  Maintain tissue perfusion and oxygenation using fluids, transfusions, and oxygen therapy. •  Restore depleted factors by blood/plasma transfusions. Use fresh frozen plasma (10–20 mL/kg) to correct bleeding due to factor deficiency. ACTIVITY Limited by disease severity. DIET Maintain nutritional support as appropriate for the clinical condition of the patient. CLIENT EDUCATION Inform the owner that the condition is life-threatening with a guarded to poor prognosis. SURGICAL CONSIDERATIONS Related to primary disease. Plasma or whole blood transfusion to restore clotting factors is a presurgical consideration. Surgery may be contraindicated with uncontrolled bleeding.

­

 MEDICATIONS

DRUG(S) OF CHOICE •  There is no specific pharmacologic therapy for DIC per se. •  Heparin may be used in patients that have overt thrombosis or in those at high risk of thrombosis with normal coagulation times. Unfractionated heparin is preferred to low molecular weight heparin in human patients with DIC. •  Heparin binds to and potentiates the action of AT. Plasma or blood transfusions may be needed to replenish AT for heparin to be an effective anticoagulant. •  Starting doses for unfractionated heparin are 150–200 U/kg SC q8h. It may also be given as a CRI starting at 20–30 U/kg/h IV (i.e., same total daily dosage). Therapy should be monitored using serial measurements of APTT or anti-Xa activity. CONTRAINDICATIONS

•  Heparin therapy should be avoided in

patients with coagulopathy.

•  Inhibitors of fibrinolysis should not be used. •  The use of antiplatelet medications in

thrombocytopenic patients is not indicated.

•  Corticosteroids impair function of

mononuclear phagocytes and do not have a clear indication for DIC unless important for therapy of the underlying disease (e.g., lymphoma). PRECAUTIONS

•  Heparin may cause hemorrhage, and

therapy should be monitored.

•  Volume overload may occur in cases with

renal or pulmonary compromise. POSSIBLE INTERACTIONS None

­

 FOLLOW-UP

PATIENT MONITORING •  Clinical improvement and the arrest of bleeding are key positive findings. •  Daily lab testing (e.g., coagulation tests, fibrinogen, platelet counts) is warranted in severe cases to identify positive or negative trends. Less frequent testing may suffice in milder cases. •  Coagulation times and fibrinogen often normalize more rapidly than FDPs and platelet counts. PREVENTION/AVOIDANCE Early detection of non-overt DIC can allow therapy before disease progresses to overt DIC. POSSIBLE COMPLICATIONS Aside from the primary disease, affected organs may have permanent dysfunction or marginal reserve capacity. EXPECTED COURSE AND PROGNOSIS For overt DIC, mortality rates for dogs range from 50% to 77%. For cats, rates may be >90%.

(continued)

SYNONYMS

•  Consumptive coagulopathy. •  Disseminated intravascular coagulopathy.

SEE ALSO

•  Coagulation Factor Deficiency. •  Thrombocytopenia.

ABBREVIATIONS

•  APTT = activated partial thromboplastin

time.

•  AT = antithrombin. •  DIC = disseminated intravascular

coagulation.

•  FDP = fibrin degradation product. •  PS = phosphatidylserine. •  PT = prothrombin time. •  RBC = red blood cell. •  TF = tissue factor.

­Suggested Reading

Dunn ME. Acquired coagulopathies. In: Ettinger SJ, Feldman EC, eds. Textbook of Veterinary Internal Medicine: Diseases of the Dog and Cat, 7th ed. St. Louis, MO: Saunders, 2010, pp. 797–801. O’Brien M. The reciprocal relationship between inflammation and coagulation. Top Companion Anim Med 2012, 27:46–52. Ralph AG, Brainard MB. Update on disseminated intravascular coagulation: when to consider it, when to expect it, when to treat it. Top Companion Anim Med 2012, 27:65–72. Stokol T. Laboratory diagnosis of disseminated intravascular coagulation in dogs and cats: the past, the present, and the future. Vet Clin North Am Small Anim Pract 2012, 42:189–202. Author John A. Christian Consulting Editor Melinda S. Camus  Client Education Handout available online

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 MISCELLANEOUS

PREGNANCY/FERTILITY/BREEDING Unlike in humans, obstetric complications are not a common cause in dogs and cats.



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Canine and Feline, Seventh Edition

Drowning (Near Drowning) hemoconcentration and increases in sodium, chloride, and urine specific gravity.

­

 BASICS

OVERVIEW •  Defined as process of experiencing respiratory impairment from submersion or immersion in liquid; near drowning defined as water submersion followed by survival for at least 24 hours; recent changes in terminology prefer the use of “death, morbidity or no morbidity following a drowning episode.” •  Following submersion, elevations in CO2 levels in the bloodstream stimulate respiration, and subsequent aspiration of water occurs. •  Fresh water aspiration dilutes pulmonary surfactant, leading to alveolar collapse ± infectious pneumonia; hypertonic seawater aspiration leads to diffusion of interstitial water into alveoli; large volumes of water are not typically aspirated, but any amount results in ventilation–perfusion mismatch, hypoxemia, and metabolic acidosis. •  Submersion time, temperature of water, and type of water (fresh vs. salt vs. chemical water) significantly affect development of organ damage. SIGNALMENT Dogs and cats. Approximately half of animals involved in immersion accidents are 30% of

cats are chronic shedders. •  Breeding catteries or multicat facilities. •  Less than 2 years of age. •  Feline leukemia virus (FeLV) or feline immunodeficiency virus (FIV) infection. •  Certain cat breeds have higher incidence of FIP, especially dry form; some breeding pairs are prone to producing litters that develop FIP.

DIFFERENTIAL DIAGNOSIS

•  Fever of unknown origin—infection,

inflammation.

•  Pleural effusion—cardiac disease; cardiac

effusion has low specific gravity and cell count. •  Neoplasia—lymphoma, other causing abdominal organ enlargement/effusion. •  CNS signs—neoplasia, toxoplasmosis. •  Anemia and icterus—blood parasites causing hemolysis. •  Pansteatitis (yellow fat disease)—classic feel and appearance of fat within abdominal cavity; pain on abdominal palpation; often a fish-only diet. •  Leukopenia, enteritis—panleukopenia (see Feline Panleukopenia). CBC/BIOCHEMISTRY/URINALYSIS

•  Leukocytosis with neutrophilia and

lymphopenia.

•  Mild to severe anemia. •  High total plasma protein, specifically

globulin fraction (serum albumin : globulin typically 106 °F (>41.1 °C) may lead to cerebral edema, bone marrow depression, arrhythmia, electrolyte disorders, multiorgan damage, DIC. Historical Findings

•  Clinical history (e.g., contact with

infectious agents, lifestyle, travel, recent vaccination, drug administration, insect bites, previous illness, allergies) and physical examination (including retinal examination) may help identify underlying disease condition. •  Fever patterns (e.g., sustained, intermittent) rarely helpful. Physical Examination Findings •  Hyperthermia. •  Lethargy. •  Inappetence. •  Tachycardia.

Lymphoma, myeloproliferative disease, plasma cell neoplasm, mast cell tumor, malignant histiocytosis, metastatic disease, necrotic tumor, and solid tumor, particularly in liver, kidney, bone, lung, lymph nodes. Other Inflammatory Conditions

Cholangiohepatitis, hepatic lipidosis, toxic hepatopathy, cirrhosis, inflammatory bowel disease, pancreatitis, peritonitis, pleuritis, granulomatous diseases, portosystemic shunting, thrombophlebitis, infarctions, pansteatitis, panosteitis panniculitis, hypertrophic osteodystrophy, blunt trauma, cyclic neutropenia, intracranial lesions, pulmonary thromboembolism. Drugs and Toxins

Tetracycline, sulfonamide, penicillins, nitrofurantoin, amphotericin B, barbiturates, iodine, atropine, cimetidine, salicylates, antihistamines, procainamide, heavy metals. FUO—Dogs

•  Infection (28%)—discospondylitis, fungal

infections, endocarditis, abscesses, bacteremia, septic arthritis, septic meningitis, pyothorax, pulmonary foreign body/abscess, stump pyometra, pneumonia, osteomyelitis, peritonitis, prostatitis, pancreatitis,

pyelonephritis, sepsis secondary to immunodeficiency, leptospirosis, leishmaniasis, toxoplasmosis, Lyme disease, infection with Ehrlichia, Anaplasma, Bartonella, others. •  Immune-mediated disease (27%)— polyarthritis, meningitis, vasculitis, others. •  Bone marrow disease, including neoplasia (16%). •  Neoplasia (7%). •  Miscellaneous (10%)—hypertrophic osteodystrophy, lymphadenitis, panosteitis, portosystemic shunting, shar-pei fever. •  Undiagnosed (12%). FUO—Cats

•  Most virally mediated (e.g., FeLV, FIV,

feline infectious peritonitis [FIP], less commonly parvo, herpes, calici). •  Occult bacterial infection with atypical bacteria, sometimes secondary to bite wounds (e.g., Yersinia, Mycobacteria, Nocardia, Actinomyces, Brucella). •  Pyothorax. •  Additional causes—pyelonephritis, blunt trauma, penetrating intestinal lesion, dental abscess, systemic fungal disease, lymphoma, solid tumors. •  Immune disorders, endometritis, discospondylitis, pneumonia, endocarditis rare. RISK FACTORS

•  Recent travel. •  Exposure to biologic agents. •  Immunosuppression. •  Very young or old animals.

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS Differentiate fever from hyperthermia. Temperatures up to 103 °F (39.4 °C) may be caused by stress or illness. Temperatures >104 °F (>40 °C) almost always important. Temperatures >107 °F (>41.7 °C) usually not fever, more likely to be primary hyperthermia. CBC/BIOCHEMISTRY/URINALYSIS •  CBC and blood smear—leukopenia or leukocytosis, left shift, monocytosis, lymphocytosis, thrombocytopenia or thrombocytosis, spherocytes, organisms. •  Biochemistry profile and urinalysis vary with organ system involved. OTHER LABORATORY TESTS

•  If infectious disease suspected, attempt to

culture an organism—urine culture, blood cultures (i.e., three anaerobic/aerobic cultures, taken 20 min apart; try to use as much volume as possible to increase diagnostic yield; use special blood culture bottles), fungal and cerebrospinal fluid cultures, synovial and prostatic fluid, biopsy specimens.



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Canine and Feline, Seventh Edition

Fever

(continued) •  FeLV and FIV test, Snap 4DX test,

serologic tests or PCR for Toxoplasma, Borrelia, Mycoplasma, Bartonella, Anaplasma, Ehrlichia, Rickettsia, FIP, systemic mycoses. •  Fecal examination. •  Tracheal wash or bronchoalveolar lavage. •  If immune disorders suspected—cytologic examination of synovial fluid; Coombs’ test, rheumatoid factor, antinuclear antibodies. •  Pancreatic lipase immunoreactivity. •  T4 in cats. IMAGING Radiography

•  Abdominal radiographs—tumors and

effusion.

•  Thoracic radiographs—pneumonia,

neoplasia, pyothorax.

•  Survey skeletal radiographs—bone tumors,

multiple myeloma, osteomyelitis, discospondylitis, panosteitis, hypertrophic osteopathy, hypertrophic osteodystrophy. •  Dental/skull radiographs—tooth root abscess, sinus infections, foreign bodies, neoplasia. •  Contrast radiography (e.g., gastrointestinal and excretory urography). Ultrasonography

•  Abdominal (plus directed aspirate or

biopsy)—abdominal neoplasia, abscess or other site of infection (e.g., pyelonephritis, pancreatitis, pyometra). •  Echocardiography if endocarditis suspected.

NURSING CARE

•  Fluid administration (IV) often lowers body

temperature. •  Topical cooling if fever is severe (convection cooling with fans, evaporative cooling with alcohol on foot pads, axilla, and groin). •  Only use antipyretic treatment when fever is prolonged and life-threatening (>106 °F, >41.1 °C) and topical cooling is unsuccessful. Impaired patients (e.g., with heart failure, seizures, or respiratory disease) require antipyretic treatment earlier. Antipyretic treatment may preclude elucidation of cause, delay correct treatment, and complicate patient monitoring (e.g., reduction of fever is important indication of response to treatment). DIET Febrile patients in hypercatabolic state require high caloric intake. CLIENT EDUCATION Work-up of patients with FUO often extensive, expensive, and invasive, and may not result in definitive diagnosis. SURGICAL CONSIDERATIONS Surgery may be necessary in some animals (e.g., pyometra, peritonitis, pyothorax, liver abscess, neoplasms).

Nuclear Imaging

­

evaluate for bone tumors, osteomyelitis, pulmonary embolism. •  CT, MRI, or positron emission tomography scan if indicated.

DRUG(S) OF CHOICE Do not use broad-spectrum (i.e., “shotgun”) treatment in place of thorough diagnostic workup unless patient’s status is critical and deteriorating rapidly.

•  Radionuclide scanning procedures to

DIAGNOSTIC PROCEDURES

•  Arthrocentesis (culture and cytology). •  Bone marrow aspirate and biopsy if

malignancy or myelodysplasia suspected. •  Lymph node, skin, or muscle biopsy if clinically indicated. •  Fine-needle aspirate or biopsy of any mass or abnormal organ. •  Central spinal fluid tap if neurologic signs. •  Endoscopy and biopsy if gastrointestinal signs. •  Exploratory laparotomy—last resort if all other diagnostic tests fail to determine cause and patient not improving.

 MEDICATIONS

 TREATMENT

APPROPRIATE HEALTH CARE Goals of treatment—reset thermoregulatory set point to lower level; remove underlying cause.

•  Do not use unless infectious causes have

been ruled out.

•  May mask clinical signs, may lead to

immunosuppression, and not recommended for use as antipyretics; administration of corticosteroids to cats with intractable FUO after ruling out infectious diseases may promote favorable response. •  Primarily indicated for fever associated with immune-mediated disease and certain steroidresponsive tumors (e.g., lymphoma). PRECAUTIONS Side effects of antipyretics include emesis, diarrhea, gastrointestinal ulceration, renal damage, hemolysis, hepatotoxicity. POSSIBLE INTERACTIONS Combination of nonsteroidal antiinflammatory drugs and steroids raises risk of gastrointestinal hemorrhage.

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 FOLLOW-UP

PATIENT MONITORING •  Body temperature at least q12h. •  If cause of fever not found, repeat history and physical exam along with screening laboratory tests. •  If fever develops or worsens during hospitalization, consider nosocomial infection or superinfection. EXPECTED COURSE AND PROGNOSIS Vary with cause; in some patients (more commonly cats), underlying cause cannot be determined.

Antibiotics

•  Based on results of bacterial culture or

serology.

•  In emergency situations, combination

antibiotic therapy can be started after culture specimens obtained (e.g., cephalothin 20 mg/ kg IV q6–8h; combined with enrofloxacin 10 mg/kg IV q24h). Additional antimicrobials depend on main clinical suspicion based on preliminary laboratory and clinical evidence. •  Do not give antibiotics longer than 1–2 weeks if ineffective. Antipyretics

•  Aspirin—dogs: 10 mg/kg PO q12h; cats:

6 mg/kg PO q48h.

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Glucocorticoids

•  Deracoxib—dogs: 1–2 mg/kg/day. •  Carprofen—dogs: 2 mg/kg q12h. •  Meloxicam—0.1 mg/kg/day. •  Dipyrone—dogs: 25 mg/kg IV. •  Flunixin meglumine—dogs: 0.25 mg/kg

SC once (give IV fluids).

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 MISCELLANEOUS

ASSOCIATED CONDITIONS •  Young animals—infectious disease more common; prognosis better. •  Old animals—neoplasia and intra-abdominal infection more common; signs tend to be more nonspecific; prognosis often guarded. SYNONYMS Pyrexia SEE ALSO Heat Stroke and Hyperthermia. ABBREVIATIONS •  DIC = disseminated intravascular coagulation. •  FeLV = feline leukemia virus. •  FIP = feline infectious peritonitis. •  FIV = feline immunodeficiency virus. •  FUO = fever of unknown origin. Authors Maria Vianna and Jörg Bucheler Consulting Editor Michael Aherne

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Fiber-Responsive Large Bowel Diarrhea CAUSES & RISK FACTORS

•  Unknown; stress or abnormal personality

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F

 BASICS

OVERVIEW •  A form of chronic idiopathic large bowel diarrhea that occurs in dogs and usually responds favorably to dietary soluble fiber supplementation. •  At the author’s institution, chronic idiopathic large bowel diarrhea is diagnosed in approximately 25% of dogs referred for evaluation of chronic large bowel diarrhea. •  Exclusion diagnosis that requires eliminating known causes of chronic large bowel diarrhea and clinical response to dietary fiber supplementation. •  No pathophysiologic studies have been performed. •  Only 3 reports in dogs comprising 83 cases. •  May overlap with a stress-associated poorly defined syndrome that has been called irritable bowel syndrome, also referred to as nervous colitis, spastic colon, or mucus colitis. Some dogs with irritable bowel syndrome respond to dietary fiber supplementation, while others require stress alleviation, antispasmodic medications, and/or anti-anxiety drugs. SIGNALMENT

•  Dogs of all ages (0.5–14 years); median 6

years.

•  Many breeds, including mixed breeds;

common breeds include German shepherd dog, miniature schnauzer, cocker spaniel, and miniature or toy poodle. SIGNS

•  Chronic diarrhea (soft to liquid) with classic

large bowel characteristics; tenesmus, excess fecal mucus, hematochezia, increased frequency (median 3.5 times/day), and urgency. •  Diarrhea usually episodic alternating with periods of normal stool; diarrhea may be continuous in approximately 25% of dogs. •  Less common signs include occasional vomiting, decreased appetite during episodes of diarrhea, abdominal pain, and anal pruritus. •  Weight loss rare. •  Stress factors or abnormal personality traits in approximately 35% of dogs; household visitation, travel, moving, construction, instillation of an invisible fence; recent adoption or considered nervous, high-strung, sensitive, or aggressive; or possess noise phobia, anxiety, or depressive disorders. •  Physical examination reveals no significant findings related to gastrointestinal tract. •  Digital rectal examination is usually normal. Feces may be normal due to episodic nature of the disease. Loose stool may be present and it may contain hematochezia (red blood) or excess mucus.

traits may play a role in some.

•  Clinical response to dietary soluble fiber

supplementation suggests abnormal colonic motility and/or dysbiosis. Dysbiosis is defined as a microbial imbalance within the gastro­ intestinal tract. Soluble dietary fiber is a prebiotic, fermented by colonic bacteria resulting in altered composition or activity of bacteria. Prebiotics are not digested by mammalian digestive enzymes and “feed” colonic bacteria, potentially correcting dysbiosis. Soluble fibers also adsorb water, improving stool quality. Fermentation of soluble fiber by colonic bacteria produces volatile fatty acids, which are energy source for colonic epithelial cells.

­

 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Dietary indiscretion. •  Highly digestible diet-responsive diarrhea. •  Hypoallergenic diet-responsive diarrhea. •  Whipworms. •  Clostridium perfringens–associated diarrhea. •  Lymphocytic plasmacytic colitis. •  Eosinophilic colitis. •  Miscellaneous types of colitis. •  Irritable bowel syndrome. •  Colonic neoplasia (adenocarcinoma, lymphoma, and adenoma are most common). •  Cecal inversion. CBC/BIOCHEMISTRY/URINALYSIS No consistent or specific abnormalities, although can recognize peripheral eosinophilia occasionally in dogs with colonic whipworms, eosinophilic colitis, and food allergy. OTHER LABORATORY TESTS Multiple fecal flotations by zinc sulfate; negative for whipworms and other parasites. IMAGING •  Abdominal radiographs within normal limits. •  Abdominal ultrasound within normal limits. DIAGNOSTIC PROCEDURES •  Clostridium perfringens enterotoxin fecal ELISA; negative. •  Therapeutic deworming for whipworms (fenbendazole 50 mg/kg PO q24h for 5 days); no improvement. •  Highly digestible diet trial for 2–3 weeks; no improvement in stool quality. During the food trial the dog must not receive any other nutrients. These diets are highly digestible, low in fiber, and restricted in fat. If the dog’s stool becomes normal during this diet trial, no further diagnostic tests are indicated. The highly digestible diet can be fed for another

2–4 weeks and then the original diet can be slowly introduced. Some dogs develop diarrhea again, others can be maintained on their original diet. •  Hypoallergenic diet trial for 2–3 weeks; no improvement in stool quality. During the food trial the dog must not receive any other nutrients, including flavored heartworm preventatives, vitamins, or any other supplements. For this diet trial the author recommends using a hydrolyzed diet. The hydrolyzed protein in these diets is hypo­ allergenic. If the dog’s stool becomes normal during this diet trial a diagnosis of dietary hypersensitivity or inflammatory bowel disease can be made. These hydrolyzed diets are also highly digestible, low in fiber, and restricted in fat. Some clinicians skip the highly digestible diet trial and go directly to the hydrolyzed diet trial. Without performing a highly digestible diet trial first, response to the hydrolyzed diet trial could also be due to digestibility, fat, and fiber content and not due to dietary hypersensitivity. Many dogs that respond to a hypoallergenic food trial can be slowly switched back to their original diet after 12–14 weeks. •  Colonoscopy; usually within normal limits or only mild nonspecific findings such as slight increases in mucosal granularity or friability. PATHOLOGIC FINDINGS •  Histopathologic evaluation of colonic biopsy samples; within normal limits. •  Multiple biopsy samples should be evaluated from throughout the colon from the cecum to the rectum. Usually at least 5–6 locations are sampled.

­

 TREATMENT

•  Health care can be provided on an

outpatient basis and consists of dietary fiber supplementation. •  Activity level does not have to be modified. •  A highly digestible “GI” diet should initially be supplemented with 1–3 tbsp daily of psyllium hydrophobic mucilloid (Metamucil 10.2 g psyllium/tbsp). •  Psyllium is a soluble fiber that adsorbs water, improving fecal consistency, and acts as a prebiotic promoting bacterial fermentation and production of volatile fatty acids, which are an energy source for colonic epithelial cells. Psyllium comes from the seeds or husks of the plant ispaghul and consists of approximately 90% soluble fiber. Psyllium has been shown to be an effective treatment in some children with chronic nonspecific diarrhea and in other people with several diarrheal disorders. •  Median dose is 2 tbsp/day, or 0.13 tbsp/kg/ day, or 1.3 g psyllium/kg/day.



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Fiber-Responsive Large Bowel Diarrhea

•  Initial response to lower amounts of fiber

supplementation or use of other types of fiber is not as successful. •  After 2–3 months without diarrhea, the amount of fiber can be slowly reduced successfully in approximately 50% of dogs. •  After resolution of diarrhea with psyllium supplementation, owners may attempt to switch to a commercial high-fiber (insoluble fiber) diet that may be more convenient to feed; however diarrhea may return in 50% of dogs. Insoluble dietary fiber helps to distend the colonic lumen; distention is necessary for normal fecal storage and colonic motility. •  After resolution of diarrhea with psyllium supplementation, owners may be able to switch from the highly digestible “GI” diet to a high-quality maintenance dog food. •  Lack of initial response to fiber supple­ mentation suggests that chronic idiopathic large bowel diarrhea may be due to irritable bowel syndrome, and pharmacologic management of that disorder should be instituted.

•  Prognosis is very favorable, as approximately

­

 MEDICATIONS

85% of dogs have excellent or very good long-term response to fiber supplementation.

None indicated.

CONTRAINDICATIONS/POSSIBLE INTERACTIONS No known interactions of fiber supplementation with commonly used drugs.

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 MISCELLANEOUS

•  There are no known associated conditions. •  Age does not play a role in diagnosis or

treatment.

­

 FOLLOW-UP

•  Patient monitoring requires periodic

assessment of stool quality, performed during recheck office examinations or via telephone interviews. •  If stresses were initially identified, stress reduction should be attempted. •  If abnormal personality traits were initially identified, they should be modified. •  Dietary soluble fiber supplementation can occasionally produce excessive flatulence, which can be managed by reduction in fiber dosage.

•  There is no known zoonotic potential. •  There are no special considerations

regarding pregnancy, fertility, or breeding.

­Suggested Reading

Lecoindre P, Gaschen FP. Chronic idiopathic large bowel diarrhea in the dog. Vet Clin North Am 2011, 41:447–456. Leib M. Treatment of chronic idiopathic large bowel diarrhea in dogs with a highly digestible diet and soluble fiber: a retrospective review of 37 cases. J Vet Int Med 2000, 14:27–32. Author Michael S. Leib Consulting Editor Mark P. Rondeau

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Fibrocartilaginous Embolic Myelopathy •  Severity of deficits—related to severity of

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F

 BASICS

DEFINITION Acute ischemic necrosis of the spinal cord caused when fibrocartilaginous emboli become lodged in the spinal vasculature. PATHOPHYSIOLOGY •  Emboli—found in spinal cord vasculature; histologically and histochemically identical to nucleus pulposus of the intervertebral disc. •  Exact mechanism of entry into the spinal vasculature unknown. SYSTEMS AFFECTED Nervous

infarction. Most display nonambulatory paresis, or plegia with intact nociception; fewer patients display ambulatory paresis, or plegia with absent nociception. •  Spinal pain—may be present briefly at onset of signs (owner report) and generally resolves by the time patient is examined. CAUSES Unknown RISK FACTORS •  Trauma/physical activity may precede the incident. •  Hyperlipoproteinemia may be a comorbidity in miniature schnauzers and Shetland sheepdogs.

­

nonchondrodystrophic breeds of dogs.

DIFFERENTIAL DIAGNOSIS •  Acute noncompressive nucleus pulposus extrusion (ANNPE)—most important clinical difference may be persistent spinal pain beyond 24 hours; differentiate with cross-sectional imaging; may be indistinguishable but treated the same. •  Thrombi/emboli from other sources can cause similar ischemic injury to the spinal cord—consider underlying predisposing conditions (cardiomyopathy, hypothyroidism, hyperthyroidism, hyperadrenocorticism, chronic kidney disease, hypertension, hyperlipidemia; especially in cats). •  Intervertebral disc disease; discospondylitis; neoplasia; fracture and luxation—typically painful with symmetric deficits; survey radiography, MRI, CT, and/or myelography help confirm the diagnosis. •  Intra- and extramedullary hemorrhage secondary to coagulopathy (e.g., anticoagulant rodenticide ingestion, thrombocytopenia, or disseminated intravascular coagulation)—rule out by examining for underlying causes of hemorrhage, performing platelet count, and determining blood clotting times. •  Infectious/immune-mediated focal myelitis—differentiate on progressive history and cerebrospinal fluid (CSF) analysis. •  Acute, nonprogressive, asymmetric, and nonpainful spinal cord disease—presence of these characteristics greatly helps in diagnosis of fibrocartilaginous embolic myelopathy (FCE).

SIGNALMENT Species

Dog and cat. Breed Predilections

•  Giant- and large-breed dogs most common,

but seen in small breeds as well.

•  Miniature schnauzers overrepresented.

Mean Age and Range

•  Median age 5 years. •  Range: 8 weeks–14.5 years.

Predominant Sex

Males overrepresented. SIGNS Historical Findings

•  May be associated with trauma or physical activity at or immediately before onset of signs. •  Sudden onset, generally nonprogressive and nonpainful. •  Discomfort occasionally noted at onset but resolves rapidly (minutes to hours). •  Signs of paresis or paralysis develop over a matter of seconds, minutes, or hours. •  Condition typically stabilizes within 24 hours.

Physical Examination Findings

N/A

Neurologic Examination Findings

•  Localization—any spinal cord segment can

be affected; T3–L3 and L4–S3 most common; multifocal lesions may rarely be seen; may see spinal shock with T3–L3 lesions, which can give the appearance of a multifocal spinal cord lesion. •  Deficits—commonly lateralized (due to spinal vascular anatomy) but can be symmetric; contralateral side may be mildly affected or normal.

•  Normal or nonspecific changes (mild

pleocytosis/elevated protein concentration). Profound elevations in cell count can occasionally be observed with severe necrosis. •  Results depend on location (lumbar vs. cerebellomedullary cistern) and time of collection in relation to onset of clinical signs. PATHOLOGIC FINDINGS hemorrhage.

INCIDENCE/PREVALENCE

•  Rarely reported in chondrodystrophic breeds. •  Uncommon in cats.

DIAGNOSTIC PROCEDURES CSF Analysis

•  Gross—focal spinal cord swelling ±

GENETICS N/A •  Common cause of spinal cord disease in

swelling at embolic site; later, often normal or shows area of cord atrophy. •  MRI—preferred imaging modality for antemortem diagnosis: may see increased T2 signal intensity within spinal cord at site of lesion; may see mild contrast enhancement.

 DIAGNOSIS

CBC/BIOCHEMISTRY/URINALYSIS Usually normal. IMAGING •  Survey spinal radiograph—usually normal, used to rule out other causes of myelopathy such as fracture, neoplasia, or discospondylitis. •  Myelography and CT myelography—in acute stage often demonstrates focal intra­medullary

•  Microscopic—emboli of fibrocartilage in

arteries and/or veins of spinal cord within or near area of focal spinal cord swelling; gray matter generally more affected than white matter. •  Histologic examination required for definitive diagnosis. Presumptive antemortem diagnosis is based on typical presentation and exclusion of other causes of acute myelopathy.

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 TREATMENT

APPROPRIATE HEALTH CARE Inpatient—for immediate medical treatment and diagnostic procedures. NURSING CARE •  Keep recumbent patients on padded surface; turn frequently to prevent pressure sores. •  Assist and encourage patients to ambulate as soon as possible. •  Assist bladder emptying (catheterize or express) several times daily if needed. •  Physical rehabilitation therapy may improve recovery and reduce residual neurologic deficits. •  Sling or harness support for assisted walking at home. ACTIVITY

•  Restrict until diagnosis is made in case of

vertebral column instability from other causes such as intervertebral disc herniation or fracture/luxation. •  Once FCE is confirmed, activity should be encouraged, not restricted. DIET Normal unless other general health comorbidities are present. CLIENT EDUCATION

•  Gradual recovery from paresis or paralysis;

most will recover ambulation, but residual neurologic deficits are common. Patients who



Canine and Feline, Seventh Edition (continued)

Fibrocartilaginous Embolic Myelopathy POSSIBLE COMPLICATIONS

are paraplegic with absent nociception have a more guarded prognosis for return of function. •  Most patients need considerable home care during recovery, including bladder management.

•  Fecal and urinary incontinence. •  Urinary tract infection. •  Urine scalding and pressure sores.

SURGICAL CONSIDERATIONS N/A

•  Generally good prognosis for recovery of

EXPECTED COURSE AND PROGNOSIS ambulation.

•  Most patients (85%) recover ambulation

within 3 weeks (range: 3 days–12 weeks).

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 MEDICATIONS

DRUG(S) OF CHOICE No specific medications are indicated for the treatment of FCE. Use of steroids such as methylprednisolone sodium succinate is controversial and unlikely to be of benefit. CONTRAINDICATIONS Nonsteroidal analgesics should not be administered with methylprednisolone sodium succinate. PRECAUTIONS N/A

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 FOLLOW-UP

PATIENT MONITORING •  Sequential neurologic evaluations—during first 12–24 hours after initial examination. •  Neurologic status—at 2, 3, and 4 weeks after onset of clinical signs. •  Urinary incontinence—manually express bladder in patients who are not voluntarily urinating. Urinalysis and culture/sensitivity to detect urinary tract infection. PREVENTION/AVOIDANCE

•  Recurrence highly unlikely but possible. •  No known method of prevention in most

cases.

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•  Most patients retain some permanent

neurologic deficits despite recovering ambulation. •  Paraplegia with loss of pain perception at presentation implies more guarded prognosis.

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 MISCELLANEOUS

ASSOCIATED CONDITIONS Disorders that lead to compromise in circulatory function may predispose or mimic FCE—hyperadrenocorticism; hypothyroidism; high systemic blood pressure; hyperviscosity syndrome; hyperlipidemia; bleeding diathesis; bacterial endocarditis. AGE-RELATED FACTORS N/A ZOONOTIC POTENTIAL N/A PREGNANCY/FERTILITY/BREEDING High-dose corticosteroid administration— may cause premature delivery. ABBREVIATIONS •  ANNPE = acute noncompressive nucleus pulposus extrusion. •  FCE = fibrocartilaginous embolic myelopathy. •  CSF = cerebrospinal fluid.

­Suggested Reading

Bartholomew KA, Stover KE, Olby NJ, Moore SA. Clinical characteristics of canine fibrocartilaginous embolic myelopathy (FCE): a systematic review of 393 cases (1973–2013). Vet Rec 2016, 179:650. De Risio L, Adams V, Dennis R, et al. Magnetic resonance imaging findings and clinical associations in 52 dogs with suspected ischemic myelopathy. J Vet Int Med 2007, 21:1290–1298. De Risio L, Platt SR. Fibrocartilaginous embolic myelopathy in small animals. Vet Clin North Am Small Anim Pract 2010, 233:129–135. Gandini G, Cizinauska S, Lang J, et al. Fibrocartilaginous embolism in 75 dogs: clinical findings and factors influencing the recovery rate. J Small Anim Pract 2003, 44:76–80. Hawthorne JC, Wallace LJ, Fenner WR, et al. Fibrocartilaginous embolic myelopathy in miniature schnauzers. J Am Anim Hosp Assoc 2001, 37:374–383. Mikszewski JS, Van Winkle TJ, Troxel MT. Fibrocartilaginous embolic myelopathy in five cats. J Am Anim Hosp Assoc 2006, 42:226–233. Summers BA, Cummings JF, de Lahunta A. Veterinary Neuropathology. St Louis, MO: Mosby, 1995, pp. 246–249. Authors Kristen Bartholomew and Sarah A. Moore Acknowledgment The authors and book editors acknowledge the prior contribution of Allen Franklin Sisson

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Fibrosarcoma, Bone •  Metastatic bone tumors (transitional cell,

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F

 BASICS

OVERVIEW •  Primary bone fibrosarcoma (FSA) arises from stromal elements within the marrow cavity and is characterized by malignant spindle cells that produce varying amounts of collagen but not any osteoid or cartilage. •  In dogs, FSA accounts for 9 mmol/L had reduced survival (13/24 = 54%) compared to those with initial lactate ≤9 mmol/L (36/40 = 90%). ◦  Dogs with initial lactate >9 mmol/L that did not decrease by ≥4 mmol/L had 10% survival rate, while those whose lactate decreased by ≥4 mmol/L with presurgical stabilization had 90% survival rate. ◦  Decrease in plasma lactate by ≥50% within 12 hours is associated with a good outcome. •  Coagulation testing—may show evidence for DIC. IMAGING

•  Abdominal radiography—right lateral

abdominal radiograph is imaging modality of choice. ◦  In a normal patient, the pylorus would be filled with fluid. ◦  In a patient with GDV, the pylorus, which is now on the left side of the peritoneal cavity, is filled with gas and visualized as such, showing the classic compartmentalization of the stomach, which is considered to be pathognomonic. ◦  Gas bubbles within the gastric wall indicate gastric necrosis. ◦  Pneumoperitoneum may be evident. •  Thoracic radiographs—three views to screen for aspiration pneumonia and metastatic disease; may also see evidence of hypovolemia (microcardia, small-caliber vessels). •  Abdominal ultrasound—may show fluid due to small volume hemoabdomen, serosanguinous effusion, or gastric perforation. DIAGNOSTIC PROCEDURES ECG to detect presence of cardiac arrhythmias. PATHOLOGIC FINDINGS

•  Splenic engorgement, ischemia,

malposition, and/or venous thrombosis.

•  Gastric wall may appear edematous and

thickened, or areas may be extremely thinned.

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 TREATMENT

APPROPRIATE HEALTH CARE •  GDV is a medical and surgical emergency. •  Aggressive emergency medical stabilization is initiated. •  Subsequent to cardiovascular stabilization, gastric decompression should be performed, ideally via orogastric intubation; the patient should be intubated with a cuffed endotracheal tube prior to performing orogastric intubation and decompression to minimize the risk of aspiration pneumonia. •  If orogastric intubation is unsuccessful,



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Canine and Feline, Seventh Edition



(continued)

percutaneous gastrocentesis may be performed for decompression by locating the point of maximal tympany, which typically corresponds to an area of the stomach that is gas filled. ◦  The largest-diameter needle or catheter that the clinician is comfortable using is passed into the stomach at this area. ◦  Considerable time is necessary to achieve gastric decompression using this technique. •  Recent studies suggest that when comparing orogastric decompression and percutaneous decompression, there is no difference in complication rates or outcome. Therefore, clinicians should select the technique that they are most familiar and comfortable with. •  Surgical management occurs once the patient is stable. NURSING CARE •  IV fluid therapy is initiated and type, rate, and duration are based on individual patient needs and personal preference. ◦  Avoid use of saphenous veins for emergency resuscitation, as venous return from the caudal half of the body is compromised. ◦  Crystalloids, colloids, or a combination can be used; initial fluid resuscitation efforts may require crystalloid boluses at 15–30 mL/kg increments, up to 90 mL/kg total; colloid boluses up to 5–10 mL/kg total may be required. •  Physical therapy may be necessary, as many patients will be recumbent for several days in the postoperative period.

Gastric Dilation and Volvulus Syndrome of a possible underlying motility disorder.

•  Failure to resect all necrotic or devitalized

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 MEDICATIONS

DRUG(S) OF CHOICE •  Lidocaine beginning with a 2 mg/kg IV bolus, followed by a CRI (0.05 mg/kg/min for 24h) in perioperative period improves morbidity but not mortality. ◦  Fewer cardiac arrhythmias. ◦  Lower incidence of AKI. ◦  Shorter hospitalization. •  Perioperative antibiotics are indicated. ◦  For patients with moderate to severe disease in which there is a risk of visceral perforation or hematogenous bacterial translocation from the GI tract, cefoxitin sodium (30 mg/kg IV q6–8h) may be an appropriate choice. ◦  For patients in which no entry into the GI tract has occurred, cefazolin sodium (22 mg/kg IVq2h intra­ operatively) is sufficient. •  Treatment for esophagitis and gastritis or gastric ulceration is indicated. ◦  Pantoprazole (1 mg/kg IV q12h) or omeprazole (1 mg/kg PO q12h) for acid suppression. ◦  Metoclopramide (2 mg/kg/day IV as CRI) or cisapride (0.5–1 mg/kg PO q8–12h) as a prokinetic. ◦  Sucralfate 0.25–1 g PO as a slurry q6–8h if gastric ulceration is present. •  Pain management based on patient needs postoperatively.

gastric tissue may result in eventual stomach perforation and septic peritonitis. •  Cardiac arrhythmias, DIC, esophagitis, AKI, and gastric ulceration may also occur. EXPECTED COURSE AND PROGNOSIS

•  Prognosis in dogs treated appropriately that

do not have gastric necrosis is excellent, with a reported survival rate of 98%. •  Dogs with gastric necrosis have a more guarded prognosis, with a reported survival rate of 66%. •  Potential negative prognostic indicators include hypotension, DIC, peritonitis, and the need to perform both a splenectomy and a partial gastrectomy.

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 MISCELLANEOUS

ASSOCIATED CONDITIONS N/A AGE-RELATED FACTORS More common in middle-aged to older dogs. ZOONOTIC POTENTIAL None

CONTRAINDICATIONS Synthetic colloids should be used cautiously in patients with DIC or AKI.

PREGNANCY/FERTILITY/BREEDING Affected dogs should not be bred due to potential genetic predisposition. SYNONYMS •  Bloat. •  Gastric torsion. •  Gastric volvulus.

•  Enteral nutrition is recommended as soon

PRECAUTIONS Patients may decompensate at any time, particularly under anesthetic intervention. Emergency drug dosages should be calculated for the patient before anesthesia and be readily available.

CLIENT EDUCATION

ALTERNATIVE DRUG(S) There is conflicting evidence to support the use of physiologic corticosteroids in patients with GDV. Use is not currently recommended.

ACTIVITY Restriction of activity for 2 weeks postoperatively is recommended. DIET

as adequate recovery from anesthesia has been achieved to stimulate GI mucosal healing and motility. •  Optimal diet is unknown; consider fat-restricted diets to improve gastric emptying.

•  Clients should be aware of the critical nature of GDV. •  Patients can still experience

gastric dilation after gastropexy, as many have gastric motility disorders.

SURGICAL CONSIDERATIONS •  Surgery is required after medical stabilization. •  Goals of surgery are: ◦  Continue decompression. ◦  Assess stomach and spleen for evidence of devitalization and necrosis that necessitates partial gastrectomy or splenectomy. ◦  Reposition stomach and spleen. ◦  Perform systematic and thorough exploratory laparotomy. ◦  Perform gastropexy to prevent recurrence of GDV—should always be performed; decreases risk of recurrent GDV from 80% to 12 hours following meal suggests abnormal gastric motility or outflow obstruction; vomiting can occur, however, any time after eating. •  Gastric distention, nausea, anorexia, belching, bloating, pica, and weight loss may occur. •  Distal esophageal sphincter may be incompetent with gastric hypomotility and signs associated with reflux esophagitis may occur.

Physical Examination Findings

•  Normal or findings associated with underlying cause. •  Palpation of large, distended stomach. •  Decreased gastric

sounds on abdominal auscultation. CAUSES

•  Rarely, idiopathic gastric motility disorders

arise from primary defects in normal myoelectric activity, e.g., myenteric ganglionitis, intestinal leiomyositis; most motility disorders occur secondary to other conditions. •  Metabolic disorders include hypokalemia, uremia, hepatic encephalopathy, and hypothyroidism. •  Nervous inhibition as result of stress, fear, pain, or trauma. •  Drugs such as anticholinergics, beta-adrenergic agonists, narcotics, and chemotherapeutics. •  Primary gastric disease such as outflow obstructions, gastritis, gastric ulcers, parvovirus, and gastric surgery. •  Gastric dilatation and volvulus syndrome (GDV) is suspected to be, in part, result of abnormal gastric motility associated with changes in myoelectric and mechanical activity, although whether primary or secondary to overstretching of gastric wall is unknown; some dogs with GDV may continue to have signs of gastric hypomotility following surgical gastropexy. •  Gastroesophageal reflux and enterogastric reflux (see Bilious Vomiting Syndrome) may result from primary gastric hypomotility. •  Dysautonomia may affect GI tract and result in abnormal esophageal, gastric, and intestinal motility. RISK FACTORS Any gastric disease may result in secondary hypomotility.

Unknown

Mean Age and Range

Signs occur at any age, though it is uncommon to observe primary motility disorders in young animals. Predominant Sex

N/A

­

 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS Differential diagnosis is extensive and should consider any gastric condition causing

vomiting, including gastritis, gastric ulcers, neoplasia, gastric surgery, and GDV. Gastric outflow obstruction as cause of delayed gastric emptying must always be ruled out. CBC/BIOCHEMISTRY/URINALYSIS Abnormalities may result from underlying cause of gastric hypomotility. Continued vomiting may result in changes indicative of dehydration, electrolyte abnormalities, or acid-base imbalance. OTHER LABORATORY TESTS Specialized testing may be required to determine specific cause of gastric hypomotility, and is individualized for each patient. IMAGING Survey Radiographs

Abdominal radiographs may reveal gas-, fluid-, or ingesta-distended stomach. (Note: important to determine when patient was last fed in relationship to when radiographs were taken.) Barium Contrast Study

May be evidence of delayed gastric emptying and decreased gastric contractions if evaluated using fluoroscopy. Some cases may have normal emptying of liquids but abnormal emptying of solids. Normal dogs should empty stomachs by approx. 6–8 hours. (Note: stress of radiographs may decrease gastric emptying even in normal animal.) Ultrasonography

Ultrasound can evaluate antral and pyloric motility. Tests Available in Specialized Practices

Radionuclide Emission Scintigraphy

Radionuclide markers mixed with a meal give most clinically accurate measurement of emptying. Gastric emptying times (time for standard meal to leave stomach) range from 4 to 8 hours.

Stable Isotope Breath Tests

C-14-labeled foods are fed and time to onset of 14CO2 emission in breath is marker of gastric emptying.

Smartpill

This is noninvasive wireless sensor capsule that is given orally and transmits data on pressures, transit time, luminal pH, and temperature as it passes through stomach and small and large bowel. Has been validated for use in healthy dog but, as yet, limited reports evaluating clinical conditions. DIAGNOSTIC PROCEDURES Endoscopy

Endoscopic findings frequently normal in primary gastric motility disorders. Food may be found in stomach when it should be empty following 12-hour pre-endoscopic fast. Endoscopy will detect obstructive or inflammatory/ulcerative diseases of stomach. PATHOLOGIC FINDINGS •  Idiopathic conditions have normal gastric mucosa; special staining may reveal disruption of enteric nervous system. •  Gastric histology





Gastric Motility Disorders

(continued)

may identify inflammatory or neoplastic causes of gastric hypomotility.

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 TREATMENT

APPROPRIATE HEALTH CARE •  Most treated as outpatients. •  With severe vomiting or dehydration and electrolyte imbalance, hospitalization, fluid support, and specific therapy required. NURSING CARE Dehydration with fluid and electrolyte imbalance requires appropriate fluid replacement. Drugs that inhibit gastric motility (e.g., opioids) should be withdrawn. ACTIVITY Dependent on underlying disease. DIET •  Dietary manipulation important in management of primary gastric motility disorders in order to speed gastric emptying. •  Optimal diets liquid or semi-liquid consistency and low in fat and fiber content. •  Small-volume meals with frequent feeding should be given. •  Occasionally dietary manipulation alone is successful. CLIENT EDUCATION Discuss possible underlying etiologies and that response to therapy varies with individual cases. SURGICAL CONSIDERATIONS

•  Large-breed dogs with chronic GDV

syndrome and gastric retention should have surgical gastropexy. •  Following gastric surgery generally takes several days but up to 14 days for return of normal motility. •  Mechanical gastric outflow obstructions require surgical correction.

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 MEDICATIONS

DRUG(S) OF CHOICE Gastric Prokinetic Agents

•  Metoclopramide increases amplitude of antral contractions, inhibits fundic receptive relaxation, and coordinates duodenal and gastric motility; dopamine receptor antagonism in proximal GI tract results in increased release of acetylcholine from enteric neurons; at higher concentrations it has serotonin (5HT4) agonist effects; also has antiemetic effects, blocking chemoreceptor trigger zone in dogs, but not in cats. ◦  Oral dosage 0.2–0.5 mg/kg q8h given 30 min before meals (use lower dose in cats) or as CRI at 1–2 mg/kg q24h. ◦  Metoclopramide generally considered to be weak prokinetic agent in dogs and recent studies suggest it has little effect at increasing lower esophageal sphincter pressure. •  Cisapride works directly by cholinergic neurotransmission (5HT4 agonist) of GI smooth muscle, stimulating motility; proposed mechanism of action is enhancement of release

of acetylcholine at myenteric plexus; increases lower esophageal sphincter pressure, improves gastric emptying, and promotes motility of small and large intestine. ◦  Oral dosage 0.2–0.5 mg/kg PO q8–12h given before meals. ◦  Cisapride currently available through compounding pharmacies—human product has been removed from market because of associated cardiac arrhythmias not yet noted to occur in dogs or cats. ◦  Mosapride (0.5–2 mg/ kg PO q12–24h) and prucalopride (0.02– 0.6 mg/kg PO q12–24h) are also 5HT4 agonist prokinetic agents. •  Macrolide antibiotics, such as erythromycin, are motilin receptor agonists and increase GI motility; motilin is hormone that promotes MMC-associated motility. ◦  Erythromycin given at low (submicrobiologic) doses binds motilin receptors promoting acetylcholine release, which speeds gastric emptying; dose of erythromycin for specific motility effects is 0.5–1 mg/kg PO q8–12h, given 30 min before meals. ◦  Chronic use of submicrobiologic doses of antibiotics not recommended. •  H2 receptor antagonists ranitidine (1–2 mg/kg q8h) and nizatidine (2.5–5 mg/kg q24h) have reported prokinetic effects on gastric motility due to acetylcho­ linesterase inhibition; are considered poor prokinetic drugs and recent studies question ranitidine’s prokinetic activity in dogs; neither cimetidine nor famotidine affects gastric emptying. CONTRAINDICATIONS Gastric prokinetic agents are contraindicated in patients with gastric outflow obstruction. PRECAUTIONS •  Metoclopramide may cause nervousness, anxiety, or depression. •  Cisapride may cause depression, vomiting, diarrhea, or abdominal cramping. •  Erythromycin may cause vomiting. POSSIBLE INTERACTIONS Metoclopramide contraindicated with concurrent phenothiazine and narcotic administration or in animals with epilepsy. ALTERNATIVE DRUG(S) •  Domperidone is peripheral dopamine receptor antagonist that regulates motility of gastric and small intestinal smooth muscle similar to metoclopramide. •  Mirtazapine is noradrenergic and specific serotonergic antidepressant and has reported gastric prokinetic effects in dogs. •  Acotiamide is acetylcholine esterase inhibitor that facilitates muscarinic activity and has been shown to stimulate postprandial gastroduodenal activity in dogs at dose of 30 mg/kg, but only available in Asia.

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 FOLLOW-UP

PATIENT MONITORING •  Response to therapy varies with underlying cause. •  Clinical signs are primary indicator of response.

PREVENTION/AVOIDANCE N/A POSSIBLE COMPLICATIONS GDV EXPECTED COURSE AND PROGNOSIS Length of treatment depends on ability to resolve underlying cause.

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 MISCELLANEOUS

ASSOCIATED CONDITIONS Gastric hypomotility may be associated with reflux esophagitis and reflux gastritis (see Bilious Vomiting Syndrome). AGE-RELATED FACTORS N/A ZOONOTIC POTENTIAL N/A PREGNANCY/FERTILITY/BREEDING Avoid gastric prokinetic agents in pregnant animals. SYNONYMS •  Delayed gastric emptying. •  Gastric atony. •  Gastric hypomotility. SEE ALSO

•  Bilious Vomiting Syndrome. •  Gastric Dilation and Volvulus Syndrome. •  Gastritis, Chronic. •  Gastroesophageal Reflux.

ABBREVIATIONS

•  GDV = gastric dilation and volvulus

syndrome.

•  GI = gastrointestinal. •  MMC = migrating myoelectric complex.

­Suggested Reading

Gaschen FP. Gastric and intestinal motility disorders. In: Bonagura JB, Twedt DC, eds., Current Veterinary Therapy XV. St. Louis, MO: Elsevier, 2014, pp. 513–518. Washabau RJ. Prokinetic agents. In: Washabau RJ, Day MJ, eds. Canine and Feline Gastroenterology. St. Louis, MO: Elsevier, 2013, pp. 530–536. Wyse CA, McLellan AM, Dickie DGM, et al. A review of methods for the assessment of the rate of gastric emptying in the dog and cat: 1898–2002. J Vet Intern Med 2003, 17:609–621. Author Edward J. Hall Consulting Editor Mark P. Rondeau Acknowledgment The author and book editors acknowledge the prior contribution of David Twedt  Client Education Handout available online

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Gastritis, Chronic

­B ASICS

G

DEFINITION Inflammation of the stomach leading to clinical signs of >3 weeks’ duration. PATHOPHYSIOLOGY •  Inflammation may be secondary to drugs, infection, neoplasia, toxins/irritants, foreign material, food antigens or bacterial antigens; may be primary as a form of inflammatory bowel disease (IBD). •  Visceral receptors stimulated by inflammation, distension, etc. send signals via vagal and sympathetic nerves to vomiting center (medulla oblangata). SYSTEMS AFFECTED •  Gastrointestinal (GI). •  Musculoskeletal— weight loss, muscle wasting, weakness. •  Integument—hair coat changes. •  Respiratory— aspiration pneumonia. GENETICS N/A INCIDENCE/PREVALENCE Common GEOGRAPHIC DISTRIBUTION N/A SIGNALMENT Species

Dog and cat. Breed Predilections

•  Norwegian lundehund—chronic atrophic

gastritis with IBD (lymphoplasmacytic); can progress to adenocarcinoma. •  Basenji and Drentse patrijshond—chronic hypertrophic gastritis.

Mean Age and Range

Any age.

Predominant Sex

None

SIGNS Historical Findings

•  Vomiting is most common—digested or undigested food, bile, frank blood, digested blood (“coffee grounds”); variable frequency. • Hyporexia to anorexia. •  Melena. •  Polydipsia. •  Diarrhea with concurrent intestinal disease. • Retching. •  Burping. •  Weight loss.

Physical Examination Findings

•  Abdominal distension ± pain. •  Ptyalism.

• Muscle wasting, weight loss, coat changes. • Pallor if bleeding ulcer. •  Dehydration or hypovolemia. CAUSES

•  Food sensitivity. •  IBD. •  Toxins, e.g., heavy

metals, environmental irritants (cleaners, herbicides). •  Metabolic/endocrine disease— renal disease, liver disease, hypoadrenocorticism, pancreatitis, hyperthyroidism. •  Neoplasia—

large or small cell lymphoma, adenocarcinoma, polyp, gastrinoma, leiomyosarcoma, plasma cell tumor, mast cell tumor. •  Foreign material. • Drugs—nonsteroidal anti-inflammatory drugs (NSAIDs), antibiotics, chemotherapeutics. • Parasitism—Toxocara spp., Physaloptera spp. (dogs and cats), Ollulanus tricuspis (cats). • Helicobacter spp. •  Pythiosis. •  Canine distemper virus. •  Hypergastrinemia—gastrinoma, achlorhydria, Basenji gastroenteropathy, hepatic or renal disease. •  Miscellaneous—stress, emphysematous gastritis (gas-forming organisms/ severe signs), benign gastric emphysema (milder disease/air trapping), eosinophilic sclerosing fibroplasia. RISK FACTORS •  Drugs (e.g., NSAIDs). •  Unsupervised/ free-roaming pets—exposure to toxin.

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DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Any cause of GI signs. •  Esophageal disease—differentiate vomiting from regurgitation. •  Hypertrophic pyloric gastropathy. •  Bilious vomiting syndrome. CBC/BIOCHEMISTRY/URINALYSIS

•  Hemoconcentration if dehydrated.

•  Anemia—if blood loss (regenerative anemia if acute blood loss such as u­lceration; microcytic, hypochromic with chronic blood loss. • Thrombocytosis with chronic blood loss leading to iron d­eficiency. •  Eosinophilia with parasitism, neoplasia, or eosinophilic gastritis. •  Biochemistry—prerenal or renal azotemia; increased blood urea nitrogen (BUN) : creatinine ratio with GI bleeding; hyperkalemia and hyponatremia with hypoadrenocorticism; hypochloremic metabolic alkalosis with gastric outflow obstruction. •  Urinalysis—unremarkable. OTHER LABORATORY TESTS •  Gastrin levels—elevated with gastrinoma; may be elevated with azotemia or use of antacids. •  T4. •  Fecal float. •  Baseline cortisol ± adrenocorticotropic hormone (ACTH) stimulation test. •  Pythium ELISA. •  Iron panel (iron deficiency with bleeding). IMAGING

•  Abdominal radiographs—radiopaque foreign

material, thickened gastric wall, gastric distension. •  Contrast radiography—radiolucent foreign material, outflow obstruction, delayed emptying, wall defects or thickening. •  Ultrasonography—wall thickening, layering loss, ulcer, foreign object, mass. DIAGNOSTIC PROCEDURES •  Upper GI endoscopy—visualize gastric mucosa, identify ulcer or mass, retrieve foreign object, biopsy (even when grossly

normal), removal of small mass lesions (cautery), evaluate duodenum. •  Exploratory laparotomy—perforated ulcer, full-thickness biopsy, partial gastrectomy, mass removal. •  Wireless capsule endoscopy—identify mass or ulcer. PATHOLOGIC FINDINGS

•  IBD—variable inflammatory infiltrate:

lymphoplasmacytic, eosinophilic, n­eutrophilic, granulomatous/histiocytic gastritis (investigate for infectious cause). •  Helicobacter spp. do not always convey pathology—significant populations deep in gastric glands may warrant treatment. •  Special stains—further evaluation of potential neoplasia and infectious organisms.

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TREATMENT

APPROPRIATE HEALTH CARE •  Many treated as outpatients pending diagnostic testing or treatment trials (i.e., diet, drugs). •  Inpatient management warranted if significant dehydration or hypovolemia present. NURSING CARE

•  IV fluids based on patient status; caution

for fluid overload with hypoproteinemia. • Enteral nutrition (nasoesophageal, nasogastric, or esophageal tubes) with persistent anorexia. •  Severe hypoalbuminemia—consider albumin, plasma, or colloids.

ACTIVITY Restrict postoperatively if surgery performed. DIET •  Novel protein or hydrolyzed diet when allergy or IBD suspected; initial response expected within 2 weeks; worsening warrants diet change or other intervention; if improvement noted, continue beneficial diet for several months before reintroducing other foods to assess tolerance. • Challenge with original diet can prove food hypersensitivity; rarely pursued. •  Low-fat diet if hyperacidity or gastric ulcer. •  Frequent, small meals (q4–6h) may provide benefit. •  Small late-night meal may decrease bilious vomiting. • Calorie requirement/diet guideline increases compliance. •  Unflavored or topical flea, tick, and heartworm preventatives. •  Treats limited to prescription diet. •  If commercial diet declined, consider home-cooked diet formulated by veterinary nutritionist. CLIENT EDUCATION •  Review multiple etiologies. •  Least invasive testing first when patient status allows; biopsy for definitive diagnosis if extra-intestinal causes ruled out and patient fails diet and drug trial (i.e.. anthelminthic).



Gastritis, Chronic

(continued) 

SURGICAL CONSIDERATIONS •  Obstructive lesion or material. •  Perforated ulcer. •  Removal of foreign objects if endoscopy unsuccessful or not available. •  Fullthickness biopsy. •  Mass resection and biopsy.

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MEDICATIONS

DRUG(S) OF CHOICE •  Anthelminthic—fenbendazole (50 mg/kg PO q24h for 5 days), pyrantel pamoate + febantel. • Gastroprotectants—proton pump inhibitor (PPI), i.e., omeprazole (1 mg/kg PO q12h 30–60 min before meal); also consider sucralfate, H2 receptor antagonist, and others per ACVIM consensus (see Suggested Reading). •  Antiemetics—maropitant (1 mg/kg SC or IV q24h; 2 mg/kg PO q24h), ondansetron, metoclopramide, mirtazapine. •  Prokinetics— metoclopramide (0.2–0.4 mg/kg PO q8h; CRI 1–2 mg/kg/day), cisapride, ranitidine, low-dose erythromycin. •  IBD suspected/confirmed— glucocorticoid (i.e., prednisone 2 mg/kg PO q24h or divided q12h; prednisolone for cat) when no clinical response to other therapeutic trials or in advanced disease; taper by 20–25% increments over time to lowest effective dose; discontinue when possible; total dose not >60 mg per day (dog); use with diet. •  If glucocorticoid not tolerated and/or relapse, consider second drug; see Alternative Drug(s). • Helicobacter gastritis—several protocols have been described (e.g., metronidazole, amoxicillin, clarithromycin); see Suggested Reading. CONTRAINDICATIONS •  Do not use prokinetics if GI obstruction possible. •  Do not use antacids or PPIs with atrophic gastritis and achlorhydria. PRECAUTIONS

•  Immune modulation predisposes to

secondary infections. •  Steroids can cause GI ulceration, diabetes mellitus. or fluid overload (especially cat: congestive heart failure); patient monitoring and client education are vital to success. •  Prolonged use of antacids or PPIs can lead to overgrowth of bacteria. POSSIBLE INTERACTIONS

•  Sucralfate will decrease absorption of other

medications; separate by 2 hours from other medications. •  Omeprazole affects clearance of many drugs. •  Never use NSAIDs with glucocorticoids; high risk for GI erosion or ulcer. ALTERNATIVE DRUG(S) •  IBD—if steroid and diet alone do not achieve disease remission, if patient relapses, and/or if steroid side effects are undesirable, second agent may be considered; options:

cyclosporine, mycophenolate, chlorambucil, azathioprine (never in cats); find lowest effective dose. •  Monitoring—exam, labwork (CBC, chemistry) for myelosuppression and other concerns (i.e., hepatic toxicity with cyclosporine, chlorambucil, and azathioprine). •  Budesonide (steroid; 1–3 mg/ patient depending on size) may have fewer systemic side effects; adrenal pituitary axis is affected.

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FOLLOW-UP

PATIENT MONITORING •  Depends on patient severity and m­edication chosen; minimum—physical exam within 2 weeks of starting treatment. •  Recheck abnormal labwork (i.e., e­lectrolytes, proteins) and monitor for medication side effects (i.e., hyperglycemia, anemia, myelosuppression, heptaopathy, etc. based on specific drugs selected). •  Recurrence warrants repeat diagnostics; repeat biopsy may be indicated (i.e., patients previously in remission of IBD can progress to lymphoma). •  Lack of response—change in medical management (i.e., alternative diet or drug); repeat biopsy (primary disease may have been missed) and labwork (CBC, chemistry, fecal, T4) for emerging comorbidity. PREVENTION/AVOIDANCE •  Avoid drugs with high incidence of GI upset (i.e., doxycycline, NSAIDs). •  Avoid rapid diet change. •  Prevent free-roaming and potential for dietary indiscretion—may need basket muzzle in dogs. POSSIBLE COMPLICATIONS

•  Gastroesophageal reflux. •  Delayed gastric

emptying/motility disorders. •  Erosions/ ulcers. •  Aspiration pneumonia. •  Electrolyte or acid-base imbalances. •  Progression from superficial to atrophic gastritis. •  Debilitation/ death in refractory cases. •  Steroids—diabetes mellitus, heart failure, calcinosis cutis, muscle weakness, ulcers. •  Other immune-modulating drugs—bone marrow suppression, pancreatitis, hepatitis, GI upset. EXPECTED COURSE AND PROGNOSIS • Varies with cause. •  Medication tapered to lowest effective dose ± stopped with diet.

AGE-RELATED FACTORS

•  Foreign objects—more common in young

animals. •  Food-responsive enteropathy—often younger animals. •  IBD—often middle-aged to older. •  Neoplasia—middle-aged to older animals more common. ZOONOTIC POTENTIAL Potential/uncommon concern secondary to parasites (i.e., Toxocara spp.—larval migrans). PREGNANCY/FERTILITY/BREEDING •  Prednisone—abortion, teratogenic, can induce parturition. •  Azathioprine—fetal harm; decrease sperm production. • Cyclosporine—fetal toxicity. SEE ALSO

•  Bilious Vomiting Syndrome. •  Gastroduodenal Ulceration/Erosion. •  Gastroenteritis, Eosinophilic. •  Helicobacter spp. •  Hypertrophic Pyloric Gastropathy, Chronic.

ABBREVIATIONS •  ACTH = adrenocorticotropic hormone. •  GI = gastrointestinal. •  IBD = inflammatory bowel disease. •  NSAID = nonsteroidal anti-inflammatory drug. •  PPI = proton pump inhibitor. INTERNET RESOURCES

•  https://veterinarypartner.vin.com/default.

aspx?pid=19239&id=4951472 •  https:// veterinarypartner.vin.com/default. aspx?pid=19239&id=4951476

­Suggested Reading

Leib MS. Gastric Helicobacter Species and Chronic Vomiting in Dogs. In: Bonagura J., Twedt D, eds., Kirk’s Current Veterinary Therapy XVI. St. Louis, MO: Elsevier, pp. 508–513. Marks SL, Kook PH, Papich MG, et al. ACVIM consensus for rational administration of gastrointestinal protectants to dogs and cats. J Vet Intern Med 2018; 32:1823–1840. Simpson KW. Diseases of the stomach. In: Ettinger SJ, Feldman EC, eds., Textbook of Veterinary Internal Medicine, 8th ed. St. Louis, MO: Elsevier, 2017, pp. 1495–1515. Author Kathryn M. McGonigle Consulting Editor Mark P. Rondeau Acknowledgment The author and book editors acknowledge the prior contribution of Michelle Pressel  Client Education Handout available online

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MISCELLANEOUS

ASSOCIATED CONDITIONS N/A

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Gastroduodenal Ulceration/Erosion Physical Examination Findings

•  Often normal. •  Melena is rare. •  Pale

­B ASICS

G

DEFINITION Ulcers are defects that extend completely through the mucosa; erosions extend part way through the mucosa. PATHOPHYSIOLOGY •  Gastroduodenal ulceration/erosion (GUE) results from factors that damage or overwhelm normal gastric mucosal defense and repair mechanisms. •  Factors protecting the stomach from GUE include the mucus/ bicarbonate layer, gastric epithelial cell turnover, gastric mucosal blood flow, and local prostaglandins. SYSTEMS AFFECTED

•  Gastrointestinal (GI)—ulcers and erosion are

most common in stomach, followed by proximal duodenum; however, neoplasia and some drugs (e.g., flunixin meglumine) can cause ulceration anywhere in GI tract. •  Cardiovascular—hemorrhage may cause anemia, tachycardia, systolic heart murmur, and/or hypotension. •  Peritoneal cavity—perforation may cause peritonitis/sepsis/ systemic inflammatory response syndrome (SIRS).

INCIDENCE/PREVALENCE •  40–60% in racing Alaskan sled dogs. •  Fairly common in dogs receiving nonsteroidal anti-inflammatory drugs (NSAIDs) or dexamethasone. SIGNALMENT Species

Dogs; rare in cats. Breed Predilections

Chow chows, rough-coated collies, Staffordshire bull terriers, and Belgian shepherd dogs have increased incidence of gastric carcinoma. Mean Age and Range

Any age.

Predominant Sex

Male dogs are predisposed to gastric carcinoma. SIGNS General Comments

Severity of clinical signs is not necessarily proportional to size/number of GUEs. Historical Findings

•  Some animals are asymptomatic (e.g.,

patients taking NSAIDs or dexamethasone, dogs working in extreme environments). •  Hyporexia is the most common clinical sign. •  Vomiting, hematemesis, and/or melena may be seen (in decreasing order of frequency). •  Cranial abdominal pain (“praying position”) is rarely seen. •  Weakness, pallor, lethargy, and/or collapse if severe anemia or SIRS develops.

mucous membranes and weakness if severely anemic. •  Tachycardia, hypotension, and prolonged capillary refill time if hypovolemic shock or perforation/SIRS. CAUSES Drugs

•  NSAIDs—cyclooxygenase (COX)-2 selective NSAIDs are usually safer than nonselective NSAIDs; however, GUE and perforation can occur with all NSAIDs. Coadministration of glucocorticoids (either systemic or local) enhances ulcerogenic potential of NSAIDs. Some NSAIDs are renowned for being extremely ulcerogenic (flunixin meglumine, naproxen, indomethacin). •  Glucocorticoids— dexamethasone is most ulcerogenic. Prednisolone less likely to cause clinically significant GUE unless there are additional stress factors (e.g., hypoxemia, hypoperfusion).

GI Diseases

•  GI neoplasia—carcinomas are most

common cause of neoplastic ulceration, but leiomyomas/leiomyosarcomas may cause severe hemorrhage. •  Foreign bodies can be associated with GUE, but not a common cause. Intestinal foreign bodies (especially linear foreign bodies) commonly cause intestinal ulceration/perforation. •  Gastric hyperacidity.

Infectious Diseases

Pythiosis can cause severe GUE. It is regionally important and is becoming increasingly widespread in North America. Metabolic Diseases

•  Hepatic disease. •  Hypoadrenocorticism.

Toxicity

Heavy metal poisoning (arsenic, zinc, thallium, iron, and lead are rare causes). Neoplasia

•  GI neoplasia (carcinoma, lymphoma, leiomyoma, GI stromal tumor). •  Paraneoplastic hyperacidity (mastocytosis, gastrinoma).

Stress/Major Medical Illness

•  Shock/severe hypotension (e.g., secondary to trauma or surgery). •  SIRS (heat stroke, sepsis). •  Burns. •  Sustained strenuous

exercise (especially in extreme environments, either cold or hot). RISK FACTORS •  Ulcerogenic drugs (NSAIDs, dexamethasone). •  Hypovolemic shock/SIRS. •  Extreme exercise.

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DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Esophageal disease (neoplasia, esophagitis, foreign body)—diagnose with radiography

and/or esophagoscopy. •  Coagulopathies (thrombocytopenia, anticoagulant poisoning)— diagnose with platelet count, coagulation testing. •  Bronchopulmonary disease causing hemoptysis—diagnose with radiography and/ or bronchoscopy. •  Regurgitation or vomiting blood (hematemesis) swallowed from respiratory tract or swallowed with food. •  Pepto-Bismol and activated charcoal cause stool to resemble melena. CBC/BIOCHEMISTRY/URINALYSIS

•  Acute blood loss (≤3–5 days)—nonregenerative anemia/hypoproteinemia. •  Blood loss

>7 days—regenerative anemia/hypoproteinemia. •  Chronic blood loss—iron deficiency anemia (i.e., low mean corpuscular volume [MCV], high red cell distribution width [RDW], hypochromic, variable reticulocytosis) and hypoproteinemia. •  Blood urea nitrogen (BUN) : creatinine ratio may be elevated with acute, severe GI hemorrhage, but this is hard to evaluate without recent pre-bleed laboratory values. OTHER LABORATORY TESTS

•  Fecal flotation (parasitism). •  Bile acids (hepatic insufficiency). •  Resting serum cortisol (screen for hypoadrenocorticism). •  Serum

gastrin concentrations (gastrinoma is rare). IMAGING

•  Abdominal radiography (GI foreign body,

abdominal mass, pneumoperitoneum, effusion, hepatic disease). •  Barium contrast radiography very insensitive for GUE. •  Ultrasonography specific but poorly sensitive for GI lesions (e.g., infiltrates, altered layering, ulcer); cannot detect erosions. DIAGNOSTIC PROCEDURES

•  Endoscopy most sensitive test for GUE.

Allows biopsy of the lesion; best to biopsy normal-appearing tissue around GUE plus periphery of ulcer. Be careful biopsying center of ulcers as this rarely causes perforation. •  Capsule endoscopy less expensive and does not require anesthesia, but not as sensitive as regular gastroscopy and does not allow for biopsy. •  Fine-needle aspirates or biopsies of infiltrative lesions in GI tract. •  Abdominocentesis may reveal septic peritonitis if ulcer perforates. •  Exploratory surgery can be done to look for GUE, but easy to miss mucosal lesions from serosal surface. Can easily look into stomach through gastrostomy incision and miss lesions. PATHOLOGIC FINDINGS •  GUEs are grossly visible. •  Gastric body and antrum most common sites of GUE (especially from NSAIDs and steroids), but GUE can occur anywhere in stomach. •  Proximal duodenal ulceration classic but not diagnostic for excessive gastric acid secretion (mast cell tumor, gastrinoma). •  Microscopically can see inflammation, neoplasia, or fungal organisms.



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Gastroduodenal Ulceration/Erosion

(continued) 

EXPECTED COURSE AND PROGNOSIS

•  Varies with underlying causes. •  GUE not

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TREATMENT

APPROPRIATE HEALTH CARE Very important: remove underlying cause if possible (e.g., drugs, toxins, poor perfusion). Many GUEs resolve spontaneously if cause is removed. NURSING CARE •  IV fluids if needed to maintain hydration, gastric mucosal perfusion, and/or treat shock. •  Transfusions if patient is severely anemic or has vigorous GI hemorrhage. ACTIVITY Based upon patient’s condition. DIET

•  Discontinue oral intake if vomiting. •  When

feeding resumed, feed small amounts of low-fat/low-fiber diet.

CLIENT EDUCATION •  Dogs are especially prone to NSAIDinduced GUE because these drugs have a longer half-life in dogs than in humans. •  Never administer NSAID (especially if sold for human use) unless specifically prescribed by veterinarian (e.g., low dose of aspirin [0.5 mg/kg q24h] is safe when used to prevent thromboembolic disease in dogs being treated with steroids). •  NSAIDassociated GUE reduced by giving drug with food. •  Proton pump inhibitors (PPIs) as effective as misoprostol in preventing NSAID-induced GUE. •  No drug shown to be effective in preventing steroid-induced GUE. SURGICAL CONSIDERATIONS

•  If GI blood loss potentially life threaten-

ing, perform gastroduodenoscopy to identify sites of hemorrhage; then either surgically resect lesions or cauterize sites endoscopically (electrically or chemically). •  Surgical excision of ulcers indicated if medical treatment shows no evidence of benefit after 5–7 days. •  May need intraoperative endoscopy to locate lesions that cannot be found at surgery. •  Rarely need surgeon to telescope intestines over tip of endoscope to thoroughly examine entire duodenal and jejunal mucosa.

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MEDICATIONS

DRUG(S) OF CHOICE •  PPIs most potent inhibitors of gastric acid secretion. Require 3–5 days to achieve maximum efficacy. Used as prophylactic drugs and as first-line therapy for existing GUE; primary therapy for gastrinomas. Omeprazole (1–2 mg/kg PO q12h) administered orally; pantoprazole (1 mg/kg IV q12h) can be administered parenterally. •  Histamine (H2) receptor antagonists also inhibit gastric acid secretion. Famotidine (0.5–1 mg/kg PO/ IV q12–24h) most potent, but all of these drugs inferior to PPIs. •  Sucralfate (0.5–1 g PO q6–8h) protects ulcerated tissue by binding to it and stimulating prostaglandin synthesis (use suspension instead of tablets). No benefit in combining with PPIs. •  Misoprostol (2–5 μg/kg PO q12h) effective, but has many side effects. •  Antiemetics if vomiting frequent or nausea severe. Maropitant (1 mg/kg SC q24h; 2 mg/ kg PO q24h); ondansetron (0.2–0.5 mg/kg PO/IV q8–12h). •  Oral antacids (e.g., calcium carbonate) poorly effective and not recommended. POSSIBLE INTERACTIONS •  Sucralfate may slow absorption of other drugs. •  Antacids may slow absorption of other drugs. •  H2 receptor antagonists decrease effectiveness of PPIs. •  Do not use misoprostol in pregnant patients.

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FOLLOW-UP

PATIENT MONITORING Effective medical therapy should result in clinical improvement within 5–7 days. PREVENTION/AVOIDANCE •  Administer NSAIDs with food. •  PPIs generally as effective as misoprostol at preventing NSAID-induced GUE. •  COX-2 selective or dual lipoxygenase (LOX)/COX inhibitors less likely to cause GUE than nonselective NSAIDs, but can still cause GUE and perforation/peritonitis. POSSIBLE COMPLICATIONS Hemorrhage, perforation, septic peritonitis.

due to local malignancy can usually be treated successfully medically (especially if one can remove cause). However, if perforation has occurred, surgery is necessary.

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MISCELLANEOUS

ASSOCIATED CONDITIONS Anemia AGE-RELATED FACTORS Neoplasia more common in older animals. SEE ALSO •  Hematemesis. •  Melena. ABBREVIATIONS

•  ACTH = adrenocorticotropic hormone. •  BUN = blood urea nitrogen. •  COX = cyclooxygenase. •  DIC = disseminated intravascular coagulation. •  GI = gastrointestinal. •  GUE = gastric ulceration/erosion. •  LOX = lipoxygenase. •  MCV = mean corpuscular volume. •  NSAID = nonsteroidal anti-inflammatory

drug.

•  PPI = proton pump inhibitor. •  RDW = red cell distribution width. •  SIRS = systemic inflammatory response

syndrome.

­Suggested Reading

Mansfield CS, Abraham LA. Ulcer. In: Washabau RJ, Day MJ, eds., Canine and Feline Gastroenterology. St. Louis, MO: Elsevier Saunders, 2013, pp. 637–642. Neiger R. Gastric ulceration. In: Bonagura JD, Twedt DC, eds., Kirk’s Current Veterinary Therapy XIV. St. Louis, MO: Elsevier Saunders, 2009, pp. 497–501. Simpson KW. Diseases of the stomach. In: Ettinger SJ, Feldman EC, Cote E, eds., Textbook of Veterinary Internal Medicine, 8th ed. St. Louis, MO: Elsevier, 2017, pp. 1495–1516. Author Michael D. Willard Consulting Editor Mark P. Rondeau  Client Education Handout available online

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Gastroenteritis, Acute Hemorrhagic Diarrhea Syndrome

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G

 BASICS

DEFINITION A peracute hemorrhagic enteritis of dogs characterized by a sudden onset of severe bloody diarrhea that is often explosive, with vomiting (typically the first clinical sign observed by the owner), hypovolemia, and usually marked hemoconcentration due to a dramatic loss of fluid into the intestinal lumen. PATHOPHYSIOLOGY •  Many conditions result in hemorrhagic diarrhea, but the acute hemorrhagic diarrhea syndrome (AHDS) of dogs appears to have unique clinical features that distinguish it from other conditions. •  AHDS results in a peracute loss of intestinal mucosal integrity with the rapid movement of fluid and electrolytes into the gut lumen. Dehydration and hypovolemic shock occur quickly. In proportion to fluid loss, blood loss is usually minor. This has to be differentiated from true gastrointestinal (GI) bleeding, in which anemia is usually observed. Protein loss can be substantial in some cases, resulting in severe hypoalbuminemia. Translocation of bacteria or toxins through the damaged intestinal mucosa can usually be compensated. In a few cases the immune defense mechanisms can be overwhelmed, resulting in septicemia/septic shock. SYSTEMS AFFECTED •  GI. •  Cardiovascular. GENETICS Unknown; small or toy breeds appear to be overrepresented. INCIDENCE/PREVALENCE Unknown; appears to be common. GEOGRAPHIC DISTRIBUTION N/A SIGNALMENT Species

Dog

Breed Predilections

•  Any breed can be affected; incidence is greater in small and toy breeds. •  Breeds most

represented include Yorkshire terrier, miniature pinscher, miniature schnauzer, miniature poodle, and Maltese.

AHDS. •  Most animals affected are previously healthy with no historical environmental changes; some dogs have a history of chronic intermittent GI disease. •  Clinical findings are variable in both the course and severity of the disease; the disease is usually acute to peracute; with adequate fluid and symptomatic treatment, rapid clinical improvement is typically observed in the first 48 hours. Historical Findings

•  Acute vomiting, anorexia, and lethargy,

followed by watery diarrhea quickly changing to bloody diarrhea. •  Signs progress rapidly and become severe within a period of 60%, with discordant plasma proteins that are normal to decreased due to protein loss into the GI tract; some dogs show significant hypoalbuminemia after rehydration; usually a stress leukogram. •  Biochemistry profile may reveal secondary hepatic enzyme elevations and high blood urea nitrogen (BUN) due to prerenal causes. OTHER LABORATORY TESTS Fecal Tests

•  Stool is negative for parasites. •  ELISA and PCR for parvovirus are negative. •  Fecal cytology shows many red blood cells (RBCs) and occasional white blood cells (WBCs). •  Clostridium spp. may be cultured from healthy dogs and should not be used as a diagnostic test for AHDS. Fecal ELISA test for detection of C. perfringens enterotoxin is often positive. A culture for other enteric pathogens is not diagnostic, since many enteropathogens can be found in feces of healthy dogs. Fecal PCR for detection of C. perfringens alpha toxin gene alone is not sufficient to diagnose this disorder. A positive PCR for netF encoding C. perfringens strains is suggestive for AHDS.

Coagulogram

Usually normal, but rarely secondary disseminated intravascular coagulation (DIC) is a complication. IMAGING Abdominal radiographs or ultrasound show fluid- and gas-filled small and large intestine. Ultrasonography often reveals fluid-filled intestinal loops without peristaltic movements due to the presence of a paralytic ileus. DIAGNOSTIC PROCEDURES Endoscopy

•  Rarely indicated. •  Stomach may appear normal, but small and large intestine will show diffuse mucosal hemorrhage, and hyperemia.

PATHOLOGIC FINDINGS •  Gross findings include intestinal congestion. •  Histological examination of the intestinal tract shows superficial mucosal hemorrhagic necrosis without significant inflammation. •  Frequently, layers of rod-shaped bacteria (e.g., C. perfringens) can be detected on the surface of the intestinal mucosa. •  Gastric mucosa is spared.

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 TREATMENT

APPROPRIATE HEALTH CARE Patients suspected of having AHDS should be hospitalized and treated aggressively, because clinical deterioration is often rapid and can be fatal.

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Gastroenteritis, Acute Hemorrhagic Diarrhea Syndrome

NURSING CARE •  Rapid volume replacement through a largebore IV catheter is required in all cases. •  Balanced electrolyte solutions are given up to the rate of 40–60 mL/kg/hour IV until PCV dogs—thickened bowel loops on abdominal palpation. •  HES—skin lesions,

enlarged peripheral lymph nodes, hepato­ splenomegaly. •  Abdominal pain. •  Muscle wasting, weight loss, ± coat changes. •  Pale mucous membranes with bleeding ulcer. •  Dehydration, hypovolemia. •  Palpable abdominal mass lesion. CAUSES

•  IBD. •  Parasites—e.g., Physaloptera spp., Ollulanus tricuspis, Spirocerca spp. •  Fungal, viral, bacterial infection. •  Loss of tolerance to normal intestinal flora. •  Systemic mastocytosis. •  HES. •  Neoplasia—mast cell tumor, lymphoma.

RISK FACTORS N/A

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Any cause of GI signs. •  Feline GI eosinophilic sclerosing fibroplasia (ulcerated intramural mass at pyloric sphincter or ileocecocolic junction most common). CBC/BIOCHEMISTRY/URINALYSIS •  Hemogram—unremarkable, mild to marked peripheral eosinophilia (cats > dogs). •  Biochemistry—blood urea nitrogen (BUN) elevation alone or disproportionally higher than creatinine suggests GI bleeding; hypoproteinemia and hypocholesterolemia common with significant disease; increased liver enzyme activity and/or azotemia may be seen with HES; prerenal azotemia with dehydration. •  Urinalysis—usually unremarkable. OTHER LABORATORY TESTS •  Buffy-coat smear—evaluate for systemic mastocytosis. •  Serum cobalamin and folate—screen for evidence of intestinal malabsorption. •  Fecal float, multiple. •  Baseline cortisol ± adrenocorticotropic hormone (ACTH) stimulation test. •  Based on location or travel history, testing for fungal organisms (i.e., histoplasmosis). •  Expanded infectious disease testing depending on patient risk and exposure. IMAGING

•  Abdominal radiography—rules out other

disease causing clinical signs; does not diagnose this condition; hepatosplenomegaly may be seen with HES. •  Barium contrast radiography may demonstrate thick intestinal walls and mucosal irregularities, but does not provide etiology. •  Ultrasonography—assess stomach and intestinal wall thickness; assess for mass lesions, ulcer, and obstruction; rule out other diseases; examine liver, spleen, and mesenteric lymph nodes with suspected HES or metastatic disease. DIAGNOSTIC PROCEDURES •  Upper and lower GI endoscopy—visualize mucosa; identify ulcer or mass; biopsy (even when grossly normal); thickened rugal folds,

increased mucosal friability, villous blunting, edema, and erythema are commonly visualized; intestinal parasites may be seen. •  Fine-needle aspirate and cytology of enlarged liver, spleen, and/or lymph nodes. •  Bone marrow aspirate cytology—when systemic mastocytosis or severe peripheral eosinophilia is present. •  Exploratory laparotomy—perforated ulcer; full-thickness biopsy; removal of obstructive lesion and/or biopsy of other affected organs (lymph node, spleen, liver). PATHOLOGIC FINDINGS

•  Eosinophilic infiltrates can be patchy in

intestine; multiple biopsies always recommended. •  Histopathology reveals diffuse mucosal infiltrate of eosinophils; submucosa and muscularis are less commonly involved in the dog (more common in the cat); infiltrate of muscularis layer associated with obstructive eosinophilic lesions; eosinophilic inflammation within fibroplasia seen in feline GI eosinophilic sclerosing fibroplasia; WSAVA guidelines from international GI Standardization Group should be followed for interpretation of normal vs. pathologic numbers of eosinophils.

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 TREATMENT

APPROPRIATE HEALTH CARE •  Many treated as outpatients (minimal dehydration) after obstruction excluded, pending diagnostic testing or treatment trials (i.e., diet trial, drugs). •  Inpatient medical management if significant dehydration or intractable vomiting. NURSING CARE

•  IV fluids to restore volume and correct

dehydration when indicated; caution for fluid overload with hypoproteinemia. •  Enteral nutrition (nasoesophageal, nasogastric, or esophageal tubes) with persistent anorexia. •  Severe hypoalbuminemia—consider albumin, plasma, or colloids. ACTIVITY Restrict postoperatively if surgery performed. DIET

•  Novel protein or hydrolyzed diet when

allergy or IBD suspected; initial response expected within 2 weeks; worsening warrants diet change or other intervention; if improvement noted, continue diet for several months before reintroducing other foods to assess tolerance. •  Challenge with original diet can prove food hypersensitivity; rarely pursued. •  Calorie requirement/diet guideline increases compliance. •  Unflavored or topical flea, tick, and heartworm preventatives. •  Treats limited to prescription diet. •  If commercial diet declined, consider homecooked diet formulated by veterinary nutritionist.





Gastroenteritis, Eosinophilic

(continued)

CLIENT EDUCATION •  Review multiple etiologies. •  Least invasive testing first when patient status allows; biopsy for definitive diagnosis if extra-intestinal causes ruled out and patient fails diet and drug trial (i.e., anthelminthic, antimicrobial). •  Potential for waxing and waning nature; necessity for lifelong vigilance regarding inciting factors; potential for long-term therapy. SURGICAL CONSIDERATIONS •  Obstructive lesion. •  Perforated ulcer. •  Full-thickness biopsy.

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 MEDICATIONS

DRUG(S) OF CHOICE •  Gastroprotectants and antiemetics often needed to control clinical symptoms initially. •  Gastroprotectants—proton pump inhibitor (PPI), i.e., omeprazole 1 mg/kg PO q12h 30–60 min before meal; also consider sucralfate, H2 receptor antagonist, and others per ACVIM consensus (see Suggested Reading). •  Antiemetics—maropitant (1 mg/ kg SC/IV q24h; 2 mg/kg PO q24h); ondansetron, metoclopramide, mirtazapine. •  Prokinetics—metoclopramide (0.2–0.4 mg/ kg PO q8h; CRI 1–2 mg/kg/day), cisapride, ranitidine, low-dose erythromycin. •Anthelminthic—fenbendazole (50 mg/kg PO q24h for 5 days), pyrantel pamoate + febantel. •  Antimicrobial—metronidazole (10 mg/kg PO q12h for 2–4 weeks), tylosin (11–20 mg/kg PO q12h for 2–4 weeks). •  IBD suspected/confirmed—glucocorticoid (i.e., prednisone 2 mg/kg PO q24h or divided q12h; prednisolone for cat) when no clinical response to other therapeutic trials or in advanced disease; taper by 20–25% increments over time to lowest effective dose; discontinue when possible; total dose not >60 mg per day (dog); use with diet. •  If glucocorticoid not tolerated and/or relapse, consider second drug; see Alternative Drug(s). CONTRAINDICATIONS Do not use prokinetics if GI obstruction possible. PRECAUTIONS

•  Immune modulation predisposes to secondary infections. •  Steroids can cause GI

ulceration, diabetes mellitus, or fluid overload (especially cat: congestive heart failure); patient monitoring and client education are vital to success. •  Prolonged use of antacids or PPIs can lead to overgrowth of bacteria.

POSSIBLE INTERACTIONS •  Sucralfate will decrease absorption of other medications; separate by 2 hours from other medications. •  Omeprazole affects clearance of many drugs. •  Never use nonsteroidal anti-inflammatory drugs (NSAIDs) with glucocorticoid; high risk of GI erosion/ulcer.

ALTERNATIVE DRUG(S)

•  IBD—if steroid and diet alone do not

achieve disease remission, if patient relapses, and/or if steroid side effects undesirable, second agent may be considered; options: cyclosporine, mycophenolate, chlorambucil, and azathioprine (never in cats); find lowest effective dose. •  Monitoring—exam, labwork (CBC, chemistry) for myelosuppression and other concerns (i.e., hepatic toxicity with cyclosporine, chlorambucil, and azathioprine). •  Leukotriene receptor blockers (i.e., montelukast) have been successful in humans. •  Budesonide (steroid; 1–3 mg/patient depending on size) may have fewer systemic side effects; adrenal pituitary axis affected.

AGE-RELATED FACTORS

•  Food-responsive enteropathy—often younger. •  IBD—often middle-aged to older. •  Neoplasia—middle-aged to older animals

more common.

ZOONOTIC POTENTIAL Potential/uncommon concern secondary to parasites (i.e., Toxocara spp.—larval migrans). PREGNANCY/FERTILITY/BREEDING •  Prednisone—abortion, teratogenic, can induce parturition. •  Azathioprine—fetal harm; decreases sperm production. •  Cyclosporine—fetal toxicity. SEE ALSO

•  Gastroduodenal Ulceration/Erosion. •  Inflammatory Bowel Disease.

ABBREVIATIONS

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 FOLLOW-UP

PATIENT MONITORING •  Depends on patient severity and medication chosen; minimum: physical exam within 2 weeks of starting treatment. •  Monitoring peripheral eosinophil count if initially elevated. •  Recheck abnormal labwork (i.e., electrolytes, proteins) and monitor for medication side effects (i.e., hyperglycemia, anemia, myelosuppression, heptaopathy, etc. based on specific drugs selected). •  Recurrence warrants repeat diagnostics; repeat biopsy may be indicated (i.e., patients previously in remission of IBD can progress to lymphoma). •  Lack of response—change in medical management (i.e., alternative diet or drug); repeat biopsy (primary disease may have been missed) and labwork (CBC, chemistry, fecal, T4) for emerging comorbidity. PREVENTION/AVOIDANCE

•  Avoid rapid diet change. •  Prevent free-

roaming and potential for dietary indiscretion— may need basket muzzle in dogs. POSSIBLE COMPLICATIONS

•  Gastroesophageal reflux disease (GERD). •  Delayed gastric emptying/motility disorders. •  Erosions/ulcers. •  Aspiration pneumonia. •  Electrolyte, acid-base imbalances. •  Debilitation/death in refractory cases. •  Steroid—diabetes mellitus, heart failure, calcinosis cutis, muscle weakness, ulcers. •  Other

immune-modulating drugs—bone marrow suppression, pancreatitis, hepatitis, GI upset.

EXPECTED COURSE AND PROGNOSIS •  Vary with cause. •  Medication tapered to lowest effective dose ± stopped with diet.

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 MISCELLANEOUS

ASSOCIATED CONDITIONS N/A

•  ACTH = adrenocorticotropic hormone. •  BUN = blood urea nitrogen. •  GERD = gastroesophageal reflux disease. •  GI = gastrointestinal. •  HES = hypereosinophilic syndrome. •  IBD = inflammatory bowel disease. •  NSAID = nonsteroidal anti-inflammatory drug. •  PPI = proton pump inhibitor.

INTERNET RESOURCES •  https://veterinarypartner.vin.com/default. aspx?pid=19239&id=7393377 •  https:// veterinarypartner.vin.com/default. aspx?pid=19239&id=4951476

­Suggested Reading

Hall EJ, Day MK. Diseases of the small intestine. In: Ettinger SJ, Feldman EC, eds., Textbook of Veterinary Internal Medicine, 8th ed. St. Louis, MO: Elsevier, 2017, pp. 1516–1564. Linton M, Nimmo JS, Norris JM, et al. Feline gastrointestinal eosinophilic sclerosing fibroplasia: 13 cases and review of an emerging clinical entity. J Feline Med Surg 2015, 17:392–404. Marks SL, Kook PH, Papich MG, et al. ACVIM consensus statement: support for rational administration of gastrointestinal protectants to dogs and cats. J Vet Intern Med 2018, 32:1823–1840. Sattasathuchana O, Steiner JM. Canine eosinophilic gastrointestinal disorders. Anim Health Res Rev 2014, 15(1):76–86. Author Kathryn M. McGonigle Consulting Editor Mark P. Rondeau Acknowledgment The author and book editors acknowledge the prior contribution of Michelle Pressel  Client Education Handout available online

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Gastroesophageal Reflux CBC/BIOCHEMISTRY/URINALYSIS Usually normal.

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 BASICS

OVERVIEW •  Reflux of gastric or intestinal fluid into the esophageal lumen. •  Incidence unknown; probably more common than clinically recognized. •  Transient relaxation of the lower esophageal sphincter (LES) or chronic vomiting may permit reflux of gastrointestinal juices into the esophageal lumen. Reflux is common in dogs with sliding hiatal hernias. A small amount of gastroesophageal reflux (GER) is a normal phenomenon in dogs and cats. •  Gastric acid, pepsin, trypsin, bicarbonate, and bile salts are all injurious to the esophageal mucosa with prolonged or repetitive contact. •  Sequelae of GER may vary from mild inflammation of the superficial mucosa to severe ulceration involving the submucosa and muscularis. •  Systems affected include gastrointestinal (regurgitation) and respiratory (aspiration pneumonia). SIGNALMENT •  Dog and cats; male or female. •  No breed predilections reported. •  May be associated with congenital hiatal hernia seen in Chinese Shar-Pei dogs and brachycephalic breeds. •  Occurs at any age; younger animals may be at increased risk because of developmental immaturity of the gastroesophageal sphincter. SIGNS •  Regurgitation. •  Hypersalivation. •  Painful swallowing (odynophagia). •  Anorexia. CAUSES & RISK FACTORS •  General anesthesia. •  Retained gastric contents. •  Acquired or congenital hiatal hernia. •  Chronic vomiting with secondary esophagitis. •  Brachycephalic airway syndrome.

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Oral or pharyngeal disease. •  Ingestion of caustic agent. •  Esophageal foreign body. •  Esophageal tumor. •  Megaesophagus. •  Hiatal hernia. •  Gastroesophageal intussusception.

OTHER LABORATORY TESTS N/A IMAGING •  Survey thoracic radiography—usually unremarkable; may be air or fluid in the distal esophagus (nonspecific finding). •  Barium contrast radiography—reveals GER in some, but not all, animals; videofluoroscopy is superior to esophagram; aspiration pneumonia may be evident in the dependent portions of the lung. DIAGNOSTIC PROCEDURES Esophagoscopy—the best means of confirming esophagitis: irregular mucosal surface with hyperemia or active bleeding often present in the distal esophagus. Refluxed gastroduodenal secretions may be seen pooling in the distal esophagus near the LES, which may or may not be open.

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 TREATMENT

•  Generally managed as outpatient. •  Not necessary to restrict activity. •  Moderate to severe cases—may withhold

food for 24 hours to promote esophageal rest and to minimize further GER; thereafter, feed low-fat, low-protein meals in small, frequent feedings; dietary fat decreases gastroesophageal sphincter pressure and delays gastric emptying; protein stimulates gastric acid secretion and may precipitate GER.

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 MEDICATIONS

DRUG(S) OF CHOICE •  Drug therapy is recommended if significant mucosal injury is present. •  Oral sucralfate slurry (0.5–1 g PO q8h). •  Proton pump inhibitors (omeprazole: 0.7–1.5 mg/kg PO q12h or pantoprazole: 1 mg/kg IV q12–24h) for robust suppression of gastric acid production. •  Prokinetic agents—cisapride (0.5 mg/kg PO q8–12h) or metoclopramide (0.5 mg/kg PO q6–8h or 1–2 mg/kg q24h as CRI). •  Gastrostomy tube placement for enteral nutrition in animals with severe mucosal trauma. CONTRAINDICATIONS/POSSIBLE INTERACTIONS Sucralfate may interfere with the absorption of other drugs.

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 FOLLOW-UP

PATIENT MONITORING •  It is appropriate in most patients to monitor clinical signs. •  Consider endoscopy for patients that do not respond to empirical medical therapies. Severe mucosal damage (esophagitis) may progress to stricture. PREVENTION/AVOIDANCE Clients should avoid feeding high-fat foods; they promote gastric retention and might exacerbate GER. POSSIBLE COMPLICATIONS Esophagitis and stricture formation. EXPECTED COURSE AND PROGNOSIS Most animals respond well to medical management and have a good prognosis.

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 MISCELLANEOUS

ASSOCIATED CONDITIONS Hiatal hernia. AGE-RELATED FACTORS May be worse in younger animals because of developmental immaturity of the gastro­ esophageal sphincter mechanism. ZOONOTIC POTENTIAL N/A PREGNANCY/FERTILITY/BREEDING N/A SEE ALSO •  Esophageal stricture. •  Esophagitis. ABBREVIATIONS

•  GER = gastroesophageal reflux. •  LES = lower esophageal sphincter.

­Suggested Reading

Kook PH, Kempf J, Ruetten M, Reusch CE. Wireless ambulatory esophageal pH monitoring in dogs with clinical signs interpreted as gastroesophageal reflux. J Vet Intern Med 2014, 28(6):1716–1723. Zacuto AC, Marks SL, Osborn J, et al. The influence of esomeprazole and cisapride on gastroesophageal reflux during anesthesia in dogs. J Vet Intern Med 2012, 26(3):518–525. Author Albert E. Jergens Consulting Editor Mark P. Rondeau Client Education Handout available online



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Gastrointestinal Obstruction SIGNS Historical Findings

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 BASICS

•  Severity of clinical signs is influenced by

location and completeness of obstruction.

DEFINITION The partial or complete physical impedance to the flow of ingesta and/or secretions aborally through the pylorus into the duodenum (gastric outflow tract obstruction [GOTO]) or through the small intestine. Obstructions in the pharynx, esophagus, large intestine, and rectum, and motility disorders, are addressed in separate chapters.

•  Patients with GOTO tend to have acute

PATHOPHYSIOLOGY •  Mechanical obstruction commonly results from indiscriminate ingestion of foreign material, the presence of a gastrointestinal (GI) mass, or intussusception. •  The accumulation of ingesta and GI secretions orad to the obstruction causes local vascular compromise, resulting in intestinal wall edema, necrosis, and possible sepsis. •  Decreased oral intake, vomiting, and sequestration of GI secretions result in acid-base and electrolyte imbalances.

Physical Examination Findings

SYSTEMS AFFECTED

•  Cardiovascular—hypovolemic or septic

shock can result from fluid loss or GI translocation of bacteria. •  GI—GI obstructions cause pathology by distension and compression of the GI tract orad to the obstruction; this results in decreased blood flow to the area with subsequent edema, ulceration, and necrosis of the mucosa; direct physical damage to the GI mucosa by foreign bodies (especially linear foreign bodies) can result in ulceration and possible perforation of the intestinal wall. •  Hemic/lymphatic/ immune—sepsis secondary to necrosis and/or bacterial translocation. GENETICS Unknown INCIDENCE/PREVALENCE Common SIGNALMENT

Species

Dog and cat. Breed Predilections

Gastric dilation and volvulus (GDV) is common in large- and giant-breed dogs (Great Dane, German shepherd). Mean Age and Range

•  Foreign bodies—more common in young animals, but can occur at any age. •  Pyloric

stenosis—occurs most often in young animals. •  Chronic hypertrophic gastropathy (CHG)—more common in middle-aged and older animals. •  Intussusceptions—most common in young animals.

Predominant Sex

None

onset of severe vomiting; some patients can present as acute abdomen (acute and severe abdominal pain, vomiting); partial obstructions can have more chronic and intermittent clinical signs. •  Duration of clinical signs varies, but usually 2–3 days. •  Patients may have vomiting, anorexia, and/ or lethargy. •  Moderate to severe dehydration is common. •  Careful oral examination is recommended

as linear foreign bodies can often be lodged at the base of the tongue. •  Abdominal palpation will often elicit a painful response; sometimes patients will vomit in response to palpation. •  Abdominal mass may be palpated. •  Cranial abdominal distension and tympany often seen with GDV. CAUSES

•  Benign pyloric outflow tract obstruction. •  Foreign body. •  Gastroenteritis (infectious, granulomatous). •  GDV. •  GI neoplasia. •  Intussusception. •  Mesenteric torsion/ volvulus. •  Pyloric stenosis. •  Stricture.

RISK FACTORS

•  Foreign bodies more commonly found in

young dogs and cats (mean age 2–4 years) due to indiscriminate eating behavior. •  Linear foreign bodies found more commonly in cats. •  GI tumors more common in older cats and dogs.

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Metabolic disease (e.g., renal failure, hepatic disease, diabetic ketoacidosis, hypoadrenocorticism). •  Infectious gastroenteritis (e.g., viral, bacterial, parasitic). •  Nonspecific gastroenteritis. •  Pancreatitis. •  Peritonitis. •  Gastroduodenal ulcer and erosion. •  CNS disease. CBC/BIOCHEMISTRY/URINALYSIS

•  CBC—will often reflect systemic

consequences of obstruction; variable degrees of neutrophilia with left shift and possible toxic changes seen with cases of sepsis. •  Biochemistry—often reveals changes secondary to dehydration (increased blood urea nitrogen [BUN] and creatinine) as well as electrolyte and acid-base disturbances; animals with GOTO classically have hypokalemic and hypochloremic metabolic alkalosis. •  Urinalysis—urine specific gravity may be increased secondary to dehydration.

OTHER LABORATORY TESTS Lactate—hypoperfusion results in hyperlactatemia (>2.5 mmol/L). IMAGING

•  Survey abdominal radiographs—radiopaque

foreign material may be seen in GI lumen; presence of soft tissue opacity in the stomach in a patient with recent history of vomiting and anorexia is highly suspicious for GOTO; indirect signs of GI obstruction can include gastric or intestinal distension with fluid or gas; linear foreign bodies characteristically cause grouping of intestinal loops on right of midline with small luminal gas bubbles (apostrophe shaped); presence of free gas in abdomen is consistent with GI perforation and septic peritonitis. •  Contrast abdominal radiographs—positive contrast agents (liquid barium) can be used to identify radiolucent material in GI lumen; retained contrast material in stomach 4–6 hours after administration is consistent with GOTO; use of barium contrast agents contraindicated if GI perforation is suspected; in these instances, use of iodinated contrast agents is recommended. •  Abdominal ultrasound— ultrasound can be very effective at identifying GI foreign bodies and intraluminal masses as well as assessing for integrity of GI tract and presence of abdominal fluid/air; luminal foreign bodies will cause distal acoustic shadowing, while linear foreign bodies often appear as hyperechoic linear objects within intestinal lumen. DIAGNOSTIC PROCEDURES

•  In cases where intestinal neoplasia is

suspected, advanced imaging techniques such as CT may provide additional information such as the nature of the mass and its degree of invasion. •  GI endoscopy may be used for removal of gastric foreign bodies causing GOTO. PATHOLOGIC FINDINGS Histopathology of GI masses causing obstruction can reveal granulomatous inflammation, fungal infection (e.g., pythiosis), and neoplasia.

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 TREATMENT

APPROPRIATE HEALTH CARE •  Emergency intervention is required to relieve the obstruction. •  Prior to definitive treatment of the obstruction, stabilization of the patient and correction of dehydration as well as electrolyte and acid-base abnormalities are imperative. •  Dogs with GDV should have gastric decompression first using orogastric intubation or percutaneous gastrocentesis in order to relieve gastric pressure.

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Gastrointestinal Obstruction

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NURSING CARE •  Aggressive IV administration of isotonic crystalloids is recommended to correct dehydration and hypovolemia, if present; recommendation is to administer ¼ shock bolus of 20 mL/kg (dog) or 10 mL/kg (cat) over 15 min and reevaluate patient’s status (heart rate, blood pressure, blood lactate); repeat 1–2 times if vital parameters fail to normalize; if crystalloid therapy not successful in stabilizing patient, colloid solutions such as hetastarch can be administered at 5 mL/kg (dog) and 2.5 mL/kg (cat), to max 20 mL/kg (dog) and 10 mL/kg (cat). •  Colloids should be used with caution, especially in cases where sepsis is suspected, due to their association with acute kidney injury.

should be initiated as soon as possible in patients with suspected GI obstruction. •  In cases where GI ulceration is suspected or confirmed, use of a proton pump inhibitor is recommended (omeprazole or pantoprazole 1 mg/kg q12h PO or IV, respectively). •  Appropriate analgesia should be provided before, during, and after surgery; mu-agonist opioids (fentanyl 2–5 μg/kg/h IV as CRI or hydromorphone 0.1 mg/kg IV q4–6h) are recommended given their strong analgesic effect.

ACTIVITY Restricted for first 10–14 days post surgery.

PRECAUTIONS •  Use of antiemetic medications is contraindicated in patients with suspected GI obstruction. •  Nonsteroidal anti-inflammatory drugs should not be used in patients with GI obstructions due to their adverse effects on the GI mucosa and renal function in patients that are not hemodynamically stable.

DIET •  Nothing by mouth until relief of obstruction and resolution of vomiting; then feed bland fat-restricted diet for 1–2 days, with gradual return to normal diet. •  Enteral tube feeding or parenteral feeding may be required postoperatively. CLIENT EDUCATION Animals with a history of GI foreign bodies have a tendency to repeat this behavior; owners should be counseled on ways to minimize ingestion of these objects.

CONTRAINDICATIONS Prokinetic agents (e.g., metoclopramide, cisapride) must be avoided until obstruction is resolved.

POSSIBLE INTERACTIONS N/A ALTERNATIVE DRUG(S) N/A

SURGICAL CONSIDERATIONS

•  Surgical exploration of the abdomen allows

for removal of the foreign body as well as resection of any nonviable tissue; if the obstruction is neoplastic, infectious, or inflammatory in nature, surgical intervention can be therapeutic as well as diagnostic as long as excised tissue is submitted for histopathology and culture. •  When GI obstruction is caused by a gastric foreign body, endoscopic removal can be attempted; if unsuccessful, foreign material can be removed from the stomach by gastrotomy. •  GOTO—GDV should be corrected and future volvulus prevented with a gastropexy. •  Intestinal obstruction—the full length of the intestinal tract should be examined and palpated; enterotomy should be performed to remove any luminal foreign material; if nonviable or perforated sections are present, resection and anastomosis should be performed. •  Although intussusceptions can be percutaneously reduced, recurrence is very common; surgical reduction and/or resection with or without enteropexy is recommended.

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 MEDICATIONS

DRUG(S) OF CHOICE •  Parenteral broad-spectrum IV antibiotic therapy (ampicillin–sulbactam 30 mg/kg IV q8h with enrofloxacin 10 mg/kg IV q24h)

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 FOLLOW-UP

PATIENT MONITORING •  Dehiscence of gastrotomy and enterotomy sites can occur 3–5 days postoperatively; patients should be watched closely during this period for signs of lethargy, recurrence of vomiting, and fever. •  Ventricular arrhythmias are documented in approximately 40% of GDV patients; in these cases, electrolyte and acid-base disturbances should be identified and treated, if present. PREVENTION/AVOIDANCE Efforts to prevent repeat ingestion of foreign bodies. POSSIBLE COMPLICATIONS

•  Aspiration pneumonia. •  Septic peritonitis. •  Functional ileus.

EXPECTED COURSE AND PROGNOSIS

•  With rapid surgical intervention of

uncomplicated cases of GI foreign bodies, prognosis is good (>95%); however, prognosis associated with septic peritonitis is significantly lower (50%); negative prognostic factors that have been identified include longer duration of clinical signs, presence of linear foreign body, and multiple surgical procedures. •  With intestinal neoplasia, prognosis remains guarded to poor, with the exception of small cell lymphoma in cats; with gastric carcinoma, complete surgical excision is rarely attainable and intestinal

(continued)

carcinoma has high rate of metastasis at time of diagnosis; large cell GI lymphoma has relatively poor response rate to commonly used chemotherapy protocols, and median survival times in cats and dogs are 4–6 months and 110 days, respectively.

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 MISCELLANEOUS

ASSOCIATED CONDITIONS N/A AGE-RELATED FACTORS See Signalment. ZOONOTIC POTENTIAL N/A PREGNANCY/FERTILITY/BREEDING N/A SYNONYMS N/A SEE ALSO •  Acute Abdomen. •  Acute Vomiting. •  Gastric Dilation and Volvulus Syndrome. •  Gastric Motility Disorders. •  Hypertrophic Pyloric Gastropathy, Chronic. •  Intussusception. •  Peritonitis. •  Pythiosis. •  Vomiting, Chronic. ABBREVIATIONS

•  BUN = blood urea nitrogen. •  CHG = chronic hypertrophic gastropathy. •  GDV = gastric dilation and volvulus. •  GI = gastrointestinal. •  GOTO = gastric outflow tract obstruction.

­Suggested Reading

Boag AK, Coe RJ, Martinez TA, Hughes D. Acid-base and electrolyte abnormalities in dogs with gastrointestinal foreign bodies. J Vet Intern Med 2005, 19:816–821. Hayes G. Gastrointestinal foreign bodies in dogs and cats: a retrospective study of 208 cases. J Small Anim Pract 2009, 50:576–583. Hobday MM, Pachtinger GE, Drobatz KJ, Syring RS. Linear versus non-linear gastrointestinal foreign bodies in 499 dogs: clinical presentation, management and short-term outcome. J Small Anim Pract 2014, 55:560–565. Author Albert E. Jergens Consulting Editor Mark P. Rondeau Acknowledgment The author and book editors acknowledge the prior contribution of Steven L. Marks.  Client Education Handout available online



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Gestational Diabetes Mellitus

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 OVERVIEW

Diabetes mellitus (DM), which occurs during mid to late gestation, most likely due to insulin resistance from increased progesterone and growth hormone production by the mammary glands. SIGNALMENT •  Middle-aged intact female dogs. •  Mean age—6 years. •  Nordic spitz breeds are overrepresented. •  Not reported in cats. SIGNS

•  Polyuria. •  Polydipsia. •  Polyphagia. •  Weight loss. •  Lethargy. •  Vomiting. •  Ketosis.

CAUSES & RISK FACTORS •  Late-term pregnancy. •  Diestrus. •  Exogenous progesterone supplementation. •  Acromegaly.

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS Acromegaly—affected bitches are listless and have increased abdominal size, increased interdental spaces, polyuria/polydipsia, weight gain, and excessive skin folds in the facial/neck areas. CBC/Biochemistry/Urinalysis

•  Hyperglycemia. •  Glucosuria. •  Metabolic acidosis if ketonemic or

ketonuric.

Continued glucose toxicity can destroy the pancreatic beta cells’ capacity to produce insulin, leading to permanent DM. •  Ovariohysterectomy is recommended. While the diabetes may resolve at the end of diestrus or after parturition, it will return on subsequent cycles and then has a greater potential to become permanent.

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 MEDICATIONS

DRUG(S) OF CHOICE •  Insulin—if ketosis not present, start at an insulin dose of 0.25 U/kg SC q12h of intermediate or long-acting insulin; will likely need to increase the dose to achieve glycemic control. If ketoacidosis is present, regular insulin (0.1–0.2 U/kg IM q4–6h) may be necessary to achieve initial glycemic control before switching to longer-acting insulin. •  Aglepristone—10 mg/kg SC days 1, 2, 9, and 17 from diagnosis. This medication is a progesterone receptor blocker, but does not affect progesterone levels. Treatment reserved for cases in which ovariohysterectomy is not possible or authorized by the owners. CONTRAINDICATIONS/POSSIBLE INTERACTIONS N/A

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 FOLLOW-UP

PATIENT MONITORING Care must be taken to avoid insulin overdose causing hypoglycemia during the immediate postpartum period (or the end of diestrus), because the speed at which insulin resistance resolves and exogenous insulin requirements decrease is unpredictable.

Other Laboratory Tests

PREVENTION/AVOIDANCE Ovariohysterectomy to remove source of progesterone.

Imaging

POSSIBLE COMPLICATIONS Lack of prompt resolution of hyperglycemia may result in diabetes mellitus becoming permanent.

Urine culture—urinary tract infections can contribute to insulin resistance. •  Ultrasonography—assess fetal viability;

deceased puppies may affect treatment decisions. •  Radiographs—determine fetal size and relative risk for dystocia. Diagnostic Procedures

N/A

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 TREATMENT

•  Nonpharmacologic considerations—

management of gestational DM requires intensive fluid and insulin therapy.

EXPECTED COURSE AND PROGNOSIS •  Diabetes usually resolves at parturition or at the end of diestrus. More likely to be transient DM if pregnancy terminated, whereas insulin-treated bitches more likely to develop permanent DM. •  May abort the litter or have dystocia as a result of the effects of chronic hyperglycemia. •  Small, unthrifty puppies may result from an abnormal placental blood supply. Conversely, some fetuses in a hyperglycemic environment experience an abnormally increased growth

rate (macrosomia). These puppies tend to be large, leading to dystocia.

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 MISCELLANEOUS

ASSOCIATED CONDITIONS Pregnancy AGE-RELATED FACTORS Older bitches are more likely to develop permanent DM. ZOONOTIC POTENTIAL N/A PREGNANCY/FERTILITY/BREEDING May abort the litter or have dystocia as a result of the effects of chronic hyperglycemia. There is thought to be a genetic component, due to a breed predisposition. It is not advised to continue to breed affected individuals. SEE ALSO Diabetes Mellitus without Complication— Dogs. ABBREVIATIONS •  DM = diabetes mellitus.

­Suggested Reading

Johnson CA. Glucose homeostasis during canine pregnancy: insulin resistance, ketosis, and hypoglycemia. Theriogenology 2008, 70(9):1418–1423. Author Carla Barstow Consulting Editor Erin E. Runcan

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Giardiasis

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 BASICS

OVERVIEW •  Enteric infection of dogs and cats with protozoan parasite, Giardia duodenalis. •  Direct transmission by ingestion of cysts that are immediately infective when shed in feces. •  Trophozoites, motile (flagellated) organisms released from ingested cysts, attach to surface of enterocytes in small intestine with ventral sucking disc; move from site to site. •  Can cause small bowel diarrhea, but infection often asymptomatic. SIGNALMENT More common in dogs than cats. SIGNS

•  Clinical signs more common in young

hosts; adults usually asymptomatic.

•  Signs can be acute, transient, intermittent,

or chronic.

•  Malabsorption syndrome with soft, frothy,

greasy, voluminous feces (diarrhea), usually with rancid odor.

identified in wet mount diluted in saline by “falling leaf ” motility; flotation media may lyse trophozoites, interfering with accurate identification. •  Cysts, ~12 μm long, oval with 2–4 nuclei, shed intermittently; centrifugal flotation of fresh feces in zinc sulfate (specific gravity 1.18) preferred method for identification of cysts. Three samples collected at 2–3-day intervals should be examined to detect >70% of infections; cysts become distorted (crescent-shaped) in sugar or other flotation solution with specific gravity >1.25; formalin–ethyl acetate sedimentation is useful in cases of steatorrhea. •  ELISA-based kits available for in-house detection of Giardia antigen in feces have high sensitivity; kits should be used to confirm suspicious cases rather than for screening healthy animals; if clinical signs resolve, continued antigen testing not recommended. •  PCR testing—commercial laboratories; studies have shown variable (usually poorer) sensitivity compared to other methods.

CAUSES & RISK FACTORS

•  Transmitted by ingestion of cysts from feces

in/on food, water, environment, or fur.

•  Indirect water-borne transmission most

common; cool, moist conditions favor cyst survival. •  Higher risk of infection in puppies and kittens, in high-density populations, and in animals with compromised immunity.

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Infectious and noninfectious causes of small bowel diarrhea, maldigestion, and malabsorption syndromes, especially pancreatic exocrine insufficiency or inflammatory bowel disease. •  In cats, differentiate from infection with Tritrichomonas foetus. CBC/BIOCHEMISTRY/URINALYSIS Generally within normal limits. OTHER LABORATORY TESTS N/A IMAGING N/A DIAGNOSTIC PROCEDURES

•  Detection of Giardia trophozoites, cysts, or

antigen in feces.

•  Trophozoites (15 × 8 μm) detectable in fresh

feces (especially diarrheic feces) and in duodenal aspirates obtained by endoscopy; trophozoites identified on Diff-Quik® or Lugol’s iodine-stained fecal smear by teardrop shape with two prominent nuclei. Trophozoites

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 TREATMENT

•  Outpatient, unless debilitated or

dehydrated. •  Drug therapy should be combined with environmental cleaning and disinfection plus bathing of patient. •  Giardia vaccines commercially available; efficacy is poor and vaccine not widely used.

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 MEDICATIONS

DRUG(S) OF CHOICE •  All extra-label. •  Fenbendazole—50 mg/kg PO q24h for 3 days (dogs) or 5 days (cats); second course of treatment may be necessary. •  Metronidazole—20–22 mg/kg PO q12h for 5–8 days in dogs. •  Metronidazole benzoate—22–25 mg/kg PO q12h for 5–7 days in cats. •  Fenbendazole (50 mg/kg PO q24h) plus metronidazole (25 mg/kg PO q12h) for 5 days—may provide better resolution and reduction in cyst shedding. •  Combination febantel, pyrantel pamoate, and praziquantel product—use for 3 days at label dose for Giardia. CONTRAINDICATIONS/POSSIBLE INTERACTIONS •  Metronidazole—efficacy reportedly 50–67% in dogs; bitter taste; can cause anorexia, vomiting, vestibular signs. •  Albendazole (25 mg/kg PO q12h for 2 days in dogs or 5 days in cats) is effective but not

recommended because it can be teratogenic and cause anorexia, depression, vomiting, ataxia, diarrhea, abortion, and myelosuppression.

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 FOLLOW-UP

•  Repeat fecal examinations to confirm

efficacy of treatment and detect reinfection.

•  Chronic infection can lead to debilitation.

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 MISCELLANEOUS

ZOONOTIC POTENTIAL •  In North America, Giardia is the most common intestinal parasite in humans. Dog and cat isolates are host specific, with little data to demonstrate transmission from pets to humans. •  Most Giardia infections in humans are anthroponotic or originate from livestock. •  Zoonotic transmission from pets to immunosuppressed humans may occur. PREGNANCY/FERTILITY/BREEDING Do not use albendazole in pregnant animals. INTERNET RESOURCES

•  https://capcvet.org •  https://www.cdc.gov/parasites/giardia

­Suggested Reading

Bowman DD. Georgis’ Parasitology for Veterinarians, 9th ed. St. Louis, MO: Elsevier Science, 2009, pp. 89–91. Uehlinger FD, Naqvi SA, Greenwood SJ, et al. Comparison of five diagnostic tests for Giardia duodenalis in fecal samples from young dogs. Vet Parasitol. 2017, 244:91–96. Authors Matt Brewer and Katy A. Martin Consulting Editor Amie Koenig



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Gingival Enlargement/Hyperplasia •  Chronic sublingual or buccal trauma with

proliferation—“gum chewer’s lesion.”

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 BASICS

OVERVIEW •  Enlargement of gingival tissue due to proliferation of its elements (abnormal multiplication or increase in the normal number of cells in normal arrangement). •  Probable familial tendency—boxers. SIGNALMENT

•  Dogs and rarely cats. •  Breed predilections—boxers, Great Danes,

IMAGING Intraoral radiography—to rule out any underlying osseous changes (more common with epulides or tumors). DIAGNOSTIC PROCEDURES

•  Biopsy—focal area or areas that do not

CAUSES Chronic inflammatory response to presence of bacteria in plaque associated with periodontal disease. RISK FACTORS

•  Breed predilection (see Signalment). •  Chronic drug administration—

diphenylhydantoin, cyclosporine, nitrendipine, nifedipine, amlodipine.

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Presumptive diagnosis based on clinical appearance, especially if generalized and found in breed with high predilection. •  Oral neoplasia—e.g., peripheral odontogenic fibromas; usually not generalized; sometimes osseous changes present. •  Oral papillomatosis—papilloma usually on mucosal surfaces. •  Operculum—seen in young animals during eruption phase of teeth; incomplete loss and/ or persistence of gingival tissue covering erupting tooth.

 MEDICATIONS

DRUG(S) OF CHOICE •  Oral antimicrobials—chlorhexidine; zinc ascorbate gel. •  Postoperative pain management.

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CONTRAINDICATIONS/POSSIBLE INTERACTIONS Patients on chronic administration of amlodipine, diphenylhydantoin or cyclosporine may be predisposed to hyperplastic changes. Dose reduction may decrease extent of gingival enlargement.

SIGNS

attached gingiva and gingival margin— sometimes completely covers tooth surface. •  Resultant formation of “pseudopockets”— increase in pocket depth due to increased gingival height; not due to loss of attachment, unless untreated and progresses to concurrent periodontal disease. •  Gingival margin may be thickened in a labial to lingual direction, especially at incisors. •  Locally affected areas possible (shelties), but typically more generalized pattern found. •  Focally affected areas, other than the marginal gingiva, may develop hyperplastic areas due to chronic irritation, such as the “gum chewer’s lesion.” These areas should be evaluated for therapeutic need (excision). •  May form as protuberant masses (grape cluster) at gingival margins—biopsy necessary to rule out neoplasia.

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respond to standard therapy. •  Histopathology—to rule out neoplasia and other causes; histologic evaluation is only way to confirm.

collies, Doberman pinschers, Dalmatians.

•  Thickening and increase in height of

•  Tincture of myrrh and benzoin—use dropper; coat cut margins and dry; 4–5 layers. •  Hemostatic solutions—to aid in hemorrhage control as needed.

 TREATMENT

Appropriate Health Care

Regular dental cleanings and homecare—to minimize effects of plaque and bacterial accumulation. Client Education

•  Chronic, recurring problem that often

needs repeated therapy.

•  Encourage the highest level of home care

and regular professional cleaning.

Surgical Considerations

Gingivectomy (Excising Excess Tissue) and Gingivoplasty (Recontouring)

•  To remove excess gingival tissue and return

pocket depths to normal.

•  Provide appropriate patient monitoring and

support during anesthetic procedures.

•  Regional and local anesthetic injections or

topical gels. •  Periodontal probe—to determine depth of pseudopocket; can mark pocket depth on outside of pocket with end of probe to mark with a bleeding “dot.” •  Excise excess tissue and reshape gingival margin. •  Cold steel—sharp, stout scissors (crown and collar scissors) or scalpel blade. •  Connect dots made by probe with blade to approximate normal gingival margin or use scissors, following pocket depth to remove bulk tissue. •  Twelve-fluted bur on high-speed handpiece—contour margin to feather angle; assists in hemostasis. •  Electrocautery or radiosurgery—use fully or partially rectified current; avoid damage to underlying bone or tissue. •  Laser—use appropriately and avoid damage to tooth and bone. •  Excessive thickness (incisor and canine region)—modified Widman technique; envelope flap to lift gingiva off tooth surfaces; excise tissue wedge to remove gingiva at inside of pocket to provide narrower width of attached gingiva; suture interdentally to secure gingiva; use digital pressure to reposition.

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 FOLLOW-UP

PATIENT MONITORING •  Postoperative comfort—give pain medication as needed. •  Regular examinations and professional cleaning and treatment—to avoid recurrence, which is common. PREVENTION/AVOIDANCE Regular professional cleaning, meticulous home care. POSSIBLE COMPLICATIONS

•  Possible exacerbation of periodontal disease

in pseudopockets if left untreated; deeper pockets are more susceptible to anaerobic bacterial infections. •  Excessive heat with electrosurgical treatment may result in damaged teeth (pulpitis, pulpal death) and alveolar bone.

EXPECTED COURSE AND PROGNOSIS

•  Good prognosis with regular care. •  Recurrence common.

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 MISCELLANEOUS

INTERNET RESOURCES https://avdc.org/avdc-nomenclature

­Suggested Reading

Lobprise HB. Blackwell’s Five-Minute Veterinary Consult Clinical Companion: Small Animal Dentistry, 2nd ed. Ames, IA: Blackwell, 2012 (for additional topics, including diagnostics and techniques). Lobprise HB, Dodd JR. Wiggs’ Veterinary Dentistry Principles and Practice. Hoboken, NJ, Wiley-Blackwell, 2019. Author Heidi B. Lobprise Consulting Editor Heidi B. Lobprise

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Glaucoma •  POAG—beagle, Norwegian elkhound,

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 BASICS

DEFINITION •  A group of diseases where elevated intra­ocular pressure (IOP) causes optic nerve and retinal degeneration with subsequent loss of vision. •  Diagnosis—IOP >20 mmHg (dogs) or >25 mmHg (cats) as determined by tonometry, with changes in vision or the appearance of the globe, optic nerve, and/or retina. PATHOPHYSIOLOGY •  Multifactorial disease where obstruction of aqueous humor outflow leads to increased IOP and optic nerve degeneration. •  Elevated IOP induces mechanical changes (stretching of sclera in lamina cribosa damages optic nerve axons) and vascular changes (decreased ocular perfusion causes ischemic damage to retina), resulting in ganglion cell death and optic nerve atrophy. SYSTEMS AFFECTED •  Ophthalmic. •  Nervous. GENETICS

•  Primary angle-closure glaucoma (PACG;

dogs)—complex trait with multiple genetic risk factors and uncertain mode of inheritance. •  Primary open-angle glaucoma (POAG; dogs)—monogenic (ADAMTS10) and autosomal recessive. •  Primary congenital glaucoma (PCG; cats)—monogenic (LTBP2) and autosomal recessive. INCIDENCE/PREVALENCE

•  Dogs—prevalence depends on breed;

primary and secondary glaucoma are each listed as approximately 0.8% of all hospital admissions in the North American Veterinary Medical Database (NAVMDB). •  Cats—relatively uncommon; less than 0.3% of diagnoses in NAVMDB. SIGNALMENT Species

•  Dog—primary and secondary common. •  Cat—primary rare; secondary more

common (due to intraocular neoplasia or chronic uveitis).

Breed Predilections

•  PACG—Alaskan Malamute, American

cocker spaniel, Australian cattle dog, basset hound, Boston terrier, bouvier des Flandres, bullmastiff, Chinese Shar-Pei, chow chow, Dalmatian, Dandie Dinmont terrier, English cocker spaniel, English springer spaniel, flat-coated retriever, golden retriever, Great Dane, Labrador retriever, Newfoundland, poodle, Samoyed, Shiba Inu, shih tzu, Siberian husky, Welsh springer spaniel.

petit basset griffon Vendéen. •  PCG—Siamese cats. •  Other forms of primary glaucoma— Burmese, Persian, Siamese cats. Mean Age and Range

•  Primary (dogs)—any age; predominantly

affects middle-aged (4–9 years).

•  Secondary (cats)—usually affects older cats

(>6 years).

Predominant Sex

Females suffer PACG compared to males at a ratio of 2 : 1. SIGNS General Comments

All well-equipped small animal hospitals should have a tonometer. Historical Findings

•  Dogs—owners may note pain (blepharospasm, tenderness about the head), serous to seromucoid ocular discharge, red or cloudy eye, dilated pupil, or altered vision; in chronic cases, globe enlargement may be apparent. •  Cats—signs are more subtle; eye may not appear painful, red, or cloudy; owners may note dilated pupil, vision changes, or enlarged globe.

CAUSES •  Congenital—severe dysgenesis/lack of formation of the iridocorneal angle. •  Primary—developmental iridocorneal angle anomalies that impede aqueous humor outflow. •  Secondary—obstruction of aqueous humor outflow by various mechanisms, e.g., uveitis (inflammatory cells or debris), anterior lens luxation (lens or attached vitreous), red blood cells, or neoplastic cells. RISK FACTORS

•  Age. •  Breed. •  Chronic uveitis. •  Goniodysgenesis—developmental defect of

iridocorneal angle.

•  Lens luxation. •  Hypermature or intumescent cataracts. •  Hyphema. •  Intraocular neoplasia. •  Topically applied mydriatics—may

precipitate acute glaucoma in predisposed animals. •  Primary glaucoma is bilateral and often asymmetric; the unaffected fellow eye is at risk for developing glaucoma.

Physical Examination Findings

Acute Primary

•  High IOP (often >30 mmHg). •  Blepharospasm. •  Enophthalmos with elevated third eyelid. •  Episcleral injection. •  Diffuse corneal edema. •  Mydriasis. •  Vision loss—may be detected by lack of

menace response, dazzle reflex, and/or direct or consensual pupillary light reflex. •  Optic nerve may be normal or swollen and hyperemic.

Chronic (End Stage)

•  High or normal IOP. •  Buphthalmos. •  Descemet’s streaks (Haab’s striae). •  Subluxated lens with an aphakic crescent. •  Optic nerve head atrophy will appear dark

and cupped. •  Retinal atrophy detected by peripapillary or generalized tapetal hyper-reflectivity.

Secondary

•  High IOP. •  Episcleral injection. •  Corneal edema. •  Aqueous flare. •  Iris changes (miosis or mydriasis, posterior

synechia, iris bombé).

•  Hyphema. •  Anterior lens luxation. •  Intumescent cataracts. •  Intraocular mass.

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  See Red Eye. •  Conjunctivitis—normal IOP and pupil size with conjunctival hyperemia (diffuse, red discoloration) instead of episcleral vessel engorgement. •  Uveitis—initially low IOP with miotic pupil. IMAGING Ocular ultrasound—facilitates evaluation of eye with opaque ocular media; may identify cause of secondary glaucoma (lens luxation, intraocular tumor). DIAGNOSTIC PROCEDURES

•  Rebound or applanation tonometry—

essential for diagnosis of glaucoma.

•  Gonioscopy—referral procedure that allows

for evaluation of iridocorneal angle and assists with diagnosis of primary vs. secondary glaucoma. •  Systemic workup may be indicated in cases of secondary glaucoma due to chronic uveitis, hyphema, or intraocular neoplasia. PATHOLOGIC FINDINGS

•  Histopathologic evaluation is required for all

eyes enucleated due to intractable glaucoma. •  Iridocorneal angle morphology assists diagnosis of primary vs. secondary glaucoma. •  Loss of retinal ganglion cells. •  Gliosis and “cupping” of optic nerve head.



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Glaucoma

(continued) •  ± Hyperosmotic agent—mannitol 1–2 g/kg

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 TREATMENT

APPROPRIATE HEALTH CARE •  Acute—outpatient medical management vs. referral. •  Chronic—outpatient medical management vs. salvage surgical management. CLIENT EDUCATION

•  Warn client that primary glaucoma is a

•  Blindness. •  Chronic ocular pain.

Secondary (Dogs and Cats)

•  Chronic disease that requires constant

•  Identify and treat primary disease. •  Topical corticosteroids—to reduce

inflammation if no ulcerative keratitis.

•  Topical carbonic anhydrase inhibitors. •  ± Topical beta blockers.

CONTRAINDICATIONS

bilateral disease; more than 50% of dogs develop glaucoma in the other eye within 8 months without prophylactic therapy. •  Warn client that up to 50% of dogs will be blind in the affected eye within the first year regardless of therapy.

•  Topical atropine—do not use with glaucoma. •  Prostaglandin analogs/miotic agents—do

SURGICAL CONSIDERATIONS

may cause bronchoconstriction and bradycardia in small dogs and cats. •  Hyperosmotic agents may initiate acute pulmonary edema in patients with cardiovascular disease or hypervolemia.

•  Acute, visual eyes (dogs)—referral surgical

procedures aim to control IOP by decreasing aqueous humor production (transscleral or endoscopic cyclophotocoagulation), increasing outflow (gonioimplants), or both; medical treatment is still required long term to control IOP and inflammation. •  Blind, painful eyes (dogs and cats)—salvage procedures include enucleation, evisceration with intrascleral prosthesis (if no intraocular infection or neoplasia), and intravitreal gentamicin or cidofovir injection to minimize long-term medical therapy.

not use with primary anterior lens luxation or uveitis; mostly ineffective in cats. PRECAUTIONS

•  Systemic absorption of topical beta blockers

POSSIBLE INTERACTIONS Concurrent administration of latanoprost with a topical nonsteroidal anti-inflammatory drug such as flurbiprofen 0.03% may decrease its hypotensive effect. ALTERNATIVE DRUG(S)

•  Prostaglandin analogs—travoprost 0.004%

q12h, bimatoprost 0.03% q12h.

•  Carbonic anhydrase inhibitor—

brinzolamide 1% q8h.

•  Beta blockers—levobunalol 0.5% q12h,

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 MEDICATIONS

DRUG(S) OF CHOICE Use multiple agents to lower IOP into the normal range as quickly as possible in an attempt to salvage vision and maintain comfort. Topical hypotensive drugs have largely replaced systemic therapy due to higher efficacy and fewer side effects. Acute Primary (Dogs)

•  Prostaglandin analog—latanoprost 0.005%

q12h. In emergency, apply one drop to affected eye, followed by another drop in 30 min. Recheck IOP in 1–2 hours. •  Carbonic anhydrase inhibitor—dorzolamide 2% q8h. Use in combination with latanoprost for long-term therapy. •  Topical corticosteroids—0.1% dexamethasone or 1% prednisolone acetate q12h. Use to control intraocular inflammation from initial hypertensive episode. •  ± Topical beta blocker—timolol maleate 0.5% q12h. Minimal effect on lowering IOP in companion animals. Use as auxiliary or prophylactic medication.

POSSIBLE COMPLICATIONS

IV over 20 min. In emergency, use to dehydrate vitreous humor and lower IOP if topical medications ineffective.

betaxolol 0.5% q12h. •  Osmotic agents—hypertonic hydroxyethyl starch 6–7.5% (4 mL/kg IV over 15–20 min).

EXPECTED COURSE AND PROGNOSIS

medical treatment (even with surgical intervention). •  With medical treatment only—most patients ultimately become blind. •  Referral surgical treatment—better chance of retaining vision longer; most patients do not remain visual for more than 2 years after initial diagnosis. •  Secondary to lens luxation—may carry fair prognosis with referral for successful removal of luxated lens and postoperative medical therapy. •  Secondary to anterior uveitis—may carry fair prognosis with control of uveitis.

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 MISCELLANEOUS

PREGNANCY/FERTILITY/BREEDING •  All listed drugs may affect pregnancy. •  Primary and lens luxation cases—inherited; do not breed affected animals. SEE ALSO

•  Anterior Uveitis—Cats. •  Anterior Uveitis—Dogs. •  Lens Luxation. •  Red Eye.

ABBREVIATIONS

•  IOP = intraocular pressure. •  PACG = Primary angle-closure glaucoma. •  POAG = Primary open-angle glaucoma. •  PCG = Primary congenital glaucoma. •  NAVMDB = North American Veterinary

Medical Database.

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 FOLLOW-UP

PATIENT MONITORING •  IOP—monitored often (weekly to monthly) after starting initial therapy, then q3-4 months long term. Client’s daily observation of comfort and vision is most important. •  Monitor for drug reactions. PREVENTION/AVOIDANCE

•  Primary—bilateral disease; recommend that

a veterinary ophthalmologist examine the unaffected eye to determine its risk of developing glaucoma. •  Prophylactic therapy for the predisposed, unaffected eye delays onset of glaucoma—0.25% demecarium bromide (miotic) q12h, or 0.5% timolol maleate q12h, or 2% dorzolamide q8–12h.

­Suggested Reading

Miller PE. The glaucomas. In: Maggs DJ, Miller PE, Ofri R, eds. Slatter’s Fundamentals of Veterinary Ophthalmology, 6th ed. St. Louis, MO: Elsevier, 2018, pp. 279–305. Pizzirani S, ed. Glaucoma. Vet Clin Small Anim 2015, 45(6): 1102–1378. Author Erin M. Scott Consulting Editor Kathern E. Myrna Acknowledgment The author and book editors acknowledge the prior contribution of J. Phillip Pickett. Client Education Handout available online

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Glomerulonephritis

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 BASICS

DEFINITION Glomerulonephritis (GN) is a term often used to describe proteinuria of glomerular origin; however, GN is immune-mediated inflammation within the glomerulus (immune complex glomerulonephritis [ICGN]). Because this can only be diagnosed from a renal biopsy, many noninflammatory conditions (glomerulosclerosis, amyloidosis, etc.) may be incorrectly labeled GN in patients who have not undergone evaluation via renal histology. PATHOPHYSIOLOGY •  Circulating antigen–antibody complexes become entrapped or antibodies can attach in situ to glomerular antigens or soluble antigens entrapped within the glomerular basement membrane; complement component C3 and/ or immunoglobulins (Ig) G, M, or A may be involved in complexes, which alter glomerular permeability and induce inflammation, causing proteinuria, nephron injury, fibrosis, and progressive loss of renal function. •  ICGN has several different morphologies depending on the location of immunecomplex deposition as well as the glomerular response to injury; membranoproliferative, membranous nephropathy, proliferative, IgA nephropathy, and minimal change disease are recognized ICGN in small animals. •  Inflammation and altered glomerular permeability result in proteinuria; subsequent oxidative damage and tubular obstruction cause renal injury, progressive nephron loss, and decreased glomerular filtration; azotemia and uremia may ensue. •  Hypercoagulability, hypoalbuminemia, and hypertension (HTN) are common complications. SYSTEMS AFFECTED

•  Renal/urologic—proteinuria is the initial

that have undergone renal biopsy have ICGN. GN may be clinically silent and undiagnosed in many patients. GEOGRAPHIC DISTRIBUTION Worldwide SIGNALMENT

•  Species—dog and cat. •  Breed predilections—American foxhound,

Bernese mountain dog, Doberman pinscher, German shepherd, golden retriever, greyhound, Labrador retriever, Shetland sheepdog, and soft-coated wheaten terrier. •  Mean age and range—middle age (4–8 years), although may occur at any time; cats often younger—mean 4 years. •  Predominant sex—dogs: none; cats: majority are male. SIGNS

•  Proteinuria caused by albuminuria is

hallmark.

•  Historical findings—nonspecific and include

weight loss, muscle wasting, decreased appetite, lethargy, vomiting, and polyuria/polydipsia. •  Physical examination findings—may be normal; subcutaneous edema, peritoneal and/ or pleural effusion seen in NS; acute dyspnea and hypoxia may be present in pulmonary TE. CAUSES

•  Most patients have ICGN secondary to

systemic infection or inflammation; many patients will not have an obvious trigger identified. * Infectious causes include rickettsial infection (Borrelia, Ehrlichia, Anaplasma, Rocky Mountain spotted fever), babesiosis, bartonellosis, leishmaniasis, brucellosis, dirofilariasis, leptospirosis, systemic fungal infections, and hepatozoonosis. •  Inflammatory conditions include pancreatitis, polyarthritis, pyometra, and systemic lupus erythematosus; reactions to sulfonamides and vaccines is possible; paraneoplastic GN is uncommon.

symptom; both acute kidney injury (AKI) and chronic kidney disease (CKD) may occur secondarily. •  Cardiovascular—HTN is common; ascites and edema occur in nephrotic syndrome (NS); hypercoagulability and thromboembolism (TE). •  Endocrine/metabolic—hypercholesterolemia in NS.

RISK FACTORS Lyme-associated GN is a severe and progressive form of ICGN found in dogs with positive Borrelia serology, but causation unknown. Labrador retrievers, golden retrievers, and several other breeds are more at risk.

GENETICS Many breeds have inheritable glomerular disease leading to protein-losing nephropathy (PLN). Most are non-ICGN; however, several breeds are more frequently affected by GN (see below).

­

INCIDENCE/PREVALENCE Glomerular disease is present in most patients with kidney disease; however, not all are ICGN. Approximately 50% of dogs and cats

CBC/BIOCHEMISTRY/URINALYSIS

•  CBC may reveal thrombocytopenia,

uncommonly leukocytosis; usually unremarkable. •  Hypoalbuminemia with normal or increased serum globulins; hypercholesterolemia seen in NS; azotemia may be present. •  Persistent proteinuria; some patients may be azotemic with preservation of urine concentration. OTHER LABORATORY TESTS

•  Urine protein : creatinine ratio (UPC) is

gold standard test for diagnosing, quantifying, and monitoring proteinuria. •  Testing for underlying systemic infectious/ inflammatory causes should be performed as indicated. •  Urine electrophoresis can be performed to fraction proteins by molecular weight to discriminate glomerular and tubular causes of proteinuria. •  Blood pressure measurement should be performed. IMAGING Thoracic radiographs and abdominal ultrasound to evaluate for systemic disease. DIAGNOSTIC PROCEDURES

•  Renal biopsy is the only way to diagnose

GN and determine the subtype; it characterizes fibrosis and chronicity, which may help predict recovery of renal function following treatment; percutaneous ultrasound-guided needle biopsy is commonly performed; small patients or those with congenital disease may benefit from a surgical wedge/punch biopsy; biopsy contraindications include uncontrolled hypertension, severe thrombocytopenia, and anticoagulant therapy. •  Histology using multiple stains, immuno­ fluorescence, and electron microscopy is required for definitive diagnosis of ICGN; biopsies should be submitted to a veterinary nephropathologist. •  Some patients are too unstable to have renal biopsy performed (thrombocytopenic, rapidly progressing azotemia, etc.); empiric immuno­ suppression should be given when ICGN is suspected in the absence of biopsy. PATHOLOGIC FINDINGS

•  Definitive diagnosis of ICGN depends on

 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Proteinuria—commonly occurs for reasons other than GN (see Proteinuria). •  Hypoalbuminemia—may result from decreased hepatic synthesis or protein-losing enteropathy. •  Azotemia—can also be due to AKI or CKD, which may not be caused by ICGN.

ultrastructural findings of electron-dense immune within glomeruli; positive immuno­fluorescence. •  Secondary changes to glomerular basement membrane, hypercellularity, and sclerosis.

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 TREATMENT

APPROPRIATE HEALTH CARE •  Many require inpatient therapy to correct hypovolemia, nausea, and anorexia; once



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(continued)

stabilized, patients can be managed as outpatient. •  Patients with AKI may require dialysis to treat severe uremia. •  Therapeutic plasma exchange may be considered. NURSING CARE IV crystalloids should be used judiciously. Hypervolemia is a common complication of aggressive fluid therapy. ACTIVITY No specific need for activity restriction; patients often have limited endurance. DIET

•  Ideal diets are protein and sodium

restricted; prescription “renal” diets are most appropriate; home-prepared diets may be used after consultation with a nutritionist. •  Feeding tubes allow for delivery of supplemental nutrition and medication. CLIENT EDUCATION

•  Prognosis is guarded for azotemic patients;

however, complete recovery may occur. •  Dialysis and plasma exchange may allow for more rapid control of disease and promote renal recovery. SURGICAL CONSIDERATIONS

•  Avoid hypotension and renal hypoperfusion. •  Discontinue anticoagulant 1 week before

biopsy.

(2–5 mg/kg q24h); newer direct factor X inhibitors may also be considered.

•  NS. •  TE.

CONTRAINDICATIONS

EXPECTED COURSE AND PROGNOSIS Guarded prognosis. Short survival has been reported for azotemic proteinuric dogs. Disease may progress despite therapy. Complete resolution of disease may occur with immunosuppression.

•  ACE inhibitors and ARBs should not be

used if patient is dehydrated or hypovolemic.

•  Anticoagulation should be avoided in

thrombocytopenic patients until platelet count is normal.

PRECAUTIONS •  ACE inhibitors and ARBs should be used cautiously in patients with serum creatinine >3.5, as they may exacerbate uremia; 30% increase in serum creatinine is generally tolerated, if uremic symptoms do not occur; hyperkalemia may occur at higher doses. •  Hypoalbuminemic patients poorly tolerate parenteral fluids; enteral hydration via feeding tube may be better tolerated. •  Immunosuppression increases risk of opportunistic infections. POSSIBLE INTERACTIONS Dual therapy of ACE inhibitor and ARB increases risk of hyperkalemia. ALTERNATIVE DRUG(S)

•  Corticosteroids not used for long-term

management, but may be considered if other therapies cannot be afforded. •  Patients who fail initial immunosuppressive therapy may benefit from alternative immunosuppression.

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 MISCELLANEOUS

ASSOCIATED CONDITIONS •  HTN. •  Hypoalbuminemia. •  Hypercoagulability. AGE-RELATED FACTORS None ZOONOTIC POTENTIAL N/A PREGNANCY/FERTILITY/BREEDING Patients with suspected genetic disease should not be bred. SYNONYMS

•  Glomerulonephropathy. •  Protein-losing nephropathy.

SEE ALSO

•  Amyloidosis. •  Nephrotic syndrome. •  Proteinuria.

ABBREVIATIONS

­

 MEDICATIONS

DRUG(S) OF CHOICE •  ICGN requires immunosuppression; mycophenolate (5–10 mg/kg q12h) is most commonly used; GI upset is most frequently observed side effect; peripheral edema is rare; short course of corticosteroids (prednisone 2 mg/kg/day) can be used as mycophenolate may require 2 weeks to take effect. •  Cyclophosphamide (50 mg/m2 4 days/ week); sterile hemorrhagic cystitis and bone marrow suppression are side effects. •  Anti-proteinuric therapy includes angiotensin-converting enzyme (ACE) inhibitors (enalapril/benazepril 0.5–1 mg/kg q12h) or angiotensin receptor blockers (ARB; telmisartan 1–3 mg/kg q24h); these have modest antihypertensive effects; begin at low doses and increase if response is inadequate; cautious use in severely azotemic patients. •  HTN treated with amlodipine (0.25– 0.8 mg/kg q24h) or telmisartan (1–3 mg/kg q24h). •  Systemic anticoagulation to prevent TE— clopidogrel (1–4 mg/kg q24h) or aspirin

­

 FOLLOW-UP

PATIENT MONITORING •  Renal values, electrolytes, blood pressure, and urinalysis with UPC should be checked 1–2 weeks after starting therapy; reduction in proteinuria may take 4–6 weeks; subsequent rechecks should occur every 1–4 months. •  Complete remission is obtaining UPC 50% reduction and therapeutic failure is 2.0 mg/dL. •  Repeat renal biopsy can document resolution of immune complexes and guide duration of immunosuppression. PREVENTION/AVOIDANCE Avoiding exposure to fleas and ticks may reduce risk of vector-borne infections causing ICGN; preventative therapies should be used. POSSIBLE COMPLICATIONS

•  AKI or CKD. •  HTN.

•  ACE = angiotensin-converting enzyme. •  AKI = acute kidney injury. •  ARB = angiotensin receptor blocker. •  CKD = chronic kidney disease. •  GN = glomerulonephritis. •  HTN = hypertension. •  ICGN = immune complex

glomerulonephritis.

•  Ig = immunoglobulin. •  NS = nephrotic syndrome. •  PLN = protein-losing nephropathy. •  TE = thromboembolism. •  UPC = urine protein : creatinine ratio.

INTERNET RESOURCES www.iris-kidney.com

­Suggested Reading

Brown S, ed. Special issue: International Renal Interest Society consensus clinical practice guidelines for glomerular disease in dogs. J Vet Intern Med 2013, 27:S1–S75. Littman MP. Protein-losing nephropathy in small animals. Vet Clin North Am Small Anim Pract 2011, 41(1):31–62. Author J.D. Foster Consulting Editor J.D. Foster

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Glucagonoma •  Other similar dermatopathies include

­B ASICS

G

OVERVIEW •  Glucagonoma is an uncommon pancreatic islet cell tumor originating from alpha cells, which secrete glucagon. They occasionally arise in extra-pancreatic locations (i.e., liver). Glucagonomas may secrete other hormones, such as gastrin, pancreatic polypeptide, and (rarely) insulin. •  Excess circulating glucagon activates glyco­ genolysis and gluconeogenesis and inhibits glycogenesis. This increases protein catabolism and lipolysis. Glucagon excess can inhibit erythropoiesis. The culmination of these biochemical changes results in hyperglycemia and occasionally diabetes mellitus (DM), hypoaminoacidemia, anemia, and weight loss. Glucagon can exert a secretory effect on the small intestine, leading to diarrhea. •  Glucagonomas may cause an overall decrease in plasma amino acid concentrations, with epidermal protein depletion in the skin, leading to the classic dermatopathy associated with glucagonoma (necrolytic migratory erythema [NME]). •  Glucagonomas can affect numerous organ systems, including musculoskeletal, integumentary, endocrine, gastrointestinal, nervous/ behavioral, and hepatobiliary. SIGNALMENT •  Dog—rare; older animals. •  Cat—rare. SIGNS •  The hallmark sign is NME, although this may be caused by glucagonoma or hepatocutaneous syndrome. NME has also been described in veterinary medicine as metabolic epidermal necrosis and superficial necrolytic dermatitis. •  Skin lesions include erythema, erosions, and crusting, generally located around mucocutaneous junctions (perineum, face, and genitalia), distal extremities, and foot­pads. Lesions are often pruritic with hyperkeratotic and painful footpads. In many cases, footpads are the only affected area. •  Other systemic signs include lethargy, polyuria, polydipsia, diarrhea, secondary pyoderma or yeast infection, anorexia, and weight loss. CAUSES & RISK FACTORS Component of the multiple endocrine neoplasia syndrome.

­

DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Other diseases that produce skin lesions consistent with NME are nonspecific liver disease, hypoaminoacidemia, DM, and pancreatic tumors.

pemphigus foliaceus, systemic lupus erythematosus, vasculitis, food dermatoses, vitamin A responsive dermatosis, and zinc deficiency dermatopathy. •  Mild–moderate hyperglucagonemia can result from nonglucagonoma diseases such as liver disease, pancreatic disease, chronic kidney disease, starvation, bacteremia, diabetic ketoacidosis, and hyperadrenocorticism.

superficial to mid-epidermal edema, diffuse parakeratotic hyperkeratosis, and irregular epidermal hyperplasia. •  Biopsies taken from the primary glucagonoma (and/or metastases) typically exhibit pleomorphic islet cells with fine cytoplasmic granules and occasional mitoses with immunohistochemical glucagon (and often other secretory hormone) expression.

CBC/BIOCHEMISTRY/URINALYSIS

•  CBC—may be normal or show a normo-

cytic, normochromic anemia or mature neutrophilia. •  Biochemistry—may be normal or show mild elevations in liver enzyme activity or total bilirubin concentration, with mild hyperglycemia and hypoalbuminemia. •  Liver function tests (e.g., bile acid concentrations) are generally normal. •  Urinalysis—decreased urine specific gravity, glucosuria with DM. OTHER LABORATORY TESTS

•  Plasma glucagon levels are generally

extremely elevated (>1,000 pg/mL); however, normal to mild elevation does not rule out glucagonoma. •  Plasma amino acid concentrations are generally severely reduced and are thought to be associated with the development of NME. •  Plasma zinc concentration is generally reduced and also thought to be associated with the development of NME. •  Serum fructosamine may be elevated in patients with DM. IMAGING

•  Ultrasonography—to detect pancreatic

glucagonomas, peripancreatic metastases, and hepatic metastases; however, ultrasound was normal in 4/9 dogs with glucagonoma. A honeycomb pattern has been described in the liver of patients with NME. •  CT, MRI, PET scans, selective visceral angiography, and somatostatin receptor scintigraphy (octreoscan and radioiodinated MIBG) are used to detect glucagonoma in humans. DIAGNOSTIC PROCEDURES

•  Increased serum glucagon and clinical

signs consistent with NME are indicative of glucagonoma, but the definitive diagnosis can only be made by biopsy, histopathologic examination, and immunohistochemical documentation of glucagon expression. •  Immunohistochemical assays for other pancreatic and gastrointestinal hormones may also be performed. PATHOLOGIC FINDINGS

•  Skin biopsies taken from glucagon-associ-

ated NME lesions typically exhibit severe

­

TREATMENT

•  Surgical excision of nonmetastatic primary

pancreatic glucagonoma is the best chance for cure. There is a high rate of postoperative morbidity and mortality in dogs, often secondary to pancreatitis. Glucagonoma syndrome reported in people is associated with thromboembolic disease. •  Combined debulking (primary tumor and/ or metastases) and octreotide therapy can temporarily resolve skin lesions and provide relief of clinical signs. •  If surgery and/or octreotide therapy are not possible, symptomatic palliative therapies may be beneficial and include high-protein diet with egg whites (approximately two to four egg whites/day for a 25 kg dog), zinc supplementation (beneficial even in the face of normal serum zinc concentration), and fatty acid supplementation. •  IV amino acid therapy may be beneficial in patients with NME. •  Secondary bacterial and/or yeast skin infections are common and should be appropriately treated. •  Concurrent DM should be treated.

­

MEDICATIONS

DRUG(S) OF CHOICE •  Octreotide—somatostatin analogue that inhibits conversion of preproglucagon to glucagon; may be beneficial in patients with unresectable or metastatic glucagonoma. Side effects reported in humans include injection site pain, vomiting, diarrhea, and cholestasis. A safe and effective dosage has not been reported in dogs; however, 10–20 μg/dog SC q8–12h has been used, and a one-time dose of 50 μg/dog SC is reported to be safe in healthy dogs. Octreotide can be difficult to obtain. •  Chemotherapeutics in humans with glucagonoma include doxorubicin and streptozotocin, although efficacy may be limited. The use of streptozotocin as an islet-cell lytic agent has been reported in a small number of dogs with insulinoma, but not in dogs with glucagonoma.



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(continued)  •  Glucocorticoids may improve the pruritis

of NME skin lesions, but are not ­recommended for use in glucagonomas as they are likely to exacerbate hyperglycemia associated with secondary DM. •  IV amino acids (500 mL of essential amino acids added to saline or lactated Ringer’s solution over 12h, or 10% amino acid solution 24 mL/kg over 8–12h) have resulted in variable improvement in NME skin lesions in dogs. Treatments may be repeated every 1–2 weeks if effective until clinical signs abate or resolve. •  Sulfur/salicylic acid–based shampoos or very mild shampoos may help remove crusts, soften skin, and improve pain and pruritus associated with footpad or skin lesions. •  Oral zinc sulfate (10 mg/kg/day PO), zinc methionine (2 mg/kg/day PO), or zinc gluconate (3 mg/kg/day PO) may be considered. •  Supplementation with oral fatty acids (80 mg/kg PO) may also be of benefit. CONTRAINDICATIONS/POSSIBLE INTERACTIONS Glucocorticoids may exacerbate hyperglycemia if DM is present.

­

FOLLOW-UP

PATIENT MONITORING •  Serial blood work should be performed postoperatively to confirm that hyperglucagonemia (and any other abnormalities) is resolving. •  Strong considerations should be given to serial ultrasounds and chest radiographs to monitor for regrowth or metastasis. POSSIBLE COMPLICATIONS

•  Pancreatitis. •  Thromboembolic disease. •  DM.

EXPECTED COURSE AND PROGNOSIS

•  Prognosis is considered poor in dogs. •  Transient improvement in skin lesions and

clinical signs may be noted in patients treated with octreotride and amino acids. •  One cat had a survival time of 11 months following surgery.

­

MISCELLANEOUS

SEE ALSO •  Glycogen-Type Vacuolar Hepatopathy. •  Superficial Necrolytic Dermatitis.

ABBREVIATIONS •  DM = diabetes mellitus. •  NME = necrolytic migratory erythema.

­Suggested Reading

Allenspach K, Arnold P, Glaus T, et al. Glucagon-producing neuroendocrine tumour associated with hypoaminoacidemia and skin lesions. J Small Anim Pract 2000, 41:402–406. Asawaka MG, Cullen JM, Linder KE. Necrolytic migratory erythema associated with a glucagon-producing primary hepatic neuroendocrine tumor in a cat. Vet Dermal 2013, 24:466–469. Chastain MA. The glucagonoma syndrome: a review of its features and discussion of new perspectives. Am J Med Sci 2001, 321(5):306–320. Feldman EC, Nelson RW. Gastrinoma, glucagonoma and other APUDomas. In: Canine and Feline Endocrinology and Reproduction, 3rd ed. St. Louis, MO: Saunders, 2004, pp. 654–655. Langer NB, Jergens AE, Miles KG. Canine glucagonoma. Compend Contin Educ Pract Vet 2003, 25(1):56–63. Author Virginia L. Gill Consulting Editor Patty A. Lathan

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Glucosuria Acquired

•  Fanconi syndrome due to toxicity such as

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G

 BASICS

DEFINITION Glucosuria is detected via routine laboratory testing, most commonly with reagent test strips. Persistent glucosuria is an abnormal finding. PATHOPHYSIOLOGY •  Glucose is a small molecule that is freely filtered through the glomerulus into the ultrafiltrate. •  Glucose is actively reabsorbed in the proximal renal tubule by a sodium– glucose co-transport system. Physiologic levels of filtered glucose are mostly reabsorbed, leaving excreted levels too low to detect using screening tests. Hyperglycemic Glucosuria

•  Glucosuria will be present when blood

glucose concentration exceeds renal tubular epithelial transport maximum. This varies by species, with dogs typically above 180 mg/dL and cats typically above 280 mg/dL. •  If hyperglycemia is present, determine whether glucosuria transient or persistent.

Transient

•  Physiologic—usually transient and

associated with release of endogenous “stress” hormones (catecholamines, glucagon, corticosteroids); especially common in cats. Serum may be normoglycemic or hyperglycemic at urine collection because different concentrations of glucose excreted in urine over time equilibrate in bladder. •  Pharmacologic—may occur following administration of glucose-containing solutions (e.g., dextrose); administration of drugs (glucocorticoids, growth hormone, thiazide diuretics, morphine, epinephrine) may also result in hyperglycemia and glucosuria. •  Toxic—ethylene glycol. •  Pathologic—possible with acute pancreatitis.

Persistent

heavy metal poisoning (e.g., lead, mercury, copper, copper associated hepatitis) or dried chicken treats made in China, drugs (e.g., gentamicin, cephalosporins, outdated tetracycline, cisplatin, streptozotocin), chemicals (Lysol, maleic acid), other miscellaneous causes. •  Acute renal failure with significant tubular lesions.

SYSTEMS AFFECTED •  Renal—normoglycemic patients have abnormal renal tubular epithelial cell function; dogs with Fanconi syndrome may develop metabolic acidosis and chronic kidney disease (CKD) with secondary multisystem involvement; glucosuria predisposes to bacterial urinary tract infection. •  Endocrine—hyperglycemic patients may have diabetes mellitus and/or hyperadrenocorticism. •  Liver—copper associated hepatitis; centrilobular hepatitis with copper accumulation.

hyperglycemic glucosuria due to adult-onset diabetes mellitus. •  Dogs with congenital Fanconi syndrome typically develop clinical disease due to defective reabsorption of glucose and amino acids at 4–5 years of age; no sex predilection. •  Familial renal tubular disorders have been reported (see Patho­ physiology). •  Primary renal glucosuria (Scottish terriers) may be recognized at early age as incidental finding. •  Copper associated hepatitis with acquired Fanconi syndrome (Labrador retrievers). •  Dogs (any breed or age) fed dried chicken treats made in China. SIGNS Clinical signs variable depending upon primary cause. Historical Findings

•  Persistent glucosuria results in polyuria

(osmotic diuresis), leading to compensatory polydipsia. •  Glucosuria predisposes to urinary tract infections; clinical signs associated with upper and/or lower urinary tract infection. •  Breed and therapeutic history (see Pathophysiology) are important.

Normoglycemic Glucosuria

Physical Examination Findings

Congenital

Primary glucosuria—Scottish terriers; Fanconi syndrome: basenji dogs; also sporadic in Norwegian elkhounds, Shetland sheepdogs, miniature schnauzers, Labrador retrievers, border terriers, whippets, Yorkshire terriers, and mixed-breed dogs; decreased reabsorption of glucose, amino acids, and phosphorus plus decreased secretion of hydrogen ions.

•  Diabetes mellitus; insulin deficiency or resistance. •  Hyperadrenocorticism; insulin resistance. •  Acute pancreatitis; insulin deficiency or resistance. •  Less common causes include pheochromocytoma, acromegaly, hyperglucagonemia, hyperpituitarism, hyperthyroidism, and chronic liver failure (due to failure to metabolize glucagon).

Normoglycemic Glucosuria

Congenital

•  Primary renal glucosuria (Scottish terrier). •  Fanconi syndrome. •  Congenital diseases

may be associated with renal dysfunction (Norwegian elkhound).

Acquired

•  Acute kidney injury associated with proximal tubular dysfunction. •  Fanconi syndrome. •  CKD (rare).

RISK FACTORS Vary with underlying causes.

SIGNALMENT

•  Adult dogs and cats develop persistent

Pathologic conditions that can result in persistent glucosuria (due to hyperglycemia) include diabetes mellitus, hyperadrenocorticism, acromegaly, extreme stress, hyperthyroidism in cats. Impaired renal proximal tubular epithelial cell reabsorptive capacity.

Persistent

•  Patients with hyperglycemic glucosuria may

exhibit systemic signs; see diabetes mellitus chapters. •  Patients with normoglycemic glucosuria may have normal body functions. •  Dogs with Fanconi syndrome may develop signs of metabolic acidosis, electrolyte abnormalities, and CKD. CAUSES Hyperglycemic Glucosuria Transient •  Physiologic—stress; common in cats. •  Pharmacologic—see Pathophysiology.

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Persistent hyperglycemic glucosuria in fasted patients is frequently associated with endocrinopathies (diabetes mellitus, hyperadrenocorticism). •  Acute pancreatitis. •  Renal tubular reabsorptive dysfunctions cause normoglycemic glucosuria. •  Stressed patients exhibit mild transient hyperglycemia and glucosuria. LABORATORY FINDINGS Screening Tests

Normally negative (urine glucose concentration below detection).

Glucose Oxidase Tests

•  Reagent strips use glucose oxidase method

that is specific for glucose; positive values occur with urine glucose concentrations greater than 100 mg/dL. •  Methodology is a two-step enzymatic process—glucose oxidase catalyzes glucose and produces gluconic acid and hydrogen peroxide; peroxidase catalyzes reaction of hydrogen with chromagen to produce color change on reagent pad; the test is time dependent, which varies with manufacturer; pigmenturia can complicate color interpretation. •  False negatives can be seen with ascorbic acid, exposure to formalin, ketonuria, marked bilirubinuria, highly concentrated urine, and refrigerated urine samples that have not been warmed to room temperature prior to performing the test. •  False positives can be seen with exposure to oxidizing agents such as hydrogen peroxide or chlorine bleach (most commonly with samples obtained from table top or floor). •  Specific for glucose; more sensitive



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(continued)

(~40–100 mg/dL) than copper reduction methods. Glucose O2 (air) H2 0 glucuronic acid H2 0 oxidase H2 0 2

horseraadish peroxidase

H2 0 O(nascent oxygen)

O color indicator 

oxidized color change complex

Copper Reduction Tests

•  Not specific for glucose; less sensitive

(250 mg/dL) and higher detection limit than glucose oxidase methods; more often used in human medicine, but can be used in veterinary medicine to verify questionable reagent strip result. •  Testing method uses copper, which reacts with reducing substance (e.g., glucose, fructose, lactose, etc.) to produce cuprous oxide and cuprous hydroxide, which results in color change. •  Results are semiquantitative and reported as negative, approximately 250 mg/dl, approxi­ mately 500 mg/dL, approximately 750 mg/dl, approximately 1000 mg/dL, or approximately 2000 mg/dL. •  Less affected by pigmenturia; false positives can be seen with cephalosporins, formaldehyde, reactions with other sugars, and high concentrations of ascorbic acid. Cupric ions glucose (blue)

(orange -red)

OTHER LABORATORY TESTS •  Hyperglycemic glucosuria—conduct appropriate screening test if hyperadrenocorticism suspected. •  Normoglycemic glucosuria— measurement of phosphorus, glucose, and amino acid concentrations in timed urine samples may help differentiate Fanconi syndrome and primary renal glucosuria; also evaluation of hepatic function for acquired Fanconi syndrome due to copper associated hepatitis. IMAGING Ultrasonography aids in diagnosis of hyperadrenocorticism and pancreatitis.

­

 TREATMENT

•  Discontinue any drugs associated with

related to specific causes.

Confirmatory Tests

Hexokinase or glucokinase dehydrogenase tests using automated chemistry analyzer may be used to confirm presence or absence of glucose when unexpected results or pigmented urine encountered. Drugs That May Alter Laboratory Results

See Screening Tests.

Disorders That May Alter Laboratory Results

See Screening Tests.

Valid if Run in Human Laboratory?

Yes

CBC/BIOCHEMISTRY/URINALYSIS

­

 MEDICATIONS

DRUG(S) OF CHOICE •  Hyperglycemic glucosuria—treat diabetes mellitus with insulin. •  Normoglycemic glucosuria—no treatment required for tubular transport disorders unless metabolic acidosis, electrolyte abnormalities, or hepatic abnormalities present (e.g., Fanconi syndrome). CONTRAINDICATIONS Patients with diabetes mellitus should not be given diabetogenic drugs such as corticosteroids or dextrose-containing fluids.

Hyperglycemic Glucosuria

•  Hyperglycemia with glucosuria and ketonuria indicates diabetic ketoacidosis; persistent hyperglycemia and glucosuria with appropriate clinical signs support diabetes mellitus. •  Dogs with pancreatitis may have leukocytosis, fever,

development of bacterial urinary tract infections (cystitis, ascending pyelonephritis). •  Osmotic diuresis with obligatory polyuria results in polydipsia, necessitating access to water to prevent dehydration.

G ­

 MISCELLANEOUS

Growth hormone–secreting pituitary tumors in older cats (especially male) may induce diabetes mellitus (insulin resistant). ASSOCIATED CONDITIONS •  Urinary tract infections. •  CKD. •  Diabetic retinopathy or cataracts. •  Copper associated hepatitis. PREGNANCY/FERTILITY/BREEDING Excess progesterone secretion in intact female dogs may induce diabetes mellitus (insulin resistant). SEE ALSO

Diseases.

•  Treatment varies with cause; see chapters



POSSIBLE COMPLICATIONS

•  Persistent glucosuria predisposes to

•  Congenital and Developmental Renal

acquired renal tubular transport defects.

alkali

cuprous ions oxidized glucose

abdominal pain and effusion, elevations in pancreatic specific enzymes, and characteristic ultrasonographic abnormalities. •  Dogs with markedly increased serum alkaline phosphatase activity, hyperglycemia, glucosuria (also hyper­ cholesterolemia, hypertriglyceridemia) should be evaluated for hyperadrenocorticism. •  Mild glucosuria with transient hyperglycemia is likely physiologic in stressed patients.

­

 FOLLOW-UP

PATIENT MONITORING Variable, depending upon underlying condition.

•  Diabetes Mellitus without Complication—

Cats.

•  Diabetes Mellitus without Complication—

Dogs.

•  Fanconi Syndrome. •  Hyperadrenocorticism (Cushing’s

Syndrome)—Cats. •  Hyperadrenocorticism (Cushing’s Syndrome)—Dogs. •  Pancreatitis—Cats. •  Pancreatitis—Dogs. ABBREVIATIONS •  CKD = chronic kidney disease.

­Suggested Reading

Latimer K. Duncan and Prasse’s Veterinary Laboratory Medicine Clinical Pathology, 5th ed. Ames, IA: Wiley-Blackwell, 2011, pp 257–264. Sink C, Weinstein N. Practical Veterinary Urinalysis. Ames, IA: Wiley-Blackwell, 2012, pp. 38–40. Stockham S and Scott M. Fundamentals of Veterinary Clinical Pathology, 2nd ed. Ames, IA: Wiley-Blackwell, 2008, pp. 462–464. Author Tracie D. Romsland Consulting Editor J.D. Foster Acknowledgment The author and book editors acknowledge the prior contributions of Cheryl L. Swenson and Carl A. Osborne.

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Gluten Enteropathy in Irish Setters

­B ASICS

G

OVERVIEW A rarely confirmed, inherited, intestinal disease in which sensitivity develops to dietary gluten (present in wheat) and similar proteins present in related grains (i.e., rye and barley). In affected dogs, the enteropathy is characterized by partial villous atrophy, reduced brush border enzyme expression, lymphocytic infiltration of the intestinal mucosa, and goblet cell hyperplasia; changes that are reversed by feeding a gluten-free diet. SIGNALMENT •  Irish setter breed—the line of affected setters originally described in the UK has been bred out. •  Signs develop in young dogs, but are modulated by the age of first exposure to gluten. •  Genetic transmission of gluten sensitive enteropathy is likely under the control of a single major autosomal recessive locus. •  Gluten enteropathy has been suspected but not proven in other dog breeds and cats. SIGNS

•  Poor weight gain (or weight loss). •  Poor body condition. •  Mild small intestinal diarrhea that can be

OTHER LABORATORY TESTS •  Serum folate concentrations are subnormal in some patients, reflecting malabsorption. •  Other tests are recommended to rule out other differentials, such as fecal flotation to rule out enteric parasites and serum trypsinlike immunoreactivity (TLI) to rule out exocrine pancreatic insufficiency. •  Serum TLI and cobalamin concentrations are usually unremarkable. IMAGING Only useful to rule out other conditions. DIAGNOSTIC PROCEDURES Intestinal biopsy specimens obtained via endoscopy or laparotomy may be helpful, but proof of gluten sensitivity requires histologic resolution in biopsies repeated following a clinically successful gluten-free diet trial. PATHOLOGIC FINDINGS

•  Histologic examination of jejunal biopsy

specimens from affected dogs reared on a wheat-containing diet reveals partial villus atrophy and accumulation of intraepithelial lymphocytes. •  Jejunal abnormalities improve following gluten withdrawal, but recur with gluten challenge.

intermittent.

CAUSES & RISK FACTORS The enteropathy and clinical signs are triggered by gluten-containing diets. Abnormal mucosal permeability precedes the development of signs, implying there is abnormal entry of gluten across the mucosal barrier. Gluten is then either directly toxic to the intestinal mucosa or induces an immunemediated reaction. An analogous condition in humans (celiac disease) is characterized by the presence of antibodies cross-reacting to gluten and tissue transglutaminase, but they have not been tested for in affected setters. These antibodies have been demonstrated in Border terriers with gluten-sensitive dyskinesia.

­

­

TREATMENT

­

MEDICATIONS

Treatment is on an outpatient basis. Avoid diets containing gluten (wheat, rye, barley, triticale, brewer’s yeast, and wheat starch) for the life of the animal.

DRUG(S) OF CHOICE Folate (0.5–2 mg PO q24h for 2–4 weeks) if serum folate concentration is markedly subnormal (75% older than 9 years); chronic systemic inflammation or neoplasia. •  Dogs of any age—iatrogenic VH subsequent to glucocorticoid administration. •  Young dogs or cats—genetic glycogen storage disease.

SIGNS General Comments

•  Reflect glucocorticoids or underlying

systemic illness.

•  Rarely, signs of hepatic disease or failure;

hepatic failure can develop with severe chronic VH. •  Hepatic encephalopathy observed in some dogs with hepatocutaneous syndrome. Historical Findings

•  Glucocorticoid excess—polyuria and

polydipsia; polyphagia; endocrine alopecia; abdominal distention: weak muscles, loss of elasticity; skeletal muscle weakness; excessive panting; lethargy; friable skin; bruising tendencies; urinary tract infections, may be asymptomatic; corneal ulcer. •  Adrenal sex hormone hyperplasia—may display some signs of glucocorticoid excess but often fewer and less severe; endocrine alopecia may be only sign; some dogs remain asymptomatic except for chronic progressive marked ALP activity and degenerative VH. •  Other causes—depend on system affected; chronic phenobarbital may cause severe VH. •  Sex hormone hyperplasia causing VH may increase risk for dysplastic hepatic foci and hepatocellular carcinoma (e.g., Scottish terriers). Physical Examination Findings

•  Hepatomegaly. •  Relate to steroid hormone excess or

underlying disease; depend on severity and duration. CAUSES

•  Glucocorticoid administration. •  Typical hyperadrenocorticism

(spontaneous).

•  Atypical adrenal hyperplasia—overproduc-

tion of cortisol precursor sex hormones (spontaneous).

•  Systemic disease provoking acute-phase

response or stress—e.g., severe dental disease, inflammatory bowel disease, chronic pancreatitis, systemic neoplasia (especially lymphoma), chronic infections (urinary tract, skin), hypothyroidism, many others. RISK FACTORS

•  Pharmacologic doses of glucocorticoids. •  Breeds at risk for hyperadrenocorticism. •  Breeds at risk for hyperlipidemia—often

also demonstrate combined glycogen VH: miniature schnauzers, Shetland sheepdogs, beagles. •  Dogs receiving chronic phenobarbital.

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DIAGNOSIS

DIFFERENTIAL DIAGNOSES •  Other diffuse hepatopathies (especially those causing hepatomegaly and increased ALP activity)—passive congestion; neoplasia (primary or metastatic to liver); necroinflammatory liver disease; anticonvulsant hepatopathy; hepatomegaly due to amyloid (rare). •  VH distinguishing features—most dogs have increase in ALP > alanine aminotransferase (ALT) or aspartate aminotransferase (AST); increased cholesterol, normal serum bilirubin; normal/mild increase in total serum bile acids (TSBA); heterogeneous or homogeneous hyperechoic hepatic parenchyma on ultrasonography (nodules or “Swiss cheese” pattern); characteristic cytology: hepatocytes engorged due to expanded “rarified” cytoplasm. CBC/BIOCHEMISTRY/URINALYSIS CBC

•  Depends on underlying disease. •  Nonregenerative anemia—anemia of

chronic disease or hypothyroidism.

•  Relative polycythemia—steroid excess. •  Stress leukogram—hyperadrenocorticism;

glucocorticoid exposure; stress of illness.

•  Thrombocytosis—neoplasia; hyperadreno-

corticism; splenic disease.

Biochemistry

•  ALP markedly increased; ALP glucocorti-

coid isoenzyme cannot differentiate cause of VH as other liver disorders also induce this isoenzyme; variable 𝛾-glutamyltransferase (GGT), ALT, AST activity. •  Serum albumin and total bilirubin—usually normal; high bilirubin typically implicates another hepatobiliary or hemolytic process. •  Hypercholesterolemia—hyperadrenocorticism, sex hormone adrenal hyperplasia; breed-related hyperlipidemias; hypothyroidism; pancreatitis; nephrotic syndrome.



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(continued) 

OTHER LABORATORY TESTS •  ALP glucocorticoid isoenzyme—see above, lacks specificity and thus clinical utility. •  TSBA—may be modestly increased; ammonia tolerance test: usually normal. •  Pituitary adrenal axis—adrenocorticotropic hormone (ACTH) response test or low-dose ± high-dose dexamethasone suppression test (LDDST ± HDDST) and endogenous ACTH may help differentiate nonadrenal illness, adrenal or pituitary disorders. •  Urine cortisol : creatinine ratio—at-home urine collection helps rule out hyperadrenocorticism; high ratio may reflect stress or nonadrenal illness. •  Adrenal ultrasound imaging—nodules, adrenomegaly; consider dog size and age. •  If VH confirmed (liver biopsy) and underlying cause not evident, patient asymptomatic or symptomatic for adrenal disease—assess cortisol and sex hormone panel with ACTH response test. •  Thyroid testing—rules out hypothyroidism. •  Triglycerides (fasting)—hyperlipidemia. •  Canine pancreatic lipase immunoreactivity (cPLI)—may indicate “subclinical” pancreatic inflammation or inflammatory bowel disease. IMAGING •  Abdominal radiography—reveals hepatomegaly or other underlying conditions. •  Thoracic radiography—may reveal lymphadenopathy, metastatic disease, cardiac or pulmonary disorders. •  Abdominal ultrasonography—discloses hepatomegaly, diffuse hyperechoic hepatic parenchyma or multifocal nodular “mottling”; multifocal lesions suggest nodules (“Swiss cheese pattern”) formed by progressive hepatocellular ballooning degeneration; may disclose underlying primary visceral abnormalities (e.g., mesenteric lymphadenopathy, neoplasia) or adrenal disorders (size/shape): adrenals may be large with hyperadrenocorticism, sex hormone adrenal hyperplasia, chronic stress, or neoplasia. DIAGNOSTIC PROCEDURES •  Hepatic fine-needle aspiration cytology—22 gauge, 2.5–3.75 cm (1–1.5 in) US-guided needle aspiration; target nodules and normal parenchyma. •  Cytology—glycogen vacuolation common in many primary liver disorders; used to rule out vacuolar change; cannot definitively confirm illness caused only by VH. •  Hepatic biopsy—verifies VH; excludes other primary hepatic disease; pursue if systemic disorder not discovered explaining high ALP and VH; use US-guided Tru-Cut® needle biopsy to confirm VH, but may miss primary hepatic disease, laparoscopy (recommended), or laparotomy (if visceral inspections and biopsies indicated).

•  Cytologic features—hepatocellular cytosolic

distention: “rarefication” or granular appearance with increased cell fragility; canalicular bile casts may be observed; primary VH not associated with inflammatory infiltrates; common association with extramedullary hematopoiesis (EMH) may be misinterpreted as suppurative inflammation. •  Tissue culture and sensitivity—if suppurative inflammation suspected, submit aerobic and anaerobic bacterial cultures. •  Coagulation assessments—prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, and mucosal bleeding time: usually normal; bench assessments have low predictive value in predicting iatrogenic hemorrhage; buccal mucosal bleeding time may be more relevant. PATHOLOGIC FINDINGS

•  Gross—variable; normal to moderate

hepatomegaly; inconsistent surface irregularity; tan or pale color; confusion with cirrhosis if nodular severe degenerative VH. •  Microscopic—marked vacuolization and ballooning of hepatocytes; no consistent zonal distribution, foci of hepatic degeneration; focal aggregates of neutrophils due to EMH; severe degenerative VH leads to parenchymal collapse, forming nodules surrounded by a thin partition with minimal collagen deposition.

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TREATMENT

DIET •  Hyperlipidemia or pancreatitis—restrict dietary fat and fatty supplements. •  Obesity—gradual energy restriction; treat predisposing disorders. SURGICAL CONSIDERATIONS •  Depend on underlying conditions. •  Adrenal masses may be resected. •  Hypophyseal masses—resection only by experienced surgeons; pituitary mass lesions may respond to radiation therapy.

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MEDICATIONS

DRUG(S) OF CHOICE •  Depend on underlying disease. •  Pituitary-dependent hyperadrenocorticism or adrenal hyperplasia syndrome (sex hormone)—usually treated medically: op’-DDD (mitotane or Lysodren®), trilostane, or ketoconazole; op’-DDD preferred for sex hormone adrenal hyperplasia, as trilostane augments sex hormone accumulation; l-deprenyl and melatonin ineffective. •  Manage primary inflammatory disorders necessitating immunosuppressive or

anti-inflammatory medications—use polypharmacy to minimize glucocorticoid exposure if symptomatic or progressive VH; see Alternative Drug(s). •  Neoplasia—tumor resection, chemotherapy, or radiation, as appropriate. •  Dental disease—antibiotics and dentistry. •  Inflammatory bowel disease—hypoallergenic/hydrolyzed protein diets and immunomodulation (avoid glucocorticoids). •  Pyelonephritis, chronic dermatitis, or other infectious disorders—long-term antimicrobial treatment based on microbial culture and sensitivity tests; other appropriate medications. •  Hypothyroidism—supplemental thyroxine. CONTRAINDICATIONS

•  Avoid hepatotoxic drugs if severe VH. •  Beware of drug interactions if using

ketoconazole for adrenal disease.

•  Avoid drugs with hepatic ALP induction

effects.

PRECAUTIONS Glucocorticoids—caution in VH patients; use lowest effective dose regimen (e.g., alternate-day protocol if prednisone or prednisolone); special caution in hyperlipidemia: may worsen clinical signs of abdominal pain, vomiting, pancreatitis; increase insulin requirements in diabetes mellitus; may augment gallbladder mucocele formation; may provoke hepatic lipidosis in cats. ALTERNATIVE DRUG(S) Polypharmacy protocol—may reduce glucocorticoid usage in management of immune-mediated or inflammatory disorders; e.g., metronidazole, azathioprine, chlorambucil, cyclophosphamide, mycophenolate, or cyclosporine.

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FOLLOW-UP

PATIENT MONITORING •  Hepatomegaly—abdominal palpation; imaging. •  Normalizing enzymes—biochemistry. •  Adrenal function—ACTH stimulation tests. •  Neoplasia—physical exams and imaging. •  Control of infection—repeat cultures. •  Hyperlipidemia—assess gross plasma lipemia; measure triglycerides and cholesterol. PREVENTION/AVOIDANCE •  Limit glucocorticoid exposure. •  Use alternate-day therapy with prednisone/ prednisolone; titrate to lowest effective dose; use alternative medications to control primary illness.

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POSSIBLE COMPLICATIONS Numerous—related to multisystemic effects of glucocorticoids and associated conditions.

PREGNANCY/FERTILITY/BREEDING Reproductive failure with glucocorticoid excess—testicular atrophy; abnormal estrus.

EXPECTED COURSE AND PROGNOSIS •  Most patients are asymptomatic for VH despite high ALP; however, progressive degenerative hepatopathy leading to diffuse nodule formation and hepatic insufficiency may develop in chronic VH in dogs with high ALP activity. •  Laboratory and pathologic features reversible before degenerative parenchymal collapse. •  Dogs with sex hormone hyperplasia, VH, and dysplastic hepatocellular foci appear at risk for development of hepatocellular carcinoma.

SYNONYMS •  Glucocorticoid hepatopathy. •  Steroid hepatopathy. •  Corticosteroid hepatopathy. •  Vacuolar change.

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MISCELLANEOUS

ASSOCIATED CONDITIONS •  Pulmonary thromboembolism and myopathy due to hyperadrenocorticism. •  Pancreatitis associated with hyperlipidemia. •  Gallbladder mucocele.

SEE ALSO

•  Gallbladder Mucocele. •  Hyperadrenocorticism (Cushing’s

Disease)—Cats.

•  Hyperadrenocorticism (Cushing’s

Disease)—Dogs.

•  Hyperlipidemia.

ABBREVIATIONS

•  ACTH = adrenocorticotropic hormone. •  ALP = alkaline phosphatase. •  ALT = alanine aminotransferase. •  APTT = activated partial thromboplastin time. •  AST = aspartate aminotransferase. •  cPLI = canine pancreatic lipase

immunoreactivity.

•  EMH = extramedullary hematopoiesis. •  GGT = 𝛾-glutamyltransferase. •  HDDST = high-dose dexamethasone

suppression test.

(continued) •  LDDST = low-dose dexamethasone

suppression test.

•  PT = prothrombin time. •  TSBA = total serum bile acids. •  VH = vacuolar hepatopathy.

­Suggested Reading

Cortright CC, Center SA, Randolph JF, et al. Clinical features of progressive vacuolar hepatopathy in Scottish Terriers with and without hepatocellular carcinoma: 114 cases (1980–2013). J Am Vet Med Assoc 2014, 245:797–808. Sepesy LM, Center SA, Randolph JF, et al. Vacuolar hepatopathy in dogs: 336 cases (1993–2005). J Am Vet Med Assoc 2006: 229:246–252. Author Sharon A. Center Consulting Editor Kate Holan Client Education Handout available online



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Canine and Feline, Seventh Edition

Grape and Raisin Toxicosis

­B ASICS OVERVIEW Syndrome resulting from ingestion of grapes, raisins, sultanas, or Zante currants (Vitis vinifera). SIGNALMENT •  Dogs are the only species in which toxicosis has been well described. •  No breed, sex, or age predisposition noted. •  Anecdotal reports of toxicosis in cats and ferrets exist, but data are lacking to confirm. SIGNS

•  Vomiting within 24 hours of ingestion;

vomitus frequently contains ingested fruit.

•  Diarrhea, anorexia, lethargy, and abdominal

pain may occur; stools may contain ingested fruit.

tending to increase 48–72 hours after exposure. Differentiate from vitamin D3 toxicosis, where calcium and phosphorus elevate first followed by elevations in BUN and creatinine as kidney injury develops. Not all cases develop hypercalcemia or hyperphosphatemia. •  Hyperkalemia, hyperamylasemia, hyperlipasemia, and elevated alanine aminotransferase (ALT) also occasionally occur. •  Isosthenuria, hyposthenuria, proteinuria, hematuria, and glucosuria have been reported. •  Granular casts may occur in the urine. OTHER LABORATORY TESTS Histopathology of kidneys reveals acute diffuse renal tubular degeneration and necrosis.

•  Within 24 hours to several days, dehydra-

tion with oliguria or anuria occurs. •  Death due to anuric renal failure or euthanasia. CAUSES & RISK FACTORS •  Although amounts of raisins and grapes reported to cause toxicosis lie in the range 2.8–9.6 g/kg and 11–31 g/kg, respectively, a minimum toxic dose has not been established. Additionally, not all exposures of dogs to Vitis vinifera have resulted in clinical evidence of renal injury. •  Ingestion of sultanas, Zante currants, and other varieties of Vitis vinifera has also been associated with renal injury in dogs, but amounts associated with toxicosis have not been reported. •  Mechanism of toxicity and toxic principle are unknown. Inconsistent development of clinical signs resulting from ingestion of Vitis vinifera may reflect idiosyncratic reactions of individual dogs or a toxic principle that is of variable presence in the fruit due to variances in growing conditions. •  Until further toxicity data are available, all exposures of dogs to Vitis vinifera should merit veterinary attention.

­

 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS Other causes of acute renal failure—ethylene glycol, heavy metal toxicosis, nephrotoxic antibiotics (e.g., aminoglycosides), nonsteroidal anti-inflammatory drug toxicosis, hemoglobinuria, myoglobinuria, leptospirosis, borreliosis, and vitamin D toxicosis. CBC/BIOCHEMISTRY/URINALYSIS •  Hypercalcemia, hyperphosphatemia, high creatinine and blood urea nitrogen (BUN) may develop within 24–48 hours of ingestion. Elevated creatinine and hyperphosphatemia tend to develop first, followed by elevation of BUN, with calcium elevation

CONTRAINDICATIONS/POSSIBLE INTERACTIONS N/A

­

monitor renal values until they return to normal. •  Some dogs may develop irreversible renal injury requiring lifelong management. •  Evidence of pancreatitis developed in 3 of 43 dogs with acute renal injury following Vitis vinifera ingestion.

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TREATMENT

•  Gastrointestinal decontamination (induc-

tion of emesis, administration of activated charcoal) should follow ingestion of grapes or raisins by dogs. •  Fluid diuresis (2–3 times maintenance) for minimum of 48 hours is recommended, longer if renal failure develops. Fluid choice may vary with circumstance, but 0.9% NaCl is most commonly recommended. •  Monitor serum chemistry values, particularly renal values, for minimum of 72 hours, longer if renal failure develops. •  Correct fluid imbalances (e.g., dehydration). •  Monitor fluid in/out. •  Diuretics (e.g., furosemide, mannitol, dopamine) if oliguria or anuria develops. •  Hemodialysis or peritoneal dialysis may be required in anuric patients.

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MEDICATIONS

DRUG(S) OF CHOICE •  Emetics—3% hydrogen peroxide 2.2 mL/ kg up to a maximum of 45 mL/dog PO; may repeat once if first dose unsuccessful; or apomorphine crushed and diluted with sterile saline and instilled in conjunctival sac, rinse eye after emesis, or 0.03 mg/kg IV. •  Activated charcoal—1–3 g/kg PO. Management of Oliguric or Anuric Renal Failure •  Mannitol 0.25–0.5 g/kg of 20–25%

solution IV over 15–20 min, repeat q4–6h or administer as CRI of 8–10% solution for 12–24h. •  Furosemide 2 mg/kg IV, repeat at 4 mg/kg if no diuresis within 1h; use with dopamine for best results. •  Dopamine 0.5–3 μg/kg/min.

FOLLOW-UP

•  In dogs developing renal insufficiency,

MISCELLANEOUS

ABBREVIATIONS •  ALT = alanine aminotransferase. •  BUN = blood urea nitrogen. INTERNET RESOURCES https://www.aspcapro.org/animal-healthtoxicology-poison-control/ people-pet-food-dangers

­Suggested Reading

Eubig PA, Brady MS, Gwaltney-Brant S, et al. Acute renal failure in dogs after ingestion of grapes or raisins: a retrospective evaluation of 43 dogs (1992–2002). J Vet Intern Med 2005;19:663–674. Mostrom MS. Grapes and raisins. In: Peterson M, Talcott PA, eds., Small Animal Toxicology, 3rd ed. St. Louis, MO: Saunders, 2006, pp. 569–572. Author Sharon Gwaltney-Brant Consulting Editor Lynn R. Hovda

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Hair Follicle Tumors

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 BASICS

OVERVIEW •  Five types—trichoepithelioma and trichoblastoma are most common types, but uncommon types include infundibular keratinizing acanthoma, tricholemmoma, and pilomatricoma; these are differentiated based on their origin: trichoepithelioma, trichoblastoma, infundibular keratinizing acanthoma, and tricholemmoma, which arise from keratinocytes in the outer root sheath of the hair follicle (± hair matrix); and pilomatricoma, which arises from the hair matrix. •  All types—generally benign; a few published reports of malignant trichoepitheliomas, trichoblastomas, and pilomatricomas. •  Approximately 5% of all skin tumors in dogs and 1% of all skin tumors in cats. SIGNALMENT •  Dog and cat. •  Age—usually >5 years. •  No sex predisposition. •  Trichoepithelioma— common in dogs; rare in cats; golden retrievers, basset hounds, German shepherds, cocker spaniels, Irish setters, English springer spaniels, miniature schnauzers, and standard poodles may be predisposed; Persian and Siamese cats. •  Trichoblastoma—common in dogs; common in cats; poodles and cocker spaniels may be predisposed; no known breed predisposition in cats. •  Infundibular keratinizing acanthoma—uncommon in dogs and cats; Norwegian elkhound, keeshond, and German shepherd dog may be predisposed; no known breed predisposition in cats. •  Tricholemmoma—uncommon in dogs and cats; Afghan hounds may be predisposed; no known breed predis­position in cats. •  Pilomatricoma—uncommon in dogs and cats; Kerry blue terriers, Old English sheepdogs, and miniature poodles may be predisposed; no known breed predisposition in cats. SIGNS •  Usually a solitary mass. •  Trichoepithelioma— common on the lateral thorax and dorsal lumbar area (dogs) and head (cats). •  Trichoblastoma—common on the head and neck, especially the base of the ear (dogs) and cranial half of the trunk (cats). •  Infundibular keratinizing acanthoma—common on the back, neck, and limbs (dogs). •  Tricholemmoma— common on the head and neck (dogs). •  Pilomatricoma—common on the back, limbs, shoulders, flanks, and tail. •  Firm, round, elevated, well-circumscribed, often hairless, or ulcerated dermoepithelial masses or nodules. CAUSES & RISK FACTORS Unknown, some genetic predisposition.

­

 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS Distinguish from other tumors, including basal cell tumor and squamous cell carcinoma, and from epidermal inclusion cysts. CBC/BIOCHEMISTRY/URINALYSIS Usually normal. DIAGNOSTIC PROCEDURES •  Fine-needle aspiration and cytopathology. •  Tissue biopsy and histopathology. PATHOLOGIC FINDINGS •  Fine-needle aspiration cytology is very similar among all hair follicle tumors with basaloid and ghost cells; the exception to this rule is trichoblastomas, which have abundant pink matrix and scattered spindle cells. •  Trichoepithelioma—varies in degree of differentiation and site of origin (root sheath or hair matrix); horn cysts, lack of desmosomes, and differentiation toward hair follicle-like structures and formation of hair common. •  Trichoblastoma—four basic subtypes including ribbon, trabecular, granular, and clear cell; ribbon have basaloid cells in branding, winding, and radiating columns; trabecular have basaloid cells with prominent peripheral palisading; granular is identical to ribbon type but many of the cells are larger cells with granular or vacuolated cytoplasm; clear cell have basaloid cells in ribbon pattern with some cells having sebaceous differentiation. •  Infundibular keratinizing acanthoma—characterized by keratin-filled crypt in the dermis that opens to the skin surface. •  Tricholemmoma—characterized by nodular proliferation of keratinocytes, of which many are clear and surrounded by thickened basement membrane. •  Pilomatricoma— characterized by a variable proliferation of basophilic cells resembling hair matrix cells and fully keratinized, faintly eosinophilic cells with a central unstained nucleus (shadow cells); calcification common; features of malignancy are present with the occasional malignant pilomatricoma.

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 TREATMENT

­

 MEDICATIONS

Complete excision, cryotherapy, or electrosurgery—curative with most cases.

DRUG(S) OF CHOICE •  Isotretinoin (1 mg/kg q24h PO) was used to successfully control multiple pilomatricomas in

one dog and multiple infundibular keratinizing acanthomas in some dogs. •  Multimodal analgesia recommended for painful lesions. CONTRAINDICATIONS/POSSIBLE INTERACTIONS N/A

­

 FOLLOW-UP

•  Monitor for local recurrence. •  Prognosis

usually excellent; multiple reports of metastatic disease with the less common canine malignant pilomatricomas.

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 MISCELLANEOUS

­Suggested Reading

Abramo F, Pratesi F, Cantile C, et al. Survey of canine and feline follicular tumours and tumour-like lesions in central Italy. J Small Anim Pract 1999, 40:479–481. Adedeji AO, Affolter VK, Christopher MM. Cytologic features of cutaneous follicular tumors and cysts in dogs. Vet Clin Pathol 2017; 46(1):143–150. Beck A, Huber D, Šćuric V, et al. A four year retrospective study of the prevalence of canine follicular tumours in Croatia. Veterinarski Arhiv 2016, 86(3):453–466. Toma S, Noli C. Isotretinoin in the treatment of multiple benign pilomatrixomas in a mixed-breed dog. Vet Dermatol 2005, 16(5):346–350. Author Jason Pieper Consulting Editor Timothy M. Fan Acknowledgment The author and book editors acknowledge the prior contribution of Louis-Philippe de Lorimier.



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Halitosis SIGNS

•  When oral malodor is secondary to oral

­B ASICS DEFINITION An offensive odor emanating from the oral cavity. PATHOPHYSIOLOGY •  The sour milk odor accompanying periodontal disease may result from bacterial populations associated with plaque, calculus, unhealthy oral cavity tissues, decomposing food particles retained within the oral cavity, and tissue necrosis. •  Contrary to common belief, neither normal lung air nor stomach aroma contributes. •  The most common cause is periodontal diseases caused by plaque bacteria. •  A bacterial biofilm forms over a freshly cleaned and polished tooth as soon as the patient starts to salivate; bacteria attach to the pellicle within 6–8 hours; within days, the plaque becomes mineralized, producing calculus; as plaque ages gingival inflammation (gingivitis) may occur and progress into periodontitis (tooth support loss). Eventually the bacterial flora changes from a predominantly nonmotile Gram-positive aerobic coccoid flora to a more motile, Gramnegative anaerobic population including Prophyromonas, Bacteroides, Fusobacterium, and Actinomyces spp. •  The rough surface of calculus attracts more bacteria-laden biofilm, irritating the free gingiva; as the inflammation continues, the gingival sulcus is transformed into a periodontal pocket, which accumulates food debris and bacterial breakdown products, generating oral malodor (halitosis). •  The primary cause of malodor is Gramnegative anaerobic bacteria that generate volatile sulfur compounds (VSCs), such as hydrogen sulfide, methyl mercaptan, dimethyl sulfide, and volatile fatty acids. •  VSCs may also play a role in periodontal disease, affecting the integrity of the tissue barrier, allowing endotoxins to produce periodontal destruction, endotoxemia, and bacteremia. SYSTEMS AFFECTED Gastrointestinal—oral cavity. SIGNALMENT Species

Dogs and cats. Breed Predilections

Small breeds and brachycephalic breeds are more prone to oral disease because the teeth are closer together, smaller animals live longer, and their owners tend to feed softer food. Mean Age and Range

Older animals are predisposed.

disease, ptyalism (with or without blood), pawing at mouth, and anorexia may occur. •  In most cases, no clinical signs are present other than the odor. CAUSES

•  Eating malodorous food. •  Metabolic—diabetes, uremia. •  Respiratory—rhinitis, sinusitis, neoplasia. •  Gastrointestinal—megaesophagus,

neoplasia, foreign body. •  Dermatologic—lip-fold pyoderma. •  Dietary—fetid foodstuffs, coprophagy. •  Oral disease—periodontal disease and ulceration, orthodontic, pharyngitis, tonsillitis, neoplasia, foreign bodies. •  Trauma—electric cord injury, open fractures, caustic agents damaging oral cavity. •  Infectious—bacterial, fungal, viral infections of oral cavity. •  Autoimmune diseases of oral cavity. •  Eosinophilic granuloma complex.

­

DIAGNOSIS

CBC/BIOCHEMISTRY/URINALYSIS Usually normal. Might see changes consistent with diabetes mellitus or renal disease. IMAGING Intraoral radiographs are appropriate to help diagnose causes of halitosis. DIAGNOSTIC PROCEDURES •  Hydrogen sulfide, mercaptans, and volatile fatty acids are the primary components of halitosis; an industrial sulfide monitor can be used to measure sulfide concentration in peak parts per billion. •  Additional diagnostic procedures to evaluate periodontal disease include intraoral radiography, probing pocket depths, attachment levels, and tooth mobility.

CLIENT EDUCATION

•  Halitosis is generally a sign of an unhealthy

oral cavity and should prompt oral assessment under general anesthesia, treatment, and prevention. •  Initiate preventive measures to ensure good oral health (e.g., twice-daily brushing or wiping teeth, recommend accepted Veterinary Oral Heath Council products). SURGICAL CONSIDERATIONS Oral assessment performed under general anesthesia with intraoral radiographs and probing treatment including extraction of teeth with greater than 50% support loss.

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DRUG(S) OF CHOICE •  Antibiotics are not indicated to treat halitosis. •  Controlling periodontal pathogens helps control dental infections and accompanying malodor; when accompanied by follow-up home care, has been shown to decrease pocket depth. •  Weekly application of a plaque-retardant gel has been shown to decrease plaque in dogs and cats. •  The use of oral care products that contain metal ions, especially zinc, inhibits odor due to the affinity of the metal ion to sulfur; zinc complexes with hydrogen sulfide to form insoluble zinc sulfide; zinc interferes with microbial proliferation and calcification of microbial deposits (by interfering with the crystal development of calculus). Topical treatment with zinc ascorbate cysteine gel usually reduces halitosis within 30 minutes.

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TREATMENT

APPROPRIATE HEALTH CARE •  Following appropriate tooth-by-tooth diagnostics (periodontal probing, intraoral imaging, mobility evaluation), under anesthesia all teeth should be ultrasonically scaled, and polished; a curette should be used to remove remaining plaque and calculus accessible subgingivally. •  Once the specific cause of halitosis is known, direct therapy at correcting existing pathology; often multiple teeth need to be extracted when advanced periodontal disease is the cause of halitosis.

MEDICATIONS

FOLLOW-UP

PATIENT MONITORING Evaluate for recurrence of signs. PREVENTION/AVOIDANCE •  Daily brushing or friction wipes to remove plaque and control dental disease and odor; periodic veterinary examinations to monitor care. •  Veterinary Oral Health Council (VOHC. org) was created to accept products that decrease the accumulation of plaque and/or tartar; additionally those products accepted are considered safe to use. EXPECTED COURSE AND PROGNOSIS Varies with underlying cause.

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Halitosis 

(continued)

­Suggested Reading

­M ISCELLANEOUS

H

SYNONYMS •  Bad breath. •  Fetor ex ore. •  Fetor oris. •  Foul breath. •  Malodor. SEE ALSO Periodontal Disease. ABBREVIATIONS

•  VSC = volatile sulfur compounds.

Di Cerbo A, Pezzuto F, Canello S, et al. Therapeutic effectiveness of a dietary supplement for management of halitosis in dogs. J Vis Exp 2015, 101:e52717. doi: 10.3791/52717 Eubanks DL. Canine oral malodor. J Am Anim Hosp Assoc 2006, 42(1):77–79. Eubanks DL. “Doggy breath”: what causes it, how do I evaluate it, and what can I do about it? J Vet Dent 2009, 26(3):192–193. Jeusette IC, Román AM, Torre C, et al. 24-hour evaluation of dental plaque bacteria and halitosis after consumption of a single placebo or dental treat by dogs. Am J Vet

Res 2016, 77(6):613–619. doi: 10.2460/ ajvr.77.6.613 Wiggs RB, Lobprise HB. Veterinary Dentistry: Principles and Practice. Philadelphia, PA: Lippincott-Raven, 1997. Author Jan Bellows Consulting Editor Heidi B. Lobprise Client Education Handout available online



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Head Pressing •  Immune-mediated/inflammatory—granu-

­B ASICS DEFINITION Compulsive pressing of the head against a wall or other object for no apparent reason. PATHOPHYSIOLOGY •  Alterations in behavior—caused by lesions in the prosencephalon (i.e., cerebrum, limbic system, thalamus, and hypothalamus), particularly those affecting the limbic system and frontal and temporal cortices. •  Lesions may result in compulsive pacing; when an obstacle (e.g., a wall) is reached, the animal may press its head against it for long periods of time, apparently unable to turn and move away. •  Apparent inability to voluntarily move away—may reflect impaired integration of sensory information, leading to inappropriate behavior. SYSTEMS AFFECTED Nervous GENETICS N/A INCIDENCE/PREVALENCE N/A SIGNALMENT Dogs and cats of any age, breed, and sex. SIGNS

lomatous meningoencephalitis; necrotizing encephalitides (Maltese encephalitis, pug encephalitis); meningoencephalitis of unknown etiology. •  Infectious (dogs)—viral (rabies virus, canine distemper virus), rickettsial (Ehrlichia canis, Rocky Mountain spotted fever), protozoal (Toxoplasma gondii, Neospora caninum), or fungal (Blastomyces, Cryptococcus); rabies is of particular importance because neurons in the limbic system are frequently infected in carnivores. •  Infectious (cats)—viral (rabies, feline infectious peritonitis, feline leukemia virus: associated immunosuppression predisposes to other encephalitides and neoplasia; feline immunodeficiency virus: can cause encephalopathy primarily and can predispose to other encephalitides and neoplasia due to immunosuppression); Bartonella henselae; Cuterebra migration; toxoplasmosis; Cryptococcus and other fungal infections. •  Toxic—e.g., lead poisoning. •  Trauma. •  Vascular—intracranial hemorrhage as a result of hypertension (consider in older cats with hyperthyroidism, diabetes, or chronic renal insufficiency); bleeding disorder (either primary or secondary to rodenticide toxicity); ischemia (feline ischemic encephalopathy or secondary to systemic metabolic, inflammatory, or neoplastic disease).

•  Head pressing—just one sign of prosen-

cephalon disease.

•  Compulsive pacing and circling toward the

side of the lesion; circling can be toward either side if lesion is centrally located. •  Change in learned behavior, including loss of sleep cycles. •  Seizures. •  Contralateral postural reaction deficits. •  Contralateral visual deficits with normal pupillary light reflexes. •  Contralateral facial hypalgesia. CAUSES & RISK FACTORS

•  Anatomic—hydrocephalus, most com-

monly in young toy-breed dogs; lissencephaly (Lhasa apsos). •  Metabolic—hepatic encephalopathy as a result of a portosystemic shunt or severe hepatic disease; severe hyper- or hyponatremia. •  Nutritional—very unusual since most pets are fed compounded diets; thiamine deficiency can occur in cats fed a diet of raw fish, if thiamine supplementation in canned food is insufficient or in cats with severe malabsorptive syndromes; however, vestibular signs predominate. •  Neoplastic—primary (e.g., glioma, meningioma) or metastatic (e.g., hemangiosarcoma) tumors affecting the brain; more common in older animals (>6 years).

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DIAGNOSIS

DIFFERENTIAL DIAGNOSIS A newly blind animal might bump into objects, but rapidly recognizes its environment and acts visual; an animal with a prosencephalic lesion continues bumping into objects despite normal ocular exam. CBC/BIOCHEMISTRY/URINALYSIS •  May reflect a metabolic or toxic cause. •  Hepatic encephalopathy—decreased serum albumin, blood urea nitrogen, cholesterol, and glucose concentrations, with or without elevated alanine phosphatase (ALP), alanine aminotransferase (ALT), and bilirubin concentrations; microcytic anemia may be present; ammonium biurate crystals may be present in the urine. •  Lead toxicity—basophilic stippling of erythrocytes; presence of reticulocytes and nucleated red blood cells (RBCs) in the absence of anemia. •  Encephalitis—findings often unremarkable, but may reflect an inflammatory process (e.g., with fungal infection). •  CNS lymphoma—may see evidence of bone marrow involvement.

OTHER LABORATORY TESTS

•  Bile acid tolerance—to diagnose hepatic

encephalopathy; blood ammonia concentrations may also be elevated. •  Acute and convalescent serologic titers— to diagnose rickettsial, protozoal, fungal, and viral diseases; for some infections (e.g., canine distemper virus, Toxoplasma, Cryptococcus) also measure cerebrospinal fluid (CSF) antibody or antigen (Cryptococcus) titers. •  PCR on CSF and serum—to diagnose rickettsial, bacterial, protozoal, fungal, and viral diseases; sensitive and specific if the infectious agent is present in CSF or serum. •  Blood lead concentration—to diagnose lead toxicity. IMAGING •  Thoracic radiography—recommended for older patients to identify metastatic disease. •  Abdominal ultrasonography— recommended for older patients if intra-abdominal neoplasia is suspected; indicated if a porto­ systemic shunt or other hepatic disease is suspected. •  Rectal scintigraphy—may be used to definitively diagnose a portosystemic shunt. •  Brain CT or MRI—to identify intracranial masses, malformations, skull fractures, inflammation, and hemorrhage. •  Ultrasonography of the brain via persistent fontanels—may be used to diagnose hydro­ cephalus in young dogs. DIAGNOSTIC PROCEDURES •  Fundic examination—to identify ­chorioretinitis (evidence of infectious/ inflammatory disease) and vascular lesions. •  Blood pressure measurement to identify hypertension. •  CSF analysis—to diagnose encephalitis. PATHOLOGIC FINDINGS Findings at necropsy will reflect the etiology.

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TREATMENT

APPROPRIATE HEALTH CARE •  Severe clinical signs—hospitalization for diagnostic workup and treatment. •  Suspected rabies—quarantine outdoor animal with no vaccination or unknown vaccination history when rapidly progressive neurologic signs are present and animal lives in a rabies-endemic area; minimize the number of people in contact with the animal, and maintain a contact log; if neurologic signs deteriorate rapidly, euthanize the animal and send it to a public health laboratory to be tested for rabies.

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Head Pressing 

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NURSING CARE •  When hospitalized, patients should be monitored closely for deterioration in mental status and for seizures. •  Maintenance IV fluids may be necessary for patients with severe prosencephalic syndrome. •  The cage may need to be padded to avoid self-trauma if constantly head pressing and pacing. •  Eyes should be monitored regularly for development of corneal ulcers due to self-induced trauma. •  Central IV catheters should be placed in the saphenous vein rather than the jugular vein if possible, to avoid increasing intracranial pressure by occlusion of the jugular veins. ACTIVITY N/A DIET •  Suspected hepatic encephalopathy—appropriate low-protein diet. •  Hand-feeding may be necessary in severely encephalopathic patients; risk of aspiration if the patient fails to prehend and swallow correctly. CLIENT EDUCATION •  Specific to the underlying condition. •  Clients should be warned about the possibility of seizures, be provided with a description of a seizure, and given instructions on what to do if a seizure occurs. •  Clients should be provided with a description of signs of acute decompensation due to brain herniation. SURGICAL CONSIDERATIONS •  If signs are due to intracranial disease, elevated intracranial pressure is likely and therefore there is a risk of herniation during anesthesia, with induction and recovery from anesthesia posing the highest risk; patients should be ventilated carefully to ensure that their partial pressure of carbon dioxide (pCO2) remains within normal limits (35–45 mmHg). •  Hydrocephalus can be treated by placement of a ventriculo-peritoneal shunt.

(continued) •  Brain neoplasia, in particular extra-axial

tumors such as meningiomas, can be treated surgically if tumor location accessible.

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MEDICATIONS

DRUG(S) OF CHOICE •  Different causes require different treatment; do not initiate therapy until a diagnosis has been established. •  If patient’s mental status deteriorates suggesting impending brain herniation, mannitol (0.25–1 g/kg IV over 10–30 min) or hypertonic saline (4 mL/kg of 7.5% or 5.3 mL/kg of 3%) can be used to transiently reduce intracranial pressure; treatment can be repeated, but recurrent use will simply result in dehydration. •  Furosemide (0.7 mg/kg IV) given prior to administration of mannitol can complement the use of mannitol and prolong its effect. CONTRAINDICATIONS N/A PRECAUTIONS Sedatives should be used with caution in patients exhibiting head pressing, because they prevent assessment of mental status changes and might suppress respiratory drive, causing an increase in pCO2 and thus causing an increase in intracranial pressure. ALTERNATIVE DRUG(S) N/A

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FOLLOW-UP

PATIENT MONITORING •  Periodic repeat neurologic examinations to monitor progress. •  See specific diseases. POSSIBLE COMPLICATIONS N/A

EXPECTED COURSE AND PROGNOSIS N/A

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MISCELLANEOUS

ASSOCIATED CONDITIONS N/A AGE-RELATED FACTORS N/A ZOONOTIC POTENTIAL •  Rabies should be considered in endemic areas. •  Fungal infections may be zoonotic if spores are released; most likely to occur if exudative skin lesions are present. SEE ALSO

•  Brain Injury. •  Encephalitis. •  Hepatic Encephalopathy. •  Hydrocephalus.

ABBREVIATIONS

•  ALP = alanine phosphatase. •  ALT = alanine aminotransferase. •  CSF = cerebrospinal fluid. •  pCO2 = partial pressure of carbon dioxide. •  RBC = red blood cell.

INTERNET RESOURCES http://www.ivis.org/advances/Vite/braund1/ chapter_frm.asp?LA=1#Cerebral_Syndrome

­Suggested Reading

Bagley RS, Platt SR. Coma, stupor and mentation changes. In: Platt SR, Olby NJ, eds. BSAVA Manual of Canine and Feline Neurology, 4th ed. Gloucester: BSAVA, 2013, pp. 136–166. Dewey CW. Encephalopathies: disorders of the brain. In: Dewey CW. ed. A Practical Guide to Canine and Feline Neurology, 2nd ed. Ames, IA: Wiley-Blackwell, 2008, pp. 115–220. Author Natasha J. Olby



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Head Tilt

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 BASICS

DEFINITION Tilting of the head away from its normal orientation with the trunk and limbs; usually associated with disorders of the vestibular system. PATHOPHYSIOLOGY •  Vestibular system—coordinates position and movement of the head with that of the eyes, trunk, and limbs by detecting linear acceleration and rotational movements of the head; includes vestibular nuclei in the rostral medulla of the brainstem, vestibular portion of the vestibulocochlear nerve (cranial nerve [CN] VIII), and receptors in the semicircular canals of the inner ear. •  Head tilt—most consistent sign of diseases affecting the vestibular system and its projections to the cerebellum, spinal cord, cerebral cortex, reticular formation, and extraocular muscles (via medial longitudinal fasciculus); usually ipsilateral to the lesion. SYSTEMS AFFECTED Nervous—peripheral or CNS. SIGNS

sheath tumor, medulloblastoma, skull tumor (e.g., osteosarcoma); metastasis (e.g., hemangiosarcoma, melanoma). •  Nutritional—thiamin deficiency. •  Inflammatory, infectious—viral (e.g., feline infectious peritonitis [FIP], canine distemper); protozoal (e.g., toxoplasmosis, neosporosis); fungal (e.g., cryptococcosis, blastomycosis, histoplasmosis, coccidioidomycosis, nocardiosis); bacterial (e.g., extension from otitis media and interna); parasitic (e.g., Cuterebra larvae); rickettsial (e.g., ehrlichiosis); algae (protothecosis). •  Inflammatory, noninfectious— granulomatous meningoencephalomyelitis (GME), meningoencephalitis of unknown etiology/origin (MUE/MUO), breed-specific meningoencephalitis (e.g., necrotizing encephalitis). •  Trauma—fracture petrosal bone with brainstem injury. •  Toxic—metronidazole. RISK FACTORS •  Hypothyroidism. •  Administration of ototoxic drugs. •  Metronidazole treatment. •  Thiamin-deficient diet. •  Otitis externa, media, and interna.

•  Ensure that abnormal head posture is true

head tilt and not a head turn; i.e., turning of the head and neck to the side as if to turn in a circle. •  Head tilt may not be present if disease is bilateral. CAUSES Peripheral Disease

•  Anatomic—congenital head tilt. •  Metabolic—hypothyroidism; pituitary

chromophobe adenoma; paraneoplastic disease. •  Neoplastic—nerve sheath tumor of CN VIII; neoplasia of the bone and surrounding tissue (e.g., osteosarcoma, fibrosarcoma, chondrosarcoma, and squamous cell carcinoma). •  Inflammatory—otitis media and interna; primarily bacterial but also parasitic (e.g., Otodectes), and fungal; foreign body; nasopharyngeal polyp(s). •  Idiopathic—canine geriatric vestibular disease; feline idiopathic vestibular disease. •  Immune-mediated—cranial nerve neuropathy. •  Toxic—aminoglycosides, lead, hexachlorophene. •  Traumatic—fracture of tympanic bulla or petrosal bone; ear flush. Central Disease

•  Degenerative—storage disease;

demyelinating disease; vascular event.

•  Anatomic—hydrocephalus. •  Neoplastic—glioma, choroid plexus

papilloma, meningioma, lymphoma, nerve

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS Vestibular Disease

•  Unilateral disease—head tilt usually toward

side of lesion; usually accompanied by other vestibular signs, e.g., abnormal nystagmus (resting, positional) with fast phase usually in the direction opposite the tilt; ventral deviation of the eye (vestibular strabismus) ipsilateral to the tilt observed with elevation of the head; ataxia and disequilibrium with tendency to fall, lean, and/or circle toward the side of the tilt. •  Bilateral disease—head tilt may be absent or mild on the more severely affected side; abnormal nystagmus may be present; physiologic nystagmus (i.e., normal vestibular nystagmus) may be depressed or absent; may have wide side-to-side swaying movements of the head (especially evident in cats); may have wide-based stance or crouched posture with reluctance to move. •  Head tilt—localizes either to peripheral (e.g., vestibular portion of CN VIII or receptors in the inner ear) or central (e.g., vestibular nuclei and their neuronal pathways) nervous system. •  Peripheral deficits—horizontal or rotatory nystagmus with fast phase opposite the head tilt; possible concomitant ipsilateral facial nerve paresis or paralysis and/or Horner’s syndrome, and/or decreased tear production because of the close association of CN VIII

with CN VII and the sympathetic nervous system in the petrosal bone and tympanic bulla. •  Central deficits—vertical, horizontal, or rotatory nystagmus that can change direction with position of the head; altered mentation; ipsilateral paresis and/or proprioceptive deficits; central signs related to cerebellum, rostral medulla, and pons; in some patients, multiple CN involvement. •  Paradoxical vestibular syndrome—with lesions in the caudal cerebellar peduncles, or flocculonodular lobes of cerebellum; vestibular signs (e.g., head tilt, nystagmus) contralateral to the lesion, whereas the cerebellar signs and proprioceptive deficits are ipsilateral to the lesion. Nonvestibular Head Tilt and Head Posture

•  Uncommon. •  Unilateral midbrain lesions can cause severe

rotation of the head (>90°) toward the side opposite the lesion; no other vestibular signs; tilt corrects when patient is blindfolded. •  Adversive syndrome—observed with rostral thalamic or frontoparietal lobe lesions; head turn, neck curvature, and/or compulsive circling can be misinterpreted as vestibular deficits; may have postural reaction, menace, and/or sensory deficits that are contralateral to the lesion; compulsive turning is usually in large circles and is without the disequilibrium and true head tilt of vestibular disease. CBC/BIOCHEMISTRY/URINALYSIS

•  Usually normal. •  Mild anemia—hypothyroidism. •  Leukocytosis with neutrophilia—otitis

media and interna.

•  Thrombocytopenia—ehrlichiosis. •  Hypercholesterolemia—hypothyroidism. •  High serum globulin concentration—FIP.

OTHER LABORATORY TESTS

•  T4, free T4, free T4 by equilibrium dialysis

(FT4 EQD), and endogenous thyroidstimulating hormone (TSH) levels—if hypothyroidism is suspected based on physical examination and associated unilateral or bilateral involvement of CN VIII and possibly VII. •  Bacterial culture and sensitivity—sample from myringotomy or surgical drainage of tympanic bulla if otitis media/interna is suspected. •  Microscopic examination of ear swab— parasites (e.g., Otodectes). •  Serologic testing—infectious causes (e.g., canine distemper; FIP; protozoal, fungal, rickettsial diseases). IMAGING

•  Radiographs of tympanic bullae and

skull—normal radiographs do not rule out bulla disease. •  CT and MRI—valuable to confirm bulla lesions, CNS extension from peripheral

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Head Tilt disease, localize tumor, granuloma, and document extent of inflammation.

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DIAGNOSTIC PROCEDURES •  Cerebrospinal fluid (CSF)—from cerebellomedullary cistern; for evaluating central vestibular disease; detects inflammatory process; protein electrophoresis and titers to match with serologic testing if indicated; collection may put the patient at risk for herniation if elevated intracranial pressure. •  Brainstem auditory-evoked response (BAER)—assess cochlear portion of CN VIII and brainstem auditory pathways; particularly valuable for evaluating peripheral vestibular disease, because some diseases may cause ipsilateral deafness (e.g., otitis media/interna), whereas other diseases (e.g., canine geriatric and feline idiopathic vestibular diseases) affect only the vestibular portion of CN VIII. •  Biopsy—bone, tissue in tympanic bulla when a tumor, polyp, or osteomyelitis is suspected; brainstem mass (e.g., cerebellomedullary angle) difficult to approach and remove surgically.

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 TREATMENT

•  Inpatient versus outpatient—depends on

severity of signs (especially vestibular ataxia), size and age of patient, and need for supportive care. •  Supportive fluids—replacement or maintenance IV fluids may be required in acute phase when disorientation, nausea, and vomiting preclude oral intake; especially important in geriatric patients; maropitant— dog: 1 mg/kg SC q24h for up to 5 days or 2 mg/kg PO q24h for up to 5 days; cat: 1 mg/kg SC/PO for up to 5 days to help manage nausea (questionable benefit). •  Diet—as usual unless there is thiamin deficiency (e.g., exclusively fish diet without vitamin supplementation); restrict oral intake if nausea and vomiting; caution: aspiration secondary to abnormal body posture in patients with severe head tilt and disequilibrium or brainstem dysfunction. •  Discontinue drug if toxicity suspected. •  Sedative for severe disorientation and ataxia—e.g., dog: acepromazine 0.02– 0.05 mg/kg IV/IM/SC to max 2 mg; dexmedetomidine 1–2 μg/kg IV; diazepam 2–10 mg/dog PO/IV q8h. •  Surgical treatment—to drain bulla with otitis media, remove nasopharyngeal polyp in cats, and resect tumor, if accessible.

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 MEDICATIONS

DRUG(S) OF CHOICE •  Otitis media and interna—broad-spectrum antibiotic (parenteral or oral) that penetrates

(continued)

bone while awaiting culture results; trimethoprim-sulfa (15 mg/kg PO q12h or 30 mg/kg PO q12–24h); first-generation cephalosporins, such as cephalexin (10– 30 mg/kg PO q6–8h) or amoxicillin– clavulanic acid (Clavamox®—dogs: 12.5 mg/ kg PO q12h; cats: 62.5 mg/cat PO q12h; Clavaseptin® 12.5 mg/kg PO q12h); treatment for 4–6 weeks. •  Hypothyroidism—T4 replacement (dogs: levothyroxine 22 μg/kg PO q12h) should be introduced gradually in geriatric patients, especially with cardiac disease; response varies, partly depending on duration of signs (i.e., in some patients neuropathy is not reversible). •  Infectious CNS—specific treatment, if indicated; for bacterial diseases, antibiotic that penetrates the blood–brain barrier (e.g., trimethoprim-sulfa 15 mg/kg PO q12h; metronidazole 15 mg/kg q12h or 10 mg/kg q8h PO or slowly IV; third-generation cephalosporin, e.g., cefotaxime 25–50 mg/ kg IV q8h); for protozoal diseases, clindamycin (12.5–25 mg/kg PO q12h); for fungal diseases, itraconazole (dogs: 2.5 mg/ kg PO q12h or 5 mg/kg PO q24h; cats: 5 mg/kg PO q12h), fluconazole (dogs: 5–8 mg/kg PO q12h, 10–12 mg/kg PO q24h; cats: 50 mg/cat PO q12–24h); prognosis usually poor for protozoal, fungal, and viral diseases (e.g., FIP). •  GME/MUE/MUO—usually initially treated with steroids: dexamethasone (0.25 mg/kg PO, IM q12h for 3 days; followed by or starting with prednisone 2 mg/kg PO q24h for a minimum of 2 weeks; then decrease slowly); depending on progress, may need stronger immunosuppression, e.g., cytosine arabinoside 50 mg/m2 q12h for four treatments repeated every 3 weeks (need to monitor CBC) or preferably starting with CRI of cytosine arabinoside at 200 mg/m2 administered IV over 4h, then follow every 3 weeks with SC injections; also consider cyclosporine and/or leflunomide or radiation therapy. •  Trauma—supportive care (e.g., antiinflammatory drugs, antibiotics, IV fluid administration); specific fracture repair or hematoma removal is potentially difficult considering the location. •  Canine geriatric and feline idiopathic vestibular disease—supportive care; maropitant—dog: 1 mg/kg SC q24h for up to 5 days or 2 mg/kg PO q24h for up to 5 days; cat: 1 mg/kg SC/PO for up to 5 days to help manage nausea (questionable benefit). •  Cranial nerve polyneuropathy—response to prednisone good if the patient has a primary immune disorder. •  Thiamin deficiency—diet modification and thiamin supplementation. PRECAUTIONS

•  Trimethoprim-sulfa administration—

keratoconjunctivitis sicca (dry eye).

•  Avoid administering drugs into external ear

canal (especially oil-based) if tympanic membrane is ruptured.

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 FOLLOW-UP

PATIENT MONITORING •  Repeat the neurologic examination as dictated by underlying cause. •  Head tilt may persist. •  Hypothyroidism—measure T4 concentration 4–6 hours after treatment 3–4 weeks after initiation of thyroid therapy or dosing change. •  Repeat CSF and brain imaging—with some central vestibular disorders. •  Monitor tear production (Schirmer tear test) with trimethoprim-sulfa administration. EXPECTED COURSE AND PROGNOSIS

•  Prognosis for central vestibular disorders

usually poorer than peripheral vestibular disorders. •  Prognosis for canine geriatric and feline idiopathic vestibular syndromes is excellent.

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 MISCELLANEOUS

ASSOCIATED CONDITIONS •  Facial nerve paresis or paralysis. •  Horner’s syndrome. SEE ALSO

•  Encephalitis. •  Otitis Media and Interna. •  Vestibular Disease, Geriatric—Dogs. •  Vestibular Disease, Idiopathic—Cats.

ABBREVIATIONS

•  BAER = brainstem auditory-evoked

response.

•  CN = cranial nerve. •  CSF = cerebrospinal fluid. •  FIP = feline infectious peritonitis. •  FT4 EQD = free T4 by equilibrium dialysis. •  GME = granulomatous

meningoencephalomyelitis.

•  MUE/MUO = meningoencephalitis of

unknown etiology/origin.

•  TSH = thyroid-stimulating hormone.

­Suggested Reading

Garosi L. Head tilt and nystagmus. In: Platt S, Garosi L, eds. Small Animal Neurological Emergencies. London: Manson, 2012, pp. 253–263. Rossmeisl JH. Vestibular disease in dogs and cats. Vet Clin North Am Small Anim Pract 2010, 40:81–100. Author Susan M. Cochrane  Client Education Handout available online



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Canine and Feline, Seventh Edition

Head Tremors (Bobbing), Idiopathic—Dogs

­B ASICS OVERVIEW •  Common, very specific, benign, often self-limiting, head and neck tremors in dogs. •  Synonyms—head bobbing, wobbling, nodding, shaking, tremors; episodic head tremor syndrome; bobble head doll syndrome. •  A movement disorder (paroxysmal dyskinesia) was suspected, but the pathophysiology remains unknown and a recent electroencephalographic (EEG) study may support an epileptic syndrome. SIGNALMENT •  All dog breeds can be affected. •  Not reported in cats. •  English bulldog (EB), French bulldog, boxer, Doberman pinscher (DP), and Labrador retriever are predisposed. •  Reported prevalence of 19–38% in EB. •  Reports that males are overrepresented in DP and EB. •  Generally starts early in life (57 °F (14 °C).

SYSTEMS AFFECTED

•  Respiratory—PH, thromboembolism,

allergic pneumonitis (some occult infections), eosinophilic granulomatosis (uncommon). •  Cardiovascular—severe PH causes right ventricular hypertrophy and, in some dogs, rCHF (ascites). •  Hemic/lymphatic/immune— venous inflow to the heart can become obstructed by worms causing traumatic hemolytic anemia and cardiogenic shock (caval syndrome). •  Renal/urologic— immune-complex glomerulonephritis. INCIDENCE/PREVALENCE Virtually 100% in unprotected dogs living in highly endemic regions. GEOGRAPHIC DISTRIBUTION

•  Most common in tropical and subtropical

zones; endemic in North, Central, and South America, southern Europe, and Australia. •  Diagnosed in all 50 states of United States; common along Atlantic/Gulf coasts and Ohio/Mississippi river basins. •  Ubiquitous mosquito vector in endemic areas. SIGNALMENT Breed Predilections

•  Medium-to-large breed dogs > small dogs. •  Outdoor dogs > indoor dogs.

Mean Age and Range

Infestation can occur at any age; most affected dogs 3–8 years old. Predominant Sex

Males > females. SIGNS

Historical Findings

•  Dogs often asymptomatic or exhibit

minimal signs such as occasional coughing (mild infestation). •  Coughing and exercise intolerance associated with moderate pulmonary damage (moderate infestation). •  Cachexia, exercise intolerance, syncope, and/or abdominal distention (rCHF) in

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Other causes of PH and thrombosis (e.g., hyperadrenocorticism, protein-losing nephropathy or enteropathy). •  Chronic obstructive lung disease. •  Pneumonia. •  Allergic lung disease. •  Other causes of ascites (e.g., dilated cardiomyopathy). •  Other causes of hemolytic anemia (e.g., immune-mediated). CBC/BIOCHEMISTRY/URINALYSIS •  Anemia—absent, mild, or moderate depending on chronicity, severity, thrombo­ embolic complications. •  Eosinophilia and basophilia—vary. •  Inflammatory leukogram and thrombocytopenia associated with thromboembolism. •  Hyperglobulinemia— inconsistent finding. •  Hemoglobinemia— evident with caval syndrome and less often thromboembolism. •  Proteinuria—common with severe and chronic infestation; due to immune-complex glomerulonephritis or amyloidosis. •  Hemoglobinuria—caval syndrome or severe lysis with thromboembolism.

death and highly predictive of thromboembolic complications post adulticide therapy. •  Microfilaria testing—mainly to confirm weak positive antigen tests, determine microfilarial status prior to using milbemycin preventatives, and identify microfilaria that may contribute to development of resistance when treated chronically with macrolide preventative. IMAGING Radiography

•  Use DV projection. •  Main pulmonary

artery segment enlargement, lobar arterial enlargement, tortuosity/pruning vary from absent to severe; right caudal artery > left caudal artery > cranial arteries. •  Parenchymal lung infiltrates of variable severity—surround lobar arteries; may extend into most or all of one or multiple lung lobes with thromboembolism and/or PH. •  Diffuse, symmetric, alveolar, interstitial infiltrates occur secondary to allergic reaction to microfilaria (allergic pneumonitis) in about 10% of occult infestations. Echocardiography

•  Often unremarkable; may reflect right

ventricular dilation and wall hypertrophy, tricuspid regurgitation, PH, small left heart due to underloading (pulmonary obstruction/ hypertension). •  Parallel, linear echodensities produced by heartworms may be detected in right ventricle, right atrium, pulmonary arteries. DIAGNOSTIC PROCEDURES ECG

•  Usually normal. •  May reflect right ventricular hypertrophy in dogs with severe infestation. •  Heart rhythm disturbances— occasionally seen (atrial premature contractions and atrial fibrillation most common) in severe infestation.

PATHOLOGIC FINDINGS

•  Large right heart. •  Pulmonary arterial myointimal proliferation. •  PTE. •  Pulmonary hemorrhage. •  Hepatomegaly

and congestion in dogs with rCHF.

OTHER LABORATORY TESTS

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identify adult female D. immitis antigen; test 7 months after end of previous transmission season; false positives possible with Spirocerca infestation; in author’s experience, false negatives occur more commonly in shelter animals due to antigen-antibody complexes (antigen blocking); if infestation suspected with negative antigen test, consider heartworm heat treatment antigen ELISA testing. •  Antigenemia absent in absence of adult female worms. •  Weak positive test verified by repeat testing using different test and/or microfilaria testing. •  Strong reaction indicates relative high worm burden or recent worm

APPROPRIATE HEALTH CARE •  Most dogs hospitalized during adulticide administration. •  Eliminate microfilaria with monthly prophylaxis and doxycycline/ minocycline; milbemycin may cause rapid decrease in microfilaria numbers and should be used with caution in that scenario; dogs should be rendered microfilaria free 3-4 months post diagnosis. •  Hospitalization recommended for dogs experiencing thromboembolic complications.

•  Highly specific, sensitive serologic tests

 TREATMENT

ACTIVITY Severely restrict activity for 4–6 weeks after adulticide administration.

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Heartworm Disease—Dogs CLIENT EDUCATION •  Good prognosis for animals with mild to moderate disease. •  Post-adulticide pulmonary complications likely in patients with moderate to severe pulmonary artery pathology and those with high worm burden. •  Reinfestation can occur without appropriate prophylaxis.

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SURGICAL CONSIDERATIONS •  Treatment of choice for caval syndrome. •  Worm removal from right heart and pulmonary artery via jugular vein, by use of fluoroscopy and long, flexible alligator forceps or horsehair brush, highly effective for treating high worm burden when employed by experienced operator.

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 MEDICATIONS

DRUG(S) OF CHOICE •  Stabilize animals in rCHF with diuretics, angiotensin-converting enzyme (ACE) inhibitor, pimobendan, sildenafil, cage rest, and moderate sodium restriction before adulticide treatment. •  Stabilize pulmonary failure with oxygen supplementation, antithrombotics (e.g., clopidogrel and heparin), and/or anti-inflammatory dosages of corticosteroid depending on clinical and radiographic findings. •  Doxycycline/ minocycline (5–10 mg/kg PO q12h) for 4 weeks followed by 1 month wait period is used prior to adulticide therapy to kill Wolbachia, a Gram-negative, endo-symbiotic, intrafilarial bacterium associated with inflammation of the lungs and kidneys; the author practices adulticide therapy after 4 weeks of treatment. •  Adulticide— melarsomine dihydrochloride (2.5 mg/kg IM/ dose): injections given into epaxial muscles using 22-gauge needles; apply pressure over injection site during and after needle withdrawal. •  Graded-kill protocol recommended in most cases—administer one injection followed in 1 month by two injections (first injection on left or right epaxial muscles, followed by injection on opposite side 24h later). •  For severe heartworm infestation with high worm burdens, administer one injection every 4–6 weeks for a total of three injections; maintain strictest patient confinement practical for 4–6 weeks; perform antigen test 6 months after third injection. •  Allergic pneumonitis— administer prednisone or prednisolone (2 mg/ kg PO q12–24h for several days) and then immediately administer melarsomine. •  Rapid microfilaricidal therapy (e.g., milbemycin or high-dose ivermectin) not recommended— eliminate microfilaria with monthly prophylaxis and doxycycline/minocycline; confirm elimination of microfilaria by testing 3–4 months after initiating therapy.

PRECAUTIONS

•  Adulticide treatment—not indicated in

patients with renal failure, hepatic failure (icterus), or nephrotic syndrome. •  Caval syndrome—remove worms surgically and stabilize patient with conservative management for at least 1 month prior to adulticide therapy. ALTERNATIVE DRUG(S)

•  Sodium heparin (75–100 units/kg SC q8h),

clopidogrel (2–4 mg/kg PO q24h), or low molecular weight heparin (dalteparin: 100 units/ kg SC q12–24h) for 1–3 weeks before, during, and for 3 weeks after adulticide administration are controversial recommendations for most severe cases; therapy is combined with strict, extended cage confinement. •  Sodium heparin (200–500 units/kg SC q8h) recommended for dogs with PTE or hemoglobinuria with goal of prolonging activated partial thromboplastin time (APTT) 1.5–2 times baseline. •  Soft or slow kill methods using any macrocyclic lactone alone are not recommended.

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 FOLLOW-UP

PATIENT MONITORING •  Perform antigen test 6 months after adulticide treatment; some dogs with persistent, low-grade antigenemia may not require retreatment. •  Weak antigenemia indicates most worms killed, pulmonary pathology will improve, and ivermectin prophylaxis will likely eventually kill remaining worms. PREVENTION/AVOIDANCE •  Heartworm prophylaxis should be provided for all dogs at risk—author recommends year-round prophylaxis; otherwise begin with mosquito season and continue for 1 month following first frost. •  In highly endemic areas, consider combination of heartworm prophylaxis, insect repellents, and ectopara­ siticides. •  Antigen test 7 months after end of previous season. •  Ivermectin (Heartgard®, Iverhart®, Tri-Heart®)—highly effective, monthly preventative; safe for microfilaremic dogs. •  Milbemycin oxime (Interceptor®, Sentinel®, Trifexis®)—highly effective, monthly prophylaxis; acute reactions may occur when given to microfilaremic dogs. •  Moxidectin (Advantage® Multi, ProHeart® 6)—topical solution administered monthly; slow-release injectable formulation (ProHeart® SR12) available in some countries. •  Selamectin (Revolution®)—highly effective monthly topical preparation. •  Administer to puppies as soon after 8 weeks of age as dictated by seasonal risk. •  All prophylactic drugs can be administered safely to collies at labeled dosages. •  For dogs infected with adult worms not already on prophylaxis, any of above drugs can be started immediately and should be started within 1 month of diagnosis; author recommends against using milbemycin in

(continued)

microfilaremic dogs. •  All macrocyclic lactones combined with 1 month doxycycline/ minocycline therapy should eliminate microfilaria in 1–3 months. •  Due to recent increase in number of lack of efficacy reports and concern of possible heartworm resistance to current heartworm preventatives, dogs should be rendered microfilaria free 3–4 months post diagnosis. POSSIBLE COMPLICATIONS

•  Post-adulticide PTE—may occur up to

4–6 weeks after treatment; more likely in dogs with severe disease and those not properly confined. •  Thrombocytopenia and disseminated intravascular coagulation. •  Melarsomine adverse effects—PTE (usually 7–30 days post therapy); anorexia; injection site reaction: myositis; lethargy or depression; elevation of hepatic enzymes; paresis/paralysis/ altered mentation; lack of efficacy. EXPECTED COURSE AND PROGNOSIS

•  Mild—usually uneventful with excellent prognosis. •  Severe or caval syndrome—

guarded prognosis with higher risk of complications.

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 MISCELLANEOUS

When anesthesia/surgery required, delay heartworm treatment until after procedure. ASSOCIATED CONDITIONS Wolbachia PREGNANCY/FERTILITY/BREEDING •  Delay adulticide treatment. •  Transplacental infestation by microfilaria can occur. SEE ALSO

•  Congestive Heart Failure, Right-Sided. •  Disseminated Intravascular Coagulation. •  Hypertension, Pulmonary. •  Nephrotic Syndrome. •  Pulmonary Thromboembolism.

ABBREVIATIONS

•  ACE = angiotensin-converting enzyme. •  APTT = activated partial thromboplastin time. •  PH = pulmonary hypertension. •  PTE = pulmonary thromboembolism. •  rCHF = right-sided congestive heart failure.

INTERNET RESOURCES www.heartwormsociety.org Author Justin D. Thomason Consulting Editor Michael Aherne Acknowledgment The author and book editors acknowledge the prior contribution of Clay A. Calvert  Client Education Handout available online



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Canine and Feline, Seventh Edition

Heat Stroke and Hyperthermia Mean Age and Range

­B ASICS DEFINITION •  Hyperthermia is defined as an elevation in body temperature above the normal range; although published normal values for dogs and cats vary slightly, it is generally accepted that body temperatures >103 °F (39.4 °C) are abnormal. •  Hyperthermia can be categorized into pyrogenic hyperthermia (pyrexia or fever) and nonpyrogenic hyper­ thermia. •  Heat stroke is a form of nonpyro­ genic hyperthermia that occurs when heat-dissipating mechanisms of the body cannot accommodate excessive heat; this can lead to multisystem organ dysfunction; temperatures of ≥106 °F (41.1 °C) without signs of inflammation are suggestive of nonpyrogenic hyperthermia. •  Malignant hyperthermia is an uncommon familial form of nonpyrogenic hyperthermia that can occur secondary to some anesthetic agents. •  Other causes of nonpyrogenic hyperthermia include excessive exercise, thyrotoxicosis, and hypothalamic lesions. PATHOPHYSIOLOGY •  The hypothalamic set point is changed with true fever; this is most likely mediated via the endogenous pyrogen interleukin-1. •  Nonpyrogenic hyperthermia does not change the hypothalamic set point. •  The critical temperature leading to multiple organ dysfunction is 109 °F (42.7 °C). •  The primary pathophysiologic processes of heat stroke are related to thermal damage, which can lead to cellular necrosis, hypoxemia, and protein denaturalization. •  Heat stroke and its sequelae can lead to systemic inflammatory response syndrome (SIRS). SYSTEMS AFFECTED

•  Cardiovascular—hypovolemia, cardiac

arrhythmias, myocardial ischemia, necrosis.

•  All ages but often age extremes. •  Young dogs may tend to overexert. •  Old dogs with

preexisting disease. SIGNS

Historical Findings

•  Identifiable underlying cause—warm

environmental conditions, locked in car or other confined area without adequate ventilation, grooming accident associated with drying cages, excessive exercise, restricted access to water. •  Predisposing underlying disease— laryngeal paralysis, brachycephalic obstructive disease, cardiovascular disease, neuromuscular disease, previous history of heat-related disease. Physical Examination Findings

•  Panting. •  Hypersalivation. •  Hyperthermia. •  Hyperemic mucous membranes. •  Pale mucous membranes. •  Cyanosis. •  Tachycardia. •  Cardiac dysrhythmias. •  Shock. •  Respiratory distress. •  Hematemesis. •  Hematochezia. •  Melena. •  Petechiation. •  Changes in mentation. •  Seizures. •  Muscle tremors. •  Ataxia. •  Coma. •  Oliguria/anuria. •  Respiratory arrest. •  Cardiopulmonary arrest.

CAUSES

•  Excessive environmental heat and humidity

(may be due to weather conditions or accidents such as enclosed in unventilated room, car, or grooming dryer cage). •  Upper airway disease. •  Exercise. •  Toxicosis (some compounds that lead to seizures, i.e., strychnine and metaldehyde). •  Anesthesia (malignant hyperthermia). RISK FACTORS •  Previous history of heat-related disease. •  Age extremes. •  Heat intolerance due to poor acclimatization. •  Obesity. •  Poor cardiopulmonary conditioning. •  Hyperthyroidism. •  Underlying cardiopul­ monary disease. •  Brachycephalic breeds. •  Thick hair coat. •  Dehydration.

•  Gastrointestinal—mucosal ischemia and

ulceration, bacterial translocation and endotoxemia. •  Hemic/lymphatic/immune— hemoconcentration, th­rombocytopenia, disseminated intravascular coagulation (DIC). •  He­patobiliary—hepatocellular necrosis. •  Musculoskeletal—rhabdomyolysis. •  Nervous—neuronal damage, parenchymal hemorrhage, cerebral edema. •  Renal/ urologic—acute renal failure. GEOGRAPHIC DISTRIBUTION May occur in any climate but more common in warm and/or humid environments. SIGNALMENT Species

Dog and, uncommonly, cat. Breed Predilections

•  May occur in any breed. •  Longhaired animals. •  Brachycephalic breeds.

­

DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  If temperature exceeds 106 °F (41.1 °C) without evidence of inflammation should consider heat stroke. •  Panting and hypersali­ vation may not be seen with true fever as hypothalamic set point has been raised. CBC/BIOCHEMISTRY/URINALYSIS •  May help identify underlying disease process and/or sequelae to hyperthermia. •  CBC abnormalities may include stress leukogram, leukopenia, anemia, nucleated red blood cells, thrombocytopenia, or hemoconcentration. •  Biochemistry profile may show azotemia, hyperalbuminemia, elevations in serum enzymes (alanine aminotransferase, aspartate aminotrans­ ferase, creatine kinase), hypernatremia, hyper­

chloremia, hyperglycemia, hypoglycemia, hyperphosphatemia, hyperkalemia, hypoka­ lemia, hyperbilirubinemia. •  Urinalysis may show hypersthenuria, proteinuria, cylindruria, hemoglobinuria, myoglobinuria. OTHER LABORATORY TESTS

•  Blood gas analysis may show mixed

acid-base disorder, respiratory alkalosis, or metabolic acidosis. •  Lactate concentrations may be elevated due to impaired perfusion. •  Coagulation profile may indicate prolonged activated clotting time (ACT), prothrombin time (PT), or partial thromboplastin time (PTT); fibrin degradation products (FDP) or D-dimers may be positive; DIC may be present if PT and PTT are prolonged along with positive FDPs or D-dimers and thrombocytopenia; if available measurement of antithrombin may be valuable. •  Thromboelastography may document hyper- or hypocoagulability. IMAGING

•  Thoracic/abdominal radiographs and/or

ultrasound may help identify underlying cardiopulmonary disease or predisposing factors. •  CT or MRI may help identify hypothalamic lesion. DIAGNOSTIC PROCEDURES Continuous temperature monitoring.

­

TREATMENT

•  Early recognition is key. •  Immediate

correction of hyperthermia—spray with water or immerse in water prior to transport to veterinary facility; convection cooling with fans; evaporative cooling such as alcohol on foot pads, axilla, and groin. •  Stop cooling procedures when temperature reaches 103 °F (39.4 °C) to avoid hypother­ mia. •  Oxygen supplementation via oxygen cage, mask, or nasal catheter. •  Airway management in cases of laryngeal paralysis or edema. •  Ventilatory support if required. •  Fluid support with shock doses of crystalloids or colloids. •  Treat complica­ tions, seizures, DIC, renal injury, cerebral edema. •  Treat underlying disease or correct predisposing factors. APPROPRIATE HEALTH CARE

•  Patients should be hospitalized until temperature is stabilized. •  Most patients

need intensive care for several days. NURSING CARE

•  External cooling—try to avoid ice as this

may cause peripheral vasoconstriction and impede heat elimination; shivering response is also undesirable as this creates heat. •  Fluid therapy—isotonic crystalloids can be administered at shock rates (dogs: 90 ml/ kg/h; cats: 45–60 mL/kg/h) based on clinical assessment; synthetic colloids may also be

H

590

Blackwell’s Five-Minute Veterinary Consult

Heat Stroke and Hyperthermia  used to treat shock (dogs: 20 mL/kg, 5 mL/kg IV boluses; cats: 5–10 mL/kg, 1–2 mL/kg boluses). •  Oxygen supplementation—can be administered via mask, cage, or nasal cannula. ACTIVITY Restricted DIET Nil PO until animal is stable.

H

CLIENT EDUCATION

•  Be aware of clinical signs. •  Know how to cool off animals. •  Seek veterinary care immediately. •  An episode of heat stroke may

predispose pets to additional episodes.

SURGICAL CONSIDERATIONS Tracheostomy may be required if upper airway obstruction is underlying cause or contributing factor.

­

MEDICATIONS

DRUG(S) OF CHOICE •  No specific drugs for hyperthermia or heat stroke; therapy dependent on clinical presentation. •  Prophylactic broad-spectrum antimicrobials may decrease incidence of bacterial translocation; first-generation cephalosporins or potentiated penicillins (clavulanate/amoxicillin, sulbactam/ ampicillin) in combination with fluoroqui­ nolones provide excellent four-quadrant coverage. •  Acute renal failure—dopamine CRI (2–5 μg/kg/min), furosemide (2–4 mg/ kg IV PRN), mannitol 0.5–1 g/kg as slow IV/ CRI. •  Cerebral edema—mannitol (1 g/kg IV over 15–30 min), furosemide (1 mg/kg IV) 30 min following mannitol infusion, corticosteroids: dexamethasone sodium phosphate (1–2 mg/kg IV), prednisone sodium succinate (10–20 mg/kg IV), methyl prednisolone (15 mg/kg IV); see Contra­ indications. •  Ventricular arrhythmia— lidocaine bolus (2 mg/kg IV) followed by CRI (25–75 μg/kg/min); procainamide (6–8 mg/kg IV). •  Metabolic acidosis— sodium bicarbonate (0.3 × BW [kg] × base excess) give ⅓ to ½ as IV bolus. •  DIC— fresh frozen plasma (20 mL/kg); heparin doses vary widely (300–500 U/kg SC q

6–8h). •  Thrombocytopenia—severe thrombocytopenia with active bleeding can be treated with fresh whole blood, plateletrich plasma, lyophilized platelets, or frozen platelet concentrate. •  Hematochezia or melena—broad-spectrum antibiotics, H2-antagonists, or proton pump inhibitors in combination with sucralfate. •  Seizures— diazepam (0.5–1 mg/kg IV) or midazolam; phenobarbital (6 mg/kg IV PRN).

(continued)

EXPECTED COURSE AND PROGNOSIS •  Depends on underlying cause or disease process. •  Prognosis may depend on time lag between event and hospital admission. •  Prognosis is guarded—dependent on complications (renal failure and DIC) and duration of episode. •  May predispose animal to further episodes due to damage to thermoregulatory center.

CONTRAINDICATIONS

•  Nonsteroidal anti-inflammatory agents are

not indicated in nonpyrogenic hyperthermia because the hypothalamic set point is not altered. •  Corticosteroid use considered controversial in heat stroke due to possible adverse effects. PRECAUTIONS N/A POSSIBLE INTERACTIONS N/A

­

FOLLOW-UP

PATIENT MONITORING •  Patients should be closely monitored during cooling-down period and for a minimum of 24 hours post episode; most animals must be monitored for several days depending on clinical presentation and clinical complica­ tions. •  Thorough physical examination should be performed daily; in addition the following parameters should be given consideration: ◦  Body temperature. ◦  Body weight. ◦  Blood pressure. ◦  Central venous pressure. ◦  ACT. ◦  PT/PTT. ◦  D-dimers. ◦  ECG. ◦  Thoracic auscultation. ◦  Urinalysis and urine output. ◦  Packed cell volume, total protein. ◦  CBC, biochemical profile. ◦  Venous blood gas analysis (electrolytes, lactate). POSSIBLE COMPLICATIONS

•  Cardiac dysrhythmias. •  Organ failure. •  Coma. •  Seizures. •  Acute renal failure. •  DIC. •  SIRS. •  Sepsis/septic shock. •  Pulmonary edema—acute respiratory distress syndrome (ARDS). •  Rhabdomyolysis. •  Hepatocellular necrosis. •  Respiratory arrest. •  Cardiopulmonary arrest.

­

MISCELLANEOUS

SYNONYMS •  Heat exhaustion. •  Heat prostration. •  Heat-related disease. •  Heat stroke. SEE ALSO Fever ABBREVIATIONS •  ACT = activated clotting time. •  ARDS = acute respiratory distress syndrome. •  DIC = disseminated intravascular coagulation. •  FDP = fibrin degradation products. •  PT = prothrombin time. •  PTT = partial thromboplastin time. •  SIRS = systemic inflammatory response syndrome.

­Suggested Reading

Bruchim Y, Klement E, Saragusty J, et al. Heat stroke in dogs: a retrospective study of 54 cases (1999–2004) and analysis of risk factors for death. J Vet Intern Med 2006; 20:38–46. Gfeller R. Heat stroke. In: Ettinger SJ, Feldman EC, eds. Textbook of Veterinary Internal Medicine, 6th ed. St. Louis, MO: Elsevier, 2005, pp. 437–440. Johnson SI, McMichael M, White G. Heatstroke in small animal medicine: a clinical practice review. J Vet Emerg Crit Care 2006; 16(2):112–119. Author Steven L. Marks Consulting Editor Michael Aherne Client Education Handout available online



591

Canine and Feline, Seventh Edition

Helicobacter spp. puppy. •  Prevalence of H. fennelliae and H. cinaedi undetermined.

­B ASICS DEFINITION Helicobacter spp. are microaerophilic, Gramnegative, urease-positive bacteria ranging in shape from coccoid to curved to spiral. PATHOPHYSIOLOGY Helicobacter spp. in the Stomach

•  The association of Helicobacter pylori with

gastritis, peptic ulceration, and gastric neoplasia fundamentally changed understanding of gastric disease in humans. •  Putative mechanisms by which H. pylori alters gastric physiology in humans include disruption of gastric mucosal barrier and alteration of gastric secretory activity. •  H. pylori in humans has been associated with increased secretion of proinflammatory cytokines and nitric oxide. •  Several Helicobacter spp. other than H. pylori have been isolated from stomachs of dogs and cats; typically, multiple species are present. •  A possible cause–effect relationship of Helicobacter spp. and gastric inflammation in cats and dogs remains unresolved; inflammation or glandular degeneration accompanies infection in some but not all. •  Experiments to determine pathogenicity of H. pylori in specific pathogen free (SPF) cats and H. pylori and H. felis in gnotobiotic dogs demonstrated gastritis, lymphoid follicle proliferation, and humoral immune responses after infection. Helicobacter Spp. in the Liver and Intestines

•  Role in intestinal and hepatic disease is unclear. •  Several Helicobacter-like organisms

(HLOs) have been identified in large intestine and feces from normal and diarrheic dogs and cats. •  H. canis has been isolated from liver of a dog with active, multifocal hepatitis. SYSTEMS AFFECTED Gastrointestinal (GI)—Helicobacter spp. may lead to gastritis in some dogs and cats, diarrhea in some dogs with H. canis, possible acute hepatitis. GENETICS N/A INCIDENCE/PREVALENCE

Gastric Helicobacter spp.

•  Gastric HLOs are prevalent in dogs and cats—86–90% of clinically healthy cats, 67–86% of clinically healthy pet dogs. •  HLOs demonstrated in gastric biopsy specimens in 57–76% of cats and 61–82% of dogs presented for investigation of recurrent vomiting. •  To date H. pylori has been identified only in a single colony of laboratory cats.

Enterohepatic Helicobacter spp.

•  H. canis isolated in 4% of 1,000 dogs evaluated. •  A single case of H. canis–

associated hepatitis reported in 2-month-old

GEOGRAPHIC DISTRIBUTION N/A SIGNALMENT Species

Dog and cat. Mean Age and Range

Gastric infection acquired at a young age. SIGNS Historical Findings

•  Asymptomatic presence of Helicobacter spp. common. •  Vomiting, anorexia, abdominal

pain, weight loss, and/or borborygmus have all been reported in dogs and cats with gastric Helicobacter spp. •  H. canis in dogs may be associated with diarrhea. •  Vomiting, weakness, and sudden death reported in puppy with hepatic H. canis.

Physical Examination Findings

•  Usually unremarkable. •  Dehydration due to vomiting or diarrhea.

CAUSES Gastric Helicobacter spp.

•  H. felis, H. heilmannii, and H. baculiformis have been identified in cats. •  H. felis, H.

bizzozeronii, H. salomonis, H. heilmannii, H. bilis, H. cynogastricus, and Flexispira rappini identified in dogs.

Enterohepatic Helicobacter spp.

•  H. bilis, H. canis, H. cinaedi, and Flexispira rappini identified in feces from normal and diarrheic dogs. •  H. cinaedi identified in one cat; its significance is unknown. •  H. canis reported in one dog with acute hepatitis.

RISK FACTORS Poor sanitary conditions and overcrowding may facilitate spread.

­

OTHER LABORATORY TESTS

•  Examination of impression smears of gastric

mucosa or gastric washings using MayGrünwald-Giemsa, Gram, or Diff-Quik® stain is sensitive for Helicobacter spp.; cannot distinguish between different HLOs. •  Rapid urease test—requires gastric biopsy specimen. •  13C-urea breath or blood test reliable in identifying infected dogs; not commercially available. •  Bacterial culture requires special techniques and media and is impractical. •  PCR of DNA extracted from biopsy specimens or from gastric juice. •  Serologic tests (ELISA) measure circulating immunoglobulin (Ig) G in serum; cannot distinguish between HLOs. •  Histopathology enables definitive diagnosis of infection, but cannot distinguish between different HLOs. IMAGING Abdominal radiography, ultrasonography usually normal. DIAGNOSTIC PROCEDURES •  Gastric helicobacteriosis—in cases of Helicobacter spp.–associated gastritis, endoscopy may reveal superficial nodules that suggest hyperplasia of lymphoid follicles, diffuse gastric rugal thickening, punctate hemorrhages, erosions. •  Hepatic helicobacteriosis—hepatic biopsy/histopathology (Warthin-Starry staining) and culture. PATHOLOGIC FINDINGS •  Identification of HLOs requires special staining of tissue samples with Warthin-Starry or modified Steiner stain; routine H&E staining may reveal larger HLOs, but smaller organisms are often missed. •  In cases of Helicobacter spp.–associated gastric disease— lymphocytic-plasmacytic gastritis and lymphoid follicle hyperplasia; rarely neutrophilic infiltrates; gastric ulcers have not been reported in dogs and cats. •  In cases of H. canis– associated hepatitis—hepatocellular necrosis; infiltration of hepatic parenchyma with mononuclear cells, and spiral-shaped to curved bacteria predominantly in biliary canaliculi.

DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  High prevalence of Helicobacter spp. in dogs and cats. Therefore, exclusion of other causes of gastric disease and a positive identification of Helicobacter spp. are crucial before a diagnosis of GI disease due to Helicobacter spp. can be suspected. •  Gastric helicobacteriosis— distinguish from other causes of vomiting. •  Intestinal helicobacteriosis—distinguish from other causes of diarrhea. •  Hepatic helicobacteriosis—distinguish from other causes of hepatobiliary disease. CBC/BIOCHEMISTRY/URINALYSIS

•  May reflect fluid and electrolyte abnormalities secondary to vomiting and/or diarrhea. •  May

indicate hepatic disease in patients with H. canis–associated hepatitis.

­

TREATMENT

APPROPRIATE HEALTH CARE •  Pathogenicity of Helicobacter spp. in dogs and cats is unclear; therefore, there are no generally accepted guidelines for treatment of HLO infections in dogs and cats. •  Currently there is no indication for treating asymptomatic infected animals. •  Eradication of gastric HLO should only be considered in infected dogs and cats that have compatible clinical signs that cannot be attributed to another disease process. NURSING CARE Fluid therapy in dehydrated patients.

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592

Blackwell’s Five-Minute Veterinary Consult

Helicobacter spp.  DIET Easily digestible diets in patients with GI disease signs. CLIENT EDUCATION Explain difficulty of establishing a definitive diagnosis, high prevalence of infections with HLOs in normal dogs and cats, potential for recurrence, and zoonotic potential, though minimal, of these infections.

H ­

MEDICATIONS

•  A triple therapy (combination of two

antibiotics and one antisecretory drug) is effective in humans with H. pylori infection, with cure rates of approximately 90%. •  Combination therapy may eliminate Helicobacter spp. infections in dogs and cats less effectively than in humans. •  Treat for 2–3 weeks. DRUG(S) OF CHOICE Antibiotics (Two Antibiotics with One Antisecretory Agent)

•  Clarithromycin (dogs: 5 mg/kg PO q12h; cats: 62.5 mg/cat PO q12h). •  Metronidazole

(dogs: 11–15 mg/kg PO q12h; cats: 12.5 mg/kg PO q12h). •  Amoxicillin (22 mg/kg PO q12h). •  Azithromycin (5 mg/kg PO q24h). •  Tetracycline (20 mg/ kg PO q8h). •  Bismuth subsalicylate has mucosal protectant, anti-endotoxemic, and weak antibacterial properties; it remains unclear which property is responsible for its beneficial effects in HLO infections (0.22 mL/kg of 130 mg/15 mL solution of Pepto-Bismol PO q4–6h). Antisecretory Agents (One with Two Antibiotics)

•  Omeprazole (0.7–1 mg/kg PO q12h). •  Famotidine (0.5 mg/kg PO q12–24h). •  Ranitidine (1–2 mg/kg PO q12h).

(continued)

ALTERNATIVE DRUG(S) Patients with HLO infections and gastritis that do not respond to antibiotic therapy usually are given immunosuppressive therapy for inflammatory bowel disease with gastric involvement.

­

FOLLOW-UP

PATIENT MONITORING •  Serologic tests not useful to confirm eradication of gastric HLOs—serum IgG titers may not decrease for up to 6 months after infection cleared. •  If vomiting persists or recurs after cessation of combination therapy, endoscopic biopsy to determine whether infection has been successfully eradicated indicated. PREVENTION/AVOIDANCE Avoid overcrowding and poor sanitation. EXPECTED COURSE AND PROGNOSIS •  Efficacy of therapeutic regimens currently employed in dogs and cats for eradicating Helicobacter spp. infections is questionable. •  Metronidazole (20 mg/kg PO q12h), amoxicillin (20 mg/kg PO q12h), and famotidine (0.5 mg/kg PO q12h) for 14 days eradicated Helicobacter spp. in 6 of 8 dogs when evaluated 3 days post treatment; all dogs were recolonized by day 28 after treatment. •  Clarithromycin (30 mg/cat PO q12h), metronidazole (30 mg/cat PO q12h), ranitidine (20 mg/cat PO q12h), and bismuth subsalicylate (40 mg PO q12h) for 4 days were effective in eradicating H. heilmannii in 11 of 11 cats by 10 days; 2 cats were reinfected 42 days post treatment. •  Amoxicillin (20 mg/kg PO q8h), metronidazole (20 mg/kg PO q8h), and omeprazole (0.7 mg/kg PO q24h) for 21 days transiently eradicated H. pylori in 6 cats; all were reinfected 6 weeks post treatment. (Note: this dose of metronidazole has potential for toxicity.)

Intestinal and Hepatic Helicobacter spp. in Dogs

Combination of amoxicillin and metronidazole may be effective.

­

CONTRAINDICATIONS Hypersensitivity to drug therapy.

ASSOCIATED CONDITIONS Other gastric diseases.

AGE-RELATED FACTORS Gastric HLOs appear to be acquired at a young age. ZOONOTIC POTENTIAL

•  High prevalence of Helicobacter spp. in

dogs and cats raises the possibility that household pets may serve as a reservoir for transmission of Helicobacter spp. to human beings. •  H. pylori, H. heilmannii, and H. felis have been isolated from humans with gastritis. •  H. fennelliae and H. cinaedi have been isolated from immunocompromised humans with proctitis and colitis. •  H. cinaedi and H. canis have been associated with septicemia in humans. •  H. pylori has not been identified in pet dogs or cats. PREGNANCY/FERTILITY/BREEDING Avoid metronidazole and tetracycline in pregnant animals. SYNONYMS •  Gastric spiral bacterial. •  Gastrospirillum. SEE ALSO

•  Gastritis, Chronic. •  Vomiting, Chronic.

ABBREVIATIONS

•  GI = gastrointestinal. •  HLO = Helicobacter-like organism. •  Ig = immunoglobulin. •  SPF = specific pathogen free.

­Suggested Reading

Leib MS, Duncan RB, Ward DL. Triple antimicrobial therapy and acid suppression in dogs with chronic vomiting and gastric Helicobacter spp. J Vet Intern Med 2007, 21:1185–1192. Simpson KW, Neiger R, DeNovo R, et al. The relationship of Helicobacter spp. infection to gastric disease in dogs and cats. J Vet Intern Med 2000, 14:223–227. Author Jan S. Suchodolski Consulting Editor Amie Koenig Acknowledgment The author and book editors acknowledge the prior contribution of Jörg M. Steiner.

MISCELLANEOUS Client Education Handout available online



593

Canine and Feline, Seventh Edition

Hemangiopericytoma •  Incisional biopsy and histopathology may

­

 BASICS

OVERVIEW •  A soft tissue sarcoma (STS) arising around blood vessels in subcutaneous tissue. •  Also known as perivascular wall tumor. •  Locally invasive—microscopic disease often extending beyond gross visible tumor margins. •  Metastasizes in less than 15% of patients with grade I/II (low/intermediate-grade) STS and less than 44% of patients with grade III (high-grade) STS. SIGNALMENT •  Common in dogs, rare in cats. •  More common in large-breed than small-breed dogs. •  Middle-aged to older dogs and cats. SIGNS Historical Findings

•  Typically, slow-growing, nonpainful,

fluctuant to firm mass (weeks to months). •  Rapid growth uncommon unless high-grade or associated with hemorrhage. •  Local tumor growth can interfere with limb function. Physical Examination Findings

•  Subcutaneous soft tissue mass, more

frequently located on extremity than on trunk. •  Soft, fluctuant, or firm. •  Nonpainful unless ulcerated or invading into deeper structures (muscle, nerve, bone). •  Generally adhered to underlying tissue. •  Regional lymph node metastasis uncommon. CAUSES & RISK FACTORS Large-breed dogs at increased risk.

­

 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Other sarcomas such as fibrosarcoma, peripheral nerve sheath tumor, myxosarcoma, malignant fibrous histiocytoma, histiocytic sarcoma, hemangiosarcoma. •  Lipoma and other subcutaneous tumors—benign and malignant. CBC/BIOCHEMISTRY/URINALYSIS Usually normal. IMAGING

•  Thoracic radiographs recommended before

treatment, although metastasis uncommonly identified. •  Contrast-enhanced CT or MRI may be recommended to determine local extent of disease and optimize surgical treatment and radiation therapy planning. DIAGNOSTIC PROCEDURES

•  Fine-needle aspiration and cytology may

provide tentative diagnosis, though cells do not exfoliate well given mesenchymal origin.

be used to confirm diagnosis, determine grade of tumor, and plan treatment approach. •  Immunohistochemistry evaluation of biopsy can aid in differentiation from other mesenchymal tumors. •  Regional lymph node evaluation (cytology or histopathology) appropriate for high-grade tumors or if regional lymphadenomegaly detected.

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 TREATMENT

Surgical Considerations

•  Early, aggressive, en bloc surgical excision is treatment of choice. •  Microscopically, cancer

cells extend beyond gross tumor borders.

•  Pseudocapsule composed of compressed cancer cells is common. •  Excise tumor en

bloc; if peeled out, healthy bed of cancer cells (pseudocapsule) is left as residual disease. •  Submit entire sample to pathologist for surgical margin evaluation; applying ink to surgical borders is advised. •  Limb amputation may be necessary with tumors affecting appendicular extremities that may be otherwise unresectable. •  Rib resection or abdominal wall resection may be required for tumors of trunk. Radiation Therapy Considerations

•  Adjuvant radiation therapy should be

considered following either planned marginal resection or unplanned incomplete resection. •  Radiation therapy most effective when directed at microscopic disease— either preoperatively or as postoperative full-course fractionated protocol. •  As single modality treatment for macroscopic disease, radiation therapy considered palliative— may be used to decrease pain and slow tumor growth.

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 MEDICATIONS

DRUG(S) OF CHOICE •  Doxorubicin-based chemotherapy not consistently reported as beneficial, but remains recommended after excision of high-grade (grade III) tumor. •  Low-dose chemotherapy (metronomic) with piroxicam and cyclophosphamide may help delay local recurrence when sarcoma incompletely resected. •  Novel therapeutic options may be available—contact veterinary oncologist for potential updated treatments. •  Analgesic therapy should be administered as needed if pain or discomfort present. CONTRAINDICATIONS/POSSIBLE INTERACTIONS N/A

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 FOLLOW-UP

PATIENT MONITORING •  If complete surgical resection achievable and tumor categorized as low-grade, tumor regrowth or metastases unlikely and continued patient monitoring may not be necessity. •  If surgical resection incomplete or tumor categorized as high-grade, further treatment should be considered and patient should be monitored for local regrowth and distant metastases, with repeat physical exam and thoracic radiographs every 3 months. EXPECTED COURSE AND PROGNOSIS

•  Local recurrence, metastasis, and overall

survival time greatly affected by surgical margin assessment and histological grade. •  Cure from disease possible when surgery aggressive and surgical margins tumor-free, especially with grade I and II tumors—median survival approaches 2 years with low-grade (I) STSs of extremities treated with surgery alone. •  Local recurrence considered inevitable if treatment not aggressive; increased risk for metastatic disease especially with high-grade (III) tumors. •  Longterm tumor control with radiation therapy after surgically debulking tumor gives 1–5-year control rates of 60–85%. •  Incomplete surgical excision should be managed with either second aggressive surgery or radiation therapy as soon as possible; low-dosage chemotherapy (metronomic) is another option.

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 MISCELLANEOUS

ABBREVIATIONS •  STS = soft tissue sarcoma.

­Suggested Reading

Bray JP. Soft tissue sarcoma in the dog – part 1: a current review. J Small Anim Pract 2016, 57:510–519. Elmslie RE, Glawe P, Dow SW. Metronomic therapy with cyclophosphamide and piroxicam effectively delays tumor recurrence in dogs with incompletely resected soft tissue sarcomas. J Vet Intern Med 2008, 22:1373–1379. Kuntz CA, Dernell WS, Poswers BE, et al. Prognostic factors for surgical treatment of soft tissue sarcomas in dogs: 75 cases (1986–1996). J Am Vet Med Assoc 1997, 211:1147–1151. Stefanello D, Morello E, Roccabianca P, et al. Marginal excision of low-grade spindle cell sarcoma of canine extremities: 35 dogs (1996–2006). Vet Surg 2008, 37:461–465. Author Matthew R. Berry Consulting Editor Timothy M. Fan Acknowledgement The author and book editors acknowledge the prior contributions of Phyllis Glawe and Louis-Philippe de Lorimier.

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Hemangiosarcoma, Bone more sensitive screening for pulmonary metastasis.

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H

 BASICS

OVERVIEW •  A highly metastatic malignant tumor of endothelial cell precursors. •  Primary bone hemangiosarcoma (HSA) is rare and accounts for 15 kg; 1 mg/kg IV 15 kg; 1 mg/kg IV for dogs 15 kg, 1 mg/kg IV for dogs 5–10 RBC/hpf ) and possibly infectious agents seen in urine sediment. •  Crystalluria in some patients with urolithiasis. OTHER LABORATORY TESTS •  Coagulation testing to rule out coagulopathy. •  Bacterial culture of urine to identify UTI. •  Examination of ejaculate to identify prostatic disease. IMAGING Ultrasonography, radiography, and possibly contrast radiography are useful in localizing the underlying cause. Cystoscopy often required to diagnose renal hematuria. DIAGNOSTIC PROCEDURES

•  Biopsy of mass lesion. •  Vaginourethrocystoscopy in females or

urethrocystoscopy in males and females.

Genitalia

•  Metabolic—estrus, benign prostatic hyperplasia. •  Neoplastic—transmissible

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 TREATMENT

•  Hematuria may indicate a serious disease process. •  Urolithiasis and renal failure may require diet modification. •  UTI may be

associated with another disease that also requires treatment—local (e.g., neoplasia and urolithiasis) or systemic (e.g., hyperadrenocorticism and diabetes mellitus). •  Renal hematuria may be treated via endoscopic sclerotherapy; nephrectomy should not be performed.

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 MISCELLANEOUS

AGE-RELATED FACTORS •  Neoplasia tends to occur in older animals. •  Immune-mediated diseases tend to occur in young adult animals. ZOONOTIC POTENTIAL Leptospirosis SEE ALSO

•  Coagulation Factor Deficiency. •  Crystalluria. •  Cylindruria. •  Dysuria, Pollakiuria, and Stranguria. •  Feline Idiopathic Lower Urinary Tract Disease. •  Glomerulonephritis. •  Hemoglobinuria and Myoglobinuria. •  Lower Urinary Tract Infection, Bacterial. •  Lower Urinary Tract Infection, Fungal. •  Nephrolithiasis. •  Prostatitis and Prostatic Abscess. •  Prostatomegaly. •  Proteinuria. •  Pyelonephritis. •  Thrombocytopenia.

ABBREVIATIONS •  DIC = disseminated intravascular coagulation. •  FIP = feline infectious peritonitis. •  RBC = red blood cell. •  TVT= transmissible venereal tumor. •  UTI = urinary tract infection.

­Suggested Reading

Bartges JW. Discolored urine. In: Ettinger SJ, Feldman EC, eds., Textbook of Veterinary Internal Medicine, 7th ed. St. Louis, MO: Elsevier, 2008, pp. 164–168. Author Joseph W. Bartges Consulting Editor J.D. Foster  Client Education Handout available online



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Red, brown, or black urine Occult blood negative Bilirubin Drugs Porphyrins Dyes Others

Occult blood positive Urine sediment examination

No RBCs

Normal serum color

Ammonium sulfate test or protein electrophoresis

RBCs

Pink color to serum Hemoglobin

Lower urinary tract signs No Hx trauma

No lower urinary tract signs

Negative RBC lysis in urine Hemoglobin

Hx trauma Female or castrated male

Normal Abnormal TVT Estrus Vaginitis Pyuria absent

Urine Protein:creatinine 24-hour protein Radiography Ultrasonography Biopsy

Abnormal

Variable pain Prostatic hyperplasia Prostatic neoplasia Prostatic cysts Prostatic metaplasia

Vaginal smear Culture Radiography Ultrasonography Ejaculate examination Culture Biopsy

Urine culture IVP Ultrasonography

Severe proteinuria Glomerulonephritis

Male: palpate prostate

Examine external genitalia

Positive Myoglobin

Pyuria present Upper UTI with or without nephroliths

H

Mild or absent proteinuria Radiography IVP Ultrasonography

Abnormalities Neoplasia Nephroliths Ureteroliths Cysto renal disease

Normal Cystitis Urethritis Uroliths Neoplasia Bladder malformation

Painful Prostatitis Prostate abscess

Urine culture Radiography Ultrasonography Biopsy

Radiography Ultrasonography Ejaculate examination Culture Aspiration/Biopsy

No abnormalities Drugs Coagulopathy Renal trauma Idiopathic renal hematuria Telangiectasia of Welsh corgis Vascular disease

Figure 1. Algorithm for the diagnosis of red, brown, or black urine.

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Hemoglobinuria and Myoglobinuria

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 BASICS

DEFINITION Hemoglobinuria—presence of free hemoglobin (HGB) within urine secondary to intravascular hemolysis. Myoglobinuria—presence of myoglobin (MGB) within urine secondary to myocyte injury or death. Presence of either protein causes discoloration of urine (pigmenturia) as well as positive blood result during reagent test strip analysis of urine, a semiquantitative measurement of heme. PATHOPHYSIOLOGY •  Hemoglobinuria—intravascular hemolysis or destruction of RBCs within vessels releases HGB from damaged red blood cells (RBCs). HGB, if free within plasma, can cause tissue injury. Haptoglobin, protein made by the liver, acts as HGB recovery system and binds free HGB. Resulting HGB–haptoglobin complexes too large to be cleared by glomerular filtration and so are removed primarily by splenic macrophages. Excessive intravascular hemolysis can saturate haptoglobin, resulting in free HGB in plasma, known as hemoglobinemia. Free HGB (4 heme-containing chains, 64,000 daltons) rapidly dissociates into unstable dimers (32,000 daltons) and passes freely through glomerular basement membrane leading to hemoglobinuria. Hemoglobinuria imparts pink, dark amber, red, or red-brown discoloration to urine. Methemoglobinemia causes analogous disease process. •  Myoglobinuria—MGB is single hemecontaining chain (approximately 17,500 daltons). MGB able to carry oxygen without oxidation of ferrous (Fe2+) to ferric (Fe3+) iron due to interaction of heme with protein portion (globin). Myocyte injury and/or death releases MGB. Unlike free HGB, MGB is freely and rapidly cleared by glomerulus given its small size and absence of carrier protein, so plasma remains colorless even in face of significant myocyte death. Myoglobinuria causes brown or red-brown discoloration to urine. •  Renal tubular injury—presence of excess HGB or MGB in renal tubular fluid may result in kidney injury. Within tubules, acidic environment favors HGB or MGB precipitation, cast formation, and tubular obstruction. Both HGB and MGB are endocytosed by renal tubular epithelial cells. Globin, from HGB, is degraded within the cell, while free heme is catabolized by heme oxygenase, resulting in lipid peroxidation and Fe deposition. MGB also causes lipid peroxidation, but without release of free iron (via redox cycling of heme center). Alkaline conditions reported to prevent MGB-induced lipid peroxidation by stabilizing reactive ferryl MGB complex and also decreasing MGB precipitation in renal tubules. Free HGB also

scavenges nitric oxide, leading to vasoconstriction of afferent renal arteriole and secondary hypoperfusion and ischemic injury. SYSTEMS AFFECTED Renal/urologic—HGB, methemoglobin, and MGB can result in tubular injury, especially with concurrent decreased renal perfusion and acidic conditions. GENETICS Some predispositions relating to breeds; see Signalment. INCIDENCE/PREVALENCE N/A GEOGRAPHIC DISTRIBUTION N/A SIGNALMENT Dog

•  Hemoglobinuria secondary to phospho­

fructokinase (PFK) deficiency in affected English springer spaniel, American cocker spaniel, English cocker spaniel, cocker spaniel, wachtelhund, whippet. •  Hemoglobinuria uncommonly seen in Bedlington terriers with inherited copper toxicosis and copper release from hepatocytes causing hemolysis. •  Myoglobinuria secondary to exertional myopathy or rhabdomyolysis in racing sled dogs and greyhounds. •  Pigmenturia rarely reported secondary to exertional lactic acidosis in English sheepdog. Cat

Hemoglobinuria secondary to neonatal isoerythrolysis in neonatal blood type A or AB kittens born to blood type B queens. SIGNS General Comments

Clinical signs diverse and related to specific causes; see Causes. Historical Findings

Patient breed, exposure to certain drugs or foreign objects, and recent exertion particularly important; see Causes.

fluid administration, shearing or microangiopathy due to disseminated intravascular coagulopathy, D. immitis caval syndrome. •  Toxin-induced RBC membrane damage— snake or spider venom; Shiga toxin in hemolytic uremic syndrome. •  Infection of RBCs—dogs: babesiosis; cats: Mycoplasma hemofelis infection, Cytauxzoon felis. •  Systemic infection—leptospirosis, E. coli or other Shiga toxin-producing bacteria causing hemolytic uremic syndrome, bacterial endocarditis. •  Immune-mediated RBC destruction—­ idiopathic or secondary immune-mediated hemolytic anemia, incompatible blood transfusions in dogs or cats, neonatal isoerythrolysis. •  Deficiencies—hypophosphatemia. •  Genetic associated—PFK deficiency, copper toxicity. •  Other—retroperitoneal hemorrhage, trans­ fusion of inappropriately stored RBC units. Myoglobinuria

•  Exertional—extreme exercise. •  Myositis—infectious (e.g., toxoplasmosis,

neosporosis), eosinophilic inflammatory (German shepherd dog, other breeds), immune mediated. •  Genetics-associated—X-linked muscular dystrophy; glycogenoses (storage diseases); mitochondrial abnormalities. •  Toxins (loss of membrane integrity)—snake or spider venom. •  Physical—ischemia, crush injury, compartment syndrome. •  Excessive body temperature (e.g., heat stroke, prolonged seizures). RISK FACTORS

•  Genetic predisposition (see Signalment). •  Exposure to specific drugs, toxins. •  Certain infectious agents. •  Extreme physical exertion. •  Heat stroke. •  Snake or spider venom.

Physical Examination Findings

­

may include pale mucous membranes, tachycardia, icterus. •  Findings associated with muscle damage may include muscle tenderness, swelling, bruising.

DIFFERENTIAL DIAGNOSIS •  Pigmenturia can result from hematuria, hemoglobinuria, methemoglobinuria, or myoglobinuria. Positive heme reaction of urine reagent test strip detects heme portion in intact RBCs, free HGB, and free MGB. Use of CBC, biochemical, and urinalysis results can aid in differentiation. •  Hematuria—supported by increased (>5/hpf) RBCs in urine sediment examination and clear plasma or serum. •  Hemoglobinuria—supported by 4–5 × upper reference limit [URL]) CK with slower increases in AST; plasma and serum expected to be clear. ◦◦ Urinalysis findings include absence of hematuria, possible proteinuria.

False-Negative Heme Urine Reagent Strip (Dipstick) Results

OTHER LABORATORY TESTS •  Ammonium sulfate precipitation test unreliable and recommendation to use CBC and chemistry changes for differentiation. •  Incubation of whole blood with new methylene blue to detect Heinz bodies. •  Methemoglobin detection confirms toxin as oxidant. •  Increased serum copper or zinc concentration. •  DNA test for PFK deficiency.

(Vitamin C).

IMAGING Abdominal radiographs or ultrasound— metallic objects in gastrointestinal tract.

False-Positive Heme Urine Reagent Strip (Dipstick) Results

•  Urine contact with bleach or hydrogen

peroxide. •  Highly pigmented urine or marked bilirubinuria. •  Large amounts of bromide or iodide. •  Bacteriuria.

•  Urine exposure to formalin. •  Patients taking captopril or ascorbic acid •  Failure to mix urine specimen prior to

chemical/dipstick reagent testing or using supernatant for testing.

Disorders That May Alter Laboratory Results

Hyposthenuria or exposure of urine to extreme cold or heat in patients with hematuria may cause in vitro RBC lysis (no intact RBCs in sediment) with positive heme urine reagent dipstick reaction; could be misinterpreted as hemoglobinuria or myoglobinuria. Valid if Run in Human Laboratory?

DIAGNOSTIC PROCEDURES

•  Liver biopsy and copper quantification. •  Genetic testing for PFK.

­

 TREATMENT

•  IV fluid therapy to maintain renal perfusion. •  Avoid hyperventilation in PFK-deficient

patients.

•  See Causes for specific treatments.

Yes

CBC/BIOCHEMISTRY/URINALYSIS •  Intravascular hemolysis and hemoglobinuria: ◦◦ CBC support includes anemia, which may be preregenerative or regenerative depending on onset of hemolysis, RBC ghost cells, RBC inclusions (Heinz bodies to support oxidative injury, infectious agents), RBC poikilocytes (eccentrocytes and pyknocytes support oxidative injury, spherocytes support immune-mediated mechanisms, schistocytes support ­microangiopathic causes, some toxins), possibly increased mean cell HGB concentration (MCHC) or discrepant increase in HGB concentration from hemoglobinemia, red-colored plasma.

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 MEDICATIONS

DRUG(S) OF CHOICE Vary with underlying cause. ALTERNATIVE DRUGS N/A

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 FOLLOW-UP

PATIENT MONITORING PCV, urinalysis and urine sediment, serum creatinine, CK, urine production. POSSIBLE COMPLICATIONS Renal tubular injury may develop.

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 MISCELLANEOUS

AGE-RELATED FACTORS Neonatal isoerythrolysis. ZOONOTIC POTENTIAL •  Leptospirosis. •  Toxoplasmosis. PREGNANCY/FERTILITY/BREEDING N/A SYNONYMS Pigmenturia SEE ALSO See Causes. ABBREVIATIONS

•  AST = aspartate aminotransferase •  CK = creatine kinase •  HGB = hemoglobin •  MCHC = mean cell HGB concentration •  MGB = myoglobin •  PCV = packed cell volume •  PFK = phosphofructokinase •  RBC = red blood cell •  URL = upper reference limit.

­Suggested Reading

Bartges JW. Hematuria and other conditions causing discolored urine. In: Ettinger SJ, Feldman EC, eds., Textbook of Veterinary Internal Medicine, 7th ed. St. Louis, MO: Elsevier, 2010, pp. 164–168. Owen JL, Harvey JW. Hemolytic anemia in dogs and cats due to erythrocyte enzyme deficiencies. Vet Clin North Am Small Anim Pract 2012, 42(1):73–84. Shelton DG. Rhabdomyolysis, myoglobinuria, and necrotizing myopathies. Vet Clin North Am Small Anim Pract 2004, 34:1469–1482. Sink C, Weinstein NM. Routine urinalysis: chemical analysis. In: Sink C, Weinstein NM, Practical Veterinary Urinalysis. Ames, IA: Wiley Blackwell, 2012, pp. 42–45. Stockham SL, Scott SA. Erythrocytes. In: Fundamentals of Veterinary Clinical Pathology, 2nd ed. Ames, IA: Blackwell, 2008, pp. 112–192. Author Nicole M. Weinstein Consulting Editor J.D. Foster Acknowledgment The author and book editors acknowledge the prior contributions of Cheryl L. Swenson, Carl A. Osborne, and Eugene E. Nwaokorie.

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Hemothorax

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 BASICS

OVERVIEW •  Accumulation of blood in pleural space. •  Can develop acutely due to trauma or a coagulopathy, or neoplasia; may also be chronic. •  Cardiovascular and respiratory systems commonly affected. SIGNALMENT Any age, breed, or sex of dog and cat; younger dogs more commonly affected with anticoagulant rodenticide and trauma, older dogs more commonly affected with cancer. SIGNS

•  Peracute to acute onset—hypovolemic signs

can occur before sufficient blood volume accumulates in the pleural space to impair respiration. •  In chronic cases, larger volumes of blood may accumulate. •  Respiratory distress, tachypnea; honking cough is possible in dogs with rodenticide poisoning; ecchymoses along ventral cervical and thoracic inlet areas. •  Pale mucous membranes. •  Weakness and collapse. •  Weak, rapid pulse. CAUSES & RISK FACTORS

•  Trauma—bleeding artery or vein of the

thoracic wall, mediastinum, or thoracic spine; damaged heart, lungs, thymus, or diaphragm; herniated abdominal viscera (liver or spleen). •  Neoplasia—involving any structure adjacent to the pleural cavity; rib tumors are particularly common. •  Coagulopathies—can be congenital or acquired; rodenticide ingestion common. •  Lung lobe torsion. •  Acute thymic hemorrhage in young animals. •  Dirofilaria immitis, Spirocerca lupi, Angiostrongylus vasorum.

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Nonhemorrhagic pleural effusions—­ chylothorax; pyothorax; modified transudates; transudates. •  Congestive heart failure. CBC/BIOCHEMISTRY/URINALYSIS

•  PCV and hemoglobin—reflect blood loss

after initial fluid compartment shifts have occurred. •  Platelet count may be low (~100,000) with acute blood loss. •  Very low platelet count (5 days inappetence and enteral route unavailable. •  No benefit shown for specific supplementation of oral branched-chain amino acids. •  No need to restrict fat. CLIENT EDUCATION

•  HE—usually episodic; relapse risk exists if

underlying cause cannot be eliminated.

•  Train owner to administer enemas to abate

acute-onset HE and judiciously adjust medications used to control ammonia formation and absorption PRN. •  APSS—see Portosystemic Shunting, Acquired. •  PSVA—see Portosystemic Vascular Anomaly, Congenital. SURGICAL CONSIDERATIONS

•  PSVA—medically treat HE before

anesthesia and surgery.

•  APSS—do not ligate this vasculature.

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 MEDICATIONS

DRUG(S) OF CHOICE •  Treatment goals include increasing dietary protein tolerance; altering enteric environment and microbiome to modify generation of encephalogenic toxins (e.g., endotoxin and ammonia); reduce bioavailability or colonic dwell time of substances provoking HE. •  Antibiotics—first choice: systemic metronidazole (7.5 mg/kg q12h) or amoxicillin (esp. cats, 12.5–25 mg/kg PO q8–12h); caution if using neomycin (10– 22 mg/kg PO q12h) chronically as enteric absorption may cause renal and otic toxicity. •  Local instillation of antimicrobials used in retention enemas—same dosages as oral but do not administer by both oral and rectal routes. •  In humans, rifaximin is as effective as single agent or combined lactulose and neomycin in management of HE and has favorable safety and tolerability profile; is expensive; no data regarding utility for management of HE in animals; suggested dose in dogs 5 mg/kg PO q24h or q12h. •  Nonabsorbable-fermentable carbohydrates— lactulose, lactitol, or lactose in milk products if patient is lactase deficient; lactulose most commonly used: start at 0.5 mL/kg q8–12h



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and titrate up to therapeutic goal of 2 or 3 soft stools/day; may also administer as enema for acute HE or patients in coma after cleansing enemas remove debris; note: concurrent use of neomycin may suppress bacterial fermentation of lactulose thereby diminishing its benefit. •  Probiotics combined with nonabsorbablefermented carbohydrates may be advantageous for altering gut flora and provoking cathartic effect. •  Enemas—cleansing enemas (warmed polyionic fluids) mechanically cleanse the colon (10–15 mL/kg, until clear return); retention enemas deliver fermentable substrates, antimicrobials, or solution directly altering colonic pH: diluted lactulose, lactitol, or lactose (1 : 2 in water); antimicrobials mixed with water: metronidazole or neomycin but do not exceed PO dose, do not dose PO and rectally; diluted betadine (1 : 10 in water, rinse well in 15 min); diluted vinegar (1 : 10 in water) modifies colonic pH, alters colonic flora. •  Zinc supplementation—two urea cycle enzymes require zinc and portosystemic shunting may deplete body zinc reserves (shown in humans); measure baseline plasma zinc (dose 1–3 mg/kg elemental zinc PO using zinc acetate) then titrate dose using sequential plasma zinc measurements to avoid >800 μg/dL (causes hemolysis), but document an increase in baseline plasma zinc concentration inferring positive zinc balance; note: plasma zinc does not reflect liver zinc concentration. •  Cerebral edema—complicates acute HE; head-up posture (15–20° incline); mannitol (1 g/kg diluted in saline, over 30 min); nasal oxygen; N-acetylcysteine (140 mg/kg IV diluted 1 : 2 in saline given through nonpyrogenic filter unless sterile IV form used, then 70 mg/kg q8h); glucocorticoids controversial, may promote enteric bleeding but some evidence supports reduced astrocyte swelling. •  Salvage therapies for intractable HE (experimental)—l-ornithine-l-aspartate (humans, rats: 180–300 mg/kg/day divided into three doses); l-carnitine (100 mg/kg PO/ IV) may attenuate HE-associated hyperammonemia. •  If epileptic seizure activity—Keppra® (levetiracetam; dose 20–60 mg/kg IV given 1 : 1 dilution over 15 min) is preferred anticonvulsant; secondary anticonvulsants include zonisamide (caution: rare idiopathic hepatotoxicity) or KBr (complicates fluid

therapy) as preferred anticonvulsants to phenobarbital; avoid benzodiazepines in HE.

and manage systemic infection or inflammation.

CONTRAINDICATIONS

POSSIBLE COMPLICATIONS Permanent neurologic damage may develop in chronic recurrent HE but uncommon; most often encountered in PSVA with acute severe HE.

•  Avoid drugs metabolized by the liver or

rapidly removed by first-pass extraction—or if used, judiciously reduce dose. •  Avoid alfaxalone. •  Avoid benzodiazepines. PRECAUTIONS •  Consider altered drug pharmacokinetics— reduced first-pass extraction due to porto­ systemic shunting; reduced protein binding if hypoalbuminemia, and compromised hepatic metabolism. •  Use anesthetics, sedatives, tranquilizers, potassium-wasting diuretics, analgesics, highly protein-bound drugs (if hypoalbuminemic) cautiously; reduce dose. •  If possible, avoid drugs predominantly reliant on hepatic metabolism, biotransform­ ation, and excretion in patients with acquired chronic liver disease associated with APSS vs. those with PSVA or ductal plate malformationassociated APSS where metabolic or synthetic failure less likely. •  Avoid drugs or reduce dose if highly reliant on first-pass hepatic extraction if PSVA or APSS. POSSIBLE INTERACTIONS Drugs that influence p450 cytochrome hepatic metabolism, e.g., cimetidine, chloramphenicol, barbiturates, ketoconazole, may provoke adverse drug interactions.

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 FOLLOW-UP

PATIENT MONITORING •  Reevaluate patient at-home behavior and cognitive function, body condition, muscle mass, and weight; owner should record diary of progress and video abnormal behaviors. •  Monitor albumin and glucose. •  Adjust nutrition to optimize protein allowance and avoid sarcopenia. •  Monitor electrolytes—especially potassium if PU/PD or if diuretics prescribed. PREVENTION/AVOIDANCE Avoid provocative conditions—dehydration, azotemia, constipation, endoparasitism, enteric or oral bleeding, infusion of stored blood, hemolysis, meal-related ammonia challenge, urinary tract infections, hypokalemia, hypomagnesemia, alkalemia;

EXPECTED COURSE AND PROGNOSIS

•  Depends on underlying disorder. •  Acute or chronic hepatic failure—may

be fully or partially reversible, or patient may die.

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 MISCELLANEOUS

AGE-RELATED FACTORS PSVA—surgical outcome may be good in young and old patients. SYNONYMS •  Hepatic coma. •  Portosystemic encephalopathy. SEE ALSO

•  Arteriovenous Malformation of the Liver. •  Ductal Plate Malformation (Congenital

Hepatic Fibrosis).

•  Hepatic Failure, Acute. •  Hepatitis, Chronic. •  Portosystemic Shunting, Acquired. •  Portosystemic Vascular Anomaly,

Congenital.

ABBREVIATIONS

•  APSS = acquired portosystemic shunt. •  BBB = blood–brain barrier. •  GI = gastrointestinal. •  HE = hepatic encephalopathy. •  PSVA = portosystemic vascular anomaly. •  PU/PD = polyuria/polydipsia. •  TSBA = total serum bile acids.

­Suggested Reading

Hajihambi A, Arias N, Sheikh M, et al. Hepatic encephalopathy: a critical current review. Hepatol Int 2018, 12 (Suppl 1):S135–S147. Lidbury JA, Cook AK, Steiner JM. Hepatic encephalopathy in dogs and cats. J Vet Emerg Crit Care 2016, 26:471–487. Author Sharon A. Center Editor Kate Holan  Client Education Handout available online

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Hepatic Failure, Acute •  Renal/urologic—renal tubule damage from

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H

 BASICS

DEFINITION •  Severe acute hepatic injury incapacitating ability to meet synthetic, metabolic, detoxification needs. •  Sudden loss of >75% of functional hepatic mass due to acute, massive hepatic necrosis. •  May lead to catastrophic multiorgan dysfunction/failure in previously healthy individual; may rapidly progress to death. PATHOPHYSIOLOGY

•  Necrosis—secondary to insufficient

perfusion, hypoxia, hepatotoxins (drugs, other xenobiotics, toxins), heat excess, infectious agents. •  Severity of hepatic dysfunction depends on insult type and lobular (zonal) distribution. •  Reduced perfusion or hypoxia usually affects zone 3 (pericentral or centrilobular region). •  Ingested toxins—affect zone where toxin metabolized or toxic product formed, or where specific organelle tropism or propensity for oxidative injury (copper accumulation increases zone 3 vulnerability). •  Panlobular hepatic necrosis leading to acute liver failure uncommon; e.g., idiosyncratic drug toxicity: dogs—zonisamide, phenobarbital, primidone, diphenylhydantoin, nonsteroidal anti-inflammatory drugs (NSAIDs, e.g., carprofen), xylitol; cats—diazepam; dogs or cats—sulfa-antibiotics; primary toxins: dogs and cats—primary copper accumulation, acetaminophen; dogs—zonisamide, xylitol, cycad (sago palm), cheese tree (Glochidion ferdinandi) roots, blue-green algae, Amanita mushrooms, aflatoxin; infectious disease: dogs—leptospirosis, infectious canine hepatitis. •  Accompanied by enzyme leakage and markers of impaired liver function, hyperbilirubinemia, acute-onset splanchnic hypertension due to sinusoidal or centrilobular collapse. •  Lethal organ failure associated with coagulopathy, enteric hemorrhage, acuteonset hepatic encephalopathy (HE). •  Hepatic failure—associates with myriad metabolic derangements: altered glucose homeostasis, protein synthesis (albumin, transport proteins, procoagulants, anticoagulants), detoxification capabilities. SYSTEMS AFFECTED •  Hepatobiliary—hepatocellular necrosis; hepatic failure, jaundice. •  Nervous—HE; cerebral edema. •  Gastrointestinal (GI)—vomiting; diarrhea; melena; hematochezia due to acute splanchnic hypertension ± coagulopathy. •  Hemic/lymphatic/immune—pro- and anticoagulant factor imbalances; disseminated intravascular coagulation (DIC).

certain toxins or physiologic vasoconstriction; tubular injury: copper associated hepatopathy, leptospirosis, xylitol toxicity, NSAID toxicity. •  Hyperdynamic circulatory status—low systemic and pulmonary vascular resistance, increased cardiac output and metabolic rate, systemic hypotension; associates with endotoxemia, TNF-α, dehydration, and splanchnic hypertension. INCIDENCE/PREVALENCE Variable depending on preexistent liver disease: hepatocellular copper accumulation, chronic immune-mediated hepatitis, cholangitis. SIGNALMENT Species

More common in dog than cat. Breed Predilections

Breeds with apparent predisposition to chronic hepatitis and copper associated hepatopathy (e.g., Labrador retriever, Doberman pinscher, Bedlington terrier) may have higher risk, e.g., Labrador retrievers and NSAID toxicity enhanced by copper associated hepatopathy. SIGNS •  Acute-onset nonspecific clinical signs; lethargy, inappetence, GI disturbances (vomiting, small intestinal diarrhea may be bloody), polyuria/polydipsia (PU/PD). •  Tender hepatomegaly. •  Bleeding tendencies. •  Jaundice. •  HE. •  Seizures. CAUSES Drugs

•  See Hepatotoxins. •  Drug-related toxicities intrinsic (direct) or

idiosyncratic (unpredictable, unrelated to dose) consequent to immune-mediated hypersensitivity or metabolic injury.

Thermal Injury

•  Heat stroke. •  Whole-body hyperthermia cancer

treatment.

Hepatic Hypoxia

•  Thromboembolic disease, shock, DIC. •  Acute circulatory failure from any cause. •  Acute centrilobular necrosis (zone 3).

RISK FACTORS

•  Administration of potentially hepatotoxic

substance or drug.

•  Exposure to environmental toxins (e.g.,

Amanita mushroom, foodborne aflatoxin, cycad, cheese tree roots, blue-green algae), artificial sweetener—xylitol (gum, candy): dogs). •  Enzyme inducers (e.g., phenobarbital)—may increase risk for toxicities by enhancing xenobiotic toxin formation, e.g., acetaminophen toxicity greatly enhanced by phenobarbital.

•  Indiscriminate substance ingestion—

puppies; polyphagic animals.

­

 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Severe acute pancreatitis or gastroenteritis— differentiated via laboratory tests and imaging. •  Acutely decompensated chronic liver disease—distinguished by review of medical records, blood tests, abdominal US, liver biopsy. CBC/BIOCHEMISTRY/URINALYSIS

•  Anemia and panhypoproteinemia—bleeding,

marrow toxicity, direct enteric toxicity. •  Thrombocytopenia—bleeding, DIC, portal hypertension. •  Liver enzyme activity—high acute alanine aminotransferase, and aspartate aminotransferase; smaller increases in alkaline phosphatase and γ-glutamyltransferase. •  Hypoglycemia—grave prognosis (esp. cats). •  Hypocholesterolemia—impaired synthesis or enteric loss with hemorrhage. •  Normal to low blood urea nitrogen concentration—reduced urea cycle function, PU/PD. •  Hyperbilirubinemia—initially absent. •  Bilirubinuria may precede hyperbilirubinemia— always abnormal in cats. •  Ammonium urate crystalluria signifies hyperammonemia, hepatic insufficiency, or portosystemic shunting. •  Acquired Fanconi syndrome—granular casts and renal glucosuria indicate proximal tubule injury (e.g., carprofen, copper, leptospirosis, other toxicities esp. in dogs). OTHER LABORATORY TESTS

•  Total serum bile acids (TSBA)—high values

indicate hepatic dysfunction, cholestasis, or portosystemic shunting. •  Plasma ammonia concentration—high values coincide with high TSBA, confirm hepatic insufficiency; hyperammonemia inconsistent but reflected by ammonium biurate crystalluria; hyperammonemia may reflect concurrent myonecrosis. •  Coagulation tests—coagulation factor deficiencies, platelet dysfunction, low fibrinogen, low antithrombin or protein C activity, and DIC suggest severe liver failure, decompensated DIC, or enteric losses with hemorrhage. IMAGING

•  Abdominal radiography—may identify

normal to slightly enlarged liver ± effusion.

•  Abdominal US—may disclose nonhepatic

disorders (e.g., pancreatitis), altered circulation (ratio hepatic vein : portal vein), altered liver echogenicity or surface contour reflecting chronic injury (e.g., remodeling



Canine and Feline, Seventh Edition

Hepatic Failure, Acute

(continued)

implicated by heterogeneous liver texture, nodularity, or hepatofugal portal blood flow); rule out biliary obstruction as source of hyperbilirubinemia. •  Brain MRI—may disclose early cerebral edema (not commonly done). DIAGNOSTIC PROCEDURES

•  Liver biopsy—confirms necrosis,

characterizes lesion zonal distribution.

•  Fine-needle liver aspirate may identify

hepatocellular degeneration, copper accumulation, dysplastic hepatocytes observed with cycad or aflatoxin ingestion; canalicular cholestasis; many toxins lead to microvesicular hepatocellular lipid vacuolation. PATHOLOGIC FINDINGS •  Gross—slightly enlarged, mottled liver. •  Microscopic—confirms necrosis; zonal involvement; may assist in determining underlying cause: hypoxia leading to zone 3 necrosis; certain toxins cause zone 1 or 3 necrosis; reticulin staining confirms zonal involvement, retention, or loss of reticulin substructure that orchestrates organized regeneration.

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 TREATMENT

APPROPRIATE HEALTH CARE Inpatient—intensive care needed. NURSING CARE •  Caution: delay inserting central catheters until bleeding diatheses controlled with vitamin K1, fresh frozen plasma (FFP), or fresh whole blood; no advantage to prophylactic FFP administration as may contribute to onset of HE and cerebral edema. •  Fluids—non–lactate-containing; initially at resuscitation rate; monitor peripheral BP, pulse oximetry; mixed acid-base disturbances common. •  Colloid replacement—when low oncotic pressure from bleeding and protein loss; plasma always preferred; synthetic colloids second line; avoid dextran 70 and hetastarch (may promote bleeding) and human albumin (may induce fatal acute allergic reaction). •  Potassium, phosphate, glucose—supplement as appropriate; low phosphate, potassium, glucose aggravate HE and other clinical signs, complicating critical supportive care. •  Fluid regimen—adjust for maintenance needs after achieving euvolemia; typically provide ⅓ normal maintenance rate with polyionic crystalloids if concurrently giving slow CRI of synthetic colloid; avoid colloids if possible as leak from microvasculature (exacerbated with some toxicities that affect endothelium) and disturb signaling that triggers albumin and transporter protein synthesis. •  Supplemental oxygen—if pulse oximetry ≤94% saturation.

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•  If suspect cerebral edema—use 30° head-up

elevation, consider mannitol, other interventions. •  Predisposition to infection from enteric bacterial translocation—cover with broadspectrum antimicrobials; patient may not manifest fever or leukocytosis with infection; sepsis/systemic inflammatory response syndrome—major risks for cerebral edema. •  Early administration of N-acetylcysteine may improve microvascular perfusion, tissue oxygenation, and mitigate oxidative damage (see below). ACTIVITY Restricted activity—conserves energy and metabolites for healing and regeneration. DIET

•  Intractable vomiting—withhold PO food

until controlled; antiemetics (see below). •  When enteric nutrition contraindicated (somnolent patient) use partial or total parenteral nutrition (TPN) until enteral feeding route established; 80% of hepatocytes. •  Untreated—leads to progressive metabolic dysregulation, hepatic failure, and death. •  Develops secondary to a primary disease or condition causing anorexia or catabolism; idiopathic HL is uncommon: a cause is usually discoverable. PATHOPHYSIOLOGY

•  Cats have a unique propensity to

accumulate triglyceride-filled hepatocellular vacuoles. •  Causal factors—negative energy and protein balance with increased peripheral fat mobilization. •  Cytosolic triglyceride vacuoles cause severe cholestasis and jaundice via canalicular compression and associated hepatic organelle dysfunction. •  Hepatic failure—with rare evidence of hepatic encephalopathy (HE). SYSTEMS AFFECTED •  Hepatobiliary. •  Gastrointestinal—anorexia; vomiting. •  Musculoskeletal—peripheral muscle wasting (sarcopenia) and fat mobilization. •  Nervous—HE, ptyalism, moribund status. •  Hemic/lymphatic/immune—abnormal red blood cell (RBC) shapes (poikilocytes), Heinz body hemolysis. •  Renal/urologic—potassium wasting; renal tubule triglyceride accumulation. INCIDENCE/PREVALENCE Most common severe hepatopathy in North America causing jaundice in pet cats. GEOGRAPHIC DISTRIBUTION Worldwide SIGNALMENT Species

Cats, rarely dogs (toy-breed failure-to-thrive puppies), juveniles with lysosomal or glycogen storage disease; may develop in small-breed puppies with portosystemic vascular anomaly (PSVA). Breed Predilection

N/A

Mean Age and Range

Middle-aged adult cats—median age 8 (range: 1–16 years).

progressing to collapse. •  Ptyalism. •  Neck ventriflexion—weakness, electrolyte depletions (potassium, phosphate), thiamine deficiency. •  Underlying disease or illness causing hyporexia/anorexia → hepatic lipidosis. Physical Examination Findings

•  Jaundice. •  Hepatomegaly. •  Dehydration. •  Weakness—neck ventriflexion, recumbency. •  Ptyalism. •  Collapse ←→ obtunded (signs of HE). •  Others, depending on underlying primary

disease.

CAUSES “Idiopathic” Hepatic Lipidosis

Idiopathic = uncommon; antecedent health problems discoverable in >85% of cases causing anorexia or malassimilation; remainder have food deprivation often attributable to adverse social interactions, environmental cause. Secondary Hepatic Lipidosis

•  Primary liver disease—PSVA; cholangitis/

cholangiohepatitis syndrome (CCHS); extrahepatic bile duct obstruction (EHBDO); cholelithiasis; neoplasia. •  Gastrointestinal—obstruction; neoplasia; inflammatory bowel disease (IBD); pancreatitis. •  Urogenital disease—renal failure, chronic interstitial nephritis (CIN), lower urinary tract syndromes. •  Neurologic conditions—cannot eat. •  Infectious diseases—toxoplasmosis; feline infectious peritonitis (FIP); feline immunodeficiency virus (FIV)– or feline leukemia virus (FeLV)–related disorders. •  Hyperthyroidism. •  Vitamin B12 deficiency and deficiency of other water-soluble vitamins may predispose cats to HL as a result of disrupted metabolism as one factor. •  Many other systemic conditions or toxins can provoke anorexia and lead to HL. •  Rapid weight loss protocols or change to restricted-calorie diet the cat refuses to eat. RISK FACTORS

•  Obesity. •  Anorexia, negative nitrogen balance. •  Catabolism or rapid weight loss. •  Water-soluble vitamin deficiency.

SIGNS

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Historical Findings

DIFFERENTIAL DIAGNOSIS •  Primary liver disease—CCHS, cholelithiasis, EHBDO, or neoplasia (esp.

•  Anorexia or hyporexia, weight loss, sarcopenia. •  Vomiting, diarrhea or constipation, jaundice.

CBC/BIOCHEMISTRY/URINALYSIS

•  Hematology—poikilocytes common;

nonregenerative anemia; hemolytic anemia (severe hypophosphatemia or Heinz bodies). •  Biochemistry—hyperbilirubinemia; high alkaline phosphatase (ALP), alanine aminotransferase (ALT), ± aspartate aminotransferase (AST) activity; normal or mild increase in 𝛾-glutamyltransferase (GGT) if no primary necro-inflammatory ductal disorder (i.e., biliary, pancreatic); low blood urea nitrogen (BUN); normal creatinine; variable glucose (hypoglycemia rare); variable cholesterol, albumin, globulins; hypokalemia; hypophosphatemia, increased ketones (beta-hydroxybutyrate); lactic acidosis. •  Urinalysis—bilirubinuria, lipiduria, and unconcentrated urine common. OTHER LABORATORY TESTS

•  Prolonged coagulation times—prothrombin

time (PT), activated partial thromboplastin time (APTT), activated clotting time (ACT); fibrinogen usually normal. •  Hyperammonemia—uncommon. •  Serum bile acids—high before hyperbilirubinemic; redundant test if hepatobiliary jaundice. •  B12 deficiency. IMAGING Survey Abdominal Radiography

•  Hepatomegaly. •  May note features of underlying disorder.

Abdominal US

•  Diffuse hyperechoic hepatic parenchyma,

hepatomegaly.

•  Look for primary disease causing HL.

DIAGNOSTIC PROCEDURES

•  Fine-needle liver aspiration cytol-

Predominant Sex

N/A

lymphosarcoma) differentiated by abdominal US, liver aspiration, and liver biopsy. •  PSVA—diagnosis by US or colorectal scintigraphy, lab testing. •  Hepatic toxoplasmosis or FIP—liver biopsy, serology, immunohistochemistry. •  Pancreatitis—differentiated by US, serum tests, pancreatic aspiration cytology, gross inspection, biopsy. •  Gastrointestinal disease—IBD differentiated by bowel biopsies; obstruction differentiated by abdominal survey or contrast radiography and US. •  Toxicities—suspected based on history (e.g., oral diazepam, acetaminophen, methimazole). •  Hyperthyroidism—serum thyroid panel, absence of jaundice.

 DIAGNOSIS

ogy—>80% hepatocytes display severe cytosolic lipid vacuolation; biopsy rarely needed to confirm HL. •  Definitive diagnosis HL—based on history, clinical features, high ALP, diffuse hyperechoic hepatic parenchyma, severe hepatocyte lipid

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Hepatic Lipidosis 

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vacuolation on aspiration cytology; however, cannot rule out primary hepatic disorders (e.g., CCHS, EHBDO, PSVA) with these tests. •  Liver biopsy—definitive diagnosis of underlying “primary” liver disorders; done only if poor response to therapy or high GGT; caution: stabilize cat before anesthesia and liver biopsy. •  Vitamin K1 (0.5–1.5 mg/kg SC/IM) three doses at 12h intervals, before aspiration sampling, liver biopsy, jugular vein catheterization, cystocentesis, or feeding appliance insertion. PATHOLOGIC FINDINGS •  Gross—diffuse hepatomegaly, smooth surface, friable greasy consistency, yellow/pale color with reticulated appearance; sample floats in formalin. •  Microscopic—diffuse, severe hepatocellular lipid vacuolation; large (macrovesicular) or small (microvesicular) vacuolation; type of vacuolation lacks prognostic value.

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 TREATMENT

APPROPRIATE HEALTH CARE •  Inpatient—recumbent cats or those with neck ventriflexion and anorectic. •  Discharge for home care—see Patient Monitoring. •  Frequent reevaluations imperative. •  Outpatient—reduces stress and thereby facilitates recovery in some cats. NURSING CARE

•  Balanced polyionic fluids—avoid lactate

and dextrose supplementation; 0.9% NaCl preferred. •  Potassium chloride supplementation essential (see Hypokalemia). •  Phosphate supplements usually needed (see Hypophosphatemia) at initial feeding; often started prophylactically, see below. •  Magnesium supplements rarely needed. Correct Hypophosphatemia

•  Serum phosphate 2 mg/dL; caution: judiciously reduce IV potassium chloride supplements concurrently given in fluids; monitor potassium. Correct Hepatic and Circulating GSH Depletion

•  Low liver glutathione (GSH) confirmed

in HL; routine GSH measurements not available.

(continued) •  Crisis intervention for low hepatic GSH or

Heinz body anemia—N-acetylcysteine (NAC) 140 mg/kg IV, then 70 mg/kg IV, 10% solution diluted 1 : 2 in saline; administered over 20 min otherwise may provoke hyperammonemia. •  When enteral feeding established, change to S-adenosylmethionine (SAMe) 200 mg/cat PO q24h; need for dosing on empty stomach complicates use. ACTIVITY Physical activity (walking), when possible, may increase gastric motility when gastroparesis complicates feeding (chronic vomiting). DIET

•  Nutritional support—cornerstone of recovery. •  High-protein, high-calorie balanced feline

diet essential. •  Energy—50–60 kcal/kg ideal weight/day; gradual transition to full energy requirement over 3–7 days; feed multiple small meals/day or trickle feed through esophageal feeding tube (E-tube). •  Forced alimentation usually required; caution: oral forced feeding may provoke food aversion syndrome. •  Correct hypokalemia and hydration before commencing feeding; associated gastroparesis may lead to vomiting and potential for aspiration pneumonia. •  Tube feeding—initially by nasogastric tube (first 1–2 days after electrolyte and vitamin deficiency improved), transition to E-tube after hydration and electrolyte status improves, and vitamin K1 protocol administered. •  Avoid laparotomy for gastric feeding tube insertion; cats with HL have high risk for mortality with general anesthesia and surgery; E-tube preferable. •  Cautiously offer PO food daily to assess interest. •  Human stress formula enteral diets (not recommended)—require supplemental arginine (or citrulline), and taurine; use feline formulated liquified diet with vitamin supplements. Supplements

•  Supplements improve survival in severely

affected cats. •  Water-soluble vitamins—in IV fluids; generally 2 mL/L. •  Thiamin—50–100 mg/day, give PO rather than SC/IM, also add via water-soluble vitamins mixed in IV fluids. •  Vitamin B12—initially 0.25–1 mg IM/SC once): determine chronic vitamin B12 needs by sequential B12 values (weekly, q2 weeks, to monthly then quarterly intervals). •  Medical-grade l-carnitine (250–500 mg/ day); over-the-counter carnitine supplements have wide variability in bioavailability; Carnitor® (liquid medical-grade carnitine) recommended.

•  Taurine 250–500 mg/day PO. •  Vitamin E 10 IU/kg/day PO in food- use

water-soluble form initially.

•  Thiol donors IV NAC, PO SAMe—as above. •  Potassium gluconate (for hypokalemia) PO,

reduce fluid potassium supplements.

•  Marine oil in food 2000 mg q24h.

CLIENT EDUCATION

•  Warn client—sequential biochemical

assessments needed to monitor recovery.

•  Educate client about feeding tube use/care

and need for chronic use (up to 4–6 months).

•  Advise client—recurrence unlikely; liver

function will not be chronically compromised.

SURGICAL CONSIDERATIONS

•  Avoid surgical interventions until

normalization of hydration, electrolyte depletions, and supplements of vitamins provided, Heinz body anemia alleviated. •  Exploratory laparotomy and liver biopsy— only indicated if failure to improve on described interventions or marked increase in GGT activity to identify underlying disorders; biopsy liver, pancreas, stomach, and small bowel if explored; lymph nodes if enlarged.

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 MEDICATIONS

DRUG(S) OF CHOICE •  Vitamin K1—recommended for all cats with suspected HL; see above, avoid overdosage. •  Drugs to ameliorate HE (see Hepatic Encephalopathy), rarely. •  Emesis control—metoclopramide: for vomiting, nausea, gastroparesis (0.2–0.5 mg/kg SC q8h 30 min before feeding, or as CRI IV drip at 0.01–0.02 mg/kg/h or 1–2 mg/kg/day); dolasetron or ondansetron; or maropitant (1 mg/ kg IV/SC/PO q24h 5 days max); pantoprazole to avert esophageal damage secondary to vomiting (0.5–1.0 mg/kg q12–24h). •  Systemic antibiotics—as appropriate for suspected infection. CONTRAINDICATIONS/PRECAUTIONS

•  Downward adjust dosages of medications

relying on hepatic metabolism or excretion.

•  Avoid benzodiazepines and barbiturates—

may provoke HE.

•  Appetite stimulants do not provide

dependable energy intake in cats with HL; some produce sedation; diazepam may cause rare fulminant hepatic failure. •  Avoid injectable medications with propylene glycol carrier; may lead to hemolysis in cats with low GSH. •  Ursodeoxycholic acid—likely not beneficial; may promote taurine deficiency. •  Dextrose supplements—may provoke hepatic triglyceride accumulation.



Hepatic Lipidosis

(continued)  •  Avoid tetracyclines or stanozolol—promote

hepatocyte triglyceride vacuolation. •  Avoid recurrent or prolonged use of propofol—may provoke hemolysis (12h after infusion) esp. in cats with Heinz body anemia; HL cats may recover slowly; alternatively use gas anesthesia.

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 FOLLOW-UP

PATIENT MONITORING •  Bodyweight and condition, hydration, electrolytes; judicious adjustment of energy, fluid, electrolyte, and vitamin provisions essential. •  Serum bilirubin—predicts recovery. •  Reduced lactate and ketones reconcile with metabolic improvement. •  Liver enzyme activity—do not predict recovery. •  Discharge for home care—when vomiting controlled, gastroparesis resolved, bilirubin declining, patient ambulatory, and tubefeeding apparatus problem-free. •  Tube feeding—discontinued only after confirmed voluntary food consumption. PREVENTION/AVOIDANCE •  Obesity—prevent; weight reduction must not exceed 2% bodyweight per week. •  Caution owner to verify food intake during weight loss regimens and at-home stress. POSSIBLE COMPLICATIONS

•  Feeding tube malfunction or obstruction—

tube obstructions relieved with papaya juice, carbonated soft drink, or pancreatic enzyme slurry; 15 min dwell time, warm water flush. •  Rare HE after dietary support introduced. •  Unremitting HL can lead to lethal hepatic failure.

•  Untreatable underlying causal disorder.

EXPECTED COURSE AND PROGNOSIS •  Optimal response to tube feeding and nutritional supplements—recovery in 3–6 weeks. •  Therapy as described—85% recovery in severely affected animals with controllable primary disease process that provoked HL. •  Underlying disease influences outcome. •  HL rarely recurs. •  HL does not cause chronic liver dysfunction, hepatitis, persistent remodeling.

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 MISCELLANEOUS

ASSOCIATED CONDITIONS •  Primary liver disorders. •  Pancreatitis. •  Malassimilation—various causes but IBD predominant. •  Diabetes mellitus—relatively uncommon. •  Neoplasia—hepatic and systemic. •  HE (rare). •  Systemic illness limiting food intake. SYNONYMS

•  Fatty liver syndrome. •  Hepatosteatosis. •  Feline hepatic vacuolation. •  Vacuolar hepatopathy. •  Vacuolar degeneration.

SEE ALSO

•  Cholangitis/Cholangiohepatitis Syndrome. •  Hepatic Encephalopathy.

•  AST = aspartate aminotransferase. •  BUN = blood urea nitrogen. •  CCHS = cholangitis/cholangiohepatitis

syndrome.

•  CIN = chronic interstitial nephritis. •  EHBDO = extrahepatic bile duct

obstruction.

•  FeLV = feline leukemia virus. •  FIV = feline immunodeficiency virus. •  GGT = gamma glutamyltransferase. •  GSH = glutathione. •  HE = hepatic encephalopathy. •  HL = hepatic lipidosis. •  IBD = inflammatory bowel disease. •  NAC = N-acetylcysteine. •  PSVA = portosystemic vascular anomaly. •  PT = prothrombin time. •  RBC = red blood cell. •  SAMe = S-adenosylmethionine.

­Suggested Reading

Center SA. Feline hepatic lipidosis. Vet Clin North Am Small Anim Pract 2005, 35:225–269. Center SA, Warner KL, Randolph JF, et al. Influence of dietary supplementation with (L)-carnitine on metabolic rate, fatty acid oxidation, body condition, and weight loss in overweight cats. Am J Vet Res 2012, 73:1002–1015. Kuzi S, Segev G, Kedar S, et al. Prognostic markers in feline hepatic lipidosis: a retrospective study of 71 cats. Vet Rec. 2017, 181(19):512. doi: 10.1136/ vr.104252 Author Sharon A. Center Consulting Editor Kate Holan

ABBREVIATIONS

•  ACT = activated clotting time. •  ALP = alkaline phosphatase. •  ALT = alanine aminotransferase. •  APTT = activated partial thromboplastin time.

 Client Education Handout available online

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Hepatic Nodular Hyperplasia and Dysplastic Hyperplasia SIGNALMENT HNH

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 BASICS

OVERVIEW Hepatic Nodular Hyperplasia (HNH)

•  Benign parenchymal feature in middle-aged

H

to older dogs; nonencapsulated, ≤2 cm (rarely up to 5 cm), expansile nodule of hepatocellular hyperplasia, maintaining a modified lobular architecture with recognizable central and portal elements that are irregularly spaced, organized hepatic cord structure 1 cell wide, without marginal parenchymal collapse or fibrosis (is not a regenerative nodule), smooth margins; hepatocyte phenotype may be similar to surrounding parenchyma but may contain glycogen of lipid vacuoles. •  May associate with increased liver enzymes in elderly dogs, especially alkaline phosphatase (ALP). •  Clinical concern derives from association with increased liver enzyme activity and US detection of hepatic nodules or hepatic nodularity during exploratory surgery. •  Variable US appearance. •  Biopsy specimens must include affected and unaffected liver for appropriate interpretation. •  Nodular hyperplasia may be mistaken for regeneration secondary to chronic hepatitis or hepatocellular neoplasia (adenoma) with needle core biopsies or when only nodular tissue without normal hepatic tissue is sampled. Hepatocellular Dysplastic Hyperplasia (HDH) •  Potentially preneoplastic proliferative

hepatocellular foci in dogs with glycogen-type vacuolar hepatopathy (VH); nonencapsulated, variably sized, reduced reticulin substructure, expansile nodules of nonvacuolated hepatocytes forming wide (2 cells wide, normal = 1 cell width) disorganized hepatic cords, an irregular (serrated) margin interfacing with adjacent “normal VH” affected hepatocytes, and lacking remodeled marginal lesions (fibrosis, parenchymal collapse). •  Associates with VH-related increased liver enzymes, dominated by increased ALP activity. •  Recognized as an antecedent hepatic lesion in dogs developing hepatocellular carcinoma (e.g., Scottish terriers, also other breeds) and is seemingly associated with increased sex hormone concentrations (androgens, progestins). •  Variable US appearance depending on size, number, distribution. •  May be mistaken for nodular regeneration without special stains to detail reticulin substructure and collagen fibril deposition.

•  Age-related lesion. •  Nodules develop by 6–8 years of age; one

study documented lesions in all geriatric dogs >14 years of age.

HDH

•  Associated with glycogen-type VH. •  Reflects adrenal hyperplasia syndromes.

SIGNS Physical Examination Findings

•  HNH does not cause clinical illness. •  Large nodules that rupture and bleed or

nodules impairing hepatic sinusoidal perfusion likely represent misdiagnosed hepatic adenomas or well-differentiated hepatocellular carcinoma. •  HDH is associated with glycogen-type VH syndromes (see Glycogen-Type Vacuolar Hepatopathy). CAUSES & RISK FACTORS

•  HNH etiology—unknown; metabolic

factors, prior injurious events. In humans associated with infarcts, but no evidence of this in dogs. •  HDH etiology—may represent hormonal influence promoting neoplastic transformation (sex hormone–related adrenal hyperplasia).

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Necroinflammatory liver disease— regenerative nodular hyperplasia involves the entire liver; formation of irregular nodules of variable size that are segregated by parenchymal collapse, often marginated by fibrous connective tissue; demonstrate loss of lobular architecture, sinusoidal fibrosis, reduced reticulin substructure, and wide disorganized hepatic cords. •  Neoplasia—hepatic adenoma: mass lesions with margins reflecting expansile compression on normal adjacent liver, encapsulated, hepatic cords double wide, disorganized, reduced reticulin substructure, and minimal atypia. Hepatocellular carcinoma: single or multiple confluent or separate mass lesions, margins reflecting irregular expansile compression on normal adjacent liver, partially encapsulated, variable width of disorganized hepatic cords >2 cells, multiple phenotypes differing from adjacent normal tissue, variable atypia (may be well differentiated), may display pseudoglandular pattern associated with giant canaliculi, well-vascularized with arterial twigs; retention of some normal lobular elements possible (primarily at the periphery).

CBC/BIOCHEMISTRY/URINALYSIS

•  CBC—no association with HNH; for HDH

see Glycogen-Type Vacuolar Hepatopathy. •  Biochemistry profile—increased serum ALP activity may be encountered with HNH and HDH; may range from 2.5- to 16-fold normal; higher with HDH and VH syndrome, see Glycogen-Type Vacuolar Hepatopathy; usually normal total protein, albumin, bilirubin, and cholesterol. •  Urinalysis—no consistent findings. OTHER LABORATORY TESTS Total serum bile acids (TSBA)—usually normal, unless lesions are diffuse and severe. IMAGING

•  Abdominal radiography—no abnormalities

except hepatomegaly with HDH due to VH.

•  Abdominal US—variable echogenicity

relating to histologic features, nodule number and size, and associated VH. HNH often not noted until liver grossly inspected at surgery or laparoscopy. DIAGNOSTIC PROCEDURES

•  Aspiration cytology—may yield normal

hepatocytes, hepatocytes with cytosolic rarefication and fragility consistent with VH (glycogen retention), or cells with discrete lipid (triglyceride) vacuoles (HNH); occasional binucleate hepatocytes may reflect cell proliferation or other concurrent disease (common in portosystemic ­vascular anomalies/ microvascular dysplasia); hepatocytes may be small with size variation in HDH. Liver biopsy—­collection of a needle biopsy specimen may not clearly differentiate HNH lesion because of small specimen size; definitive diagnosis requires targeted sampling of a large enough tissue specimen to include lesion and adjacent normal hepatic tissue. HDH may be recognized on needle samples. •  Recommended biopsy methods—­laparoscopy, open-wedge biopsy during laparotomy, or multiple 14-G needle samples. •  Special stains—reticulin staining illustrates hepatocyte reticulin substructure, lobular collapse/remodeling, and changes associated with nodule margins. Masson’s trichrome staining illustrates collagen deposition and remodeling typical of regenerative nodules secondary to chronic liver injury; periodic acid-Schiff staining with and without amylase predigestion confirms excess glycogen in vacuolated hepatocytes (see Glycogen-Type Vacuolar Hepatopathy). PATHOLOGIC FINDINGS

•  HNH gross—single or multiple mass

lesions, rarely >2 cm in diameter; color similar to adjacent normal hepatic tissue or paler if vacuolated with glycogen or lipid. •  HDH gross—single or multiple lesions, usually small, may appear darker colored compared to adjacent tissue. Microscopic— see above.



Canine and Feline, Seventh Edition (continued)



Hepatic Nodular Hyperplasia and Dysplastic Hyperplasia •  Scottish terrier syndrome does not

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 TREATMENT

•  Usually none required; rupture of large

nodules indicates hepatocellular carcinoma misdiagnosis; may necessitate blood transfusion and emergency mass excision. Palliate or alleviate underlying cause of VH. •  HDH—recommend biochemical assessments for rising ALP or alanine aminotransferase (ALT) that may indicate transformation of mass lesion to a neoplastic phenotype; US inspection of adrenal glands for adrenomegaly or nodules, US surveillance for expanding mass lesions that should be surgically removed; assess pituitary adrenal axis for typical or atypical hyperadrenocorticism; if increased sex hormones >2.5 × upper reference interval consider adrenal modulation with agent that does not increase sex hormones.

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 MEDICATIONS

DRUG(S) OF CHOICE •  HDH—if increased sex hormones, progressive VH, nodule formation, increasing ALP, or confirmed hepatocellular carcinoma (after mass resection), consider adrenal modulation with a drug that does not increase sex hormone concentrations (Lysodren® or mitotane); trilostane increases sex hormone concentrations and would be inappropriate.

respond to adrenal modulation; instead use surveillance to detect emerging hepatocellular carcinoma.

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 FOLLOW-UP

PATIENT MONITORING •  Quarterly biochemical profiles. •  Sequential abdominal US to evaluate progression of hepatic nodules. •  See Glycogen-Type Vacuolar Hepatopathy for related disorders. POSSIBLE COMPLICATIONS Distinction of HNH from neoplastic foci is not possible based only on clinical, laboratory, or imaging data, although lesions >2 cm are unlikely to be this diagnosis. EXPECTED COURSE AND PROGNOSIS More extensive numbers of nodules may develop in some dogs with HNH and HDH; HDH predicts risk for primary hepatocellular neoplasia, which requires surveillance and surgical treatment.

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 MISCELLANEOUS

SEE ALSO •  Cirrhosis and Fibrosis of the Liver. •  Glycogen-Type Vacuolar Hepatopathy.

•  Hepatitis, Chronic. •  Hepatocellular Adenoma. •  Hepatocellular Carcinoma.

ABBREVIATIONS

•  ALP = alkaline phosphatase. •  ALT = alanine aminotransferase. •  HDH = hepatic dysplastic hyperplasia. •  HNH = hepatic nodular hyperplasia. •  TSBA = total serum bile acids. •  VH = vacuolar hepatopathy.

­Suggested Reading

Cortright CC, Center SA, Randolph JF, et al. Clinical features of progressive vacuolar hepatopathy in Scottish Terriers with and without hepatocellular carcinoma: 114 cases (1980–2013). J Am Vet Med Assoc 2014, 245:797–808. Sepesy LM, Center SA, Randolph JF, et al. Vacuolar hepatopathy in dogs: 336 cases (1993–2005). J Am Vet Med Assoc 2006, 229:246–252. Stowater JL, Lamb CR, Schelling SH. Ultrasonographic features of canine hepatic nodular hyperplasia. Vet Radiol 1990, 31:268–272. Author Sharon A. Center Consulting Editor Kate Holan Acknowledgment The author and book editors acknowledge the prior contribution of Sean P. McDonough.

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Hepatitis, Chronic •  Sinusoidal hypertension—leads to hepato­

­

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 BASICS

DEFINITION •  Hepatic injury associated with active chronic necroinflammatory liver injury; “chronic active hepatitis” should not be used. •  Nonsuppurative inflammation—most common; lymphocytes, plasma cells, macrophages, occasional neutrophils. •  Chronicity—progressive remodeling, regenerative nodule formation, evolving sinusoidal fibrosis with location dependent on zonal tropism of inflammation; changes eventuate in cirrhosis. PATHOPHYSIOLOGY

•  A multitude of initiating events or agents

cause hepatic injury; damage to cell and/or organelle membranes usually involves oxidative injury; activated cytokines and cell-mediated immune responses widen and perpetuate inflammation; hepatic neoepitopes may become targeted foci. •  Initial injury may include infectious agents, toxins, xenobiotics, or pathologic Cu accumulation; with exception of Cu-mediated injury, cause often remains undetermined. •  Inflammatory cells—predominantly lymphocytes, fewer Kupffer cells (resident hepatic sinusoidal macrophages), and variable neutrophils are initial effectors. •  Injury zone demarcates area of predominant necroinflammatory damage—zone 1 (periportal) common to idiopathic hepatitis or inflammation involving portal tract structures; zone 3 incriminates Cu, nonsteroidal anti-inflammatory drug (NSAID), other xenobiotic or toxin-mediated injury, or repeated ischemic/hypoxic insult; panlobular inflammation common. •  Lesion progression—variable, may include portal and periportal lymphoplasmacytic infiltrates with interface hepatitis (inflammation breaching limiting plate of portal tract), and otherwise variable lobular injury; chronic inflammation: leads to progressive fibrosis with bridging of involved zones. •  Bridging fibrosis and regenerative nodules distort lobular architecture; fibrosis, intrahepatic sinusoidal hypertension, neovascularization, and impaired hepatic function evolve into cirrhosis. •  Progressive cholestasis due to mechanical compression/distortion of bile ducts may occur. •  Cirrhosis and hepatic failure—late stage. •  Fibrosis—usually reflects chronic injury from sustained inflammation. •  Cirrhosis—associated with hepatic dysfunction, sinusoidal hypertension; intrahepatic shunting through collagenized sinusoids or neovascular pathways in fibrotic partitions that segregate regenerative nodules.

fugal portal circulation (flow away from liver); mesenteric splanchnic hypertension; development of acquired portosystemic shunt(s) (APSS); episodic hepatic encephalopathy (HE); ascites; portal hypertensive enteric vasculopathy predisposes to enteric bleeding.

SYSTEMS AFFECTED •  Hepatobiliary—inflammation; necrosis; cholestasis; fibrosis. •  Gastrointestinal (GI)—emesis; diarrhea; anorexia, portal hypertension, ascites, and propensity for enteric bleeding. •  Neurologic—HE (advanced stage, associated with APSS). •  Hemic—red blood cell (RBC) microcytosis reflects APSS; bleeding or thrombotic tendencies: failed factor or anticoagulant synthesis or activation, thrombocytopenia or thrombopathia; coagulopathies typically observed with advanced injury or severe diffuse hepatic necrosis. •  Renal/urologic—polyuria/polydipsia (PU/ PD); isosthenuria; ammonium biurate crystalluria (advanced stage with APSS and HE). •  Endocrine/metabolic—hypoglycemia if end-stage liver failure. •  Respiratory—tachypnea if tense ascites; bicavitary effusion or pulmonary edema. GENETICS

•  Breed or familial predisposition for chronic

hepatitis—Doberman pinscher, Labrador retriever, West Highland white terrier, and Dalmatian may develop chronic hepatitis secondary to pathologic Cu accumulation; cocker spaniel hepatopathy, anecdotal in other breeds or breeding lines. •  Inherited Cu associated hepatopathy only proven in Bedlington terrier— autosomal recessive, genetic test available. SIGNALMENT Species

Dog

Breed Predilection

See Genetics.

Mean Age and Range

Average age 6–8 years (range: 2–14 years). Predominant Gender

Inconsistent among reports for any breed. SIGNS General Comments

•  Initially—vague and nonspecific, often

•  PU/PD. •  Jaundice—later stage unless portal hepatitis

involves bile duct injury.

•  Ascites—late stage. •  HE—late stage, infers APSS with cirrhosis.

Physical Examination Findings

•  May be no signs in early disease. •  Lethargy, poor coat, declining body

condition.

•  Variable jaundice. •  Liver size—normal to small, depends on

chronicity.

Late-Stage Physical Findings

•  Ascites. •  HE. •  Obstructive uropathy—ammonium

biurates.

•  Bleeding or thrombotic tendencies.

CAUSES

•  Chronic necroinflammatory, oxidant, and

immune-mediated liver injury has many causes.

•  Infectious—canine hepatitis virus; lepto­

spirosis, enteric-portal bacteremia or endotoxemia affiliated with inflammatory bowel disease; accidental parenteral administration of intranasal Bordetella vaccine. •  Immune-mediated—autoimmune with positive antinuclear antibody (ANA); acquired immune sensitization, nonsuppurative inflammation. •  Toxic—Cu associated hepatopathy; acute or chronic exposure to drugs—predictable or idiosyncratic toxicity: e.g., azole antifungals, trimethoprim-sulfa, zonisamide, pheno­ barbital, primidone, phenytoin, CCNU, NSAIDs (esp. carprofen); repeat exposure to environmental or food-borne toxins, e.g., dimethylnitrosamine, aflatoxin, cycad, cyanobacteria. RISK FACTORS

•  Immunostimulants (vaccinations?) and

molecular mimicry of cell epitopes by infectious agents or infection of sinusoidal endothelium. •  Cu associated hepatopathy. •  Hepatic iron accumulation—from inappropriate supplementation. •  Xenobiotics (drugs, herbal, holistic, or Chinese remedies), inducers or inhibitors of microsomal enzymes, impaired hepatic antioxidant status; xenobiotic metabolites foster inflammation or augment direct initial liver injury.

includes lethargy and inappetence.

•  Later—relate to complications of portal

hypertension; impaired hepatic function including cholestasis.

Historical Findings

•  May be no signs in early disease or mild

lethargy.

•  Anorexia, vomiting, weight loss, reduced

body condition.

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Acute hepatitis—history, sequential biochemistry profiles or liver biopsy. •  Congenital portosystemic shunt (portosystemic vascular anomaly [PSVA]).



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(continued) •  Primary hepatic neoplasia. •  Metastatic neoplasia or carcinomatosis. •  Chronic pancreatitis. •  Other causes of abdominal effusion—

hypoalbuminemia; passive congestion; carcinomatosis; chemical peritonitis (bile, urine, pancreatitis), hepatic or nonhepatic causes of portal hypertension: see Hypertension, Portal. •  Jaundice—extrahepatic bile duct occlusion (EHBDO); bile peritonitis, cholangitis/ cholangiohepatitis syndrome, ductopenia, hemolysis. CBC/BIOCHEMISTRY/URINALYSIS Hemogram

CBC—nonregenerative anemia; RBC microcytosis if APSS; variable leukogram, occasional thrombocytopenia; low total protein if chronic disease with synthetic failure and portal hypertension causing enteric protein loss. Biochemistry

High liver enzymes; variable bilirubin, albumin, blood urea nitrogen (BUN), glucose, cholesterol; hepatic failure—suggested by low albumin, BUN, glucose, and cholesterol in absence of alternative causes. Urinalysis

Variable urine concentration; escalated bilirubinuria; ammonium biurate crystalluria if APSS. OTHER LABORATORY TESTS •  Total serum bile acids (TSBA)—variable; depends on extent of hepatic remodeling, sinusoidal hypertension, and cholestasis; superfluous test if hepatic hyperbilirubinemia. •  Ammonia intolerance—reflects APSS; insensitive to cholestasis, lability impairs accuracy. •  Coagulation tests—reflect panlobular injury, chronicity, vascular injury, impaired synthetic capacity or vitamin K adequacy; early disease: few abnormalities except possible high fibrinogen; advanced stage or severe pan­ lobular injury: single or multiple abnormalities including prolonged prothrombin, activated partial thromboplastin time, low fibrinogen, increased D-dimers. •  Low protein C or antithrombin activity— may reflect PSVA, APSS, hepatic failure, or consumptive coagulopathy. •  Abdominal effusion—chronic liver disease portal hypertension: pure or modified transudate. •  Liver tissue zinc—low with chronic disease and APSS. •  Serologic or PCR tests—possible infectious agents, e.g., leptospirosis, rickettsial diseases, Borrelia, Bartonella, endemic fungal agents. •  ANA titer—if potential for autoimmune disease; note: low-level positive titers nonspecific and more common with advanced age.

•  Immunohistochemical staining of liver

biopsy—can confirm infectious agents or phenotype of infiltrating cells (inflammatory or neoplastic). IMAGING

Abdominal Radiography

•  Microhepatia—suggests late-stage disease or

APSS causing lobular atrophy.

•  Abdominal effusion—obscures image. •  Ammonium biurate calculi—radiolucent

unless combined with radiodense minerals.

US

•  Liver size depends on disease stage. •  Normal to variable parenchymal and biliary

tract echogenicity; may note nodularity and irregular liver margins with chronicity due to regenerative nodules. •  APSS—tortuous vessels most commonly identified caudal to left kidney or near splenic vein. •  Abdominal effusion—US facilitates fluid sampling. •  Uroliths—renal pelvis or urinary bladder; may signify ammonium biurate urolithiasis but cannot differentiate mineral composition without stone analysis. •  Rule out—EHBDO; identify mass lesions; cholelithiasis; gallbladder mucocele (GBM); cholecystitis; choledochitis; cystic lesions (abscess or ductal plate malformation–related). •  Enables fine-needle aspiration—cytology and cholecystocentesis for bile collection. Colorectal/Splenoportal Scintigraphy (CRS/SPS)

•  99MTechnicium pertechnetate isotope time

activity curve displays chronologic isotope distribution: delivery to liver first = no shunting, delivery to heart first = shunting. •  CRS—sensitive, noninvasive; cannot differentiate PSVA from APSS. •  SPS—no diagnostic advantage, US-guided splenic injection, uses a lower isotope dose and therefore has faster discharge from hospital. DIAGNOSTIC PROCEDURES Aspiration Cytology

•  Fine-needle aspiration cytology—cannot

define fibrosis or nonsuppurative inflammation; cannot recommend therapy. •  Cannot definitively diagnose chronic hepatitis, hepatic fibrosis, or Cu associated hepatopathy.

Metal Analyses

•  Measure Cu, iron, and zinc concentrations

in liver (dry matter basis).

•  Low hepatic zinc associated with portosystemic

shunting requires supplementation. •  Iron commonly accumulates in necroinflammatory disorders; must be reconciled with distribution for relevance: e.g., Prussian blue staining defines distribution in macrophages (chronic inflammation) vs. predominantly in hepatocytes (hemochromatosis). •  Cu quantification and rhodanine staining— ascertains relevance to parenchymal injury. PATHOLOGIC FINDINGS

•  Gross—early: no gross change; late stage:

irregular surface contours, microhepatica, ± tortuous APSS varices. •  Microscopic—nonsuppurative inflammation in zone(s) of necroinflammatory injury; variable cholestasis and biliary hyperplasia; interface hepatitis: invasion of limiting plate; late-stage disease: fibrotic bridging partitions between or within involved zones and marginating regenerative nodules, sinusoidal dissecting fibrosis; final transition to cirrhosis. Histopathology

•  Immune-mediated hepatitis—periportal,

lobular, centrilobular, or panlobular with lymphoplasmacytic infiltrates, hepatic cord injury causing disorganization, sinusoidal fibrosis, biliary hyperplasia. •  Cu associated hepatopathy—initially centrilobular, may evolve panlobular immune-mediated hepatitis. •  Cirrhosis—diffuse, unresolvable; fibrosis, nodular regeneration distorting lobular architecture.

­

 TREATMENT

APPROPRIATE HEALTH CARE •  Inpatient—for diagnostic testing, supportive care, treatment initiation in severe illness. •  Outpatient—if condition stable at diagnosis; slowly titrated onto medical therapy.

Liver Biopsy

NURSING CARE •  Depends on underlying condition. •  Fluid therapy—balanced polyionic fluids supplemented to correct hydration, electrolyte aberrations, or hypoglycemia; restricted sodium if ascites, may require fresh frozen plasma, avoid synthetic colloids. •  Water-soluble vitamins—2 mL/L fluids. •  Ascites (see Cirrhosis and Fibrosis of the Liver).

Bacterial Culture

ACTIVITY Keep patient warm and hydrated; restricted activity may improve hepatic regeneration, euglycemia, and ascites mobilization.

•  Liver biopsy—needed for definitive diagnosis; acquire biopsies from multiple liver lobes. •  Tru-Cut® needle biopsy—use 14–16 G. •  Laparoscopy—best biopsy method; lower morbidity and faster recovery vs. exploratory laparotomy.

Aerobic and anaerobic bacterial culture and sensitivity of liver and bile; use particulate biliary debris if possible.

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DIET •  Conserve body condition and muscle mass. •  Adequate calories and protein—to avoid negative nitrogen balance and catabolism. •  Dietary protein—restrict protein quantity only if signs of HE or observe ammonium biurate crystalluria; feed balanced speciesspecific diet; if HE, avoid fish and red meat source protein (dogs). •  Fat restriction rarely needed. •  If Cu associated liver injury, see Copper Associated Hepatopathy. •  Meal frequency—feed several small meals per day. •  Sodium restriction—with ascites or severe hypoalbuminemia: 0.5 cm lesions); solitary, variably echogenic, cavitated, hyperechoic rim. •  Dystrophic tissue mineralization or entrapped gas. •  Highly echogenic interface with cavitated mass—may be gas; combination with an abdominal effusion and hyperechoic perilesional effect supports an abscess. •  Multiple masses, may be complex.

Cytology

•  Cytology is essential; histologic specimens

may not reveal bacterial organisms.

•  Samples—effusion; hepatic parenchyma,

discrete lesions; cholecystocentesis: transhe­ patic approach, liquid bile and biliary debris. •  Stains—Wright-Giemsa for bacterial detection; Gram stain for morphology. •  Look for bacteria within biliary debris, in WBCs; primary or predisposing disease (e.g., neoplasia, VH reflecting adrenal disease or diabetes mellitus). Culture and Sensitivity Testing

•  If suppurative or pyogranulomatous—culture for aerobic, anaerobic bacteria, fungal organisms. •  Blood—aerobic and anaerobic culture. •  Polymicrobial infections ~30%.

­

 TREATMENT

•  Inpatient—if signs of sepsis. •  IV fluids and antibiotics—essential. •  Fluid support—correct dehydration; rectify

acid-base and electrolyte disturbances.

•  Abscess—drain via lobectomy during

laparotomy or under ultrasound guidance before surgery; if endotoxic shock, ultrasound facilitated drainage is best; after drainage, monitor body temperature, liver enzymes, WBC count, and sequentially image with ultrasound (monitor abscess size, focal or diffuse peritonitis); judiciously repeat drainage (may require insertion of an indwelling catheter for short-term continuous drainage); consider alcoholization of abscess after drainage. •  In middle-aged/older dogs—lobectomy for abscess removal and possible wide-margin resection of an HCA. •  If extrahepatic bile duct obstruction (EHBDO)—see Bile Duct Obstruction (Extrahepatic).

­

 MEDICATIONS

DRUG(S) OF CHOICE •  Antibiotics—initially based on cytology and Gram stain, then adjusted based on culture and sensitivity results; continue for 2–4 months, perhaps longer. •  Initial treatment—combine antimicrobials for possible polymicrobial infection; common effective empirical combination includes



Canine and Feline, Seventh Edition (continued)

Hepatitis, Suppurative and Hepatic Abscess

ticarcillin (25–50 mg/kg over 15 min CRI) or amoxicillin clavulanate (13.75–20 mg/kg PO q12h), enrofloxacin (5–10 mg/kg PO/IV/ SC q12h in dogs or cats), and metronidazole (15 mg/kg IV q12h; reduce dose by 50% if hepatic dysfunction or severe cholestasis) or clindamycin (10–16 mg/kg SC per day; reduce dose if hepatic dysfunction or severe cholestasis to 5 mg/kg SC per day). •  Choleretics advised if biliary tree involved, but if EHBDO not until biliary decompression; see Bile Duct Obstruction (Extrahepatic); Cholangitis/Cholangiohepatitis Syndrome. •  Antioxidants advised (see Hepatitis, Chronic). CONTRAINDICATIONS/POSSIBLE INTERACTIONS •  Aminoglycosides—do not use until normal hydration. •  Avoid drugs metabolized or excreted by the liver or those known to be hepatotoxic if compromised liver function; adjust dosages or frequency of drugs if suspect reduced hepatic elimination, cholestasis, or hepatic dysfunction.

­

 FOLLOW-UP

PATIENT MONITORING •  Assess vital signs, labwork abnormalities, and physical condition.

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•  Sequential ultrasound examinations—mon­

itor for abscess recrudescence or suppurative peritonitis. •  If percutaneous drainage and alcoholization of an abscess—ultrasound monitoring at 24 and 48 hours post procedure and 15, 30, 60, and 120 days is recommended. POSSIBLE COMPLICATIONS

•  DIC. •  Septicemia/endotoxemia. •  Fulminant hepatic failure. •  Septic peritonitis. •  Acute renal failure.

EXPECTED COURSE AND PROGNOSIS

•  Favorable prognosis—early detection and

aggressive antimicrobial treatment, with judicious surgical intervention. •  Guarded prognosis—concurrent disorders, especially hepatic neoplasia.

­

 MISCELLANEOUS

ABBREVIATIONS •  ALP = alkaline phosphatase. •  ALT = alanine aminotransferase. •  AST = aspartate aminotransferase. •  CCHS = cholangitis/cholangiohepatitis syndrome. •  DIC = disseminated intravascular coagulation.

•  EHBDO = extrahepatic bile duct

obstruction.

•  HCA = hepatocellular carcinoma. •  WBC = white blood cell.

­Suggested Reading

Schwarz LA, Penninck DG, Leveille-Webster C. Hepatic abscesses in 13 dogs: a review of the ultrasonographic findings, clinical data, and therapeutic options. Vet Radiol Ultrasound 1998, 39:357–365. Sergeeff JS, Armstrong PJ, Bunch SE. Hepatic abscesses in cats: 14 cases (1985–2002). J Vet Intern Med 2004, 18:295–300. Zatelli A, Bonfanti U, Zini E, et al. Percutaneous drainage and alcoholization of hepatic abscesses in five dogs and a cat. J Am Anim Hosp Assoc 2005, 41:34–38. Author Ashleigh Seigneur Consulting Editor Kate Holan Acknowledgment The author and book editors acknowledge the prior contribution of Sharon A. Center.

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Hepatocellular Adenoma Abdominal Ultrasonography

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 BASICS

OVERVIEW •  A benign liver tumor of epithelial origin. •  May be more common than primary malignant liver tumors.

H

SIGNALMENT •  Rare in dog and very rare in cat. •  Affected dogs commonly >10 years of age. •  Breed predispositions unknown.

Abdominal CT

•  May allow for improved assessment

regarding surgical feasibility, especially for large tumors, or tumors associated with critical structures, such as the gallbladder. •  May detect additional lesions, depending on the contrast enhancement protocol. DIAGNOSTIC PROCEDURES

SIGNS

•  Usually asymptomatic; when clinical signs

present, symptoms may be nonspecific; typically incidental finding. •  Acute tumor rupture may cause hemoperitoneum with resultant weakness and hypovolemic shock-like symptoms. •  Occasionally, large tumors may cause cranial abdominal pain, vomiting, and inappetance. CAUSES & RISK FACTORS Definitive cause or risk factors for tumor development are unknown.

­

May identify discrete mass effect with variable echogenicity, ranging from normal liver echogenicity to mixed echogenicity, presence of multiple nodules, or cystic mass appearance.

 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Hepatocellular carcinoma. •  Hepatic nodular hyperplasia. •  Hepatic abscess. •  Abdominal mass. •  Splenomegaly. CBC/BIOCHEMISTRY/URINALYSIS CBC

•  Usually unremarkable. •  Anemia—regenerative anemia if tumor is

graphic guidance may allow the identification of normal hepatocytes or cells with mild atypia; this diagnostic will not be useful to differentiate between benign and low-grade malignant hepatic tumors, but will be useful to exclude other neoplastic diseases. •  Hepatic biopsy with Tru-Cut® needle—several core biopsies are necessary to provide enough tissue for histopathologic characterization; due to the overlap between the hepatocellular adenoma and the low-grade hepatocellular carcinoma, it may be difficult to obtain a definitive diagnosis. •  Abdominal exploratory surgery followed by mass resection (liver lobectomy) and histo­ pathology is the best way to obtain a definitive diagnosis and treat the disease. Gross Pathology

•  Usually well-circumscribed single nodules

20 cm).

with necrotic centers (rare).

nodular hyperplasia, normal liver tissue, or low-grade hepatocellular carcinoma. •  Usually well-defined trabecular pattern; not necessarily encapsulated. •  Compression of adjacent hepatic parenchyma common. •  Mitotic figures infrequent.

•  Liver enzymes variable. •  Serum total bilirubin values—usually normal.

Urinalysis

Unremarkable OTHER LABORATORY TESTS •  Serum bile acids are usually normal unless tumor growth compromises hepatic perfusion and biliary flow. •  Coagulation abnormalities consistent with disseminated intravascular coagulation (DIC) occur rarely with large necrotic or hemorrhagic tumors. IMAGING Radiography

•  May demonstrate a single mass lesion or

apparent asymmetry of hepatic silhouette. •  Rarely, gas in necrotic center of tumor.

­

 MEDICATIONS

­

 FOLLOW-UP

None

PATIENT MONITORING •  Liver enzymes—serial evaluation, especially if they were elevated at the time of diagnosis. •  Abdominal ultrasonography— every 3–4 months for the first year; preferred method of reevaluation. POSSIBLE COMPLICATIONS Risk of tumor necrosis and massive abdominal hemorrhage if not resected. EXPECTED COURSE AND PROGNOSIS Excellent

PATHOLOGIC FINDINGS

Microscopic Findings

Biochemistry

resected if the patient is healthy, and appropriate postoperative supportive care is available. •  Biopsy of local lymph nodes, normalappearing liver, and any abnormal tissue identified during the exploratory surgery is of paramount importance.

•  Hepatic aspiration cytology with ultrasono-

bleeding, or anemia of chronic disease.

•  Leukocytosis with a left shift—large tumors

•  Between 60% and 70% of the liver can be

•  May be difficult to distinguish from

­

 TREATMENT

•  Surgical resection for large tumors, or

tumors that cause clinical signs or organ dysfunction. •  Bleeding tumor—requires immediate emergency care: hemodynamic stabilization, blood transfusion, and exploratory surgery. Surgical Considerations

•  Excision recommended for large, single-

mass lesions.

­

 MISCELLANEOUS

SYNONYMS Hepatoma—should be avoided; refers to hepatocellular carcinoma in human medicine and hepatocellular adenoma in veterinary medicine. SEE ALSO Hepatocellular Carcinoma ABBREVIATIONS •  DIC = disseminated intravascular coagulation.

­Suggested Reading

Cave TA, Johnson V, Beths T, et al. Treatment of unresectable hepatocellular adenoma in dogs with transarterial iodized oil and chemotherapy with and without an embolic agent: a report of two cases. J Vet Comp Oncol 2004, 1:191–199. Warren-Smith CM, Andrew S, Mantis P, Lamb CR. Lack of associations between ultrasonographic appearance of parenchymal lesions of the canine liver and histological diagnosis. J Small Anim Pract 2012, 53(3):168–173. Author Nick Dervisis Consulting Editor Timothy M. Fan



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Hepatocellular Carcinoma

­

 BASICS

OVERVIEW •  Malignant epithelial liver tumor. •  Accounts for about 50% of malignant hepatic tumors. •  Metastasis to regional lymph nodes, lungs, and peritoneal cavity in dogs is associated with the nodular and diffuse forms of hepatocellular carcinoma.

disseminated intravascular coagulation (DIC) in patients with massive or necrotic tumors, or intra-abdominal bleeding. Radiography

•  May demonstrate a single-mass lesion,

apparent asymmetry of hepatic silhouette, or hepatomegaly. •  Rarely, gas in necrotic center of tumor. •  Loss of serosal detail in case of hemoabdomen.

SIGNALMENT

retrievers, miniature schnauzers, and male dogs are overrepresented in some studies.

genicity, depending on the presence of intratumoral necrosis, hemorrhage, gas, or cystic cavities. •  Massive enlargement of a single liver lobe is occasionally observed. •  Mixed echogenic pattern—most common. •  Nodular pattern of lesions.

SIGNS •  Typically absent until disease is advanced, unless it causes biliary obstruction. •  Many times incidental finding. •  Lethargy. •  Weakness. •  Anorexia. •  Weight loss. •  Polydipsia. •  Diarrhea. •  Vomiting. •  Hepatomegaly (asymmetric)—consistent; precedes development of overt clinical signs. •  Abdominal hemorrhage. CAUSES & RISK FACTORS •  Unknown. •  May be associated with chronic inflammation or hepatotoxicity.

­

 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Hepatic adenoma. •  Nodular hyperplasia. •  Biliary cystadenoma. •  Bile duct adenoma/ carcinoma. •  Metastatic neoplasia. •  Polycystic liver disease—less common form; fibrous stroma hyperplasia with anaplastic duct cells; few cysts. •  Hepatic lymphoma, hemangiosarcoma, carcinoid. CBC/BIOCHEMISTRY/URINALYSIS CBC

•  Usually unremarkable. •  Anemia in >50% of cases with massive hepatocellular carcinoma in one study. •  Anemia may be regenerative if tumor is bleeding. •  Leukocytosis with a left shift—tumors with necrotic centers.

Biochemistry

•  Liver enzymes variable. •  Serum total bilirubin values—usually normal. •  May note hypoalbuminemia, hypoglycemia, and hypocholesterolemia.

OTHER LABORATORY TESTS

•  Serum bile acids—normal unless tumor

impairs hepatic perfusion and biliary flow.

•  Coagulation parameters— consistent with

can be resected if the patient is healthy and is given appropriate postoperative care.

IMAGING

Abdominal Ultrasonography

•  Uncommon in dogs and rare in cats. •  Affected dogs commonly >10 years of age. •  No breed predispositions, although golden

•  Between 60% and 70% of the liver lobes

•  Discrete mass lesion with variable echo-

CT/MRI

CT is indicated for surgical planning (determine divisional or lobar origin), or when tumor involves/close proximity to critical anatomic structures, such as major vessels and the bile duct. DIAGNOSTIC PROCEDURES •  Aspiration cytology—to exclude other types of neoplasia (lymphoma, sarcoma, etc.); aspirate cytology cannot reliably differentiate between hepatocellular carcinoma and benign hepatocellular proliferation (adenoma, hyperplasia). •  Surgical hepatic biopsy for confirmation. •  If tumor is not surgically resectable, ultrasound-guided needle biopsy may be useful in obtaining definitive diagnosis. PATHOLOGIC FINDINGS

•  Three clinical subtypes of this tumor are

described—massive, nodular, and diffuse.

­

 MEDICATIONS

DRUG(S) OF CHOICE While toceranib administration has resulted in short-term tumor control for some dogs, no medical treatment options have been successful in reducing tumor recurrence or risk for metastasis.

­

 FOLLOW-UP

PATIENT MONITORING •  Abdominal ultrasonography—2 weeks postoperative for baseline and every 3–4 months for the first year. •  Abdominal CT appears more sensitive than ultrasonography for detection of small, recurrent lesions. •  Monitor liver enzymes serially. POSSIBLE COMPLICATIONS Risk of tumor necrosis and massive abdominal hemorrhage if unresected. EXPECTED COURSE AND  PROGNOSIS •  Massive forms treated with surgery have a better prognosis than do the nodular or diffuse forms. •  Median survival of dogs with massive form treated with surgery may be >1,460 days. •  Local tumor recurrence or de novo tumor growth is not uncommon.

•  Nodular forms account for 30% and diffuse

types account for 10% of all reported hepatocellular carcinomas in dogs, and both types involve multiple liver lobes. •  Massive form that is confined to one lobe accounts for about 60% of canine hepatocellular carcinoma cases. •  Presence of necrotic areas. •  Diffusely infiltrated tumors may not be grossly apparent other than hepatomegaly.

­

 MISCELLANEOUS

ASSOCIATED CONDITIONS Polycystic liver disease in cats. ABBREVIATIONS •  DIC = disseminated intravascular coagulation.

­Suggested Reading

­

 TREATMENT

Surgical Considerations

•  Complete excision (liver lobectomy)

recommended when possible; excision with microscopically dirty margins can still afford durable tumor control and long survival times. •  Massive form is often amenable to surgical resection. •  Nodular and diffuse forms are often not amenable to surgery.

Goussev SA, Center SA, Randolph JF, et al. Clinical characteristics of hepatocellular carcinoma in 19 cats from a single institution (1980–2013). J Am Anim Hosp Assoc 2016, 52(1):36–41. Liptak JM, Dernell WS, Withrow SJ. Liver tumors in cats and dogs. Compend Contin Educ Pract Vet 2004, 26:50–56. Author Nick Dervisis Consulting Editor Timothy M. Fan

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Hepatocutaneous Syndrome

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H

 BASICS

OVERVIEW •  Liver lesion—severe degenerative vacuolar hepatopathy, hepatocyte degeneration leads to parenchymal collapse associated with marked proliferative hepatocyte response; this process leads to severe hepatic nodularity; hepatocutaneous syndrome (HCS) hepatopathy often associated with syndromic pressure point crusting, painful dermatosis, and diabetes mellitus (DM). •  Liver lesions—may precede cutaneous lesions and DM. •  Hepatopathy—recognized on abdominal US, pursued because of marked alkaline phosphatase (ALP) increase. •  Occasionally HCS hepatopathy develops in dogs treated chronically with phenobarbital. SIGNALMENT

•  Middle-aged to older dogs. •  Males may have a greater predilection. •  Familial syndrome in shih tzu dogs

described. SIGNS

Historical Findings

•  Acute to subacute onset; may be few initial

signs.

•  Common signs— anorexia, weight loss,

lethargy, polyuria/polydipsia, diarrhea, vomiting, ± jaundice, often with prominent cutaneous pressure point and painful foot pad lesions characterized as fissured crusted oozing wounds.

Physical Examination Findings

•  Lethargy, poor body condition, with foot

pad and elbow lesions causing pain in standing and recumbent postures, may be jaundiced. •  Cutaneous lesions—see Superficial Necrolytic Dermatitis. •  Normal, small to large hepatic size. •  Rare abdominal effusion—signifies late-stage HCS hepatopathy. CAUSES & RISK FACTORS

•  Etiology—associated with pathologic

hypoaminoacidemia and aminoaciduria; low amino acid (AA) concentrations seemingly have causal association with cutaneous and liver lesions. Most significantly low AA affiliated with urea cycle and synthesis of glutathione and collagen. •  Hyperglucagonemia associated with glucagonoma—originally proposed as causal mechanism but that remains unproven; ~30–40% of tested dogs have increased plasma glucagon concentrations; glucagonoma confirmed in 1.5 cm beyond

costal margin (normal liver palpable in some cats). •  May be undetected in obese animals.

CAUSES Inflammation

•  Infectious or chronic (early) hepatitis. •  Acute toxic hepatopathy. •  Feline

cholangitis/cholangiohepatitis syndrome (CCHS). •  EHBDO. •  Lymphoreticular/ pyogranulomatous—immune-mediated disease (hemolytic anemia, hemophagocytic syndrome, systemic lupus erythematosus, idiopathic), infectious disorders. •  Venous outflow obstruction—sinusoidal occlusion syndrome or Budd Chiari syndrome. Congestive Hepatopathy

•  Increased central venous pressure—right-

sided congestive heart failure: tricuspid valve disease; cardiomyopathy; congenital anomaly (cor triatriatum dexter); neoplasia; pericardial disease; heartworm disease; pulmonary hypertension; severe arrhythmias or bradycardia reducing cardiac output. •  Vena caval or hepatic vein occlusion—thrombosis; tumor invasion or extramural caval occlusion; heartworm vena cava syndrome; vena caval stenosis or congenital kink (rare); diaphragmatic hernia; vena caval or large hepatic vein thrombosis (Budd Chiari syndrome); intrahepatic hepatic vein occlusion (thrombi, neoplasia, centrilobular parenchymal collapse causing sinusoidal occlusion syndrome). •  Sinusoidal occlusion syndrome—collapsed centrilobular parenchyma and/or damage to hepatic venules impairing circulatory egress; causes include xenobiotic or herbal toxicity (e.g., pyrrolizidine alkaloids), severe nonsteroidal inflammatory drug–induced injury, severe copper hepatopathy. •  Liver lobe torsion (acute). Infiltration

•  Neoplasia. •  Metabolic abnormalities— amyloid; lipid (see Hepatic Lipidosis [cats]), glycogen (see Glycogen-Type Vacuolar Hepatopathy [dogs]); cats and dogs: diabetes mellitus (DM), hyperlipidemic syndromes; neonatal metabolic storage disorders. •  Lymphohistiocytic/pyogranulomatous—

infectious disease, immune response, antigen stimulation, neoplasia (histiocytic/dendritic cells: histiocytic sarcoma), hemophagocytic syndrome. Extramedullary Hematopoiesis

Regenerative anemias—hemolytic (immunemediated, congenital, metabolic, infectious); oxidant injury; erythroparasitism; severe blood loss, bone marrow failure; idiopathic. Neoplasia

•  Infiltrative, diffuse, or large focal tumors— primary or metastatic. •  Primary hepatic— lymphoma; massive HCA; cholangiocarcinoma (bile duct carcinoma ± EHBDO); hemangiosarcoma. •  Metastatic—lymphosarcoma, hemangiosarcoma, histiocytic sarcoma, fibrosarcoma, leiomyoma/sarcoma, neuroendocrine, osteosarcoma, others.

Major Bile Duct Obstruction

•  Pancreatitis; pancreatic neoplasia. •  Neoplasms in porta hepatis—bile duct carcinoma, lymphoma. •  Granuloma/fibrosis of common bile duct. •  Inspissated bile syndrome, choledochal cyst (DPM phenotype), or gallbladder mucocele. •  Cholelithiasis. •  Proximal duodenitis; duodenal foreign body. •  Fluke migration (cats).

Cystic Lesions

•  Primary single hepatic or biliary cysts. •  Acquired cysts within neoplastic masses. •  DPM—may associate with renal cysts (common in Persian cats). •  Biliary

cystadenoma (cats; DPM phenotype).

•  Hepatic abscesses (cystic cavitation);

hepatocellular carcinoma housing abscess. •  Parasitic—echinococcus (hydatid cyst). Other

•  Drugs—corticosteroids (see Glycogen-Type

Vacuolar Hepatopathy), phenobarbital (dogs).

•  Hepatic nodular hyperplasia (rare cause). •  Acromegaly—cats.

RISK FACTORS

•  Cardiac disease. •  Heartworm disease. •  Neoplasia. •  Primary hepatic disease—

inflammatory, neoplastic, cystic, or other DPM phenotypes. •  Corticosteroids— exogenous or endogenous. •  Phenobarbital treatment. •  Poorly controlled DM. •  Anorexia in obese cats—hepatic lipidosis. •  EHBDO. •  Cystic malformations— DPM. •  Certain anemias—diffuse hepatic EMH.

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS Similar Signs

Distinguish from other disorders causing visceromegaly (gastric, splenic), cranial abdominal masses, or effusions via radiography and US.



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Hepatomegaly

(continued)

Differential Causes

•  Cardiac disorders—heart murmur, weak

femoral pulses, hepatojugular reflex, jugular distention and jugular pulses, muffled heart sounds, arrhythmias, cough, dyspnea/ tachypnea. •  Symptomatic anemia—pallor ± jaundice; tachycardia; tachypnea; exercise intolerance; bounding pulses. •  Parenchymal liver disease—lethargy, anorexia, vomiting, diarrhea, weight loss, variable liver enzymes ± jaundice, coagulopathies, polyuria/polydipsia (PU/PD), if advanced may see hepatic encephalopathy (HE) or ascites. •  Glycogentype vacuolar hepatopathy (VH; dog)—signs of hyperadrenocorticism or adrenal hyperplasia or other chronic disease imposing stress; DM—persistent hyperglycemia; PU/PD, signs of underlying endocrinopathy. •  Hepatic lipidosis—jaundice in obese hyporexic cat, poorly controlled DM (dog or cat); failure-to-thrive puppies or kittens; congenital lysosomal or glycogen storage disorders. CBC/BIOCHEMISTRY/URINALYSIS CBC

•  Identify anemia and cause; spherocytes (immune-mediated hemolytic anemia, microangiopathic anemia); schistocytes (vascular shearing-microangiopathic, vena cava syndrome, hemangiosarcoma, disseminated intravascular coagulation (DIC), Heinz bodies (oxidant injury); erythroparasitism (Mycoplasma haemofelis or haemominutum, Babesia). •  Circulating blast cells—myeloproliferative or lymphoproliferative disorders. •  Nucleated red cells—EMH, splenic disease, regenerative anemia. •  Macrocytosis and nonregenerative anemia—feline immunodeficiency virus (FIV), feline leukemia virus (FeLV), myelophthisis. •  Thrombocytopenia—increased consumption, destruction, or reduced platelet production. •  Thrombocytosis—neoplasia; inflammation; hyperadrenocorticism; splenic disease.

Biochemistry

•  Inflammatory hepatic disorders—usually

high liver enzyme activity; variable hyperglobulinemia, bilirubin, and albumin concentrations. •  Reticuloendothelial hyperplasia—variable liver enzyme activity. •  Primary hepatic neoplasia—moderate to marked increases in liver enzyme activity (alkaline phosphatase [ALP] and 𝛾-glutamyltransferase [GGT] usually predominate with HCA, variable alanine aminotransferase [ALT]. •  Metastatic neoplasia—variable liver enzymes; occasional high calcium or globulin. •  Infiltrative disorders—minor liver enzyme change; variable bilirubin concentration. •  Glycogentype VH (dogs)—markedly high ALP; high cholesterol ± triglycerides with increased glucocorticoids or sex steroids; DM—high

ALP, cholesterol, hyperglycemia. •  Hepatic lipidosis (cats)—high ALP, aspartate aminotransferase (AST), ALT; minor increase in GGT unless concurrent pancreatitis, CCHS, or EHBDO. •  Storage diseases— may display few abnormalities. •  EHBDO— markedly high ALP, GGT, other enzymes; high bilirubin and cholesterol. •  Cystic lesions—normal, except with hepatic abscess (markedly high ALT and AST) or CCHS (high ALP, ALT, GGT, variable bilirubin); DPM often presents with suppurative CCHS. •  Phenobarbital-associated—high liver enzymes (especially ALP in dogs). •  Nodular hyperplasia—normal to moderately high ALP, elderly dogs: rare cause of hepatomegaly. OTHER LABORATORY TESTS •  FeLV and FIV testing—cats. •  Buffy coat— circulating blasts with neoplasia or uncommon cell type observed. •  Coagulation panel—DIC common with hemangiosarcoma or diffuse lymphoma; prolonged coagulation times common with EHBDO >5 days esp. in cats. •  Total serum bile acids (TSBA)—high in diffuse disorders or EHBDO; redundant test if nonhemolytic jaundice. •  Pituitary-adrenal axis testing (dogs)—see Glycogen-Type Vacuolar Hepatopathy; Hyperadrenocorticism (Cushing’s Syndrome)—Dogs. •  Insulin-like growth factor-1 (IGF-1) in acromegalic cats; typically males with DM. •  Heartworm testing—in endemic areas. •  Fungal serology—in endemic areas. •  Other serology—e.g., Rickettsial, Bartonella, Leishmania, Toxoplasmosis. IMAGING Abdominal Radiography

•  Hepatomegaly—rounded margins

extending beyond costal arch; caudal-dorsal gastric displacement; caudal displacement: cranial duodenal flexure, right kidney, transverse colon. •  May suggest cause.

Thoracic Radiography

•  Three views (lateral [right, left], dorsal-­ ventral)—metastasis, other disorders, cranial displacement of diaphragm, wide vena cava if passive congestion. •  Cardiac, pulmonary, pericardial, and vena caval disorders usually need US imaging. •  Sternal lymphadenopathy— reflects abdominal inflammation or neoplasia. •  Puppies, kittens, deep inspiration, and certain canine breeds—spurious hepatomegaly.

Abdominal US

•  Liver size and surface contour. •  Diffuse

enlargement with normal echogenicity—­ congestion; cellular infiltration (lymphoma); inflammation; EMH; reticuloendothelial hyperplasia, diffuse amyloid deposition expanding space of Disse. •  Diffuse enlargement with hypoechoic parenchyma—normal variation; congestion, lymphoma, diffuse sarcoma; amyloidosis expanding space of

Disse. •  Diffuse enlargement with hyperechoic parenchymal (minor nodularity)— lipid or glycogen; inflammation; fibrosis; lymphoma; DPM fibrotic bridging portal trabeculae. •  Diffuse enlargement with hypoechoic nodules—neoplasia; abscess; degenerative glycogen-type VH (dog); HCS, cystic lesions (DPM). •  Identify EHBDO. •  Identify concurrent abdominal diseases— kidneys; intestines; lymph nodes; effusion; interrogation of porta hepatis for obstructions and lymphadenopathy. •  Identify portal or vena caval thrombi. •  Identify abdominal effusion—distribution and echogenic patterns. •  Cannot distinguish benign from malignant disease. DIAGNOSTIC PROCEDURES ECG/Echocardiography

Characterize cardiac rhythm, structure, function, pulmonary pressure gradient. Fine-Needle Aspiration

•  Procedure—22-G, 2.5–3.75 cm (1–1.5 in)

needle; diffusely large liver directly aspirated without US; focal lesions aspirated under US guidance. •  Cytology—may disclose infectious agents, vacuolar change, neoplasia, inflammation, or EMH; definitive diagnosis seldom confidently confirmed (false-positive and -negative results). •  Hepatic biopsy—if US rules out EHBDO, cytology does not indicate septic inflammation or neoplasia, and no obvious diagnoses made; percutaneous ultrasound–guided Tru-Cut® needle biopsy for suspected neoplasia or amyloid (avoid if abscess or EHBDO possible); otherwise, best sampling with laparoscopic or surgical exploratory approaches. •  Microbial culture—aerobic and anaerobic bacterial; fungal as appropriate. •  Staining—H&E (routine); reticulin (architectural substructural remodeling, infiltration, compression), Masson’s trichrome (collagen deposition, amyloid detection); rhodanine (copper); periodic acid–Schiff (glycogen ± amylase predigestion); acid-fast stain (mycobacteria if granulomatous inflammation); Congo red (amyloid); Oil Red O (lipid, requires frozen section), infectious disease stains (see Hepatitis, Granulomatous). •  Coagulation testing—before liver sampling, consider measurement of prothrombin time, activated partial thromboplastin time, fibrinogen, buccal mucosal bleeding time (BMBT); prediction of iatrogenic hemorrhage poor with bench tests; BMBT may be more relevant. •  Abdominal effusion—cytology; protein content; culture; evaluate before tissue sampling. •  Pericardiocentesis—if pericardial tamponade. •  Cyst aspiration sampling—if possible infectious cause when plausible treatment might be recommended; risk for abdominal contamination if hepatic abscess.

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Hepatomegaly

(continued)

SURGICAL CONSIDERATIONS

•  Resection of primary or focal hepatic mass

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 TREATMENT

APPROPRIATE HEALTH CARE •  Outpatient—except cardiac/pericardial causes or hepatic failure. •  General supportive goals—eliminate or manage inciting cause; prevent complications; palliate derangements reflecting hepatic failure. •  Important derangements—dehydration and hypovolemia; HE; hypoglycemia; acid-base and electrolyte abnormalities; coagulopathies; enteric hemorrhage; sepsis; endotoxemia. NURSING CARE •  Heart failure or ascites—impose sodium restriction: fluids and food ( post-meal TSBA; this reflects individual differences in physiologic coordination of gallbladder contraction, and gastric and enteric transit rate relative to food intake; thus, do not apply fasting TSBA reference ranges. •  “Shunting pattern”—common: higher post-meal TSBA; post-meal TSBA concentration usually 0.5- to 3-fold > pre-meal TSBA. •  Best assessments—young small breed dogs at 6 months; avoids serendipitous discovery of high TSBA when dog later presents for nonhepatic illnesses, when inappropriate testing may be pursued chasing abnormal TSBA values. •  Magnitude of increased TSBA—typically lower for MVD vs. PSVA; but wide overlapping of values invalidates utility of TSBA as standalone test to distinguish MVD from PSVA; however, TSBA values ≥200 μM/L usually associate with PSVA or APSS. •  Quantitative abnormal TSBA values cannot discriminate severity of MVD between dogs; sequential testing demonstrates vacillating abnormal values (reflects physiologic variables). •  Avoid qualitative TSBA tests.

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Hepatoportal Microvascular Dysplasia Protein C

•  Protein C reflects severity of portosystemic

shunting in dogs; not valid for this use in cats. •  Generalities—MVD: protein C usually ≥70%; symptomatic PSVA: protein C 1.6% in diet on dry-matter basis, increase phenotypic expression, development of hip dysplasia (HD), and progression of disease. •  Decreased gluteal and caudal thigh muscle mass—increase expression and progression. RISK FACTORS

•  Overweight puppies fed in excess of caloric

requirements for normal growth at risk for increased incidence of HD. •  Additional calcium supplementation in diet of young large-breed dogs contraindicated and may predispose to development of HD.

Mean Age and Range

•  Onset of clinical signs varies with severity of hip laxity in immature dog and with worsening secondary OA in mature dog. •  Clinical signs—may develop after 4 months of age in dogs with severe laxity; may also develop at any age after onset of secondary OA. •  Clinical signs are biphasic in dogs; young dogs often exhibit most severe clinical signs

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for lameness in large-breed dogs until definitively eliminated from consideration. •  Degenerative myelopathy. •  Lumbosacral instability. •  Unilateral or bilateral stifle disease. •  Panosteitis. •  Polyarthropathies. IMAGING

•  Ventrodorsal hip-extended radiographs—

commonly used for diagnosis; may need sedation or general anesthesia for accurate positioning. •  Early radiographic signs—subluxation of hip joint with poor congruence between femoral head and acetabulum; initially normally shaped acetabulum and femoral head; with disease progression, shallow acetabulum and flattened femoral head. •  Radiographic evidence of OA—flattening of femoral head; shallow acetabulum; periarticular osteophyte production; thickening of femoral neck; sclerosis of subchondral bone; periarticular soft tissue fibrosis. Remodeling of femoral neck is uncommon in cats. •  Distraction radiographs—quantify joint laxity; may accentuate laxity for more accurate diagnosis. Distraction radiographic procedures such as PennHip® have been standardized and allow better prediction of dogs likely to develop secondary hip OA and better selection of dogs for breeding potential. •  Dorsal acetabular rim view radiographs— evaluate acetabular rim; assess dorsal coverage of femoral head. Clinical efficacy of such views in diagnosis and treatment of HD has not been definitively established. DIAGNOSTIC PROCEDURES

•  Commercial genetic markers are under

development but not in widespread use at this time. •  Arthroscopy of hip joint has been described in diagnosis of HD, but does not add useful clinical information regarding treatment. PATHOLOGIC FINDINGS

•  Early—normal conformation of femoral

head and acetabulum; may note joint laxity and excess synovial fluid. •  With progression—malformed acetabulum and femoral head; synovitis; articular cartilage degeneration. Formation of periarticular osteophytes leads to radiographic formation of “Morgan’s line,” linear formation of enthesiophytes at origin of joint capsule on femoral neck. •  Chronic—may note full-thickness cartilage erosion.

 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Cranial cruciate ligament rupture—up to ⅓ of dogs referred for treatment of HD actually suffer from concurrent cranial cruciate rupture; cranial cruciate ligament rupture must remain alternative diagnosis

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 TREATMENT

APPROPRIATE HEALTH CARE •  May treat with conservative medical therapy or surgery.

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Hip Dysplasia •  Depends on patient’s size, age, and

intended function; severity of joint laxity; degree of OA; clinician’s preference; financial considerations of owner. NURSING CARE

•  Physical therapy (passive joint motion)—

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decreases joint stiffness; helps maintain muscle integrity. •  Swimming (hydrotherapy)—excellent nonconcussive form of physical therapy; encourages joint and muscle activity without exacerbating joint injury. ACTIVITY

•  As tolerated. •  Swimming—recommended to maintain

joint mobility while minimizing weightbearing activities.

DIET •  Weight control—important and first goal of therapy; decrease load applied to painful joint; minimize weight gain associated with reduced exercise. •  Supplementation with omega-3 fatty acids (in commercial diets or as food additive) beneficial to decrease pain and inflammation and improve function. While optimum dosage/feeding of omega-3 fatty acids yet to be determined, clinical efficacy of commercial diets containing 1.7–3.4% of omega-3 fatty acids and precursors has been established. CLIENT EDUCATION •  Discuss heritability of the disease, recommend neutering of affected animals and elimination as breeding sources. •  Explain that medical therapy is palliative. •  Warn client that joint degeneration often progresses unless corrective osteotomy procedure is performed early in disease. •  Explain that surgical procedures can salvage joint function once severe joint degeneration occurs. SURGICAL CONSIDERATIONS Triple, Double, or 2.5 Pelvic Osteotomy •  Corrective procedure; designed to

reestablish congruity between femoral head and acetabulum. •  Immature patient (6–10 months of age) without signs of OA. •  Rotate acetabulum—improve dorsal coverage of femoral head; correct forces acting on joint; minimizes progression of OA, but OA frequently progresses on radiographs even though progression not clinically apparent. •  Surgical procedure necessitates implantation of surgical implants, commonly bone plate and screws specially designed for procedure; large dogs may necessitate use of two bone plates; outcomes improved and complication rates decreased with use of locking implants. Juvenile Pubic Symphysiodesis

•  Pubic symphysis is fused at early age (8–16

weeks) using electrocautery.

(continued) •  Requires extremely early diagnosis of

condition, or use as preventative in nonbreeding animals to decrease need for more aggressive surgical procedure in dogs likely to develop secondary OA or more several clinical signs. •  Causes ventroversion of acetabulum during growth to better cover femoral head. •  Improves joint congruence and stability— similar effects to triple pelvic osteotomy without osteotomy and surgical implants. •  Minimal morbidity; easy to perform—must be performed very early (ideally 3–4 months of age) to achieve effect; minimal effect achieved if performed after 5 months of age. Total Hip Replacement

•  Indicated to salvage function in mature

dogs with severe degenerative disease unresponsive to medical therapy. •  Multiple systems exist to replace both acetabular and femoral head surfaces and comprising both cemented and noncemented (ingrowth) implants; noncemented implants have best prognosis for long-term use and implant stability. •  Pain-free joint function—reported in >90% of cases. •  Unilateral joint replacement—provides acceptable function in ~80% of cases. •  Staged bilateral joint replacement now chosen by 50% of owners. •  Complications—luxation; femoral fracture, sciatic neuropraxia; infection; incidence of infection decreased with use of noncemented implant systems compared to cemented systems. Excision Arthroplasty

•  Removal of femoral head and neck to

eliminate joint pain. •  Extremely important to achieve smooth osteotomy close to femoral shaft. •  Primarily a salvage procedure—for significant OA; when pain cannot be controlled medically; when total hip replacement is cost-prohibitive. •  Best results—small, light dogs (122 mEq/L in dogs and >129 mEq/L in cats).

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PATHOPHYSIOLOGY •  Chloride is the most abundant anion in extracellular fluid. •  Hyperchloremia is associated with free water loss or excessive NaCl intake (oral or parenteral). •  Serum chloride concentration varies inversely to bicarbonate concentration; high bicarbonate loss (i.e., vomiting or renal wasting) is followed by renal chloride resorption and hyperchloremia. SYSTEMS AFFECTED Relate to underlying cause. SIGNALMENT Species

Dog and cat. SIGNS General Comments

•  Related to concurrent hypernatremia (i.e., free water loss) or underlying disorder, or both. •  Severity of neurologic signs related to degree of hypernatremia and rate of development.

Historical and Physical Examination Findings •  Polydipsia. •  Disorientation. •  Seizures. •  Coma.

CAUSES High Total Body Chloride

•  Oral ingestion (salt or salt water)—rare. •  NaCl (0.9% or hypertonic) or other

chloride salts administered IV.

Normal Total Body Chloride with Water Deficit •  High urinary water loss (e.g., diabetes

•  Normal anion gap. •  Renal tubular acidosis—renal tubular

disorders causing wasting of bicarbonate or low hydrogen ion secretion. •  Diarrhea causing gastrointestinal loss of bicarbonate and renal resorption of chloride. •  Chronic respiratory alkalosis.

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Diabetes insipidus. •  Dehydration. •  Renal tubular acidosis. •  Diabetic ketoacidosis. •  Salt or salt water ingestion—rare. LABORATORY FINDINGS Drugs That May Alter Laboratory Results

A falsely high chloride concentration can occur with high serum concentrations of iodide or bromide (e.g., patients treated with potassium bromide) if ion-selective electrodes are used for measurement. Disorders That May Alter Laboratory Results

Hemoglobin and bilirubin cause falsely high chloride readings if colorimetric tests are used. Lipemia may result in an artifactual hyperchloremia. Valid if Run in Human Laboratory?

Yes

CBC/BIOCHEMISTRY/URINALYSIS •  Often coupled with hypernatremia. •  Diabetes insipidus—hyposthenuria, azotemia. •  Diabetic ketoacidosis—hyperglycemia, ketonemia, and ketonuria. •  Dehydration—urine specific gravity >1.030, prerenal azotemia. •  Renal tubular acidosis—metabolic acidosis in the presence of alkaline urine, hypokalemia, other causes of metabolic acidosis (e.g., azotemia, hyperlactatemia, ketonemia) not present.

 MEDICATIONS

DRUG(S) OF CHOICE •  Sodium bicarbonate—calculate bicarbonate deficit (0.3 * bodyweight (kg) * [24 mEq – current [HCO3−] ]) and give ⅓–½ of this dose slowly IV. •  5% dextrose in water—calculate free water deficit (see hypernatremia) and administer so that serum sodium does not decrease by more than 0.5 mEq/h (or 12 mEq/day). PRECAUTIONS

•  Rapid correction of hypernatremia can

cause cerebral edema.

•  Hypocalcemia may develop during correction

of serum pH, in patients with borderline low serum ionized calcium concentrations.

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 FOLLOW-UP

PATIENT MONITORING Electrolytes, bodyweight, and hydration status. PREVENTION/AVOIDANCE Animals should always have access to water. POSSIBLE COMPLICATIONS Rapid correction of hypernatremia can lead to cerebral edema. EXPECTED COURSE AND PROGNOSIS Vary with underlying cause.

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may have respiratory compensation.

SEE ALSO Hypernatremia

•  Blood-gas analysis—metabolic acidosis,

Low Total Body Chloride with Hypotonic Fluid Loss

hyperchloremia or bicarbonate loss.

corticism, osmotic diuresis, postobstructive diuresis. •  Drugs that interfere with ability to concentrate urine—lithium, demeclocycline, and amphotericin. •  Drugs that cause renal chloride retention— acetazolamide, ammonium chloride, androgens, cholestyramine, and spironolactone.

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OTHER LABORATORY TESTS

insipidus). •  Low intake (e.g., no access to water). •  Insensible water loss (e.g., panting).

•  Urinary loss—diabetes mellitus, hypoadreno­

orally or IV (see below); target a sodium concentration decrease of 12 mEq/day; serum sodium concentration should be rechecked every 4–6 hours and fluids adjusted as necessary to maintain appropriate rate. •  If renal tubular acidosis, treat underlying cause (usually pyelonephritis). •  If renal or gastrointestinal bicarbonate loss, administration of NaHCO3 can be considered.

•  Anion gap—normal if primary

IMAGING CT or MRI in patients with diabetes insipidus to rule out pituitary tumor.

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 TREATMENT

APPROPRIATE HEALTH CARE •  If hyperchloremia and hypernatremia due to free water loss, administer free water either

 MISCELLANEOUS

­Suggested Reading

DiBartola SP. Fluid, Electrolyte and AcidBase Disorders in Small Animal Practice, 3rd ed. Philadelphia, PA: Saunders, 2005. Rose DB, Post T. Clinical Physiology of Acid-Base and Electrolyte Disorders, 5th ed. New York: McGraw-Hill, 2000. Author Patty A. Lathan Consulting Editor Patty A. Lathan Acknowledgment The author and book editors acknowledge the prior contribution of Melinda Fleming.



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Hypercoagulability •  Antithrombin (AT)—decreased activity

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 BASICS

OVERVIEW •  Hypercoagulability (aka thrombophilia) is an imbalance between procoagulant and anticoagulant factors that favors thrombosis. •  Thrombus formation occurs in the presence of endothelial injury, altered blood flow, and/ or hypercoagulability (Virchow’s triad). •  Hypercoagulability may result from platelet hyperaggregability, increased amounts or activation of clotting factors, reduced or inhibited anticoagulant proteins, or defective fibrinolysis. •  Common sites of thrombosis—pulmonary arteries, distal aorta, cranial vena cava, intestinal/mesenteric vessels, portal vein. SIGNALMENT Depends on underlying condition. SIGNS

•  Hypercoagulability is symptomless;

increases risk of thrombosis. •  Prothrombin time (PT), activated partial thromboplastin time (APTT)—shortened clotting times are unreliable markers for thrombophilia. •  Thromboelastography, thromboelastometry, rotational thromboelastometry—can potentially identify hypercoagulability. •  Arterial blood gas, pulse oximetry— hypoxemia. IMAGING •  Ultrasonography—confirm presence of arterial or venous thrombi. •  Echocardiography—identify cardiac disease, intracardiac thrombi, or spontaneous echocontrast (“smoke”); pulmonary hypertension associated with PTE.

paresis/paralysis, limb pain (ischemic myopathy), decreased pulse and cold limbs; onset in dogs may be gradual vs. peracute in cats. •  Portal vein or caudal vena cava thrombosis—ascites. CAUSES & RISK FACTORS •  Immune-mediated hemolytic anemia (IMHA). •  Protein-losing nephropathy. •  Hypoproteinemia. •  Systemic inflammation. •  Neoplasia. •  Cardiac disease. •  Hyperadrenocorticism or corticosteroid therapy.

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  PTE may mimic pneumonia, pulmonary edema, dirofilariasis. •  Distal ATE—other causes of paraparesis and paraplegia (e.g., neurologic). CBC/BIOCHEMISTRY/URINALYSIS Reflect underlying disease or effects of thrombosis in specific organs. Animals with protein-losing nephropathy have proteinuria and elevated urine protein : creatinine ratio, possibly signs of nephrotic syndrome. OTHER LABORATORY TESTS •  D-dimer—sensitive for fibrinolysis; thrombosis unlikely if normal; nonspecific for cause.

Thrombolysis

•  Severe side effects possible. Reperfusion

injury is common.

•  Tissue plasminogen activator (tPA)—1 mg/

kg incrementally IV once; most effective in first 3–6 hours after thromboembolism.

CONTRAINDICATIONS/POSSIBLE INTERACTIONS •  Do not treat with warfarin initially; overlap with heparin therapy for 2 days. •  Reassess coagulation with any medication changes. •  If bleeding occurs, discontinue and administer protamine or vitamin K and plasma as indicated to correct hemorrhage.

DIAGNOSTIC PROCEDURES support diagnosis of PTE.

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 FOLLOW-UP

•  Monitor patients for clinical signs or

thrombosis causes site-dependent signs. acute severe dyspnea and tachypnea.

dogs: 0.5–5.0 mg/kg PO q12–24h.

•  Angiography (standard or CT angiography). •  Nuclear perfusion scintigraphy—can

imaging evidence of resolution of thrombosis.

•  Pulmonary thromboembolism (PTE)— •  Arterial thromboembolism (ATE)—acute

•  Aspirin—prophylaxis, after thrombosis;

•  Risk of future thromboembolic events.

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 TREATMENT

•  Inpatient—supportive care, analgesia,

anticoagulation.

•  Supportive care—ensure hydration,

maintain perfusion, minimize vascular stasis, correct and monitor acid-base and electrolyte abnormalities, use venous catheters appropriately. •  Oxygen therapy for hypoxemia.

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 MEDICATIONS

DRUG(S) OF CHOICE Anticoagulants

•  Unfractionated heparin for initial therapy,

starting dose: 150–200 IU/kg SC q6-8h; titrate to achieve 1.5-fold increase in APTT; check APTT daily (4h post heparin dose). •  Low molecular weight heparin— enoxaparin: 1 mg/kg (1,000 U/kg) SC q6–12h; dalteparin: 150 mg/kg SC q 6–8h. Monitor anti-Xa activity. •  Rivaroxaban—0.5 mg/kg PO q24h for chronic therapy; no reversal agents available. •  Warfarin for chronic therapy, starting dose: 0.1–0.2 mg/kg PO q24h; adjust dose based on international normalized ratio. Platelet Inhibition

•  Clopidogrel—prophylaxis, prevents repeat

thrombosis; dogs: 0.5–1 mg/kg PO q24h; cats: 18.75 mg PO q24h; more effective than aspirin in preventing recurrence of ATE in cats.

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 MISCELLANEOUS

SEE ALSO •  Amyloidosis. •  Anemia, Immune-Mediated. •  Aortic Thromboembolism. •  Disseminated Intravascular Coagulation. •  Pulmonary Thromboembolism. ABBREVIATIONS

•  APTT = activated partial thromboplastin

time.

•  AT = antithrombin. •  ATE = arterial thromboembolism. •  IMHA = immune-mediated hemolytic

anemia.

•  PT = prothrombin time. •  PTE = pulmonary thromboembolism. •  tPA = tissue plasminogen activator.

­Suggested Reading

deLaforcade A, Bacek L, Blais MC, et al. Consensus on the Rational Use of Antithrombotics in Veterinary Critical Care (CURATIVE): domain 1—defining populations at risk. J Vet Emerg Crit Care 2019, 29(1):37–48. Wiinberg B, Kristensen AT. Hypercoagulable states. In: Bonagura JD, Twedt DC, eds. Kirk’s Current Veterinary Therapy XV. St. Louis, MO: Elsevier Saunders, 2014, pp. 297–301. Author John A. Christian Consulting Editor Melinda S. Camus

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Hypereosinophilic Syndrome (HES)

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 BASICS

OVERVIEW •  Idiopathic, persistent eosinophilia with infiltration of organs causing dysfunction, often leading to death. •  May be caused by a severe reaction to an unidentified antigen and/or dysregulation of immunologic control of eosinophilopoiesis. •  Organ damage caused by effects of eosinophil granule products and eosinophilderived cytokines that are released in tissues from activated and/or necrotic cells. •  Common sites of infiltration: gastrointestinal (GI) tract (especially intestine and liver), spleen, bone marrow, lung (dogs), and lymph nodes (especially mesenteric). •  More common in cats than dogs. •  Unclear whether HES is a distinct entity from eosinophilic leukemia. •  Generally poor prognosis, especially cats. SIGNALMENT •  Cats—occurs more frequently in female, middle-aged domestic shorthairs. •  Dogs—Rottweilers may be overrepresented. SIGNS

•  Lethargy. •  Anorexia. •  Intermittent vomiting and diarrhea. •  Hepatosplenomegaly. •  Weight loss. •  Thickened (diffuse or segmental) intestine

that is often nonpainful.

•  Lymphadenopathy (especially mesenteric). •  Dyspnea. •  Mass lesions caused by eosinophilic

granulomatous inflammation and infiltration. •  Less frequently—fever, pruritus, seizures, thromboembolic events. CAUSES & RISK FACTORS

•  Unknown; probably severe reaction to

unidentified antigen.

marrow higher (>10 : 1) with more immature/ blast forms and disorderly maturation; tissue infiltrates consist of immature eosinophils and may show sinusoidal pattern in liver without fibrosis; in cats, chloroma-like masses in kidneys are reported. CBC/BIOCHEMISTRY/URINALYSIS •  Leukocytosis with marked eosinophilia, possibly with left shift in eosinophil series; mature eosinophil count from 5,000 to >130,000/μL. •  Basophilia. •  Mild anemia. •  With organ damage or dysfunction, associated abnormalities seen. OTHER LABORATORY TESTS Rule out identifiable etiologies—fecal flotation, heartworm test, biopsy.

 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Reactive eosinophilia—parasitism, allergic/ hypersensitivity reactions, infectious disease, immune-mediated disease, fungal infections, neoplasia; with these conditions, eosinophilia usually limited in magnitude and remains confined to specific organ. •  Eosinophilic leukemia—differentiating criteria: eosinophilic leukemia tends to have immature eosinophils seen in higher numbers in circulation, constituting higher percentage of leukocyte differential; anemia more common and often more severe; myeloid : erythroid (M : E) ratio in bone

if not normal or near normal after 7–14 days of steroid treatment; used long term if effective in conjunction with steroids. •  Cyclosporine A—suppresses production of eosinophilopoietic factors by T cells. •  Vincristine and alkylating agents such as chlorambucil effective in humans. •  Reduce dosage or discontinue drugs if bone marrow suppression or thrombocytopenia develops. CONTRAINDICATIONS/POSSIBLE INTERACTIONS •  Specific drug toxicities for each agent, most notably myelosuppression. •  Imatinib mesylate may lead to proteinlosing nephropathy, although association uncertain.

IMAGING

•  Organ enlargement/infiltration may be

visualized with survey radiographs and/or ultrasound. •  Intestinal mucosal irregularities and thickening seen on ultrasound or contrast radiography. DIAGNOSTIC PROCEDURES

•  Bone marrow aspiration and/or core biopsy. •  Fine-needle aspirate or biopsy of affected

tissues.

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 FOLLOW-UP

•  Serial CBC monitoring of eosinophil count

(not always indicative of tissue infiltrates) and to detect myelosuppression if myelotoxic drugs used. •  Monitor clinical signs and any physical abnormalities. •  Other testing for specific organ function.

PATHOLOGIC FINDINGS

•  Spleen—eosinophilic infiltrates in red pulp,

sometimes white.

•  GI tract—mucosal and submucosal

eosinophilic infiltrates in small intestine, sometimes in colon and stomach. •  Bone marrow—hypercellularity, eosinophilic hyperplasia (up to 40% of all nucleated cells), unremarkable maturation and morphology with high M : E ratio (mean 7.27 : 1). •  Lymph nodes—reactive with eosinophilic infiltration. •  Other (less frequent)—eosinophilic infiltrates in skin, myocardium, body cavity effusions.

•  Cats—eosinophilic enteritis may be early form.

­

•  Hydroxyurea—to reduce eosinophil count

­

 TREATMENT

­

 MEDICATIONS

•  Eliminate identifiable primary disease. •  Address any specific organ dysfunction/failure.

DRUG(S) OF CHOICE •  Corticosteroids—prednisone 1–2 mg/kg/ day PO initially, then taper therapy if eosinophilia suppressed; if eosinophilia returns, resume higher daily dose. •  Imatinib mesylate approved in humans to treat chronic myelogenous leukemia as well as HES, used with possible efficacy in cats at 9.6 mg/kg PO q24h.

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 MISCELLANEOUS

SEE ALSO Eosinophilia ABBREVIATIONS •  GI = gastrointestinal. •  HES = hypereosinophilic syndrome. •  M : E = myeloid : erythroid.

­Suggested Reading

Lilliehook I, Tvedten H. Investigation of hypereosinophilia and potential treatment. Vet Clin North Am Small Anim Pract 2003, 33:1359–1378. Author Craig A. Thompson Consulting Editor Melinda S. Camus



Canine and Feline, Seventh Edition

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Hyperestrogenism (Estrogen Toxicity) •  Epistaxis, hematuria (thrombocytopenia);

­

 BASICS

OVERVIEW •  A syndrome characterized by high serum concentration of estrogen (estradiol, estriol, or estrone). •  Can occur secondary to endogenous estrogen secretion or exogenous admin­ istration of estrogens, such as diethylstilbestrol or estriol. •  Sites of endogenous estrogen production include ovarian follicles, follicular ovarian cysts, Leydig cells, and the adrenal cortex (zona fasciculata and reticularis); can also occur as a result of peripheral conversion of excessive androgens. •  Endogenous estrogens in females are responsible for normal sexual behavior and development and function of the reproductive tract; in the male, estrogens are responsible for Leydig cell function. •  In females, estrogens potentiate the stimulatory effect of progesterone in the endometrium and permit cervical relaxation; these two effects increase the risk of cystic endometrial hyperplasia and pyometra. In the male, estrogens potentiate the action of androgens in the prostate. Estrogens also increase osteoblastic activity, retention of calcium and phosphorus, total body protein, and metabolic rate. •  High serum concentration of estrogen provides a source of negative feedback in the hypothalamic-pituitary axis, suppressing gonadotropin secretion, and interferes with stem cell differentiation in the bone marrow and erythrocyte iron metabolism. SIGNALMENT Endogenous Hyperestrogenism

•  Older male dog (secondary to functional

testicular tumors).

•  Older female dog (secondary to granulosa

cell or other functional ovarian tumors, follicular ovarian cysts). •  Young female dog (follicular ovarian cysts). Exogenous Hyperestrogenism

•  All breeds, genders, and ages, associated

with estrogen administration or exposure.

•  Toy breed dogs are at increased risk for

exposure to human transdermal hormone medications. SIGNS

Historical Findings

•  Attractive to intact male dogs. •  Infertility. •  Prolonged proestrus and estrus (female). •  Decreased libido (male). •  Nymphomania (female). •  Variable vulvar bleeding and enlargement,

excessive vulvar licking.

lethargic, febrile (neutropenia); lethargic (anemia).

Physical Examination Findings

•  Skin/endocrine—nonpruritic, symmetric

alopecia (endocrine alopecia), hyperpig­mentation. •  Reproductive (male)—palpable testicular mass, testicular asymmetry (tumor and/or atrophy), cryptorchidism (unilateral or bilateral), prostatomegaly (squamous metaplasia), gynecomastia. •  Reproductive (female)—vulvar edema and enlargement, vulvar discharge, gynecomastia mammary gland enlargement. •  Hemic/lymphatic/immune—pale mucous membranes, petechia, fever, lethargy (blood loss). CAUSES & RISK FACTORS

•  Follicular ovarian cysts. •  Functional ovarian tumor (granulosa cell

tumor and other ovarian tumors).

•  Testicular tumor (specifically Sertoli cell

tumor, but also Leydig and interstitial cell tumors). •  Exogenous estrogen exposure.

­

 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS Nonpruritic, Symmetric Alopecia

•  Hypothyroidism—diagnose on clinical

signs, biochemistry, CBC, and thyroid function testing. •  Hyperadrenocorticism—diagnose on clinical signs (polyuria, polydipsia, exercise intolerance), CBC, serum biochemistry, specific testing (urine cortisol : creatinine ratio, adrenal function testing). •  Growth hormone–responsive dermatosis (breed risk: Pomeranian). Attractive to Male Dogs

•  Vaginitis, perivulvar dermatitis

(differentiate from hyperestrogenism by lack of vaginal superficial epithelial cell predominance on vaginal cytology), lack of evidence of ovarian abnormalities, or confirmation of complete ovariohysterectomy or ovariectomy. •  Genitourinary tract infection, inflammation, foreign body, or neoplasia. Infertility

•  Testicular degeneration/atrophy/immune-

mediated orchitis—diagnosis based on physical examination, lack of testicular or intra-abdominal masses, semen evaluation, and testicular biopsy or fine-needle aspirate. •  Intersex abnormalities—uncommon; diagnosis supported by abnormal external genitalia, abnormal karyotype, and histologic examination of the reproductive tract, when available.

CBC/BIOCHEMISTRY/URINALYSIS

•  CBC—variable; initially characterized by

thrombocytopenia or thrombocytosis, progressive anemia, and leukocytosis (may exceed 100,000 white blood cells [WBCs]/μL); after 3 weeks, pancytopenia and aplastic anemia seen. •  Chemistry panel and urinalysis are usually unremarkable, but hematuria can be present with thrombocytopenia. OTHER LABORATORY TESTS •  Serum estrogen (estradiol) concentrations—prolonged (>30 days) elevation at levels above baseline is responsible for clinical signs rather than the actual concentration; serum concentrations may be within normal limits, and accuracy of radioimmunoassay is variable. •  Vaginal and preputial cytology—extremely reliable as a bioassay for estrogen; under the influence of estrogen, cytology reveals a predominance of superficial epithelial cells that are anuclear or have pyknotic nuclei; preputial cytology with greater than 20% superficial cells is consistent with elevated serum estrogen. •  Evaluation for ovarian remnant syndrome (ORS)—anti-Müllerian hormone (AMH) testing: a positive test in a bitch >6 months of age or >30 days from ovariohysterectomy supports the presence of ovarian tissue; in cases with negative AMH but convincing clinical evidence supporting ORS, some investigators advise measurement of serum progesterone to identify persistent luteal structures lacking AMH; the AMH test will differentiate between ORS and exogenous estrogen exposure. •  The semi-quantitative luteinizing hormone (LH) assay (Zoetis), if elevated, suggests a lack of ovaries, but cannot differentiate exogenous vs. endogenous estrogen exposure if low. IMAGING

•  Thoracic radiography—to evaluate for

metastatic neoplasia.

•  Ultrasonography of the abdomen, inguinal

canal, and testes—to assess for testicular masses, cystic or enlarged ovarian structures, intra-abdominal masses, lymphadenopathy, and prostatomegaly. •  Vaginoscopy to evaluate the vaginal mucosa; under the influence of estrogen, the vaginal mucosa should appear edematous and pink. DIAGNOSTIC PROCEDURES

•  Fine-needle aspiration of testicular

masses—cytologic diagnosis prior to surgery.

•  Percutaneous ultrasound-guided aspiration

of large ovarian follicular cysts—rarely results in clinical resolution (cystic structure persists); hormone concentration can be measured in the cystic fluid.

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Blackwell’s Five-Minute Veterinary Consult

Hyperestrogenism (Estrogen Toxicity) •  Examination and aspiration/biopsy of local

H

lymph nodes—for evaluation of metastatic disease (via ultrasound or surgical biopsy). •  Bone marrow aspirate or core biopsy— assess myelosuppression. •  Skin biopsy—may reveal nonspecific changes associated with endocrine alopecia such as orthokeratotic hyperkeratosis, epidermal atrophy and melanosis, follicular keratosis, predominance of telogen hair follicles, and sebaceous gland atrophy.

­

 TREATMENT

•  Treatment of choice in the intact or

partially neutered female and male is surgical neutering; the prognosis is good if residual or malignant gonadal tissue can be completely removed. •  Unilateral orchiectomy or ovariectomy of the affected neoplastic testicle or cystic or neoplastic ovary may be considered in valuable breeding animals; use of testicular prosthetic devices is neither advised nor ethical; contralateral testicular changes (male) or endometrial changes (female) secondary to prolonged estrogen exposure can contribute to subfertility even if the abnormal gonad has been removed, with a guarded prognosis for fertility; histopathology should always be performed to evaluate for neoplasia and local lymphatic metastasis. •  Discontinue estrogen exposure in cases of exogenous hyperestrogenism; discontinue or reduce the dose of exogenous estrogen if used therapeutically; prognosis is good.

­

 MEDICATIONS

DRUG(S) OF CHOICE •  Supportive care—including administration of appropriate antimicrobial therapy, IV

fluids, and blood products to treat febrile neutropenia or anemia. •  Synthetic erythropoietin, darbopoietin, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colonystimulating factor (GM-CSF)—may be considered to stimulate erythroid and granulocytic production at the level of the bone marrow; lithium has reportedly been of benefit in cases of estrogen-induced bone marrow aplasia. •  Gonadotropin-releasing hormone (GnRH)— unlikely to induce ovulation in cases of follicular cysts. •  Iron dextran to support erythrocyte regeneration—dog: 10–20 mg/kg (max 300 mg/dog) IM monthly PRN; cat: 10 mg/ kg IM monthly PRN. CONTRAINDICATIONS/POSSIBLE INTERACTIONS Chemotherapeutic agents for treatment of metastatic testicular or ovarian neoplasia should be used cautiously due to increased risk of bone marrow suppression. Consult with a veterinary oncologist.

(continued)

neoplasia or removal of follicular cysts is associated with a grave prognosis.

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 MISCELLANEOUS

ASSOCIATED CONDITIONS •  ORS. •  Prostatomegaly. •  Cystic endometrial hyperplasia and subfertility/infertility. •  Hepatic insufficiency. •  Bone marrow aplasia, pancytopenia. •  Sepsis. ABBREVIATIONS

•  AMH = anti-Müllerian hormone. •  G-CSF = granulocyte colony-stimulating

factor.

•  GM-CSF = granulocyte-macrophage

colony-stimulating factor.

•  GnRH = gonadotropin-releasing

hormone.

•  LH = luteinizing hormone. •  ORS = ovarian remnant syndrome. •  WBC = white blood cell.

­Suggested Reading

­

 FOLLOW-UP

•  Serial CBC analysis to evaluate response to

therapy and progression of disease.

•  Serial bone marrow cytology—to evaluate

bone marrow response and erythroid, myeloid, and megakaryocytic regeneration when myelosuppression is chronic; peripheral signs of regeneration may not occur for weeks to months after initial insult. •  Clinical signs of male feminization syndrome should resolve 2–6 weeks after testicular tumor removal. •  Lack of resolving pancytopenia and continued bone marrow hypoplasia 3 weeks after surgical removal of ovarian or testicular

Davidson AP. Reproductive system disor­ ders. In: Nelson RW, Couto GC, eds., Small Animal Internal Medicine, 5th ed. St. Louis, MO: Elsevier, 2014, pp. 897–966. Authors Autumn P. Davidson and Sophie A. Grundy Consulting Editor Patty A. Lathan  Client Education Handout available online



681

Canine and Feline, Seventh Edition

Hyperglycemia Historical Findings

•  Polydipsia and PU—PU might manifest as

­

 BASICS

DEFINITION •  Blood glucose (BG) concentration above the reference interval: >130 mg/dL (>7 mmol/L). •  For cats >8 years of age, BG concentration >189 mg/dL (10.5 mmol/L). PATHOPHYSIOLOGY

•  Physiologic (stress hyperglycemia)—normal,

transient response to stress, especially in cats. •  Laboratory or portable glucometer error— anemia results in artificially high BG concentration with some portable glucometers. •  IV infusion of dextrose-containing fluids. •  Drugs that inhibit insulin secretion (e.g., dexmedetomidine). •  Diabetes mellitus (DM)—absolute or relative insulin deficiency. SYSTEMS AFFECTED

•  Endocrine/metabolic—insulin deficiency

causes disorders of carbohydrate, protein, and fat metabolism; insulin resistance occurs via various mechanisms. •  Renal/urologic—osmotic diuresis from BG exceeding renal threshold causes polyuria (PU) with secondary polydipsia. •  Pancreas/hepatobiliary—beta cell loss; endocrine hepatopathy, hepatomegaly. •  Ophthalmic—persistent hyperglycemia can cause cataracts in dogs. •  Nervous—severe hyperglycemia may cause CNS dehydration from high serum osmolality; diabetic neuropathy in cats causes hind limb weakness and plantigrade, ± palmigrade, gait; other neuropathies are also possible (e.g., Horner’s syndrome). GENETICS Breed predispositions indicate likely genetic influences for DM in dogs and cats. INCIDENCE/PREVALENCE Prevalence of DM in hospital populations is 6 in 1,000 cats and 3 in 1,000 dogs. SIGNALMENT Species

Dog and cat. Mean Age and Range

Onset of DM typically occurs after 5 years of age; highest prevalence from 8–12 years of age. Predominant Sex

Neutered males (cats and dogs) and intact females (dogs) are predisposed to DM. SIGNS General Comments

•  DM—signs have insidious onset over weeks

to months.

•  Animals with concurrent disease, such as

pancreatitis, might not show “classic” signs of hyperglycemia.

inappropriate urination or urinary incontinence. •  Weight loss with normal or increased appetite. •  Lethargy. •  Vision loss due to diabetic cataracts (dogs). •  Weak plantigrade gait due to diabetic neuropathy (cats). •  Previous overweight/obesity (especially cats and intact female dogs). •  Severe hyperglycemia can cause decreased mentation, coma. Physical Examination Findings

•  May be normal. •  Obese, normal, or underweight. •  Sarcopenia. •  Lethargy. •  Dehydration. •  Plantigrade ± palmigrade gait (cats). •  Cataracts (dogs). •  Hepatomegaly. •  Chronic infections—respiratory, skin,

urinary tract.

•  Poor hair coat. •  Ketotic or sweet odor to breath. •  Separation of incisors, broadening of the

face, and organomegaly in cats with hypersomatotropism. CAUSES

•  DM—a heterogeneous group of diseases

characterized by hyperglycemia resulting from inadequate insulin secretion, inadequate insulin action, or both. •  Inadequate insulin action (insulin resistance) is associated with hyperadreno­ corticism, pheochromocytoma, glucagonoma, hypersomatotropism, hyper- and hypothyroidism, high progesterone during diestrus (dogs), and drugs (e.g., thiazide diuretics, progestogens [e.g., megestrol acetate], growth hormone, topical and systemic corticosteroids, and dexmedetomidine. •  Chronic hyperglycemia (glucose toxicity) can cause insulin resistance. RISK FACTORS

•  Breed predispositions for DM vary with

geographic region.

•  Older age. •  Obesity. •  Sedentary/indoor lifestyle. •  Stress. •  Concurrent disease, particularly hyper-

adrenocorticism, hypersomatotropism, pancreatitis. •  Diestrus in dogs. •  Diabetogenic drugs—corticosteroids, progestogens. •  Dextrose-containing fluids.

­

 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Stress hyperglycemia—differentiated from DM by documentation of persistent fasting hyperglycemia for more than 24 hours, or increased serum glycated protein concen­trations. •  DM. •  Diagnosis of DM in cats: ◦◦ Random (fasted or unfasted) BG ≥270 mg/dL (15 mmol/L) with clinical signs of hyperglycemia (with no other plausible cause) or hyperglycemic crisis and at least one of the following: increased serum glycated protein concentrations; glycosuria on more than one occasion on a voided sample acquired in a home environment at least 2 days after any stressful events. ◦◦ Random (fasted or unfasted) BG between 130 and 270 mg/dL (7–15 mmol/L) and at least two of the following: clinical signs of hyperglycemia or hyperglycemic crisis; increased serum glycated protein concentrations; glycosuria on more than one occasion on a voided sample acquired in a home environment at least 2 days after any stressful events. •  Diagnosis of DM in dogs: ◦◦ Fasted or unfasted BG ≥200 mg/dL (11 mmol/L) with clinical signs of hyperglycemia or hyperglycemic crisis. ◦◦ Fasting BG 130–200 mg/dL (7–11 mmol/L) with or without clinical signs of hyperglycemia or hyperglycemic crisis. •  DM is likely when hyperglycemia occurs in combination with ketosis and/or ketonuria. LABORATORY FINDINGS Factors That May Alter Laboratory Results •  Delayed serum or plasma separation lowers

glucose concentration; glucose concentration should be measured within 30 minutes of collection; whole blood samples collected in fluoride oxalate anticoagulant may be stored. •  Lipemia, hemolysis, and icterus may interfere with spectrophotometric assays. •  Glucometers intended for human use tend to underestimate the true BG in cats and dogs; wide variability in the accuracy of different meters necessitates correlation of results from each meter with results from a veterinary diagnostic laboratory prior to use. •  Veterinary-specific glucometers provide more accurate results than human glucometers. •  BG reagent strips require whole blood, must be stored correctly, and be in date. CBC/BIOCHEMISTRY/URINALYSIS

•  Hyperglycemia might be the only abnormal

finding.

•  For findings associated with DM, see

specific chapters.

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Blackwell’s Five-Minute Veterinary Consult

Hyperglycemia

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OTHER LABORATORY TESTS •  Fructosamine concentration identifies degree of glycemia over the previous 2–3 weeks; results are assay dependent and may be affected by hemolysis or lipemia; provides no information on variability of BG concentrations. •  Glycosylated hemoglobin concentration identifies degree of glycemia over the previous 10 weeks (cats) or 16 weeks (dogs); provides no information on variability of BG concentrations. •  Adrenocorticotropic hormone (ACTH) stimulation test or low-dose dexamethasonesuppression test to diagnose hyperadrenocorticism in dogs; false-positive results might be obtained if there is poor diabetic control. •  Serum insulin-like growth factor 1 (IGF-1) assay to diagnose hypersomatotropism in cats; false-negative results are more likely when there is severe insulin deficiency; cats should be treated with insulin for 4–6 weeks prior to testing.

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 TREATMENT

APPROPRIATE HEALTH CARE •  Stress hyperglycemia is self-limiting. •  Diabetic cats and dogs that are eating well—outpatient management. •  Those that are unwell, inappetent, or have other signs such as vomiting require inpatient management with insulin and IV fluids. •  Concurrent disease can compromise DM management and should be promptly diagnosed and treated. NURSING CARE Glucose monitoring is recommended for all hospitalized hyperglycemic patients. Venous or capillary blood testing using a veterinary glucometer is appropriate. Real-time continuous glucose monitoring systems (CGMS) or flash glucose monitoring systems (FGMS) can simplify glucose monitoring of hospitalized patients. ACTIVITY Activity does not need to be limited in dogs and cats with DM and may decrease insulin requirement in working diabetic dogs. DIET

•  See relevant chapters on DM. •  Nutritional requirements for concurrent

diseases take precedence over nutritional requirements for DM; good diabetic control can be achieved with insulin treatment regardless of diet. CLIENT EDUCATION

•  Client education is critical, because most

treatment and monitoring of a diabetic patient will be done by the owner at home, and clinical signs will guide treatment decisions. •  Owner concerns relating to the impact that treating their pet will have on their lifestyle should be addressed.

(continued)

SURGICAL CONSIDERATIONS

•  Approximately 8% chance of diabetic

remission following neutering and insulin therapy in female dogs; those that do not achieve remission generally have improved diabetic control. •  Improved diabetic control and possibly remission will occur following hypophysectomy in cats with hypersomatotropism; however, this treatment is expensive with limited availability.

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 MISCELLANEOUS

ASSOCIATED CONDITIONS •  Hyperosmolality. •  Diabetic ketoacidosis. •  Hyperadrenocorticism. •  Hypersomatropism. •  Pancreatitis. PREGNANCY/FERTILITY/BREEDING

•  In intact bitches, a form of diabetes

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 MEDICATIONS

DRUG(S) OF CHOICE •  Exogenous insulin is the mainstay of treatment of DM. •  See chapters on DM. PRECAUTIONS

•  See chapters on DM. •  Drugs that cause insulin resistance (e.g.,

systemic or topical corticosteroids) should be used with caution in hyperglycemic animals; an increased insulin dose may be necessary. POSSIBLE INTERACTIONS Concurrent use of insulin and oral hypoglycemic agents might lead to hypoglycemia.

ALTERNATIVE DRUG(S) •  Glipizide and acarbose. •  See chapters on DM.

analogous to human gestational diabetes can occur during diestrus or pregnancy; if insulin therapy is initiated promptly, diabetic remission can sometimes be achieved following spay or whelping. •  Increased incidence of dystocia (large fetal size) and hypoglycemia in neonates when hyperglycemia has been present during pregnancy. SYNONYMS High blood sugar. SEE ALSO

•  Diabetes Mellitus with Ketoacidosis. •  Diabetes Mellitus Without Complication—

Cats.

•  Diabetes Mellitus Without Complication—

Dogs.

•  Hyperosmolality.

ABBREVIATIONS

•  ACTH = adrenocorticotropic hormone. •  BG = blood glucose. •  CGMS = continuous glucose monitoring

system.

­

 FOLLOW-UP

PATIENT MONITORING •  See chapters on DM. •  Animals in diabetic remission require ongoing monitoring for recurrence of hyperglycemia. PREVENTION/AVOIDANCE •  Minimize use of diabetogenic drugs, particularly in susceptible individuals. •  Prevent obesity in cats and intact female dogs. •  Neuter female dogs at risk of developing DM. POSSIBLE COMPLICATIONS

•  Severe hyperglycemia may be associated

with CNS depression and coma because of hyperosmolality. •  Diabetic cataracts (dogs). •  Diabetic neuropathy in cats with poor diabetic control. •  Insulin-induced hypoglycemia. EXPECTED COURSE AND PROGNOSIS

•  Transient stress hyperglycemia is self-limiting. •  Treatment of DM often is associated with

an excellent prognosis, and typically results in a very good quality of life and similar life expectancy to animals without diabetes.

•  DM = diabetes mellitus. •  FGMS = flash glucose monitoring system. •  IGF-1 = insulin-like growth factor 1. •  PU = polyuria.

INTERNET RESOURCES https://esve.org/alive/search.aspx

­Suggested Reading

Behrend E, Holford A, Lathan P, et al. AAHA diabetes management guidelines for dogs and cats. J Am Anim Hosp Assoc 2018, 54(1):1–21. Reeve-Johnson MK, Rand JS, Vankan D, et al. Cutpoints for screening BG concentrations in healthy cats. J Fel Med Surg 2017, 19(12):1181–1191. Sparkes AH, Cannon M, Church D, et al. ISFM consensus guidelines on the practical management of diabetes mellitus in cats. J Fel Med Surg 2015, 17:235–250. Thompson A, Lathan P, Fleeman L. Update on insulin treatments for dogs and cats: insulin dosing pens and more. Vet Med Res Reports 2015, 6:129–142. Authors Linda M. Fleeman and Sarah B. Pierard Consulting Editor Patty A. Lathan



683

Canine and Feline, Seventh Edition

Hyperkalemia

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 BASICS

DEFINITION Serum potassium concentration higher than the testing laboratory’s upper limit of normal, generally >5.7 mEq/L (mmol/L). PATHOPHYSIOLOGY •  Potassium is primarily intracellular; serum concentrations do not accurately reflect tissue concentrations. •  Hyperkalemia is often associated with cellular injury (e.g., trauma and ischemia) and other causes of translocation of potassium out of the intracellular space (e.g., acidosis). •  Potassium is eliminated in the kidneys and elimination is enhanced by aldosterone; conditions that inhibit renal elimination of potassium will cause hyperkalemia. SYSTEMS AFFECTED •  Cardiovascular—potassium affects cardiac conduction, and changes are reflected on the ECG; as potassium rises, the T waves become tall and spiked with a narrow base, the QRS complexes widen, and the P–R intervals lengthen; the P waves become smaller and wider and, in animals with severe hyperkalemia, disappear (atrial standstill); higher concentrations of potassium cause fusion of the QRS–T, which causes a wide complex idioventricular brady­ arrhythmia followed by ventricular fibrillation or asystole; ECG changes in animals with hyperkalemia vary and are diminished by hypernatremia, hypercalcemia, and alkalosis. •  Nervous—neuromuscular weakness. SIGNALMENT •  Dog and cat. •  Pseudohyperkalemia in certain East Asian dog breeds (e.g., Akita, Shiba, Jindo, and Chinese Shar-Pei). SIGNS Historical Findings

•  Weakness. •  Collapse. •  Stranguria, pollakiuria, pigmenturia (animals with urethral obstruction). •  Flaccid paralysis. •  Death.

Physical Examination Findings

•  In addition to historical findings, arrhythmias, especially bradyarrhythmias. •  Firm, non­ expressible urinary bladder, abdominal pain in animals with urethral obstruction. •  Abdominal fluid wave, distended abdomen in patients with urinary bladder rupture.

CAUSES •  Pseudohyperkalemia—some blood cells (generally reported in red blood cells [RBCs] of East Asian dog breeds including Akita, Shiba, Jindo, and Chinese Shar-Pei; also platelets and white blood cells [WBCs] in any breed) contain high concentrations of potassium; if the blood sample is not analyzed or separated promptly, this intracellular potassium is released into the serum, causing the potassium concentration to be artificially high (pseudohyperkalemia); seen in patients with thrombocytosis or severe leuko­ cytosis. •  Low potassium elimination—anuric or oliguric renal failure; hypoadreno­corticism; renal

hypoperfusion; urinary tract rupture or urethral obstruction; administration of potassium-sparing diuretics, angiotensin-converting enzyme (ACE) inhibitors, trimethoprim, nonsteroidal antiinflammatory drugs, or heparin (causing hypoaldosteronism); some gastrointestinal diseases (e.g., salmonellosis, trichuriasis). •  Translocation of potassium—metabolic acidosis, reperfusion syndrome, thrombolysis in feline aortic thromboembolism, tumor lysis syndrome, muscle injury (trauma, phosphofruc­ tokinase deficiency), digitalis overdose, infusion of mannitol and hyper­glycemia (causing hyperosmolality). •  High potassium intake—oral or parenteral potassium supplements or potassium bromide toxicosis. •  Miscellaneous— third space fluid accumulation (e.g., pleural effusion, ascites). RISK FACTORS •  IV fluid therapy with excessive potassium supplementation. •  Administration of potassiumsparing diuretics (e.g., spironolactone) and ACE inhibitors (e.g., enalapril, benazepril), primarily in patients with renal disease. •  Hypoadrenocorticism. •  Trauma. •  Renal disease. •  Lower urinary tract disease including cystic calculi. •  Thrombocytosis and leukemia. •  Akita, Shiba, Jindo, and Chinese Shar-Pei— pseudohyperkalemia; not all animals within a breed are at risk for pseudohyperkalemia; approximately 20% of Akitas have the high potassium phenotype. •  Phosphofructokinase deficiency.

­

 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Waxing and waning history of gastrointestinal complaints, weakness, collapse—consider hypoadrenocorticism. •  Straining to urinate or low urine output—consider urinary obstruction or oliguric/anuric renal failure. LABORATORY FINDINGS Disorders That May Alter Laboratory Results

Thrombocytosis (>1,000,000 cells/mm3), leukocytosis (>200,000 cells/mm3), and abnormal (leukemic) leukocytes can cause release of large amounts of potassium into the serum. CBC/BIOCHEMISTRY/URINALYSIS •  In patients with Na : K ratio 7.0 or patient showing signs or ECG changes consistent with hyperkalemia

H

NO

YES Evaluate CBC, serum chemistry profile, and urinalysis

Elevated CK, AST, LDH

K > 5.7 mEq/L

Na:k < 27 or unexplained hyperkalemia

R/O muscle trauma, tumor lysis syndrome, reperfusion postthrombolysis

None of these

Azotemia

Normal or exaggerated responses: R/O gastrointestinal disease (recheck when signs resolve), primary hypoaldosteronism

R/O translocation secondary to acidosis

Specific gravity > 1.029 (dog) or 1.034 (cat) R/O prerenal causes and post-renal obstruction or tear

Specific gravity < 1.029 (dog) or 1.034 (cat) R/O Addison’s disease, oliguric or anuric renal failure

R/O pleural or abdominal effusion, hyperosmolality [hyperglycemia] pseudohypoadrenocorticism, hyperkalemic periodic paralysis

Measure aldosterone following ACTH stimulation Decreased aldosterone: R/O primary hypoaldosteronism

Hypercholoremic acidosis (normal anion gap)

Check urine specific gravity

ACTH response test

Depressed response: R/O Addison’s disease or prior corticosteroid therapy

Repeat with lithium heparin plasma to rule-out pseudohyperkalemia (acute, severe thrombocystosis or leukocytosis) and lab error

Recheck after effusions resolved. Recheck after hyperosmolality corrected. Challenge with low-dose oral KCI

Figure 1. Algorithm for diagnosing hyperkalemia.

CONTRAINDICATIONS •  Avoid IV fluids with high concentrations (>10 mEq/L) of potassium and fluids that cause hyponatremia, acidosis, or hypocalcemia. •  Avoid drugs that contain potassium or interfere with potassium elimination (e.g., ACE inhibitors, trimethoprim antibiotics, potassium-sparing diuretics) or interfere with renal function (e.g., nonsteroidal anti-inflam­ matory drugs). PRECAUTIONS

•  Kayexalate and sodium bicarbonate cause a

sodium load that may lead to fluid retention in patients with cardiac or renal failure. •  Sodium bicarbonate lowers ionized calcium levels—use cautiously in hypocalcemic patients. •  Sodium bicarbonate elevates blood carbon dioxide concentration—use cautiously in patients with hypoventilation. ALTERNATIVE DRUG(S) Patiromer and sodium zirconium cyclosilicate are recently approved agents that bind potassium within the intestinal tract, limiting absorption and reabsorption; rarely used in

veterinary practice; may have application in chronic hyperkalemia.

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 FOLLOW-UP

PATIENT MONITORING •  Recheck potassium at frequency dictated by the underlying disease. •  Continuous ECG monitoring until rhythm disturbances resolve. PREVENTION/AVOIDANCE

•  Monitor potassium in patients receiving drugs that alter potassium elimination. •  The

maximum rate of IV potassium administration is 0.5 mEq/kg/h, and should be used only in the face of severe hypokalemia (average supplementation rate is between 0.05 and 0.2 mEq/kg/h in patients without acute renal disease).

POSSIBLE COMPLICATIONS •  Prolonged hypoglycemia following insulin administration. •  Death of animals with severe hyperkalemia.

 MISCELLANEOUS

PREGNANCY/FERTILITY/BREEDING Combined hyperkalemia and hyponatremia may be seen in pregnant dogs due to thirdspace fluid accumulation in the uterus. SEE ALSO •  Acidosis, Metabolic. •  Acute Kidney Injury. •  Atrial Standstill. •  Hypoadrenocorticism (Addison’s Disease). •  Phosphofructokinase Deficiency. •  Urinary Tract Obstruction. ABBREVIATIONS

•  ACE = angiotensin-converting enzyme. •  ACTH = adrenocorticotropic hormone. •  RBC = red blood cell. •  WBC = white blood cell.

­Suggested Reading

Kogika MM, deMorais HA. A quick reference on hyperkalemia. Vet Clin North Am Small Anim Pract 2017, 47(2):223–228. Author Francis W.K. Smith, Jr. Consulting Editor Patty A. Lathan



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Canine and Feline, Seventh Edition

Hyperlipidemia •  Megestrol acetate (cat).

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 BASICS

DEFINITION •  Increased concentration of lipid in the blood of a fasted (>12 hours) patient; includes hypercholesterolemia, hypertri­ glyceridemia, or both. •  Lipemia—serum or plasma separated from blood that contains an excess concentration of triglycerides (>200 mg/dL). •  Lactescence—opaque, milk-like appearance of serum or plasma that contains an even higher concentration of triglycerides (>1,000 mg/dL) than lipemic serum. PATHOPHYSIOLOGY Primary Hyperlipidemia

•  Primary (idiopathic) hyperlipidemia—defect

in lipid metabolism causing hypertriglyceridemia with or without hyperchylomicronemia; likely hereditary in miniature schnauzer, but the genetic defect has yet to be determined. •  Idiopathic hyperchylomicronemia in cats— familial, autosomal recessive defect in lipoprotein lipase activity. •  Primary hypercholesterolemia—occurs in some families of briard, rough collie, Shetland sheepdog, Doberman pinscher, and Rottweiler; low-density lipoprotein (LDL) cholesterol is high. Secondary Hyperlipidemia

•  Postprandial—absorption of chylomicrons

from the gastrointestinal tract occurs 30–60 minutes after ingestion of a meal containing fat; may increase serum triglycerides for up to 12 hours. •  Diabetes mellitus—low lipoprotein lipase (LPL) activity; high synthesis of very-lowdensity lipoprotein (VLDL) by the liver. •  Hypothyroidism—low LPL activity and lipolytic activity by other hormones (e.g., catecholamines); reduced hepatic degradation of cholesterol to bile acids. •  Hyperadrenocorticism—increased synthesis of VLDL by the liver and low LPL activity causes both hypercholesterolemia and hypertriglyceridemia. •  Cholestatic liver disease—hypercholester­ olemia caused by reduced excretion of cholesterol in the bile. •  Nephrotic syndrome—upregulation of common synthetic pathway for albumin and cholesterol and possibly low oncotic pressure lead to increased cholesterol synthesis. •  Pancreatitis—associated with hypertri­ glyceridemia in dogs, especially miniature schnauzers. •  Obesity—excessive hepatic synthesis of VLDL. Drug-Induced Hyperlipidemia •  Glucocorticoids.

SYSTEMS AFFECTED

•  Endocrine/metabolic. •  Gastrointestinal. •  Hepatobiliary. •  Nervous. •  Ophthalmic.

SIGNALMENT

•  Dog and cat. •  Variable, depending on the cause. •  Hereditary hyperlipidemias—age of onset

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS Fasting Hyperlipidemia

Rule out postprandial lipemia with a 12-hour fast. Primary Hyperlipoproteinemia

•  Idiopathic hyperlipidemia is observed most

SIGNS

commonly in the miniature schnauzer breed. •  Hyperchylomicronemia in cats often manifests as polyneuropathies and lipogranulomas. •  Idiopathic hypercholesterolemia is observed in a variety of breeds; animals are often asymptomatic.

Historical Findings

Secondary Hyperlipidemia

is >8 months in cats and >4 years in predisposed breeds of dog such as the miniature schnauzer.

•  Asymptomatic. •  Recent ingestion of a meal. •  Seizures, neurologic signs. •  Abdominal pain and distress. •  Neuropathies.

Physical Examination Findings

•  Lipemia retinalis. •  Lipemic aqueous. •  Neuropathy. •  Cutaneous xanthomata. •  Lipid granulomas in abdominal organs.

CAUSES Increased Absorption of Triglycerides or Cholesterol

Postprandial

Increased Production of Triglycerides or Cholesterol

•  Diabetes mellitus. •  Hypothyroidism. •  Pancreatitis. •  Hyperadrenocorticism. •  Hepatic disease and cholestatic disorders. •  Nephrotic syndrome.

LABORATORY FINDINGS Sample Handling

•  Submit serum. •  Lipemia causes hemolysis if serum remains

with red blood cells for a long time; inquire about the laboratory method of clearing lipemic samples before submission. •  Two samples may be submitted—one for biochemical analysis, which may be cleared, and one for triglycerides and cholesterol concentrations.

Drugs That May Alter Laboratory Results

•  Idiopathic. •  Nephrotic syndrome. •  Pregnancy. •  Defects in lipid clearance enzymes or lipid

•  Corticosteroids. •  Phenytoin. •  Prochlorperazine. •  Thiazides. •  Phenothiazines.

•  Idiopathic hyperchylomicronemia. •  Hyperchylomicronemia in cats.

Disorders That May Alter Laboratory Results

carrier proteins.

Decreased Clearance of Triglycerides or Cholesterol •  Hypothyroidism. •  Hyperadrenocorticism. •  Diabetes mellitus. •  Pancreatitis. •  Cholestasis.

RISK FACTORS •  Obesity. •  High dietary intake of fats. •  Genetic predisposition in miniature schnauzer and Himalayan cat. •  Idiopathic hypercholesterolemia observed in families of briard, rough collie, Shetland sheepdog, Doberman pinscher, and Rottweiler.

•  Falsely high cholesterol. •  Nonfasted samples (150 mg/dL; cats: >100 mg/dL. •  High serum cholesterol concentration— dogs: >300 mg/dL; cats: >200 mg/dL. •  Serum biochemistry may reveal abnormalities consistent with causes of secondary hyperlipidemia.

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Blackwell’s Five-Minute Veterinary Consult

Hyperlipidemia •  Results of urinalysis often normal;

proteinuria if nephrotic syndrome present. OTHER LABORATORY TESTS

•  High-density lipoprotein (HDL) and

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LDL determinations—used in human medicine; values reported for HDL and LDL in dogs and cats cannot be assumed to be reliable. •  Chylomicron test—obtain serum sample after a 12-hour fast and refrigerate for 12–14 hours; do not freeze; chylomicrons rise to the surface and form a creamy layer. •  Lipoprotein electrophoresis—separates LDL, VLDL, and HDL1 and HDL2 subfractions. •  LPL activity—collect serum for triglycerides and cholesterol concentrations and lipoprotein electrophoresis before and 15 minutes after administration of heparin (90 IU/kg, IV); if there is no change in values before and after heparin administration, a defective LPL enzyme system should be suspected. •  Definitive diagnostics for hypothyroidism or hyperadrenocorticism, if suspected.

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 TREATMENT

Diet should contain 0.58 mmol/L. •  Cats—serum magnesium >2.99 mg/dL; ionized magnesium >0.65 mmol/L. PATHOPHYSIOLOGY •  Hypermagnesemia is less clinically significant than low total body magnesium in veterinary patients. •  Magnesium is second only to potassium as the most abundant intracellular cation. Found primarily in bone and muscle, it is required for many metabolic functions. •  Serum magnesium is present in three forms—protein-bound form (approximately 25–30%) and chelated and ionized forms (together account for 70–75%). •  Magnesium absorption occurs primarily in the ileum, but also in the jejunum and colon. •  Magnesium is an important cofactor in the sodium-potassium ATPase pump that maintains electrical gradients across membranes. •  Interference with the electrical gradient can change resting membrane potentials; repolarization disturbances result in neuromuscular and cardiac abnormalities. •  The kidneys maintain magnesium balance with 10–15% reabsorbed in the proximal tubule, 60–70% in the thick ascending limb of the loop of Henle, and 10–15% reabsorbed in the distal convoluted tubule. Reabsorption within the distal convoluted tubule is under hormonal and neurohormonal control and determines the final urine concentration of magnesium. •  Any condition that severely lowers the glomerular filtration rate can elicit hyper­ magnesemia because magnesium homeostasis is largely controlled by renal elimination. •  Clinically significant hypermagnesemia is more commonly associated with acute kidney injury, and the degree of hyper­ magnesemia is proportional to the severity of renal failure. •  Exuberant supplementation of magnesium can lead to iatrogenic hypermagnesemia, especially in patients with decreased renal function. •  High magnesium concentration impairs transmission of nerve impulses and decreases postsynaptic responses at the neuromuscular junction. When magnesium was given to anesthetized dogs at 0.12 mEq/kg/min, cardiovascular effects were not noted until plasma levels exceeded 12.2 mEq/L. The total dose of magnesium required to reach that level was 1–2 mEq/kg. It took cumulative doses of 5.9–10.9 mEq/kg to cause fatal cardiac arrhythmias (ventricular fibrillation).

blocker; the most serious complications of hypermagnesemia result from calcium antagonism in the cardiac conduction system. SYSTEMS AFFECTED

•  Cardiovascular. •  Musculoskeletal. •  Nervous.

INCIDENCE/PREVALENCE Increased plasma ionized magnesium concentration was found in 2% of 9,950 canine submissions to a clinical laboratory. In that study, 40% of the cases were caused by azotemia, 19% were iatrogenic, 11% had tissue damage, and 6% had endocrine disease. In another study, hypermagnesemia was found in 18% of hospitalized cats and 13% of hospitalized dogs. Most of these patients also had renal insufficiency or postrenal azotemia.

given in conjunction with activated charcoal, magnesium-containing laxatives, and excess magnesium in peritoneal dialysis solutions. •  Iatrogenic oversupplementation, especially in patients with concurrent renal disease. RISK FACTORS

•  Dehydration. •  Renal disease. •  Intestinal hypomotility. •  Massive hemolysis. •  Hypoadrenocorticism. •  Hyperparathyroidism. •  Hypothyroidism. •  Patients receiving angiotensin-converting

enzyme inhibitors and spironolactone concurrently. •  Excessive use of magnesium-containing cathartic solutions, especially in patients with renal insufficiency.

GEOGRAPHIC DISTRIBUTION N/A SIGNALMENT Species

Dog and cat. Breed Predilections

N/A

SIGNS General Comments

•  Usually caused by renal failure; clinical signs might be referable to azotemia and renal insufficiency. Clinical hypermagnesemia is reported most often in patients with preexisting renal disease that are oversupplemented with parenteral magnesium salts. •  Characterized by progressive loss of neuromuscular, respiratory, and cardiovascular function.

Historical and Physical Examination Findings

•  Nausea, vomiting, weakness, bradycardia,

flaccid paralysis, mental depression, and hyporeflexia (including menace and palpebral reflex). •  Hypotension and ECG changes, including delayed intraventricular conduction and prolonged QT interval. •  Atrioventricular block, respiratory depression, coma, and cardiac arrest have been observed in humans with serum magnesium concentrations >16 mg/dL. CAUSES

•  Renal failure. •  Intestinal hypomotility disorders and

constipation. •  Endocrine disorders including hypoadrenocorticism, hypothyroidism, and hyperparathyroidism. •  Combined angiotensin-converting enzyme inhibitors and spironolactone administration. •  Excessive magnesium administration from magnesium-containing cathartic solutions

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Signs are most similar to those of hypocalcemia, which often occurs simultaneously. •  Bradycardia can be caused by neurologic disease, hyperkalemia, hypertension, hypo­ thyroidism, sick sinus syndrome, and various drugs. LABORATORY FINDINGS Note: 12 mg of magnesium = 1 mEq of magnesium; to convert from mg/dL to mEq/L, divide by 1.2. Drugs That May Alter Laboratory Results •  Serum is favored over plasma because the

anticoagulant used for plasma samples can contain citrate or other ions that bind magnesium. •  EDTA, sodium fluoride-oxalate, sodium citrate, and intravenous calcium gluconate can cause falsely low serum magnesium values. Disorders That May Alter Laboratory Results

•  Hemolysis can result in falsely increased

serum magnesium; the magnesium concentration in erythrocytes is approximately three times that in serum. •  Storage of serum or urine in metal containers can falsely elevate magnesium values. •  Hyperbilirubinemia can cause falsely decreased serum magnesium. Valid if Run in Human Laboratory?

Yes

CBC/BIOCHEMISTRY/URINALYSIS •  Serum magnesium—dogs: >2.5 mg/dL; cats: >2.99 mg/dL. •  Hypocalcemia is common. •  Azotemia in some patients.

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Hypermagnesemia

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OTHER LABORATORY TESTS •  Ionized magnesium can be measured with an ion-selective electrode or by ultrafiltration of plasma; alternative methods of evaluating magnesium status include mononuclear blood cell magnesium levels or quantifying retention from a loading dose. •  Ionized hypermagnesemia is characterized as >0.58 mmol/L in dogs and >0.65 mmol/L in cats, but may vary slightly with the analyzer. DIAGNOSTIC PROCEDURES

(continued)

necrosis (bed sores), and urine and fecal scalding. ACTIVITY Patient activity is dependent on underlying conditions and response to therapy. DIET Any magnesium supplementation should be discontinued. CLIENT EDUCATION Clients should be advised if preexisting conditions contributed to hypermagnesemia.

•  Electrodiagnostics (e.g., electromyelography

and electrocardiography) reveal effects of hypermagnesemia but do not differentiate the cause. •  Though not described in critically ill veterinary patients, hypermagnesemia can cause prolonged PR intervals and QRS duration in humans.

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 TREATMENT

APPROPRIATE HEALTH CARE •  Management involves enhancing elimination from the body and symptomatic therapy. •  Discontinue all magnesium-containing medications and nutritional supplements. •  Saline diuresis and loop diuretics enhance renal clearance of magnesium. •  Fluid therapy with 0.9% NaCl provides fluid volume to address hypovolemia, hypotension, and azotemia. •  Patients with oliguria might require peritoneal dialysis to treat severe hypermagnesemia. •  Parenteral calcium supplementation directly antagonizes the effects of magnesium, reversing respiratory depression, cardiac arrhythmias, and hypotension; calcium also enhances magnesium excretion. •  Hypermagnesemia associated with combined angiotensin-converting enzyme inhibitors and spironolactone is rare, mild, and unlikely to be clinically significant. •  Physostigmine, an anticholinesterase, can be used to treat severe neurotoxic effects. NURSING CARE Patients with neurologic manifestations of hypermagnesemia might require intensive nursing care to prevent aspiration pneumonitis, pulmonary atelectasis, pressure

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likely to survive their illness than patients with normal serum magnesium levels.

EXPECTED COURSE AND PROGNOSIS •  Veterinary patients with iatrogenic overdose can have a good outcome with prompt recognition and supportive care. •  Increased ionized magnesium is rare and indicative of severe disease in noniatrogenic cases, particularly patients with acute renal disease, and can be associated with increased mortality.

 MEDICATIONS

DRUG(S) OF CHOICE •  Furosemide promotes renal excretion of magnesium by decreasing absorption of magnesium in the loop of Henle. •  Enteral and parenteral calcium adminis­ tration helps reverse clinical manifestations of hypermagnesemia and correct concurrent hypocalcemia; oral supplementation with any preparation can be given at a dosage of 25–50 mg/kg/day; severe hypermagnesemia can be treated with 10% calcium gluconate: 1–2 mL/kg (diluted 1 : 1 with saline) IV or SC q8h, administered slowly (may cause bradycardia). CONTRAINDICATIONS Magnesium-containing compounds and fluids. PRECAUTIONS Monitor ECG during calcium infusion.

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•  Hypermagnesemic dogs were 2.6 times less

 FOLLOW-UP

PATIENT MONITORING •  Serum magnesium and calcium concentrations. •  Renal function—azotemia and urine output. •  Continuous ECG if possible. PREVENTION/AVOIDANCE Magnesium supplementation should be approached cautiously in patients with renal insufficiency. POSSIBLE COMPLICATIONS

•  Severe hypermagnesemia and hypocalcemia

can be fatal.

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 MISCELLANEOUS

ASSOCIATED CONDITIONS •  Hypocalcemia. •  Hyperphosphatemia. •  Azotemia. PREGNANCY/FERTILITY/BREEDING Effects on the fetus are identical to effects on the dam. SEE ALSO Hypocalcemia

­Suggested Reading

Bateman SW. Disorders of magnesium: magnesium deficit and excess. In: DiBartola SP, ed., Fluid, Electrolyte and Acid-Base Disorders in Small Animal Practice, 4th ed. Philadelphia, PA: Elsevier, 2011, pp. 212–229. Humphrey S, Kirby R, Rudloff E. Magnesium physiology and clinical therapy in veterinary critical care. J Vet Emerg Crit Care 2015, 25(2):210–225. Jackson CB, Drobatz KJ. Iatrogenic magnesium overdose: 2 case reports. J Vet Emerg Crit Care 2004, 14(2):115–123. Martin LG, Allen-Durrance AE. Magnesium and phosphate disorders. In: Silverstein DC and Hopper K, eds., Small Animal Critical Care Medicine, 2nd ed. Philadelphia, PA: Elsevier, 2015, pp. 283–284. Nakayama T, Nakayama H, Hiyamoto M, Hamlin RL. Hemodynamic and electrocardiographic effects of magnesium sulfate in healthy dogs. J Vet Intern Med 1999, 13:485–490. Author Timothy B. Hackett Consulting Editor Patty A. Lathan



689

Canine and Feline, Seventh Edition

Hypermetria and Dysmetria

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 BASICS

DEFINITION •  Dysmetria—incoordination of the limbs during voluntary movement because of an inability to judge the rate, range, and force of movements. •  Hypermetria—overreaching limb movements giving a characteristic goosestepping gait; the term dysmetria includes both hypo- and hypermetria. PATHOPHYSIOLOGY •  The cerebellum plays a central role in generating skilled movements and maintaining muscle tone and body posture; it does not initiate but coordinates and smoothes movements. •  Damage to the cerebellum results in inaccurate gauging of voluntary movements; motor strength is preserved; conscious proprioception is unaffected. •  Rarely, compression of the spinocerebellar tracts in spinal cord disorders can produce dysmetria; this is more likely to occur with dorsally located lesions. SYSTEMS AFFECTED Nervous system. GENETICS

•  The hereditary ataxias are an important group

of diseases in which cerebellar degenerations causes dysmetria and hypermetria in dogs. •  The majority of breed-related hereditary ataxias are autosomal recessive, highly penetrant traits. •  An X–linked hereditary ataxia has been described in pointers. •  Lysosomal storage diseases are genetic disorders, typically autosomal recessive in both dogs and cats. •  Immune-mediated encephalitis likely has a hereditary component—the mode of inheritance has not been described but is complex. INCIDENCE/PREVALENCE The incidence and prevalence of this presenting problem have not been reported.

GEOGRAPHIC DISTRIBUTION There are no data on geographic distribution. SIGNALMENT Dog and cat of any age, breed, or sex. SIGNS Other signs of cerebellar disease that may be present include truncal sway, intention tremor, wide-based stance, head tilt, opsoclonus, spontaneous nystagmus, loss of menace response with normal vision, and anisocoria. CAUSES Cerebellar

•  Dogs—hypoplasia (inherited or secondary

to infection with canine herpesvirus in the

perinatal period); hereditary ataxia (cerebellar abiotrophy or cerebellar cortical degeneration); lysosomal storage diseases; canine distemper virus (CDV); protozoal infections (Neospora caninum is most common, Toxoplasma gondii is possible but rare); rickettsial infections (Ehrlichia canis and Rocky Mountain spotted fever); Cryptococcus and other fungal infections; granulomatous meningoencephalitis; meningoencephalitis of unknown etiology; steroid-responsive tremor syndrome; neoplasia; trauma; infarct; hemorrhage; metronidazole toxicity. •  Cats—hypoplasia secondary to in utero infection with feline panleukopenia virus; lysosomal storage diseases; feline infectious peritonitis (FIP), feline leukemia virus (FeLV), feline immunodeficiency virus (FIV; associated immunosuppression predisposes to other encephalitides and to neoplasia); protozoal infections (Toxoplasma gondii); Cryptococcus and other fungal infections; neoplasia; hemorrhage; trauma.

•  Vascular events, both thromboembolic and

Spinal

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disease, centro-dorsally located cervical lesions are more likely to produce hypermetria. •  Dogs—subarachnoid diverticula; neoplasia; vertebral malformation (atlantoaxial subluxation); and calcinosis circumscripta.

DIFFERENTIAL DIAGNOSIS Some dogs, especially small breeds, have a high-stepping gait in their thoracic limbs as a normal finding. If there are no other signs of cerebellar disease, establish with the owners whether a high-stepping thoracic limb gait is normal for the dog.

•  While there are many causes of spinal cord

RISK FACTORS Cerebellar

•  Hereditary ataxia reported in Gordon and

Irish setters, Kerry blue terriers, Airedale terriers, Finnish harriers and hounds, Samoyeds, Bern running dogs, cocker spaniels, Cairn terriers, Australian kelpies, bull mastiffs, Italian spinones, the terrier group, Lagotto-Romangolos, Old English sheepdogs, Rhodesian ridgebacks, border and rough-coated collies, Brittany spaniels, beagles, and Scottish terriers. •  Cerebellar hypoplasia has been reported in chow chows, Irish setters, and wire fox terriers. •  Lysosomal storage diseases causing dysmetria have been reported in Siamese, Balinese, Persian, and domestic shorthair cats, and in English springer spaniels, American Staffordshire terriers, Portuguese water dogs, German shorthaired pointers, Australian silky terriers, schipperkes, English setters, border collies, salukis, Chihuahuas, Queensland blue heelers, dachshunds, Yugoslavian shepherds, and Tibetan terriers. •  Small-breed dogs, such as Maltese, Yorkshire and West Highland white terriers, miniature pinschers, and Chihuahuas, are predisposed to immune-mediated encephalitis, including meningoencephalitis of unknown etiology and steroid-responsive tremor syndrome. •  Metronidazole at dosages >60 mg/kg/day can induce cerebello-vestibular signs in dogs; signs are induced in some dogs at lower doses.

hemorrhagic, can cause cerebellar signs, typically due to thrombosis of the rostral cerebellar artery; disorders that cause a hypercoagulable state (such as hyperadrenocorticism) or hypertension (such as hyperthyroidism in cats, or chronic renal disease) can predispose to stroke; hypothyroidism has also been associated with cerebellar stroke; thrombosis of the rostral cerebellar artery occurs in older dogs—an underlying cause is not always identified.

Spinal

•  Giant-breed dogs are predisposed to

vertebral malformation.

•  Toy-breed dogs are predisposed to

atlanto-axial instability.

•  Young large-breed dogs are predisposed to

subarachnoid diverticula and calcinosis circumscripta.

 DIAGNOSIS

CBC/BIOCHEMISTRY/URINALYSIS •  CBC may reflect infectious/inflammatory disease. •  Storage products may be present in leukocytes in some lysosomal storage diseases. OTHER LABORATORY TESTS

•  Acute and convalescent serologic titers—to

diagnose rickettsial, protozoal, fungal, and viral diseases. •  Cerebrospinal fluid (CSF) antibody or antigen (Cryptococcus) titers—for some infections (e.g., Toxoplasma, Cryptococcus), measure in addition to serologic titers. •  PCR on CSF and serum—to diagnose rickettsial, bacterial, protozoal, fungal, and viral diseases; sensitive and specific if the infectious agent is present in the CSF or serum. •  Genetic tests available for hereditary ataxia in beagles, Finnish hounds, Italian spinones, Gordon setters, Old English sheepdogs, Lagotto-Romangolos, and the terrier group (Jack and Parson Russell terriers). IMAGING

•  Thoracic radiography—to identify

metastatic disease in older patients.

•  Abdominal ultrasonography—if intra-

abdominal neoplasia is suspected.

•  Brain CT or MRI—to diagnose neoplasia,

vascular disease, encephalitis, cerebellar atrophy due to hypoplasia or abiotrophy; MRI is the preferred modality for evaluating the caudal fossa.

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Hypermetria and Dysmetria

(continued)

•  Survey spinal radiography—if spinal cord

disease is suspected; may be helpful in identifying vertebral malformations and calcinosis circumscripta. •  Spinal MRI—noninvasive and informative about spinal cord parenchyma. DIAGNOSTIC PROCEDURES

•  Fundic examination—to identify

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chorioretinitis (evidence of infectious/ inflammatory disease) and vascular lesions associated with vasculitis or hypertension. •  CSF—to diagnose encephalitis; storage products may be present in CSF leukocytes in some lysosomal storage diseases. •  Liver biopsy—may be helpful in diagnosing certain lysosomal storage diseases in animals with hepatomegaly. PATHOLOGIC FINDINGS •  These will depend on the underlying condition. •  Hereditary ataxias are associated with loss of neurons of the cerebellar cortex, as well as axonal pathology and gliosis. •  Lyososomal storage diseases are associated with accumulation of storage product within neurons and glial cells; frequently the Purkinje neuron is most severely affected. •  Infectious encephalitis is associated with infiltration of the cerebellum with inflammatory cells, and infectious organisms may be present (e.g., Neospora caninum; Cryptococcal infections); meningitis and perivascular cuffing may be present and there is frequently multifocal involvement of the CNS; there is profound cerebellar atrophy associated with Neospora caninum infections. •  Immune-mediated encephalitis is associated with infiltration of the CNS by inflammatory cells.

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 TREATMENT

APPROPRIATE HEALTH CARE •  Severe and/or rapidly progressive clinical signs—hospitalization for diagnostic workup and treatment. •  Mild and slowly progressive clinical signs—outpatient, but diagnostic tests requiring anesthesia necessitate hospitalization. •  Appropriate treatment of the underlying cause should be undertaken once a diagnosis has been established. NURSING CARE Severe intention tremors may make handfeeding and IV fluids necessary. ACTIVITY Patients should be restricted to areas and activities where they are unlikely to fall and injure themselves. DIET No change. Dogs may benefit from a raised feeding bowl or hand-feeding. SURGICAL CONSIDERATIONS Surgical decompression of the spinal cord indicated for compressive myelopathies.

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 MEDICATIONS

DRUG(S) OF CHOICE Discontinue metronidazole, regardless of the dose rate, to see if signs improve.

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 FOLLOW-UP

PATIENT MONITORING •  Periodic repeat neurologic examinations. •  Additional monitoring will depend on the underlying cause (e.g., serial monitoring of blood pressure in hypertensive patients).

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 MISCELLANEOUS

ZOONOTIC POTENTIAL Fungal infections can be zoonotic. ABBREVIATIONS •  CDV = canine distemper virus. •  CSF = cerebrospinal fluid. •  FeLV = feline leukemia virus. •  FIP = feline infectious peritonitis. •  FIV = feline immunodeficiency virus.

­Suggested Reading

de Lahunta A, Glass E, Kent M. Veterinary Neuroanatomy and Clinical Neurology, 4th ed. St. Louis, MO: Elsevier Saunders, 2015, pp. 368–390. Urkasemsin G, Olby NJ. Canine hereditary ataxia. Vet Clin North Am Small Anim Pract 2014, 44:1075–1089. Author Natasha J. Olby



691

Canine and Feline, Seventh Edition

Hypernatremia •  Alterations

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 BASICS

DEFINITION Serum sodium (Na+) concentration >158 mEq/L in dogs or >165 mEq/L in cats. PATHOPHYSIOLOGY •  Na+ is the most abundant cation in the extracellular fluid, so hypernatremia usually results in hyperosmolality. •  Hypernatremia can be caused by excessive free water loss, increased intake of Na+, or a combination of both. •  Common causes of hypernatremia include renal or gastrointestinal loss of water in excess of sodium loss and low water intake. Excessive Na+ ingestion is a rare cause. SYSTEMS AFFECTED •  Endocrine/metabolic. •  Nervous. SIGNALMENT Dog and cat.

in thirst reaction pathway—rare. •  Salt ingestion—rare. LABORATORY FINDINGS Disorders That May Alter Laboratory Results

Lipemia or hyperproteinemia (>11 g/dL) can artifactually raise Na+ concentration when the flame photometry method is used. Valid if Run in a Human Laboratory?

Yes

CBC/BIOCHEMISTRY/URINALYSIS •  Consistent with underlying disease, if applicable. •  Diabetes insipidus—polyuria, hyposthenuria, and low urinary Na+ concentration. •  Diabetes mellitus—hyperglycemia, isosthenuria. IMAGING CT scan or MRI in patients with diabetes insipidus to rule out pituitary tumor.

SIGNS

•  Polydipsia. •  Disorientation. •  Coma. •  Seizures. •  Other findings depend on underlying

cause.

•  Severity of signs usually correlates to the

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 TREATMENT

•  Fluid therapy and treatment of underlying

disease. •  Water must be available at all times for patients with diabetes insipidus.

1 L of solution – patient [Na+]) / (0.6 × Wt (kg) +1). •  If the patient has oral water intake, this should be calculated as part of the free water restoration. PRECAUTIONS

•  Rapid correction of hypernatremia can

cause cerebral edema. More rapid correction is only recommended if the hypernatremia is acute (180 mEq/L often

associated with residual CNS damage.

degree of hypernatremia. CAUSES

•  Free water deficit (most common cause)—

low water intake (e.g., no access to water, adipsia, or hypodipsia); high urinary water loss; high insensible water loss (e.g., panting, hyperthermia). ◦  Urinary loss (e.g., diabetes insipidus, diabetes mellitus, osmotic diuresis, diuresis after acute urinary obstruction). ◦  Gastrointestinal sodium loss (e.g., administration of osmotic cathartic, vomiting, diarrhea). ◦  A wide variety of drugs interfere with renal capacity to concentrate urine, leading to water loss in excess of Na+; these drugs include lithium, demeclocycline, and amphotericin. •  Oral sodium ingestion (rare); IV administration of 0.9% or 7% NaCl; hyperaldosteronism (rarely hypernatremic); hyperadrenocorticism (mild).

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Central diabetes insipidus (due to neoplasia or head trauma).

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 MEDICATIONS

DRUG(S) OF CHOICE •  If hypovolemia is present, replace volume with an isotonic crystalloid with a Na+ concentration within 10 mEq/L of the patient’s Na+ concentration (0.9% saline has a Na+ of 154 mEq/L, while lactated Ringer’s has 130 mEq/L and Normosol®-R has 140 mEq/L). Volume replacement with this fluid may be continued as the free water deficit is replaced (below). •  Following volume resuscitation, administer hypotonic fluids (e.g., 5% dextrose in water or 5% dextrose with 0.45% saline) to reduce serum sodium by 0.5 mEq/h (12 mEq/L/ day); supplement with potassium and phosphate if needed. •  Free water deficit—Wt (kg) × {[Na(presentation)]/ [Na(previous or normal)] – 1}: administer this amount to achieve an ideal decrease of 0.5 mEq/h (i.e., if the sodium is 20 mEq above reference range, this should be administered over 40 hours). •  Formula to estimate how much each L of fluids will decrease the patient’s serum Na+—Δ in patient [Na+] = ([Na+] + [K+] in

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 MISCELLANEOUS

AGE-RELATED FACTORS None SYNONYMS None SEE ALSO •  Diabetes Insipidus. •  Hyposthenuria.

­Suggested Reading

DiBartola SP. Fluid, Electrolyte, and Acid-Base Disorders in Small Animal Practice, 4th ed. Philadelphia, PA: Saunders, 2012. Rose BD. Clinical Physiology of Acid-Base and Electrolyte Disorders, 5th ed. New York: McGraw-Hill, 2001. Author Patty A. Lathan Consulting Editor Patty A. Lathan Acknowledgment The author and book editors acknowledge the prior contribution of Melinda Fleming.

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Hyperosmolarity Historical Findings

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 BASICS

DEFINITION •  Osmolarity—mOsm/L: the number of solute particles per liter of solution. •  Osmolality—mOsm/kg: the number of solute particles per kilogram of solution. •  Hyperosmolarity—a high concentration of solute particles per liter of solution. •  Serum concentrations >310 mOsm/L in dogs and >330 mOsm/L in cats are considered hyperosmolar. •  Morbidity from hyperosmolarity is related more to rapid changes in osmolarity than to the actual amount of change. PATHOPHYSIOLOGY

•  Serum sodium is responsible for most of the

osmotically active particles that contribute to serum osmolarity; serum glucose and urea also contribute. •  Anything that causes free water loss increases concentrations of solutes in plasma or serum, thereby increasing serum osmolarity. •  Blood volume, hydration status, and anti­ diuretic hormone (ADH) are intimately involved in controlling extracellular fluid volume. •  Low circulating blood volume and low blood pressure stimulates carotid and aortic baroreceptors to cause ADH secretion. •  Hyperosmolarity affects the osmoreceptors in the hypothalamus and stimulates ADH secretion from the posterior pituitary; the hypothalamic thirst center is also stimulated and causes an increase in water consumption. •  Rapid increases in serum osmolarity cause water movement along its concentration gradient from intracellular to extracellular spaces, resulting in neuronal dehydration, cell shrinkage, and cell death; cerebral vessels may weaken and hemorrhage.

SYSTEMS AFFECTED •  Cardiovascular—hypovolemia, hypotension, decreased ventricular contractility. •  Nervous—excessive thirst may be the first sign of hyperosmolarity. CNS depression may lead to coma. •  Renal/urologic—low urine output unless kidneys are source of free water loss. SIGNALMENT

•  Dog and cat. •  Hypodipsia and hyperosmolarity have been

reported in young female miniature schnauzers. SIGNS

General Comments

•  Primarily neurologic or behavioral. •  Severity is related more to how quickly

hyperosmolarity occurs than to the absolute magnitude of change. •  Clinical signs most likely if serum osmolarity is >350 mOsm/L and severe if >375 mOsm/L.

Anorexia, lethargy, vomiting, weakness, disorientation, ataxia, seizures, and coma; polydipsia followed by hypodipsia. Physical Examination Findings

•  Normal, or abnormalities may reflect

underlying disease.

•  In addition to historical findings,

dehydration, tachycardia, hypotension, weak pulses, and fever may be detected. CAUSES

Increased Solute Concentrations

Hypernatremia, hyperglycemia, severe azotemia, ethylene glycol toxicosis, salt poisoning, sodium phosphate enemas in cats and small dogs, mannitol, radiographic contrast solution, administration of ethanol, aspirin toxicosis, shock, and parenteral nutrition solutions. Decreased Extracellular Fluid Volume

Dehydration—gastrointestinal loss, cutaneous loss, third-space loss, low water consumption, polyuria without adequate compensatory polydipsia, excessive losses from panting. RISK FACTORS •  Medical conditions that predispose—renal failure, diabetes insipidus (DI), diabetes mellitus (DM), hyperadrenocorticism, hyperaldosteronism, and heat stroke. •  Therapeutic hyperosmolar solutions— hypertonic saline, sodium bicarbonate, sodium phosphate enemas in cats and small dogs, mannitol, and parenteral nutrition solutions. •  High environmental temperatures, pain. •  Fever.

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Primary CNS disease and neoplasia may be characterized by altered mentation, but serum osmolarity is usually normal. •  Physical evidence or history of injury usually helps to rule out CNS depression caused by cranial trauma. •  Perform a thorough physical examination to assess hydration status and obtain information regarding previous therapy that may have included sodium-containing fluids or hyperosmolar solutions. LABORATORY FINDINGS Drugs That May Alter Laboratory Results

N/A

Disorders That May Alter Laboratory Results

N/A

Valid if Run in Human Laboratory?

Yes

CBC/BIOCHEMISTRY/URINALYSIS High hematocrit, hemoglobin, and plasma proteins in dehydrated patients; serum electrolytes may also be increased. OTHER LABORATORY TESTS

•  Osmolarity is generally measured in the

laboratory using freezing point depression but can be estimated from serum chemistry results (assuming the absence of unmeasured osmoles) using the formula: 2(Na+ + K+) + glucose∕18 + BUN∕ 2.8 = mOsm∕L. Na+ and K+ concentrations are in mEq/L, glucose and blood urea nitrogen (BUN) concentrations are in mg/dL. •  Hyperosmolarity is an indication to evaluate serum sodium and glucose concentrations. •  Calculated osmolarity should not exceed measured osmolarity; if it does, consider laboratory error. ◦  If measured osmolarity exceeds calculated osmolarity, determine the osmolar gap. ◦  Osmolar gap = measured osmolarity – calculated osmolarity. ◦  High measured osmolarity and normal calculated osmolarity with a high osmolar gap indicate the presence of unmeasured solutes (not Na+, K+, glucose, BUN). ◦  High measured osmolarity and high calculated osmolarity with a normal osmolar gap usually indicate that the hyperosmolarity is caused by hyperglycemia or hypernatremia. •  Serum sodium concentration may be low in patients with severe hyperglycemia. •  Fasting hyperglycemia and glucosuria support a diagnosis of DM. •  Calcium oxalate monohydrate crystalluria suggests ethylene glycol toxicosis. •  High urine specific gravity (USG) rules out DI. •  Low USG, especially hyposthenuria, suggests DI. •  Urinary osmolarity lower than serum osmolarity suggests DI; concentrated urine rules out DI. IMAGING Renal ultrasonography may reveal bright hyperechoic kidneys in patients with ethylene glycol toxicosis. TREATMENT

•  Mild hyperosmolarity without clinical signs

may not warrant specific treatment, but underlying disease(s) should be diagnosed and treated. •  Hospitalize patients with moderate to high osmolarity (>350 mOsm/L) and patients exhibiting clinical signs, and gradually lower serum osmolarity with IV fluids while a definitive diagnosis is pursued. •  Free water deficit can be calculated by the following formula: Free water deficit = 0.4 × lean bodyweight (kg) × [(Plasma Na∕140) − 1].



Hyperosmolarity

(continued) •  Administer 5% dextrose in water (D5W) or 0.45% saline to slowly replace free water deficit. •  The goal is to not drop sodium more than 12 mEq/L in an 24-hour period. For example, if the free water deficit is 1 L and serum sodium concentration is 180 mEq/L, to normalize serum sodium concentration (to 145 mEq/L), the sodium concentration should drop over 35 hours (0.5 mEq/h). Thus, the 1 L of free water deficit should be given over 35 hours, or a rate of 28.5 mL/h (1000 mL/35h) if using D5W. Maintenance isotonic IV fluids should be administered concurrently. •  Initially, 0.9% saline may be used to restore vascular volume; once hemodynamically stable, D5W or 0.45% saline therapy may be initiated. •  If hyperosmolarity is acute (e.g. in patients with salt intoxication) and the duration is less than 6-8 hours, the free water deficit can be replaced more rapidly, through a combination of oral and IV water. •  If the patient is able to drink, free water deficit may be replaced orally; however, care must be taken to prevent excessive water ingestion.

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PRECAUTIONS

•  Initial volume replacement should use a

fluid with a Na+ concentration closest to that of the patient. •  Rapid administration of hypotonic fluids (e.g., D5W and 0.45% saline) may cause cerebral edema and worsen neurologic signs due to acute fluid shifts in the brain. ALTERNATIVE DRUG(S) Regular insulin 0.1 unit/kg IM/IV can be administered if a hyperglycemic crisis occurs secondary to parenteral nutrition administration.

CONTRAINDICATIONS Hypertonic saline and hyperosmolar solutions.

Hyperglycemic State.

•  Hyperglycemia. •  Hypernatremia.

ABBREVIATIONS

•  ADH = antidiuretic hormone. •  BUN = blood urea nitrogen. •  D5W = 5% dextrose in water. •  DI = diabetes insipidus. •  DM =diabetes mellitus. •  USG = urine specific gravity.

­Suggested Reding

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 FOLLOW-UP

PATIENT MONITORING •  Hydration status; avoid overhydration. •  Bladder size, urine output, serial bodyweight, and breathing patterns during IV fluid administration. •  Anuria, irregular breathing patterns, worsening depression, coma, or seizures are signs of deterioration. POSSIBLE COMPLICATIONS Altered consciousness and abnormal behavior.

 MEDICATIONS

DRUG(S) OF CHOICE •  Intravenous free water replacement is best performed using D5W or 0.45% NaCl. •  Seizures can be controlled with benzodiazepines or phenobarbital.

SEE ALSO

•  Diabetes Mellitus with Hyperosmolar

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 MISCELLANEOUS

ASSOCIATED CONDITIONS Hypernatremia and hyperglycemia. AGE-RELATED FACTORS None PREGNANCY/FERTILITY/BREEDING N/A

DiBartola SP, ed. Fluid Therapy in Small Animal Practice. Philadelphia, PA: Saunders, 1992. DiBartola SP, Green RA, Autran de Morais HS. Osmolality and osmolal gap. In: Willard MD, Tvedten H, Turnwald GH, eds., Small Animal Clinical Diagnosis by Laboratory Methods, 2nd ed. Philadelphia, PA: Saunders, 1994, pp. 106–107. Goldcamp C, Schaer M. Hypernatremia in dogs. Compend Contin Educ Pract Vet 2007, 29(3):148–152. Koenig A, Drobatz KJ, Beale AB, King LG. Hyperglycemic, hyperosmolar syndrome in feline diabetics: 17 cases (1995–2001). J Vet Emerg Crit Care 2004, 14:30–40. Schermerhorn T, Barr SC. Relationships between glucose, sodium, and effective osmolality in dogs and cats. J Vet Emerg Crit Care 2006, 16:19–24. Author Patty A. Lathan Consulting Editor Patty A. Lathan Acknowledgment The author and book editors acknowledge the prior contribution of Melinda Fleming.

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Hyperparathyroidism SIGNS General Comments

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 BASICS

DEFINITION A pathologic, sustained, high, circulating concentration of parathyroid hormone (PTH).

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PATHOPHYSIOLOGY •  PTH is secreted by the parathyroid glands in response to changes in the concentration of ionized calcium in the serum, and causes an increase in serum calcium concentration through direct effects on bone and renal tubular calcium resorption and indirectly by vitamin D–dependent intestinal calcium absorption. •  Hyperparathyroidism can develop as a primary condition or be secondary to a disorder of calcium homeostasis; primary hyperparathyroidism is usually associated with benign adenoma of the parathyroid gland(s), although adenocarcinoma and hyperplasia are possible; secondary hyperparathyroidism can be caused by a deficiency of calcium and vitamin D associated with malnutrition or chronic renal disease. SYSTEMS AFFECTED

•  Cardiovascular. •  Gastrointestinal. •  Neuromuscular. •  Renal/urologic.

GENETICS

•  Autosomal dominant with possible

age-dependent penetrance in the keeshond; genetic test available from Cornell. •  Secondary hyperparathyroidism can develop in association with hereditary nephropathy. INCIDENCE/PREVALENCE

•  Prevalence of primary form is unknown. •  More common in dogs than in cats. •  Common among causes of hypercalcemia,

but less common than hypercalcemia of malignancy in dogs; more common in middle-aged to geriatric dogs. •  Chronic renal failure with secondary hyperparathyroidism is extremely common, more so in cats than in dogs. •  Nutritional secondary hyperparathyroidism is decreasing in prevalence as the public becomes more educated in pet nutrition. SIGNALMENT Species

Cat and dog. Breed Predilections

•  Keeshond, but seen in almost any breed. •  Siamese and domestic shorthair cats.

Mean Age and Range

•  Cats—mean age 13 years; range: 8–20 years. •  Dogs—mean age 10 years; range: 4–17 years.

Predominant Sex

None

•  Most dogs and cats with primary hyper­

parathyroidism do not appear ill.

•  Signs are usually mild and due to the effects

of hypercalcemia, or lower urinary tract signs if urolithiasis is present. •  Signs become apparent when hypercalcemia is severe and chronic. Historical Findings •  Polyuria. •  Polydipsia. •  Anorexia. •  Lethargy. •  Vomiting. •  Weakness. •  Urolithiasis. •  Stupor and coma.

Physical Examination Findings

•  Often unremarkable. •  Parathyroid adenoma is not palpable in

dogs but often is in cats.

•  Nutritional secondary disease is sometimes

associated with pathologic bone fractures and general poor body condition. CAUSES

•  Primary hyperparathyroidism—PTH-

secreting adenoma of the parathyroid gland; in most cases only one gland is adenomatous; malignant tumors of the parathyroid glands are uncommon and usually noninvasive. •  Renal secondary hyperparathyroidism— renal calcium loss and reduced gut absorption of calcium due to deficiency in calcitriol production by the renal tubular cells. •  Nutritional secondary hyperparathyroidism— a nutritional deficiency of calcium and vitamin D. RISK FACTORS

•  Primary hyperparathyroidism—unknown. •  Secondary hyperparathyroidism—renal

tubular disease or calcium/vitamin D malnutrition.

human anti-psoriasis topical creams, and vitamin supplements. •  Granulomatous diseases. •  Idiopathic hypercalcemia in cats. CBC/BIOCHEMISTRY/URINALYSIS

•  High serum total and ionized calcium

concentrations.

•  Low or low-normal serum phosphorus

concentration in primary hyperparathyroidism. •  Hyperphosphatemia in renal secondary hyperparathyroidism or hypervitaminosis D. •  Serum blood urea nitrogen (BUN) and creatinine concentrations are usually normal in patients with primary hyperparathyroidism, except those with hypercalcemia-induced renal failure. OTHER LABORATORY TESTS

•  Serum ionized calcium determination is

often normal (or low) in patients with chronic renal failure and high in patients with primary hyperparathyroidism or hypercalcemia associated with malignancy. •  High serum intact PTH concentration is diagnostic for primary hyperparathyroidism in the absence of azotemia; a serum PTH concentration within the normal reference range in an animal with ionized hypercalcemia should be considered abnormal and can signal parathyroid-dependent hypercalcemia. •  Measurement of PTH-related peptide (PTH-rp) may detect hyperparathyroidism related to neoplasia. IMAGING

•  Radiography can be useful to identify

urolithiasis and occult neoplasia, as well as to assess renal morphology and bone density. •  Ultrasonography of the ventral cervical area sometimes reveals a parathyroid gland adenoma. •  Ultrasound of the abdomen can reveal lymphadenomegaly, urolithiasis, or renal morphologic abnormalities. DIAGNOSTIC PROCEDURES Surgical exploration of the ventral cervical area. PATHOLOGIC FINDINGS

•  Parathyroid adenoma is usually a solitary,

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  The differential list includes causes of hypercalcemia. •  Lymphoma—common to cause hyper­ calcemia in dogs, rare to do so in cats. •  Anal sac apocrine gland adenocarcinoma— dogs. •  Other miscellaneous carcinomas—dogs and cats. •  Myeloproliferative disease—cats. •  Fibrosarcoma—cats. •  Chronic kidney disease. •  Hypoadrenocorticism. •  Vitamin D intoxication—cholecalciferolcontaining rodenticides, plant sources,

small (=1 cm), round, light brown or reddish mass located in the proximity of the thyroid gland. •  Occasionally multiple adenomas are found. •  The histologic distinctions between adenomas, hyperplasia, and carcinomas of the parathyroid gland are often unclear.

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 TREATMENT

APPROPRIATE HEALTH CARE •  Primary hyperparathyroidism generally requires inpatient care and surgery. •  Nutritional or renal secondary hyper­ parathyroidism in noncritical patients can be managed on an outpatient basis.



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Hyperparathyroidism

(continued)

ACTIVITY No alterations recommended. DIET Calcium supplementation for secondary forms. CLIENT EDUCATION Explain signs referable to changes in calcium status, because hypocalcemia is a potential complication of parathyroidectomy. SURGICAL CONSIDERATIONS •  Surgery is the treatment of choice for primary hyperparathyroidism and is often important in establishing the diagnosis. •  Percutaneous ultrasound-guided heat ablation has been used successfully for treatment of parathyroid adenomas, and may be recommended if available. •  Percutaneous ultrasound-guided ethanol ablation has been reported to be less successful than surgery or heat ablation.

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 MEDICATIONS

DRUG(S) OF CHOICE •  Normal saline is the fluid of choice for treatment of hypercalcemia. •  Diuretics (furosemide) and corticosteroids can be useful in treating hypercalcemia. •  No medical treatment exists for primary hyperparathyroidism per se. •  Renal secondary hyperparathyroidism is sometimes treated with calcitriol, but its use has not gained uniform acceptance. •  A new class of calcimimetic drugs is being used to treat renal secondary hyperpara­ thyroidism in human patients, but studies of these drugs in dogs and cats have not been reported and expense limits their use. CONTRAINDICATIONS Do not use glucocorticoids until the diagnosis of lymphoma has been excluded; they can obfuscate the diagnosis. PRECAUTIONS Use furosemide only in patients with adequate hydration. ALTERNATIVE DRUG(S) Pamidronate and other bisphosphonate drugs have been used to treat hypercalcemia of various causes in dogs and cats.

AGE-RELATED FACTORS N/A

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 FOLLOW-UP

PATIENT MONITORING •  Postoperative hypocalcemia is relatively common after treatment of primary hyperparathyroidism; recent studies have shown that preoperative ionized calcium and PTH concentrations are poor predictors of postsurgical hypocalcemia, so monitoring is essential in all cases. •  Postoperative hypocalcemia requires treatment with vitamin D (calcitriol is recommended) and calcium supplements (see treatment of hypoparathyroidism), and ionized calcium should be monitored to guide dosage adjustments; contradictory evidence exists with respect to preoperative admini­ stration of calcitriol. •  In patients with renal impairment, check serum concentrations of BUN and creatinine. PREVENTION/AVOIDANCE

•  Avoid breeding affected keeshonden. •  Nutritional secondary hyperparathyroidism

is prevented by proper nutrition.

POSSIBLE COMPLICATIONS

•  Irreversible renal failure secondary to

hypercalcemia.

•  Fractures due to decreased bone density

with chronic hyperparathyroidism.

EXPECTED COURSE AND PROGNOSIS

•  Untreated primary hyperparathyroidism may

progresses to end-stage kidney or neuro­muscular disease depending on severity; many dogs clinically seem to do well even with no treatment, provided urolithiasis does not develop. •  Prognosis for surgical treatment of parathyroid adenoma is excellent. •  Recurrence is seen in a small percentage of cases. •  In animals that develop postoperative hypoparathyroidism, the return of normal parathyroid function is unpredictable and can take weeks to months.

PREGNANCY/FERTILITY/BREEDING N/A SEE ALSO

•  Chronic Kidney Disease. •  Hypercalcemia. •  Hyperparathyroidism, Renal Secondary.

ABBREVIATIONS

•  BUN = blood urea nitrogen. •  PTH = parathyroid hormone. •  PTH-rp = PTH-related peptide.

­Suggested Reading

Dear JD, Kass PH, Della Maggiore AM, Feldman EC. Association of hypercalcemia before treatment with hypocalcemia after treatment in dogs with primary hyperparathyroidism. J Vet Intern Med 2017, 31(2):349–354. Feldman EC, Hoar B, Pollard R, Nelson RW. Pretreatment clinical and laboratory findings in dogs with primary hyperparathyroidism: 210 cases (1987–2004). J Am Vet Med Assoc 2005, 227(5):756–761. Milovancev M, Schmiedt CW. Preoperative factors associated with postoperative hypocalcemia in dogs with primary hyperparathyroidism that underwent parathyroidectomy: 62 cases (2004–2009). J Am Vet Med Assoc 2013, 242(4):507–515. Richter KP, Kallet AJ, Feldman EC, Brum DE. Primary hyperparathyroidism in cats: seven cases (1984–1989). J Am Vet Med Assoc 1991, 199(12):1767–1771. Schaefer C, Goldstein RE. Canine primary hyperparathyroidism. Compend Contin Educ Vet 2009, 31(8):382–389. Author Brett A. Wasik Consulting Editor Patty A. Lathan Acknowledgment The author and book editors acknowledge the prior contribution of Thomas K. Graves.  Client Education Handout available online

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 MISCELLANEOUS

ASSOCIATED CONDITIONS Calcium-containing urolithiasis.

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Hyperparathyroidism, Renal Secondary

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 BASICS

OVERVIEW •  Syndrome characterized by a high parathyroid hormone (PTH) concentration secondary to chronic kidney disease (CKD); results from impaired renal excretion of phosphorus leading to hyperphosphatemia and ionized hypocalcemia, elevation of FGF-23, and suppression of renal calcitriol synthesis. •  In advanced CKD the diminished renal tubular mass produces less calcitriol. Calcitriol exerts negative feedback on PTH synthesis within the parathyroid gland. Low calcitriol, ionized hypocalcemia, and hyperphosphatemia result in increased PTH production and parathyroid gland hyperplasia. •  PTH may act as a uremic toxin, promoting nephrocalcinosis and progression of CKD. SIGNALMENT Dog and cat; see Chronic Kidney Disease for age and breed predilections. SIGNS •  Uremia due to underlying CKD. •  Renal osteodystrophy or “rubber jaw” most commonly occurs in young dogs with severe renal secondary hyperparathyroidism (RSHPT). •  Pain around the head or long bones. CAUSES & RISK FACTORS •  Any disease that causes CKD. •  Excess consumption of phosphorus.

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Hypercalcemic nephropathy—kidney disease caused by ionized hypercalcemia; can be difficult to differentiate from longstanding RSHPT, in which hyperplasia of the parathyroid glands disrupts the normal feedback arc between PTH release and ionized calcium (tertiary hyperparathyroidism). •  Ionized serum calcium concentration is usually low or normal with RSHPT, but high with hypercalcemic nephropathy. •  Low serum PTH and PTH-related protein (PTHrP) high in animals with hypercalcemia of malignancy. •  Primary hyperparathyroidism— characterized by hypercalcemia, normal or low serum phosphorus, and inappropriate PTH concentration; kidney function is initially normal but may become compromised later. CBC/BIOCHEMISTRY/URINALYSIS

•  Azotemia.

•  Hyperphosphatemia. •  Dilute urine. •  Total serum calcium does not reliably

predict ionized calcium.

OTHER LABORATORY TESTS Definitive diagnosis and therapeutic monitoring of RSHPT require measurement of serum PTH concentration using validated assay. IMAGING Radiographs may reveal low bone density, loss of the lamina dura around the teeth, and soft tissue mineralization of the gastric mucosa or other tissues.

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 TREATMENT

•  See Chronic Kidney Disease for general

treatment principles.

•  Minimize hyperphosphatemia by feeding a

low phosphorus diet formulated for kidney disease and intestinal phosphate binders in order to achieve IRIS phosphorus goals.

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 MEDICATIONS

DRUG(S) OF CHOICE Intestinal Phosphate Binders

•  If dietary management alone does not

achieve the IRIS target serum phosphorus concentration, phosphorus binders can be used to further reduce serum phosphorus. Serum phosphorus targets based on the IRIS stages are stages 1 and 2: >2.7 to 2.7 to 2.7 to 70. Use aluminumor lanthanum-containing intestinal phosphate binders initially to correct hyperphosphatemia. Calcium-containing phosphate binders can be used once the serum phosphorus concentration is within the target range.

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 FOLLOW-UP

PATIENT MONITORING •  Initially and in unstable patients, serum concentrations of calcium, phosphorus, creatinine, and urea nitrogen—monitor weekly to monthly depending on therapy and the severity of CKD. •  Patients receiving calcitriol should be monitored for hypercalcemia and hyper­ phosphatemia weekly for 4 weeks, then every 3–4 months. •  Serial evaluations of PTH concentration— most treated with low-dose calcitriol achieve near-normal levels of PTH within 3 months; it may be necessary to increase the dose in those with severe parathyroid gland hyperplasia. •  If hypercalcemia develops discontinue calcitriol; calcium should normalize within 5 days of discontinuation. Measurement of ionized calcium is recommended—animals with CKD may develop nonionized hyper­calcemia that is unrelated to calcitriol treatment. PREVENTION/AVOIDANCE Dietary phosphorus restriction may delay the onset of RSHPT. POSSIBLE COMPLICATIONS Renal osteodystrophy and pathologic fractures (rare). EXPECTED COURSE AND PROGNOSIS •  Progression of the underlying CKD may be slowed by minimizing phosphorus retention and RSHPT. •  Long-term prognosis is guarded to poor for patients with CKD and RSHPT.



Canine and Feline, Seventh Edition



(continued)

Hyperparathyroidism, Renal Secondary •  PTHrP = PTH-related protein. •  RSHPT = renal secondary

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 MISCELLANEOUS

AGE-RELATED FACTORS Young animals can develop severe renal osteodystrophy; calcitriol may be beneficial. ABBREVIATIONS •  CKD = chronic kidney disease. •  PTH = parathyroid hormone.

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­Suggested Reading

Foster J. Update on mineral and bone disorders in chronic kidney disease. Vet Clin North Am Small Anim Pract 2016, 46(6):1131–1149. Polzin D. Chronic kidney disease. In: Ettinger SJ, Feldman EC, eds., Textbook of Veterinary Internal Medicine, 7th ed. St.

Louis, MO: Elsevier, 2009, pp. 2036–2067. Polzin DJ, Ross SJ, Osborne CA. Calcitriol therapy in chronic kidney disease. In: Bonagura J, ed., Current Veterinary Therapy XIV. Philadelphia, PA: Saunders, 2008, pp. 892–895. Author David J. Polzin Consulting Editor J.D. Foster

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Hyperphosphatemia

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 BASICS

DEFINITION •  Serum total phosphorus >5.5 mg/dL (dogs). •  Serum total phosphorus >6 mg/dL (cats).

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PATHOPHYSIOLOGY •  Control of phosphorus is complex and is influenced by the actions of parathyroid hormone (PTH) and vitamin D and the interaction of these hormones with the gastrointestinal tract, bone, kidneys, and parathyroid glands. The phosphatonin fibroblast growth factor-23 (FGF-23) also regulates phosphorus levels. •  High serum phosphorus results from excessive gastrointestinal absorption of phosphorus, excessive bone resorption of phosphorus, and/or reduced renal excretion of phosphorus. SYSTEMS AFFECTED

•  Endocrine. •  Metabolic. •  Renal.

GENETICS N/A INCIDENCE/PREVALENCE N/A GEOGRAPHIC DISTRIBUTION N/A SIGNALMENT

•  Dogs and cats. •  Any age, but commonly young, growing

animals or older animals with renal insufficiency. SIGNS

Historical Findings

•  Depends on the underlying cause of

hyperphosphatemia.

•  No specific signs directly attributable to

hyperphosphatemia.

•  Acute hyperphosphatemia causes

hypocalcemic tetany, seizures, or vascular collapse.

Physical Examination Findings

Chronic hyperphosphatemia causes calcification of soft tissues, resulting in chronic renal failure and tumoral calcinosis. CAUSES •  Reduced glomerular filtration rate. •  Renal hypoperfusion (e.g., hypovolemia, systolic cardiac disease). •  Renal disease. •  Postrenal urinary tract disease (e.g., obstruction, ruptured urinary bladder). •  Metabolic acidosis. •  Excessive bone resorption. •  Rhabdomyolysis or massive tissue trauma. •  Young growing dogs.

•  Hypoparathyroidism. •  Hypersomatotropism. •  Excessive gastrointestinal absorption of

phosphorus. •  Osteolysis. •  Disuse osteoporosis. •  Osseous neoplasia. •  Hyperthyroidism. •  Phosphorus-containing enemas. •  Vitamin D toxicosis. •  Dietary supplementation. •  Nutritional secondary hyperparathyroidism. RISK FACTORS

•  Renal disease. •  Use of phosphorus-containing enemas,

especially in smaller animals.

•  Massive tissue injury.

Disorders That May Alter Laboratory Results •  Hemolysis, hyperbilirubinemia, and

lipemia can falsely raise phosphorus concentrations. •  Collection in citrate, oxalate, or EDTA. Valid If Run in Human Laboratory?

Yes

CBC/BIOCHEMISTRY/URINALYSIS •  Serum phosphorus >6 mg/dL. •  Low serum calcium in patients with primary hypoparathyroidism. •  High serum calcium in patients with vitamin D intoxication. •  Degree of azotemia and urine specific gravity help define level renal impairment. •  Hyperkalemia and hyponatremia suggest hypoadrenocorticism. OTHER LABORATORY TESTS

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Hypoparathyroidism—also characterized by clinical signs of hypocalcemia such as seizures and tetany. •  Prerenal azotemia as a cause of hyperphosphatemia—associated with disease states that result in low cardiac output such as congestive heart failure, hypovolemia, hypoadreno­ corticism, and shock. •  Renal insufficiency, either acute or chronic renal failure—attended by azotemia and abnormal findings on urinalysis (low urinary specific gravity). •  Postrenal azotemia—associated with urinary obstruction or uroabdomen. •  Young, growing animals—can have serum phosphorus concentrations twice those of adults. •  Vitamin D intoxication—history of vitamin D supplementation or ingestion of rodenticides (e.g., Rampage® and D-CON®) or calcipotriene. •  Nutritional secondary hyperparathyroidism— history of dietary calcium–phosphorus imbalance. •  Hyperthyroidism in cats—clinical signs of weight loss, polyphagia, and polydipsia and polyuria. •  Hypersomatotropism—attended by a history of progesterone administration in dogs and insulin-resistant diabetes mellitus in cats. •  Nonazotemia tumoral calcinosis—observed in human beings as an autosomal dominant disorder; rare cause of hyperphosphatemia associated with large bone lesions. •  Jasmine toxicity—history of plant ingestion. •  Massive tissue injury. •  Rhabdomyolysis. •  Tumor lysis syndrome. •  Spurious. LABORATORY FINDINGS Drugs That May Alter Laboratory Results

Intravenous potassium phosphate.

•  Serum PTH measurement—intact

molecule and two-site assay methods have the greatest specificity; high-normal or high concentrations with concurrent hyperphosphatemia suggest primary hyperparathyroidism; low concentrations with concurrent hypocalcemia and hyperphosphatemia suggest neoplasia. •  Thyroxine concentrations—indicated in cats with hyperphosphatemia and clinical signs consistent with hyperthyroidism. •  Insulin-like growth factor 1 (IGF-1) concentrations—indicated in dogs or cats with unexplained hyperphosphatemia and clinical signs consistent with acromegaly; IGF-1 concentrations are elevated in animals with hypersomatotropism. •  Vitamin D assays are not readily available. •  Adrenocorticotropic hormone (ACTH) stimulation testing to confirm hypoadreno­corticism. IMAGING

•  Abdominal radiography to assess renal size

and symmetry.

•  Renal ultrasonography to detect soft tissue

mineralization.

•  Nuclear scintigraphy to rule out

hyperthyroidism. •  Radiography of long bones to detect osteoporosis or neoplasia. DIAGNOSTIC PROCEDURES Renal biopsy. PATHOLOGIC FINDINGS Mineralization of soft tissues may be noted radiographically or histopathologically.

­

 TREATMENT

APPROPRIATE HEALTH CARE Inpatient, because of the deleterious effects of hyperphosphatemia and the need for fluid therapy; consider severe hyperphosphatemia a



Canine and Feline, Seventh Edition

Hyperphosphatemia

(continued)

medical emergency. Long-term monitoring and management may be necessary. NURSING CARE Isotonic crystalloid fluids to increase glomerular filtration rate and promote phosphorus excretion. ACTIVITY N/A DIET Restrict dietary phosphorus. CLIENT EDUCATION Long-term monitoring and management may be necessary with phosphorus-restricted diets and/or oral phosphate binders. SURGICAL CONSIDERATIONS N/A

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 MEDICATIONS

DRUG(S) OF CHOICE Acute Hyperphosphatemia

•  Dextrose (0.5–1 g/kg IV) and regular

insulin (0.25–0.5 U/kg IV), to shift phosphorus intracellularly. •  Avoid phosphorus-containing fluids. Chronic Hyperphosphatemia

Oral administration of phosphorus binders (e.g., aluminum hydroxide or aluminum carbonate, 30–100 mg/kg/day PO, or calcium carbonate at 90–150 mg/kg/day PO, both with meals). CONTRAINDICATIONS N/A PRECAUTIONS Calcium carbonate should be avoided with hypercalcemia. POSSIBLE INTERACTIONS N/A ALTERNATIVE DRUG(S) The oral phosphate binders sevelamer hydrochloride and lanthanum carbonate may

699

be used as oral phosphate binders, but relatively little information is available in the veterinary literature.

AGE-RELATED FACTORS Mild elevations in phosphorus may be normal in growing animals. ZOONOTIC POTENTIAL N/A

­

 FOLLOW-UP

PATIENT MONITORING •  Serum calcium every 12 hours. •  Renal function tests—urine output must be monitored, particularly if oliguric renal failure is suspected, in which case urine output should be measured carefully; oliguria cannot be determined unless the patient is fully hydrated. •  Hydration status—indicators of over­ hydration include increased bodyweight, chemosis, increased central venous pressure, and edema (pulmonary or subcutaneous). •  Long-term serial monitoring of phosphorus is used to make dose adjustments in oral phosphate binders. PREVENTION/AVOIDANCE

•  Avoid ingestion of cholecalciferol

rodenticides, calcipotriene, or Vitamin D supplementation. •  Avoid phosphate-containing enemas. •  Well-balanced veterinary diets prevent nutritional secondary hyperparathyroidism. POSSIBLE COMPLICATIONS

•  Hypophosphatemia resulting in hemolysis. •  Soft tissue mineralization.

EXPECTED COURSE AND PROGNOSIS Depends on the underlying cause. Chronic kidney disease often causes chronic hyperphosphatemia and has a poor to guarded prognosis in dogs.

­

 MISCELLANEOUS

ASSOCIATED CONDITIONS Hypocalcemia

PREGNANCY/FERTILITY/BREEDING N/A SYNONYMS N/A SEE ALSO •  Acute Kidney Injury. •  Chronic Kidney Disease. •  Hypoparathyroidism. ABBREVIATIONS

•  ACTH = adrenocorticotropic hormone. •  FGF-23 = fibroblast growth factor-23. •  IGF-1 = insulin-like growth factor I. •  PTH = parathyroid hormone.

­Suggested Reading

Allen-Durrance AE. A quick reference on phosphorus. Vet Clin North Am Small Anim Pract 2017, 47:257–262. Aurbach GD, Marx SJ, Spiegel AM. Parathyroid hormone, calcitonin, and the calciferols. In: Wilson JD, Foster DW, eds., Williams Textbook of Endocrinology, 7th ed. Philadelphia, PA: Saunders, 1985, pp. 1208–1209. Willard MD, Tvedten H, Turnwald GH. Clinical Diagnosis by Laboratory Methods. Philadelphia, PA: Saunders, 1989. Author Alyssa M. Sullivant Consulting Editor Patty A. Lathan Acknowledgment The author and book editors acknowledge the prior contribution of Deborah S. Greco.

H

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Blackwell’s Five-Minute Veterinary Consult

Hypersomatotropism/Acromegaly in Cats ◦  Roughly one-third of cats with HST have

­

H

 BASICS

OVERVIEW •  Caused by excessive growth hormone (GH) secretion from the anterior pituitary by an adenoma or somatotroph hyperplasia. •  GH induces hepatic insulin-like growth factor-1 (IGF-1) secretion. The combination of increased GH and IGF-1 causes lipolysis, protein synthesis, impaired carbohydrate metabolism, and insulin resistance (IR). •  Prevalence in Europe ranges from 1 : 3 to 1 : 5.5 diabetic cats. SIGNALMENT

•  Median age—11 years (range: 9.5–13 years). •  Male : female ratio is 2 : 1. •  No breed predisposition.

SIGNS

•  Clinical signs of diabetes mellitus (DM;

e.g., polyuria, polydipsia, and polyphagia) occur from GH-induced IR. IR can be variable or persistent, which makes the DM difficult to control. •  Many (~40%) diabetics with hypersomato­ tropism (HST) lose weight due to poorly controlled DM; a small proportion (~17%) gain weight. •  Anabolic state—patients may present with polyphagia (without DM), or soft tissue growth resulting in upper airway obstruction, broad facial features, or clubbed feet. •  A small proportion (~2%) develop neurologic signs due to pituitary adenoma. CAUSES & RISK FACTORS

•  GH-secreting pituitary adenoma or

somatotroph hyperplasia.

•  In dogs, but not cats, progestins can result

in increased GH concentration.

­

 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Uncomplicated DM. •  Pituitary-dependent hyperadrenocorticism. •  Causes of polyphagia such as exocrine pancreatic insufficiency, gastrointestinal inflammatory diseases, hyperthyroidism, and inflammatory liver diseases. Cats with HST and polyphagia but without DM typically gain weight, unlike other differentials. CBC/BIOCHEMISTRY/URINALYSIS •  Consistent with DM. •  Diabetic ketoacidosis uncommon. OTHER LABORATORY TESTS

•  Serum IGF-1 concentration using validated

assays is test of choice. ◦  Positive predictive value of IGF-1 >1000 ng/mL (131 nmol/L) of 95%.

a low IGF-1 at diagnosis, which increases to >1000 ng/mL after insulin therapy. ◦  IGF-1 concentrations between 700 and 1000 ng/mL (92–131 nmol/L) is a “gray” zone—many non-HST diabetic cats are in this range. •  There is no commercially available GH assay. IMAGING •  Abdominal ultrasound might identify organomegaly. •  Contrast-enhanced CT can assess pituitary size. •  Echocardiographic findings—increased left ventricular wall thickness, left atrial enlargement, aortic insufficiency.

­

 TREATMENT

Surgery

Hypophysectomy most consistently normalizes IGF-1 concentration (80% of cases) and results in highest diabetic remission rates (50% achieve long-term remission). Medical Management

•  Somatostatins (SSTs) are primary negative

regulatory hormones of GH secretion.

•  Pasireotide is an SST analogue. Short-

acting pasireotide (0.03 mg/kg SC q12h) decreased IGF-1 in 12 cats after 3 days of treatment, while long-acting pasireotide (8 mg/kg SC monthly) resulted in normalization of IGF-1 in 2/8 cats; all cats experienced increased insulin sensitivity and 3/8 cats achieved diabetic remission. •  Octreotide is an SST analogue with a different binding profile that temporarily decreases GH without improvement in clinical control of HST or DM. •  Dopamine receptor 2 inhibits GH secretion. Cabergoline, a dopamine receptor 2 agonist, decreases IGF-1 and increases insulin sensitivity in some cats with HST. Radiotherapy

Fractionated radiotherapy improves neurologic signs and may improve diabetic control. Stereotactic radiotherapy might be more favorable as improved diabetic control and diabetic remission is more likely. Palliative Treatment

•  Maximizing diabetic control (e.g. with

insulin and diet) is recommended but may be challenging. •  Comorbidities (e.g., osteoarthritis, cardiac disease) should be managed. •  Controlling polyphagia in some cats with HST is challenging. Despite lack of endocrine improvement after cabergoline, many owners reported normalization of appetite.

­

 MEDICATIONS

­

 FOLLOW-UP

See Medical Management.

•  Depends on treatment modality. •  Survival varies from months to years; most

euthanized due to poor quality of life or causes unrelated to HST. •  Diabetic control should be monitored as for an uncomplicated diabetic. A small proportion of cats gain weight despite poor diabetic control and have persistent polyphagia despite good diabetic control.

­

 MISCELLANEOUS

ABBREVIATIONS •  DM = diabetes mellitus. •  GH = growth hormone. •  HST = hypersomatotropism. •  IGF-1 = insulin like growth factor-1. •  IR = insulin resistance. •  SST = somatostatin.

­Suggested Reading

Berg RI, Nelson RW, Feldman EC, et al. Serum insulin-like growth factor-I concentration in cats with diabetes mellitus and acromegaly. J Vet Intern Med 2007, 21(5):892–898. Gostelow R, Scudder C, Keyte S, et al. Pasireotide long-acting release treatment for diabetic cats with underlying hypersomatotropism. J Vet Int Med 2017, 31(2):355–364. Wormhoudt TL, Boss M-K, Lunn K, et al. Stereotactic radiation therapy for the treatment of functional pituitary adenomas associated with feline acromegaly. J Vet Int Med 2018, 32(4):1383–1389. Author Christopher J. Scudder Consulting Editor Patty A. Lathan Acknowledgment The author and book editors acknowledge the prior contributions of Deborah S. Greco and David Church.



Canine and Feline, Seventh Edition

701

Hypertension, Portal

­

 BASICS

DEFINITION Portal pressure >13 cm H2O (10 mmHg). PATHOPHYSIOLOGY •  Causes—increased portal blood flow (arterialized system), increased resistance to portal blood flow, or combination. •  Increased portal flow—arterialization of portal circulation occurs in arteriovenous (AV) malformation or subsequent to increased hepatic resistance causing retrograde blood flow into valveless splanchnic portal circulation. •  Hepatofugal—portal splanchnic circulation away from liver. Increased Resistance Relative to Liver

•  Prehepatic—abdominal portion of portal

vein.

•  Hepatic—within liver. •  Posthepatic—cranial to liver: terminal

hepatic veins, vena cava, heart, pericardium.

Intrahepatic Increase in Resistance

•  Presinusoidal—within portal tract. •  Sinusoidal—within sinusoid or space of Disse. •  Postsinusoidal—hepatic venular outflow

tract causing sinusoidal occlusion or Budd Chiari syndrome. •  Consequences—development of multiple acquired portosystemic shunts (APSS), abdominal effusion due to increased lymph formation, predisposition to hepatic encephalopathy (HE). •  Acquired portosystemic shunts (APSS)— develop within 1–2 months of acquired portal hypertension (PH). Effusion Protein Content

•  Hepatic causes—pure transudate reflects

concurrent PH and hypoalbuminemia (protein 2.5 g/dL). •  Prehepatic causes—pure or modified transudate, low cellularity. SYSTEMS AFFECTED •  Hepatobiliary disorders—obstructed blood flow in any zone or diffusely across sinusoids causes intrahepatic PH, splanchnic PH, ± passive splenic congestion (splenomegaly). •  Posthepatic disorders—hepatic passive congestion, hepatomegaly, variable PH; APSS usually absent. •  Prehepatic disorders—cause splanchnic PH, splenic congestion, APSS; portal venous thrombi, stenosis, stricture, entrapment in porta hepatis (e.g., pancreatitis, neoplasia), mass compression (pancreatic inflammation; neoplasia). •  Nervous—HE due to APSS. •  Cardiovascular—APSS and ascites may develop with vena caval/hepatic vein

obstruction (at level of diaphragm), but not with congestive heart failure or pericardial tamponade. •  Portal thrombi—caused by gastrointestinal (GI) inflammation/necrosis and splanchnic vasculitis, neoplasia, disseminated intravascular coagulation, loss of anticoagulants, accelerated thrombosis. •  GI—splanchnic hypertension can provoke enteric edema, increased gut wall permeability provoking transmural bacterial translocation (endotoxemia, bacteremia), hypertensive enteric vasculopathy (enteric bleeding, ulceration), diapedesis blood loss, protein malassimilation. GENETICS

•  Vascular malformations causing portal

atresia (intrahepatic, prehepatic) are congenital and represent severe phenotype of polygenic portal venous malformations in small-breed dogs. •  Ductal plate malformation (DPM)—congenital hepatic fibrosis (CHF) phenotype causes APSS; occurs in numerous dog breeds and Persianrelated cats; increased frequency in boxers. •  Noncirrhotic PH—adult-onset diminution of tertiary portal branches, affects individual dogs of many breeds, described in Doberman pinschers (rare). •  Acquired sinusoidal PH due to necroinflammatory liver injury—immune-mediated chronic hepatitis (anecdotal in some breeds). •  Copper associated hepatopathy— Bedlington terrier COMMD1 mutation, predisposition for copper associated hepatopathy in Labrador retrievers, Dalmatian, Doberman pinscher, and numerous other dogs may reflect pharmacogenetic breed differences in copper transporters.

•  Middle-aged and older animals—acquired

hepatobiliary disorders and portal thrombi. SIGNS

General Comments

•  Depend on site, degree, rate of onset of PH,

and causal factors.

•  Acquired disorders—slowly progressive,

chronic in onset.

Historical Findings

•  Portal thromboembolism may acutely

appear but remain unnoticed until APSS form; vague GI signs at occurrence including bloody diarrhea, ileus, abdominal pain, lethargy, inappetence. •  Abdominal distention—ascites. •  HE—secondary to APSS. •  Cardiac disorders or pericardial restriction— cough; exercise intolerance; dyspnea, jugular pulse, weak femoral pulses or pulsus alternans, reduced heart sounds on auscultation. Physical Examination Findings

•  Abdominal effusion. •  Hepatomegaly—posthepatic causes only. •  Splenomegaly—reflects splanchnic

congestion or venous thrombi, inconsistent.

•  Jugular vein distention—posthepatic

cardiac or pericardial causes.

•  Muffled heart sounds—pericardial or

pleural effusion.

•  Cardiac arrhythmias or murmur—cardiac

disease.

•  Pulmonary “crackles” (edema)—cardiac or

pericardial causes.

•  Confusion, stupor, coma, blindness, other

neurobehavioral abnormalities—HE.

•  Jaundice—hepatic causes. •  Hepatic bruit (hepatic AV malformation). •  Signs consequent to surgical ligation of

SIGNALMENT

portosystemic venous anomaly (PSVA).

Species

CAUSES

Dog > cat. Breed Predilections

Familial hepatic vascular disorders— Doberman pinschers (noncirrhotic PH); Saint Bernard (AV malformation); cocker spaniel hepatopathy; copper associated hepatopathy: Bedlington terriers, Doberman pinschers, Labrador retriever, others; DPM with CHF phenotype: boxers predisposed, any large or small dog breed, cats. Mean Age and Range

•  Juveniles—inherited or congenital

disorders; vena caval and cardiac malformations. •  Young dogs and cats 1.1) consistent with PH. IMAGING Radiography

•  Thoracic radiography—may reveal cause of

posthepatic PH.

•  Abdominal radiography—may reveal

effusion, splenomegaly, hepatomegaly; microhepatica in most hepatic disorders and portal atresia causing APSS. ABDOMINAL US

•  Identify abnormalities involving abdomi-

nal or extrahepatic portal vein—atresia, stricture, thrombi, occlusive lesions in porta hepatis. •  Identify lobe(s) containing AV malformations. •  Inspect splanchnic circulation using Doppler color flow; document hepatofugal circulation, identify portal thrombi, APSS, PSVA. •  Evaluate echogenicity of nonhepatic viscera, identify lymphadenomegaly, mass lesions, adhesions. •  Estimate hepatic venous distention—intrahepatic and supradiaphragmatic segments. Echocardiography

Detects congenital and acquired cardiac and pericardial disorders, neoplasia, thrombi, heartworms, pleural effusion, malformed or thrombosed vena cava, diaphragmatic hernia. Angiography and Nuclear Imaging

•  Colorectal or splenoportal scintigraphy—

confirms portosystemic shunting but not anatomic details. •  Radiographic angiography—celiac trunk and hepatic artery contrast studies confirm hepatic AV malformation; nonselective or selective studies: congenital cardiac disease, TE, hepatic vein disorders, AV malformation. •  Portovenography—confirms APSS. •  Multisector CT—displays arterial and venous phases. DIAGNOSTIC PROCEDURES

•  ECG and central venous pressure—with

cardiac disease, cranial mediastinal obstructions. •  Liver biopsy—required for diagnosis of hepatobiliary disorders. •  Portal pressure—may be measured during laparotomy but not recommended; PH adequately confirmed with imaging studies and on gross inspection.

(continued)

­

 TREATMENT

APPROPRIATE HEALTH CARE Inpatient—for severe HE, amelioration of tense ascites by therapeutic abdominocentesis, supportive care for acute TE. NURSING CARE •  Fluid therapy—restrict sodium concentration (avoid 0.9% NaCl); avoid iatrogenic pulmonary edema during fluid therapy (caution: if hypoalbuminemia, monitor respiration rate/effort). •  Monitor bodyweight and condition, girth circumference, plasma proteins, packed cell volume—assess hydration status, volume of abdominal effusion, IV fluid tolerance. •  Low oncotic pressure—may require plasma or colloid administration (plasma preferred for liver patient); Voluven® or VetStarch® (6%; 130 MW/0.4 molar substitution) 10–20 mL/ kg/day IV CRI) may be necessary for acute adjustments; avoid hetastarch as can reduce platelet function. •  Glucose supplementation—with hepatic dysfunction and hypoglycemia; 2.5–5.0% dextrose with half-strength polyionic fluids initially; avoid hyperglycemia. Mobilization of Ascites

•  Abdominal effusion—sequentially assess:

bodyweight, girth, body condition score; initially exercise restrict; enforce dietary sodium restriction. •  Conventional diuretics—combine furosemide and spironolactone; furosemide (0.5–2 mg/kg PO q12–24h) and spironolactone (0.5–2 mg/kg PO q12h, use single doubled dose for loading one time): dose titrations based on response q4 days; adjust using incremental 25–50% dose increase; serum : effusion albumin ratio (>1.1) may predict response to diuretics. •  Vasopressin V2 antagonists (aquaretics) may assist with management of diuretic-resistant ascites; tolvaptan successful in dogs with experimentally induced (rapid pacing) congestive heart failure; human dose in cirrhosis 7.5 mg/day; metabolized exclusively in liver primarily by cytochrome P450; dose undetermined in dogs with liver disease. •  Telmisartan—angiotensin receptor blocker is alternative diuretic worthy of consideration; administration PO at 1.0 mg/kg/day significantly increased urine volume and sodium excretion in healthy dogs in one study. •  Taper diuretic dose after initial positive response; individualize chronic treatment to response; may be used intermittently for recurring ascites. •  Avoid dehydration, can lead to HE. •  Avoid hypokalemia, can provoke HE. •  If ascites due to right-sided congestive heart failure, treat accordingly.



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Hypertension, Portal

(continued) •  Diuretic-resistant ascites—large-volume

(therapeutic) abdominocentesis if ascites resistant to medical intervention or compromises food intake, ventilation, or sleep: requires aseptic technique, fluid removal over 45–90 min, concurrently provide polyionic fluids in moderation with colloids to reduce risk for postcentesis hypotension and acute renal failure (ARF); repeated large-volume fluid removal may result in hypovolemia, hypoproteinemia, electrolyte depletion; iatrogenic infection; postcentesis hypovolemia/hypoperfusion syndrome, ARF; general rule in humans: provide 4–8 g albumin per L of ascites removed (consider colloids, discussed above). •  If ascites fails to mobilize, consider measuring urine sodium output vs. sodium intake (dietary) to determine whether intake requires restriction or diuretics upward titration; urine output should be measured over min 12h. ACTIVITY Depends on cause—restrict activity if ascites. DIET •  Ascites—restrict dietary sodium 35 mmHg and/or peak diastolic PA pressure >15 mmHg.

H

PATHOPHYSIOLOGY •  Causes of elevated PA pressure: ◦  PA vasoconstriction. ◦  PA obstruction. ◦  High left atrial (LA) pressure. ◦  Excessive pulmonary blood flow. •  As a result of pulmonary hyper­ tension (PH) right heart pressures increase to maintain pulmonary blood flow. ◦  May result in dysfunction of right ventricle RV and decreased pulmonary blood flow, which interferes with left heart filling and can lead to reduced cardiac output. ◦  High right heart pressures can cause venous congestion, tricuspid regurgitation (TR), and right-sided CHF. SYSTEMS AFFECTED •  Cardiovascular. •  Respiratory. •  Hepatobiliary (if right-sided CHF). GENETICS •  No specific genetic basis found. •  Causes of primary disease (congenital heart disease [CHD], left heart disease, pulmonary disease) may have a genetic basis. GEOGRAPHIC DISTRIBUTION Unknown; higher prevalence in heartwormendemic areas and high altitudes. SIGNALMENT Species

Dog and cat. Breed Predilections

•  Possibly based on underlying cause of PH. •  Increased incidence suggested in terrier breeds.

•  Abnormalities in endothelial derived vasodilator/vasoconstrictor substances result in vascular obstruction and vasoconstriction. •  Not reported in companion animals.

Pulmonary Parenchymal Disease

•  Vascular obstruction—resulting from

pulmonary lesions (e.g., fibrosis, neoplasia), vascular hypertrophy/inflammation. •  Vasoconstriction—secondary to hypoxia and acidemia. •  Causes—pneumonia (bacterial, viral, fungal, parasitic); chronic bronchitis; pulmonary fibrosis; eosinophilic bronchitis; pulmonary neoplasia; acute respiratory distress syndrome. Pulmonary Thromboembolism (PTE)

•  Vascular obstruction—secondary to thrombus. •  Vasoconstriction—secondary to

hypoxia and vasoconstrictive substances released from the thrombus. •  Causes— hyperadrenocorticism; protein-losing nephropathy/enteropathy; sepsis; immunemediated hemolytic anemia; neoplasia; pancreatitis; endocarditis; disseminated intravascular coagulation; primary cardiac disease (typically right-sided).

Heartworm Disease (HWD)

•  Vascular obstruction—vascular hypertrophy,

inflammation, thromboembolism, and presence of heartworms. •  Vasoconstriction— secondary to hypoxia/thrombi.

Left-to-Right-Shunting CHD

•  Excessive pulmonary blood flow—results in

damage to pulmonary vasculature. •  Vasoconstriction/vascular obstruction—due to vascular damage and hypertrophy. •  Causes— patent ductus arteriosus; ventricular septal defect; atrial septal defect; atrioventricular septal defect.

Predominant Sex

Left Heart Disease

SIGNS

vascular obstruction—result of elevated pressure and vascular hypertrophy. •  Causes— mitral regurgitation; cardiomyopathy (dilated, hypertrophic, restrictive, unclassified); mitral stenosis; congenital pulmonary venous obstruction; LA tumors.

Increased incidence reported in females. General Comments

Signs due to hypoxia and cardiac dysfunction. Historical Findings

•  Exercise intolerance. •  Dyspnea/tachypnea. •  Coughing/hemoptysis. •  Syncope. •  Abdominal distention. •  Weight loss. •  Lethargy. •  Sudden death.

Physical Examination Findings

•  Dyspnea/tachypnea. •  Coughing/ hemoptysis. •  Loud and/or split second heart sound. •  Pulmonary crackles and/or

increased bronchovesicular sounds. •  Cyanosis. •  Heart murmur. •  Abdominal distention. •  Jugular distention. •  Subcutaneous edema. •  Weight loss. CAUSES Primary/Idiopathic/Familial PH

•  Congenital disorders of the pulmonary vasculature identified in humans.

•  High LA pressure—results in pulmonary venous hypertension. •  Vasoconstriction/

Extrapulmonary Causes of Chronic Hypoxia

•  Vasoconstriction and secondary vascular hypertrophy—due to environmental/ extrapulmonary factors that result in hypoxia and acidemia. •  Causes— hypoventilation (Pickwickian syndrome, neuromuscular disorders); high altitude disease.

RISK FACTORS •  Cardiac and pulmonary disease. •  HWD. •  Diseases causing hypercoagulability. •  Obesity. •  High altitude.

­

 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Left-sided CHF*. •  Tracheal collapse. •  Right-sided CHF*. •  Primary pulmonary disease*. •  HWD*. •  Pneumothorax. •  Pleural effusion (pyothorax, chylothorax, hemothorax, hydrothorax). •  Laryngeal disease. * = without concurrent PH. CBC/BIOCHEMISTRY/URINALYSIS

•  Polycythemia if hypoxemic. •  Leukocytosis with infectious lung disease. •  Possible

evidence of hypercoagulability.

OTHER LABORATORY TESTS

•  Arterial blood gases (hypoxemia). •  Occult heartworm test. •  Workup for PTE (urine

protein : creatinine ratio, antithrombin III level, D-dimer, coagulation profile, urine cortisol : creatinine ratio, adrenocorticotropic hormone stimulation test, dexamethasone suppression test). •  Cytology of effusions. IMAGING

Radiography

•  Dilated PA and/or torturous pulmonary vessels. •  Enlarged RV and right atrium (RA). •  Dilated caudal vena cava. •  Pleural effusion. •  Hepatomegaly. •  Ascites. •  Evidence of

primary pulmonary disease, PTE, or HWD.

Echocardiography

•  RV concentric/eccentric hypertrophy. •  Flattening of interventricular septum and/or paradoxical septal motion. •  RA dilation. •  PA dilation with decreased distensibility. •  Pleural/ pericardial effusion. •  Evidence of left heart disease, HWD, CHD, or PTE. •  Asymmetric, notched pulmonary outflow tracing. •  TR

gradient, if present without pulmonic stenosis or PA stenosis, estimates systolic PH severity. ◦  Systolic pressure gradient between PA and RA estimated with spectral Doppler using modified Bernoulli equation: 4 × (peak TR velocity)2. ◦  Pressure gradient >35 mmHg (TR velocity ≥3.0 m/s) suggestive of PH. ◦  Gradient determines severity—mild: 35–50 mmHg; moderate 51–80 mmHg; severe: >80–mmHg. •  Pulmonary valve insufficiency (PI), if present without PA stenosis, estimates diastolic PH severity. ◦  Diastolic pressure gradient between PA and RV estimated with spectral Doppler using modified Bernoulli equation: 4 × (end PI velocity)2. ◦  Pressure gradient >15 mmHg (end PI velocity >2.0 m/s) suggestive of PH. CT/MRI

May be of value if pulmonary neoplasia or other infiltrative/obstructive disease. DIAGNOSTIC PROCEDURES Transtracheal wash, bronchoscopy/ bronchoalveolar lavage, or lung aspirate/ biopsy may be of value if evidence of primary pulmonary disease.



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Hypertension, Pulmonary

(continued)

ECG

•  Right mean electrical axis deviation. •  Deep S waves (leads I, II, III, and aVF), •  Widened QRS complex. •  P-pulmonale. •  ST segment depression/elevation. •  Hypoxia-induced

arrhythmias (ventricular premature complexes [VPCs]).

Cardiac Catheterization and Pulmonary Angiography

•  Gold standard for diagnosis. •  Uncommonly

performed due to risk and usefulness of echocardiography. •  Indicated if necessary to confirm diagnosis or cause.

PATHOLOGIC FINDINGS Depend on underlying disease and severity— primary pulmonary lesions; PTE; dilated PA/ RV/RA/vena cava; heartworms; pleural/ pericardial/abdominal effusions; medial hypertrophy, intimal proliferation, and sclerosis of pulmonary vessels; necrotizing arteritis.

Phosphodiesterase Type V (PDE5) Inhibitors

•  Inhibit the breakdown of cyclic guanosine monophosphate (cGMP) causing increased nitric oxide and pulmonary vasodilation. •  Avoid other drugs with similar effects (nitrates). •  Sildenafil (1–2 mg/kg q8–12h)—drug of choice for most causes of PH in dogs. •  Tadalafil—limited studies suggest benefit in dogs.

 TREATMENT

APPROPRIATE HEALTH CARE •  Hospitalize patients in severe respiratory distress. •  Perform diagnostics based on patient stability. NURSING CARE

•  Judicious fluid therapy may help improve pulmonary blood flow. •  Risk of CHF must be considered. •  Maintain low-stress environment.

CLIENT EDUCATION •  Prognosis varies with the underlying disease but generally very guarded. •  Avoid respiratory triggers—heat/humidity extremes, secondhand smoke, high altitudes.

useful with other causes of PH.

­

Other Vasodilators

PATIENT MONITORING •  Serial echocardiography to assess improvement/progression. •  Repeat thoracic radiographs, ECG, labwork, blood pressure as needed.

•  Pimobendan. •  Causes pulmonary and systemic vasodilation. •  Positive inotropic effect supports right heart dysfunction. •  Indicated if PH secondary to left heart disease. •  Unclear if

•  Limited benefit due to concurrent systemic vasodilation and hypotension. •  Important in PH due to left heart disease. •  Amlodipine,

Bronchodilators

•  May help patients with pulmonary disease. •  Sympathomimetics (e.g., terbutaline). •  Methylxanthines (e.g., theophylline)—may

also cause mild PA vasodilation.

Anticoagulants

•  Common therapy for all causes of PH due to primary and/or secondary thromboembolism in humans. •  Use in companion animals unclear except in patients with PTE.

Thrombolytics

•  Streptokinase and tissue plasminogen

activator indications and effectiveness debated in companion animals. •  Likely only indicated if acute PTE with significant cardiac compromise.

Anti-inflammatories and Antibiotics

­

Other Therapies

DRUG(S) OF CHOICE •  Treat the primary underlying disease whenever possible. •  The ideal therapeutic agent for PH causes pulmonary vasodilation without causing significant systemic hypotension. Oxygen

•  Treatment of choice but long-term administration unfeasible. •  Useful in acute

setting to correct hypoxia and cause pulmonary vasodilation.

PRECAUTIONS

•  Vasodilators can cause systemic hypotension. •  Pulmonary vasodilation in patients with left

heart disease may induce pulmonary edema. •  Bronchodilators can cause tachycardia and hyperexcitability. •  Hypovolemia may reduce pulmonary blood flow.

SURGICAL CONSIDERATIONS Surgical heartworm extraction is a consideration in patients with severe infestation.

 MEDICATIONS

myocardial depressants (e.g., beta blockers).

•  Bronchoconstrictors (e.g., nonspecific beta blockers). •  Vasoconstrictors.

Phosphodiesterase Type III (PDE3) Inhibitor

hydralazine, and angiotensin-converting enzyme (ACE) inhibitors.

­

CONTRAINDICATIONS

•  Respiratory depressants. •  Cardiac

•  Steroids may help if cause of PH has

inflammatory component (e.g., HWD or primary pulmonary disease). •  Antibiotics if bacterial component.

•  No large veterinary clinical trials to support use. •  Endothelin receptor

antagonists (Bosentan®)—pulmonary vasodilator that improves outcome in humans; cost prohibitive in veterinary patients. •  Platelet-derived growth factor antagonists (toceranib, sorafenib, imatinib)— shown to decrease right heart pressure in rat PH model; preliminary studies of imatanib in dogs is promising. •  L-arginine—possible benefit due to conversion to nitric oxide.

 FOLLOW-UP

POSSIBLE COMPLICATIONS

•  Right-sided CHF. •  Syncope. •  Arrhythmias. •  Sudden death.

EXPECTED COURSE AND PROGNOSIS •  Based on ability to reverse underlying disease. •  Often very guarded prognosis.

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 MISCELLANEOUS

ABBREVIATIONS •  ACE = angiotensin-converting enzyme. •  cGMP = cyclic guanosine monophosphate. •  CHD = congenital heart disease. •  CHF = congestive heart failure. •  HWD = heartworm disease. •  LA = left atrium. •  PA = pulmonary artery. •  PH = pulmonary hypertension. •  PI = pulmonary valve insufficiency. •  PTE = pulmonary thromboembolism. •  RA = right atrium. •  RV = right ventricle. •  TR = tricuspid valve regurgitation. •  VPCs = ventricular premature complexes.

­Suggested Reading

Poser H, Guglielmini C. Pulmonary hypertension in the dog. Acta VeterinariaBeograd 2016, 66:1–25. Authors Donald P. Schrope and Jennifer M. Mulz Consulting Editor Michael Aherne  Client Education Handout available online

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Hypertension, Systemic Arterial SIGNALMENT

Breed Predilections

dosages), erythropoietin/darbepoetin, phenylpropanolamine, phenylephrine, ephedrine, toceranib phosphate. •  Intoxicants—cocaine, methamphetamine/ amphetamine, 5-hydroxytryptophan.

Mean Age and Range

RISK FACTORS Renal disease or endocrinopathy.

Species

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 BASICS

DEFINITION Sustained increase in arterial blood pressure, corresponding to systolic BP (SBP) ≥160 mmHg confirmed during multiple measurement sessions. BP increases may be transient and related to the measurement process (situational or “white-coat” hypertension), or sustained and pathologic. In veterinary patients, systemic arterial hypertension (HT) usually occurs in association with a clinical disease or treatment known to cause HT and is categorized as secondary. If an underlying disease is not present or able to be determined, HT is considered idiopathic. PATHOPHYSIOLOGY •  BP is the force exerted by a blood column against the vessel wall, and is determined by cardiac output, aortic impedance and systemic vascular resistance. •  Normally, BP is under close regulation, such that rapid or wide swings are avoided. •  Factors that favor BP increases by augmenting cardiac output (e.g., increases in intravascular volume, heart rate, or myocardial contractility) or systemic vascular resistance (e.g., arteriolar vasoconstriction, increased blood viscosity) are usually balanced by autonomic, renal, and local vascular responses that restore normal BP. •  Systemic HT may develop in association with diseases or pharmacologic agents that overwhelm or interfere with normal homeostatic mechanisms or with vascular responsiveness to these mechanisms. •  Chronic, sustained BP increases may cause injury to several organs, referred to as target organ damage (TOD). SYSTEMS AFFECTED

•  Renal/urologic. •  Cardiovascular. •  Ophthalmic. •  Nervous.

GENETICS Rare instances of familial idiopathic HT are reported. INCIDENCE/PREVALENCE •  Prevalence estimates are difficult to interpret due to differences in HT definitions, inclusion criteria, and measurement techniques among studies. •  Pathologic HT are rare in young, healthy dogs and cats. •  Reported prevalence in HT-associated diseases—chronic kidney disease (CKD), 9–93% (dogs) and 19–65% (cats); diabetes mellitus, 24–67% (dogs) and 0–15% (cats); hyperadrenocorticism, 20–80% (dogs); hyperthyroidism, 5–25% (cats); pheochromo­ cytoma, 43–86% (dogs).

Dog and cat. None

•  Usually older animals; median age 13–15

years (cats).

•  May be noted in younger animals, especially

those affected by infectious (e.g., leptospirosis) or heritable (e.g., polycystic kidney disease, renal dysplasia) disease. SIGNS

General Comments

Clinical signs vary with affected target organ and underlying disease; may be apparently asymptomatic or display signs that are acute, severe, or rapidly progressive. Historical Findings

•  Signs attributable to underlying disease (e.g., polyuria/polydipsia, anorexia, vomiting, weight loss with CKD; hindlimb weakness, cervical ventroflexion with hyperaldosteronism). •  Acute-onset or progressive blindness. •  Altered mental state, lethargy, seizures (generalized or focal), or ataxia. •  Rarely, respiratory signs due to congestive heart failure (CHF), e.g., dyspnea/orthopnea (cats/dogs), cough (dogs). •  Epistaxis (rare). •  Headaches, blurred vision, and anxiety, reported by people with HT, may manifest as nonspecific signs in dogs and cats.

Physical Examination Findings

•  Ocular—blindness, mydriasis, exudative

retinal detachment, retinal hemorrhage/ edema, retinal vascular tortuosity or perivascular edema, vitreal hemorrhage, bullous retinal detachment, hyphema, glaucoma, retinal degeneration. •  Neurologic—abnormal mentation, central blindness, nystagmus, ataxia. •  Renal—palpable renal abnormalities. •  Cardiovascular—heart murmur, arrhythmia, gallop sound, pulmonary crackles. CAUSES Idiopathic

Subclinical CKD thought to contribute in some cases. Secondary Hypertension

•  CKD. •  Acute kidney injury (AKI). •  Hyperadrenocorticism. •  Hyperthyroidism. •  Diabetes mellitus. •  Pheochromocytoma. •  Primary hyperaldosteronism. •  Hypothyroidism. •  Polycythemia. •  Drug-related—glucocorticoids

(uncommon), mineralocorticoids (high

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS Differential signs—differentiate from other causes of acute-onset blindness, central neurologic signs, CHF, or epistaxis, depending on presenting signs and clinical findings. CBC/BIOCHEMISTRY/URINALYSIS •  Abnormalities vary depending on underlying disease. •  Packed cell volume may be decreased (CKD) or mildly increased (hyperthyroidism). •  CBC may reveal stress leukogram and/or thrombocytosis (hyperadrenocorticism). •  May note azotemia, hyperphosphatemia, hyperkalemia (AKI, CKD); hyperglycemia (diabetes mellitus); increased serum alkaline phosphatase (hyperadrenocorticism); increased serum alanine aminotransferase (hyperthyroidism); hypokalemia (hyperaldosteronism). •  Urinalysis may reveal low urine specific gravity, proteinuria, hematuria, pyuria, bactiuria (AKI, CKD, hyperadrenocorticism); glucosuria (diabetes mellitus). OTHER LABORATORY TESTS

•  Assessment of glomerular filtration rate

may detect early renal dysfunction.

•  Urinary protein : creatinine ratio may

disclose proteinuria.

•  Serum total T4 concentration, T3 suppression

test to evaluate for hyperthyroidism (cats). •  Serum T3, T4, free T3, free T4, and thyroid-stimulating hormone concentrations; T3 and T4 autoantibodies to evaluate for hypothyroidism (dogs). •  Screening tests for hyperadrenocorticism in dogs with other suggestive findings. •  Plasma aldosterone concentration if primary hyperaldosteronism suspected (cats). •  Plasma and urinary catecholamine concentrations if pheochromocytoma suspected. IMAGING •  Abdominal ultrasonography to evaluate kidneys, liver, and adrenal glands. •  Echocardiography to evaluate for cardiac TOD—may be normal, or disclose left ventricular concentric and/or eccentric hypertrophy, diastolic dysfunction, left atrial enlargement. •  CT or MRI if cerebral hemorrhage, hyperadrenocorticism suspected. •  Thyroid scintigraphy to evaluate hyperthyroidism.



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Hypertension, Systemic Arterial

(continued)

DIAGNOSTIC PROCEDURES •  Diagnosis requires documentation of persistently (i.e., during ≥2 sessions, performed on different days) high SBP, using reliable direct or indirect measurement methods. •  Methods should be standardized to avoid inaccuracies caused by common technical errors. •  Substantial effort should be made to minimize patient stress to reduce risk of falsely diagnosing “true” HT in patient with situational HT. •  See Suggested Reading to consult detailed published guidelines for BP measurement. Direct (Invasive) BP Measurement Methods

•  Gold standard—involve catheterization or

needle puncture of peripheral artery. •  Reserved for monitoring under anesthesia or during emergency management of severe HT.

Indirect (Noninvasive) BP Measurement Methods •  More clinically useful than direct methods

for outpatient setting.

•  Utilize devices that rely on Doppler

ultrasonography or oscillometry. •  Require placement of inflatable cuff to temporarily occlude arterial blood flow in extremity by applying external, compressive force. Ancillary Diagnostics

Fundoscopic examination to evaluate for retinal lesions. PATHOLOGIC FINDINGS •  Widespread, multisystemic arteriolosclerosis. •  Increased cardiac mass due to left ventricular hypertrophy. •  Aortic aneurysm/dissection (rare). •  Lesions associated with underlying disease.

“prehypertensive”), or suspected situational HT, should not be treated. •  Therapeutic targets—ideally, normotension (SBP 120–140 mmHg); SBP 200 mmHg or ocular/neurologic TOD; angiotensin-converting enzyme (ACE) inhibitor or telmisartan may be added if proteinuria or poor control with amlodipine alone. •  Dogs—ACE inhibitor or angiotensin receptor blocker (ARB) first line; amlodipine coadministered as first line if SBP >200 mmHg, or added if SBP 160–200 mmHg and poor control with ACE inhibitor or ARB. •  In hypertensive emergency (HT with severe ocular or neurologic TOD), parenteral

Phenoxybenzamine—dogs: 0.25 mg/kg PO q8–12h; cats: 2.5 mg/cat PO q8–12h. Aldosterone Antagonist

Spironolactone—dogs and cats: 1.0–2.0 mg/ kg PO q12h. CONTRAINDICATIONS Decrease or discontinue vasoconstricting drugs (e.g., phenylpropanolamine). PRECAUTIONS •  Abrupt BP reduction and hypotension (SBP 5 g/dL; 50 gm/L). •  Azotemia and hypercalcemia, if hyperviscosity caused by paraneoplastic syndrome. •  Isosthenuria and marked proteinuria. OTHER LABORATORY TESTS

SIGNALMENT •  Dogs more frequently affected than cats. •  No sex or breed predilections. •  More common in older animals due to increased incidence of malignancy.

•  High concentration of IgG, IgA, or IgM, as

SIGNS

partial thromboplastin time, abnormal platelet function testing. •  Other testing as indicated by primary disease. •  Bence-Jones proteinuria in patients with multiple myeloma.

Historical Findings

•  No consistent signs. •  Anorexia. •  Lethargy. •  Depression. •  Polyuria and polydipsia. •  Blindness, ataxia, seizures, syncope. •  Bleeding tendencies. •  Respiratory distress. •  Congestive heart failure.

Physical Examination Findings

detected by radial immunodiffusion.

•  High plasma or serum viscosity (>3× greater

than water).

•  Prolonged prothrombin time or activated

IMAGING Hepatosplenomegaly, cardiomegaly, and osteolytic lesions (in association with multiple myeloma) are possible. DIAGNOSTIC PROCEDURES Bone marrow aspirate or core biopsy—plasma cell or lymphoid infiltrate.

•  Neurologic deficits, including seizures and

disorientation.

•  Tachycardia and tachypnea due to volume

overload (e.g., congestive heart failure) or pulmonary thromboembolism. •  Epistaxis or other mucosal bleeding. •  Hepatomegaly, splenomegaly, lympha­denopathy. •  Visual deficits associated with engorged retinal vessels, retinal hemorrhage or detachment, and papilledema.

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 TREATMENT

Appropriate Health Care

•  Generally treat as inpatient. •  Treat underlying disease. •  Phlebotomy (15–20 mL/kg) with isotonic

crystalloid fluid volume replacement.

•  Plasmapheresis, either manual or automated.

CAUSES & RISK FACTORS

Nursing Care

immunoglobulin (Ig) M > IgA > IgG. •  Lymphocytic leukemia or lymphoma. •  Marked polycythemia—hematocrit (HCT) >65%, usually >75%. •  Chronic atypical inflammation with monoclonal gammopathy (e.g., ehrlichiosis or leishmaniasis in dogs).

­

•  Multiple myeloma and plasma cell tumors—

As dictated by underlying disease.

 MEDICATIONS

DRUG(S) OF CHOICE Provide treatment for underlying neoplastic or inflammatory condition.

CONTRAINDICATIONS/POSSIBLE INTERACTIONS •  Avoid use of medications that might increase vascular volume, including synthetic colloids (e.g., hetastarch); do not try to correct compensatory low albumin. •  Avoid medications that alter platelet function.

­

 FOLLOW-UP

•  Monitor serum or plasma proteins

frequently as marker of treatment efficacy.

•  CBC, biochemistry panel, and urinalysis to

monitor other laboratory abnormalities.

­

 MISCELLANEOUS

SEE ALSO •  Ehrlichiosis and Anaplasmosis. •  Erythrocytosis. •  Leukemia, Chronic Lymphocytic. •  Lymphoma—Cats. •  Lymphoma—Dogs. •  Multiple Myeloma. •  Plasmacytoma, Mucocutaneous. ABBREVIATIONS

•  HCT = hematocrit. •  Ig = immunoglobulin.

­Suggested Reading

Hohenhaus AE. Syndromes of hyperglobulinemia: diagnosis and therapy. In: Kirk RW, ed., Current Veterinary Therapy XII. Philadelphia, PA: Saunders, 1995, pp. 523–530. Author Elizabeth Rozanski Consulting Editor Melinda S. Camus



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Hyphema SIGNS

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 BASICS

DEFINITION Blood inside the anterior chamber in the form of a blood clot, settled blood in the ventral anterior chamber, or red blood cells suspended throughout the aqueous. PATHOPHYSIOLOGY •  Breakdown of the blood–aqueous barrier and/ or direct injury to the iris and ciliary body blood vessels; causes include direct trauma to the cornea or anterior uvea (iris and ciliary body), inflammation, and damage to blood vessel walls (e.g., caused by systemic hypertension, antigenantibody complexes, or circulating infectious organisms or neoplastic cells). •  Abnormal hemostasis due to a coagulopathy or thrombocytopenia. •  Bleeding from abnormal vessels within the eye; this is most commonly due to pre-iridal fibrovascular membranes (PIFMs), which form in response to chronic intraocular disease (uveitis, retinal detachment, glaucoma, neoplasia); rarely, abnormal congenital blood vessels in the eye such as persistent pupillary membranes, tunica vasculosa lentis, or hyaloid artery may bleed, causing hyphema. SYSTEMS AFFECTED Ophthalmic INCIDENCE/PREVALENCE Not uncommon ophthalmic finding and one that is important to recognize, as it may be the presenting clinical sign for serious underlying systemic disease. SIGNALMENT Species

Dog and cat. Breed Predilections

Collies with collie eye anomaly.

Historical Findings—Primary Ophthalmic Causes •  Usually a unilateral presentation in an

otherwise systemically normal patient.

•  Blunt globe trauma will often have a

compatible history. •  Corneal perforation may have a history of a corneal ulcer, or preceding encounter with a cat resulting in a cat claw laceration, especially in puppies. Historical Findings—Systemic Causes

•  Unilateral or bilateral presentation; bilateral

presentation is strongly supportive of systemic etiology. •  Weight loss, anorexia, lethargy, decreased vision, or loss of vision may accompany some systemic causes. •  Ocular pain usually accompanies infectious and neoplastic causes due to accompanying uveitis. Physical Examination Findings—Primary Ophthalmic Causes •  Except in cases of generalized trauma, the

physical exam will be unremarkable with abnormalities restricted to the globe and periorbital soft tissues. •  Blunt trauma patients will have painful periorbital soft tissue swelling and uncommonly orbital rim fractures; there is often total hyphema obscuring other intraocular structures. •  Perforating trauma is associated with severe pain, a bloody or clear (aqueous) ocular discharge, varying degrees of hyphema, miosis, and anterior synechia, and a shallow anterior chamber; corneal edema will surround the perforation site and an iris prolapse may be present through the perforation. •  Hyphema due to PIFMs, retinal detachment, neoplasia, or congenital vasculature is usually nonpainful with very

little intraocular inflammation (absent aqueous flare, miosis). •  Hypermature cataract supports the development of either PIFM or retinal detachment as a cause of hyphema. Physical Examination Findings— Systemic Disease Causes

•  Ophthalmic examination findings will

vary depending on the etiology of the hyphema. •  When an underlying systemic disease is suspected, a thorough physical exam is warranted; the exam may be unremarkable or have significant findings such as lymphadeno­ pathy, fever, or petechiae. •  Hyphema due to noninflammatory etiologies such as hypertension, thrombocytopenia, and coagulopathies will usually manifest minimal discomfort and uveitis (trace or no aqueous flare, no miosis, no conjunctival hyperemia); hypertension is almost always associated with retinal involvement such as retinal hemorrhages and/or retinal detachment. •  Patients with coagulopathies may have bleeding elsewhere, including the subconjunctival tissue and retrobulbar space; thrombocytopenia may create petechia on the palpebral or nictitans conjunctiva. •  Infectious and neoplastic etiologies often cause significant pain, anterior uveitis (miosis, aqueous flare, fibrin, iridal hyperemia and swelling), chorioretinitis with retinal detachment, and possible secondary glaucoma. CAUSES See Table 1. RISK FACTORS

•  Ophthalmic—hypermature cataract, retinal

detachment, chronic anterior uveitis.

•  Systemic—any disease or disorder

predisposing to the systemic diseases known to cause uveitis or direct vascular damage

Table 1 Causes of hyphema. Primary Ophthalmic Etiologies

Systemic Disease Etiologies

Trauma (blunt or perforating) Extraocular vascular compression (choking, chest compression) PIFM Retinal detachment Primary intraocular neoplasia (iris melanoma, ciliary body adenoma/adenocarcinoma) Golden retriever pigmentary uveitis Patent anomalous congenital blood vessels (persistent pupillary membranes, tunica vasculosa lentis, hyaloid artery)

Hypertension Hyperviscosity syndrome Thrombocytopenia Coagulopathy Metastatic neoplasia (especially lymphoma) Rickettsial disease FIP Fungal disease Prototheca Parasitic (aberrant intraocular larval migration)

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Hyphema (e.g., chronic renal disease, hyperthyroidism, systemic hypertension); living in geographic areas with endemic tick-borne disease.

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS Deep corneal vascularization, along the ventral limbus, can be mistaken for hyphema. CBC/BIOCHEMISTRY/URINALYSIS Abnormal findings may help support a diagnosis of systemic disease. OTHER LABORATORY TESTS Based on history and physical examination findings, coagulation profile and serology (rickettsial, fungal) may be indicated if systemic disease is suspected. IMAGING •  Ocular ultrasound is indicated to evaluate for retinal detachment or uveal tumors when not visible on the ophthalmic examination. •  Based on history and physical exam­ ination findings, thoracic radiographs, abdominal radiographs, and abdominal ultrasound may be indicated if systemic disease is suspected. DIAGNOSTIC PROCEDURES •  Systemic arterial blood pressure measurement using Doppler ultrasonic flow probe or oscillometric techniques, if hypertension is suspected. •  Lymph node aspirates if lymphadenopathy is present or if neoplasia or fungal disease is suspected. PATHOLOGIC FINDINGS Gross hemorrhage in the anterior chamber.

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 TREATMENT

APPROPRIATE HEALTH CARE Outpatient medical care is appropriate unless an underlying systemic disease is identified that requires hospitalization. ACTIVITY No restricted activity is required unless the patient is blind (restrict environment to fenced yards, no in-ground pools, leash walks, etc.) or the hyphema is due to thrombocytopenia or coagulopathy (avoid rough play, unrestricted running, etc.). CLIENT EDUCATION •  Hyphema itself, although it appears dramatic, is not painful. •  It is very important to identify the underlying cause of the hyphema, as some

(continued)

etiologies pose a serious health threat.

•  Ophthalmic treatment should be initiated

immediately to try to prevent painful and sometimes irreversible and blinding sequelae like glaucoma. SURGICAL CONSIDERATIONS

•  Hyphema secondary to a perforating

corneal laceration or ulceration should be surgically repaired by direct suturing of the cornea (laceration) or corneal graft (perforated ulcer) when a visual outcome is expected; for a severe perforation with extensive iris prolapse and loss of the pupil, enucleation is recommended. •  Permanently blind and painful eyes should be enucleated (with histopathology) for permanent comfort. •  Surgical irrigation/removal of the hyphema is not successful, as the trauma of the surgery results in exacerbation of the hyphema and intraocular inflammation.

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 FOLLOW-UP

PATIENT MONITORING •  Tonometry should be used to monitor for secondary glaucoma, which lowers the prognosis for a visual outcome. •  Perform tonometry every 1–2 days if the intraocular pressure (IOP) is high normal or greater, or if risk factors such as fibrin and/or posterior synechia are present. •  Perform tonometry weekly if the IOP is low, or if the hyphema and anterior uveitis are mild to moderate in severity. •  Tonometry is contraindicated with a corneal perforation. POSSIBLE COMPLICATIONS Secondary glaucoma, posterior synechia/ dyscoria, cataract formation, loss of vision, possible loss of the eye if the eye becomes permanently blind and painful. EXPECTED COURSE AND PROGNOSIS

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 MEDICATIONS

DRUG(S) OF CHOICE •  Topical prednisolone acetate 1% or dexamethasone 0.1% q4–8h to help stabilize the blood–aqueous barrier; do not use if a corneal ulcer or perforation is present. •  Atropine 1% q6–24h to help prevent posterior synechia; atropine is contraindicated if secondary glaucoma is present. •  Systemic nonsteroidal anti-inflammatory drug (NSAID—carprofen, meloxicam, deracoxib) for analgesia in patients with perforating trauma; may help stabilize blood–aqueous barrier. •  Systemic prednisone/prednisolone with known or suspected choroidal/retinal involvement, depending on the underlying cause; anti-inflammatory dose (0.5–1.0 mg/kg PO q24h) can be used for blunt trauma, feline infectious peritonitis (FIP), and rickettsial and fungal disease with proper antimicrobial therapy. •  Topical carbonic anhydrase inhibitors (dorzolamide 2%, brinzolamide 1%, q8h), beta blocker (timolol 0.5% q8–12h), and/or sympathomimetic (dipivefrin 0.1% q8–12h) can be used if secondary glaucoma is present. CONTRAINDICATIONS

•  Topical NSAIDs (flurbiprofen, diclofenac,

ketorolac, etc.) are generally considered contraindicated with hyphema. •  Topical prostaglandin analogues (latanoprost, travoprost, bimatoprost) are contraindicated in secondary glaucomas.

•  If the underlying cause of the hyphema can

be successfully treated, such as repair of a corneal laceration or control of hypertension, and intraocular damage is not extensive, the prognosis is good for complete resolution of the hyphema. •  If trauma to the eye is severe or if the underlying disease is not controlled, the hyphema will persist and blindness can result; no improvement in hyphema after 2 weeks following blunt trauma has a poor prognosis for return of vision; enucleation should be performed in any cat with permanent blindness from trauma due to the risk of developing traumatic ocular sarcoma. •  Hyphema caused by bleeding from PIFMs usually does not resolve or will resolve and recur. •  If the eye is painful due to a perforated globe or secondary glaucoma, with no reasonable hope of regaining vision, enucleation is recommended.

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 MISCELLANEOUS

ABBREVIATIONS •  FIP = feline infectious peritonitis. •  IOP = intraocular pressure. •  NSAID = nonsteroidal anti-inflammatory drug. •  PIFM = pre-iridal fibrovascular membrane. Author Margi A. Gilmour Consulting Editor Kathern E. Myrna



Canine and Feline, Seventh Edition

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Hypoadrenocorticism (Addison’s Disease)

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 BASICS

DEFINITION •  Endocrine disorder resulting from deficient production of glucocorticoids and, usually, mineralocorticoids. •  Primary hypoadrenocorticism (Addison’s disease) is due to destruction of the adrenal cortices resulting in glucocorticoid and mineralocorticoid deficiency. •  The term atypical hypoadrenocorticism has been applied to the subset of dogs with primary hypoadrenocorticism and normal electrolyte concentrations. •  Secondary hypoadrenocorticism results from pituitary adrenocorticotropic hormone (ACTH) insufficiency, resulting in inadequate glucocorticoid production by the adrenal cortices. PATHOPHYSIOLOGY •  Mineralocorticoid (aldosterone) deficiency results in a diminished ability to excrete potassium and retain sodium, disrupting sodium and potassium balance in the body. •  Sodium loss leads to diminished effective circulating volume; this contributes to pathophysiologic changes and clinical abnormalities, including prerenal azotemia, hypotension, dehydration, weakness, and depression. •  Hyperkalemia can result in weakness, lethargy, and anorexia; it may result in bradyarryhthmias. •  Glucocorticoid (cortisol) deficiency contributes to anorexia, vomiting, diarrhea, melena, lethargy, and weight loss; due to its role in glucose homeostasis, hypocortisolemia predisposes to hypoglycemia. SYSTEMS AFFECTED

•  Gastrointestinal. •  Musculoskeletal. •  Cardiovascular. •  Renal/urologic.

GENETICS A genetic basis has been determined in standard poodles, bearded collies, Nova Scotia duck tolling retrievers, and Leonbergers. INCIDENCE/PREVALENCE Unknown; considered uncommon in dogs and very rare in cats. SIGNALMENT Species

Dog and cat. Breed Predilections

•  Great Danes, Rottweilers, Portuguese water

dogs, standard poodles, bearded collies, Leonbergers, West Highland white terriers, Novia Scotia duck tolling retrievers and soft coated wheaten terriers have increased relative

risk; golden retrievers and Chihuahuas have decreased relative risk. •  No predilection in cats. Mean Age and Range

•  Dogs—range: 12 years; median:

4 years; young to middle-aged.

•  Cats—range: 1–9 years; middle-aged.

Predominant Sex

Female dogs at increased relative risk; no predilection in cats. SIGNS General Comments

•  Signs vary from mild in patients with

chronic hypoadrenocorticism to severe and life-threatening in an acute Addisonian crisis. •  Multiple organ systems may be involved; type and extent of involvement vary with case. Historical Findings

•  Dogs—lethargy, anorexia, vomiting,

weakness, weight loss, diarrhea, waxing/ waning course, previous response to therapy, polyuria/polydipsia (PU/PD), melena. •  Cats—lethargy, anorexia, weight loss, vomiting, waxing/waning course, previous response to therapy, PU/PD. Physical Examination Findings

•  Dogs—depression, weakness, hypovolemia,

dehydration, collapse, hypothermia, melena, hypotension, bradycardia, painful abdomen, hair loss. •  Cats—dehydration, hypovolemia, weakness, hypothermia, depression, hypotension, bradycardia, collapse. CAUSES

•  Primary hypoadrenocorticism—idiopathic

(immune-mediated), mitotane or trilostane overdose, granulomatous disease, metastatic tumors, fungal disease, coagulopathy, adrenal hemorrhage or necrosis. •  Secondary hypoadrenocorticism— iatrogenic following withdrawal of long-term glucocorticoid administration, ACTH deficiency, panhypopituitarism, pituitary or hypothalamic lesions. RISK FACTORS N/A

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Signs are nonspecific and often mimic gastrointestinal and renal diseases; differential diagnoses for gastrointestinal distress include intestinal obstruction (e.g., foreign body, intussusception, neoplasia), gastrointestinal perforation, pancreatitis, infectious disease, and others (see Acute Vomiting). •  Differential diagnoses for hyperkalemia include acute kidney injury, urinary tract obstruction, third-space fluid loss (e.g.,

peritoneal or pleural effusion, uroabdomen), and Trichuriasis. •  Although no signs are pathognomonic, a waxing and waning course and previous response to nonspecific medical intervention should alert the clinician. CBC/BIOCHEMISTRY/URINALYSIS

•  Hematologic abnormalities may include

anemia, eosinophilia, and lymphocytosis.

•  The absence of a stress leukogram in a sick

patient should prompt consideration of hypoadrenocorticism. •  Serum biochemical findings may include hyperkalemia, azotemia, hyponatremia, hypo­ chloremia, hyperphosphatemia, hypercalcemia, hypoalbuminemia, increased alanine amino­ transferase (ALT) activity, and hypoglycemia. •  Urinalysis often reveals impaired urineconcentrating ability and in some cases isothenuria; some patients with isothenuria are also azotemic, potentially causing confusion with primary renal disease. •  Some patients with hypoadrenocorticism exhibit normal electrolyte levels (so-called atypical hypoadrenocorticism). OTHER LABORATORY TESTS

•  Definitive diagnosis is by demonstration of

undetectable to low (50% of patients); reduction of proteinbound calcium but not ionized calcium; not associated with clinical signs. •  Alkalosis—causes a reduction in ionized calcium while total can remain normal; not associated with clinical signs except in cases of borderline low serum ionized calcium concentrations.

Pathologic Hypocalcemia

•  Primary hypoparathyroidism. •  Hypoparathyroidism secondary to bilateral

thyroidectomy (or other corrective hyperthyroid therapies) causing parathyroid damage. •  Posthyperparathyroid correction due to prolonged negative feedback–induced hypofunction of normal parathyroid glands. •  Renal disease—acute or chronic. •  Ethylene glycol toxicosis. •  Oxalate toxicosis (lily, philodendron, etc.). •  Acute pancreatitis. •  Puerperal tetany—eclampsia. •  Phosphate-containing enemas. •  Nutritional secondary hyperparathyroidism. •  Hypomagnesemia. •  Intestinal malabsorption. •  Citrate toxicosis—multiple blood transfusions or improper citrate–blood ratio.

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Clinical signs of hypocalcemia—primary or secondary hypoparathyroidism, eclampsia, intoxication leading to rapid calcium binding/complexing (e.g., phosphatecontaining enemas, ethylene glycol); other causes rarely lower serum calcium enough to cause clinical signs. •  Neurologic signs—ethylene glycol toxicosis, primary neurologic disease. •  Vomiting—acute pancreatitis, intestinal malabsorption, renal failure, ethylene glycol toxicosis. •  Bone pain or fractures—nutritional secondary hyperparathyroidism, neoplasia. LABORATORY FINDINGS Drugs That May Alter Laboratory Results •  Sodium bicarbonate causes alkalosis and

lowers ionized calcium concentration.

•  Samples collected in or contaminated by

EDTA or citrate will be hypocalcemic.

Disorders That May Alter Laboratory Results

Hypoalbuminemia can lower total calcium concentration and is generally not associated with decreased ionized calcium. Patients with concurrent hypoalbuminemia and ionized hypocalcemia likely have a concurrent condition causing ionized hypocalcemia. CBC/BIOCHEMISTRY/URINALYSIS •  Hypocalcemia. •  Hypoalbuminemia with conditions causing protein loss, translocation, or decreased production. •  High total CO2 with metabolic alkalosis. •  Azotemia—with acute and chronic kidney injury. •  Hyperphosphatemia with acute and chronic kidney injury, primary or secondary hypopara­ thyroidism, acute tumor lysis syndrome, or in



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Hypocalcemia

(continued)

patients receiving phosphate-containing enemas. •  High amylase and lipase in many, but not all, patients with acute pancreatitis or renal disease. •  Mild to moderate anemia possible with chronic renal failure, nutritional secondary hyperpara­ thyroidism, or intestinal malabsorption. •  Leukocytosis possible with acute pancreatitis. •  Isosthenuria with chronic kidney injury, moderate to advanced acute kidney injury. •  Glucosuria in some patients with acute kidney injury, diabetes with acute pancreatitis, ethylene glycol toxicosis, or oxalate toxicosis. OTHER LABORATORY TESTS •  Ionized calcium—helps determine if clinical signs are due to hypocalcemia. •  Ethylene glycol test—in patients suspected of ingesting ethylene glycol within previous 12–16 hours (questionable reliability). •  Pancreatic lipase immunoreactivity—in patients suspected of having acute pancreatitis (questionable reliability if only test used). •  Intact PTH assay—if primary hypopara­ thyroidism is suspected. •  Serum magnesium concentration— hypomagnesemia is rare cause of hypocalcemia. •  Plasma calcitriol (vitamin D, 1,25 dihydroxycholecalciferol) concentration—to screen for rickets or vitamin D–dependent rickets type 2 (rare). IMAGING •  Radiography usually normal. •  Small kidneys with chronic renal disease and large kidneys with acute kidney injury. •  Osteopenia and pathologic fractures with nutritional secondary hyperparathyroidism. •  Ultrasound—hyperechoic renal parenchyma with ethylene glycol or oxalate toxicosis, may identify pancreatitis or abdominal effusion. DIAGNOSTIC PROCEDURES ECG—prolongation of ST and QT segments; sinus bradycardia and wide T waves or T wave alternans in some patients.

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 TREATMENT

APPROPRIATE HEALTH CARE •  Inpatient treatment for clinical hypocalcemia. •  Emergency treatment indicated for primary or secondary hypoparathyroidism, eclampsia, hyperphosphatemia, citrate and ethylene glycol toxicosis. •  Long-term treatment for primary hypoparathyroidism and sometimes postthyroidectomy-associated PTH deficiency. •  Eclampsia—remove puppies from bitch and hand-nurse until weaned.

DIET Diet change recommended for nutritional secondary hyperparathyroidism (to a balanced diet) and renal failure (see Chronic Kidney Disease).

following initial treatment, then (if normocalcemic) monthly for first 6 months, then every 2–4 months. •  Goal—maintain serum calcium concentration between 8 and 10 mg/dL. EXPECTED COURSE AND PROGNOSIS

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 MEDICATIONS

DRUG(S) OF CHOICE Emergency Treatment

•  Vary dependent on underlying cause. •  Recurrence of hypocalcemia following

calcium administration for primary hypopara­ thyroidism is common if calcitriol is not also administered; monitoring is advised.

•  Calcium gluconate 10% solution—

5–15 mg/kg (0.5–1.5 mL/kg); give IV slowly to effect over 10 min; monitor heart rate and stop temporarily if bradycardia occurs; if ECG monitoring is possible, QT interval shortening is an indication to temporarily stop administration. Vomiting can indicate excessive calcium administration. •  Calcium chloride 10% solution—also effective but not recommended in small animals because it is extremely caustic if administered extravascularly. Three times more potent than calcium gluconate; mg/kg dosage is the same, but only one-third the volume is needed (0.15–0.5 mL/kg). Short-Term Treatment Immediately after Correction of Tetany for Hypoparathyroidism

•  Relapse of clinical signs can be prevented by

use of IV CRI of calcium gluconate 10% solution (60–90 mg/kg/day [6.5–9.75 mL/ kg/day]) added to fluids that do not contain bicarbonate. Rarely necessary for postparturient eclampsia. •  Subcutaneous calcium gluconate 10% diluted 2–4 times with saline can be administered 3 or 4 times daily for initial control of tetany (reported to be safe in most patients, but there have been reports of marked and disabling inflammatory calcinosis cutis associated with subcutaneous use). Long-Term Treatment

See Hypoparathyroidism. CONTRAINDICATIONS Avoid bicarbonate, as alkalinization may further decrease serum ionized calcium levels. POSSIBLE INTERACTIONS Calcium salts may precipitate if added to solutions containing bicarbonate, lactate, acetate, or phosphates.

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 FOLLOW-UP

PATIENT MONITORING •  For patients requiring long-term therapy, serum calcium should be assessed 4–7 days

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 MISCELLANEOUS

PREGNANCY/FERTILITY/BREEDING •  Hypocalcemia can lead to weakness and dystocia. •  Eclampsia in dogs is usually seen in first 21 days of nursing a litter. SEE ALSO

•  Acute Kidney Injury. •  Chronic Kidney Disease. •  Eclampsia. •  Ethylene Glycol Toxicosis. •  Hypoalbuminemia. •  Hypomagnesemia. •  Hypoparathyroidism. •  Lily Toxicosis. •  Pancreatitis—Cats. •  Pancreatitis—Dogs.

ABBREVIATIONS

•  PTH = parathyroid hormone.

­Suggested Reading

Drobatz K, Casey KK. Eclampsia in dogs: 31 cases (1995–1998). J Am Vet Med Assoc 2000, 217:216–219. Feldman EC. Hypocalcemia and primary hypoparathyroidism. In: Feldman EC, Nelson RW, Reusch CE, et al., eds., Canine and Feline Endocrinology and Reproduction, 4th ed. St. Louis, MO: Saunders, 2015, pp. 625–648. Waters CB, Scott-Moncrieff JCR. Hypocalcemia in cats. Compend Contin Educ Pract Vet 1992, 14:497–507. Author Michael Schaer Consulting Editor Patty A. Lathan  Client Education Handout available online

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Hypochloremia LABORATORY FINDINGS Drugs That May Alter Laboratory Results

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 BASICS

DEFINITION Serum chloride concentration below the lower limit of reference interval—dogs: 0.35 ppm, although somewhat variable) owing to acute or chronic exposure to some form of lead.

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PATHOPHYSIOLOGY •  Cell damage is due to the ability of lead to substitute for other polyvalent cations (especially divalent cations such as Ca and Zn) important for cell homeostasis. •  Diverse biological processes are affected, including metal transport, energy metabolism, apoptosis, ion conduction, cell adhesion, inter- and intracellular signaling, enzymatic processes, protein maturation, and genetic regulation. SYSTEMS AFFECTED

•  Gastrointestinal—unknown mechanism;

likely damage to peripheral nerves.

•  Nervous—capillary damage; alteration of

membrane ionic channels and signaling molecules. •  Renal/urologic—damage to proximal tubule cells due to enzyme disruption and oxidative damage. •  Hemic/ lymph/immune—interference with hemoglobin synthesis; increased fragility and decreased survival of red blood cells (RBCs); release of reticulocytes and nucleated RBCs from bone marrow; inhibition of 5′-pyrimidine nucleotidase causing retention of RNA degradation products; aggregation of ribosomes resulting in basophilic stippling.

predominant with chronic, low-level exposure. •  CNS—occur more often with acute exposure, more common in younger animals. •  Renal—proximal tubular nephropathy has been reported.

•  Urinalysis—mild nonspecific renal damage; glucosuria; proteinuria; hemoglobinuria.

Historical iFindings

•  Toxic—antemortem whole blood: >0.35 ppm (35 μg/dL); postmortem liver and/or kidney: >5 ppm (wet weight). •  Blood lead concentrations fluctuate and do not necessarily correlate with total body burden. •  Lower values—must be interpreted in conjunction with history and clinical signs. •  No normal “background” blood lead concentrations; typically less than 0.05 ppm. •  Blood concentrations— do not correlate with occurrence or severity of clinical signs. •  CaNa2EDTA mobilization test—collect one 24-hour urine sample; administer CaNa2EDTA (75 mg/kg IM); collect a second 24-hour urine sample; with toxicosis, urine lead increases 10- to 60-fold post-EDTA (succimer could conceivably be substituted for CaNa2EDTA but this has not been evaluated). •  Pointof-care testing is available, but results might underestimate true blood lead concentrations; confirmation of results using other techniques such as GFAAS or ICP-MS is recommended.

History of renovation of older house or building or ingestion of lead objects. Physical Examination Findings

•  Vomiting. •  Diarrhea. •  Anorexia. •  Abdominal pain. •  Regurgitation due to megaesophagus. •  Lethargy. •  Hysteria. •  Seizures. •  Blindness. •  Cats—central

vestibular abnormalities such as vertical nystagmus and ataxia reported.

CAUSES •  Ingestion of some form of lead—paint and paint residues or dust from sanding; car batteries; linoleum; solder; plumbing materials and supplies; lubricating compounds; putty; tar paper; lead foil; golf balls; lead object (e.g., shot, fishing sinkers, drapery weights); leaded glass. •  Use of improperly glazed ceramic food or water bowl. •  Lead paint or lead-contaminated dust or soil are common sources for exposure; cats ingest lead as a result of self-grooming. RISK FACTORS

•  Age 40 mmHg.

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 MISCELLANEOUS

ABBREVIATIONS •  IOP = intraocular pressure.

­Suggested Reading

Davidson MG, Nelms SR. Diseases of the lens and cataract formation. In: Veterinary Ophthalmology, 5th ed. Ames, IA: Wiley Blackwell, 2013, pp. 1199–1233. Maggs DJ, Miller PE, Ofri R. Diseases of the lens. In: Slatter’s Fundamentals of Veterinary Ophthalmology, 6th ed. St. Louis, MO: Saunders, 2018, pp. 306–333. Author Renee T. Carter Consulting Editor Kathern E. Myrna Acknowledgment The author and editors acknowledge the prior contribution of Filipe Espinheira.

828

Blackwell’s Five-Minute Veterinary Consult

Leptospirosis Mean Age and Range

•  Young dogs without maternal antibodies

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 BASICS

DEFINITION •  Caused by pathogenic members of genus Leptospira; each serovar has own virulence factors, infectious dose, route of exposure. •  Acute and chronic diseases of dogs (mainly nephritis and hepatitis) and rarely cats. •  Dogs—serovars causing disease vary by geographic area; recent serovars of concern in the United States are L. grippotyphosa, L. autumnalis, and L. pomona; vaccines should include regional serovars.

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PATHOPHYSIOLOGY •  Leptospira penetrate intact/cut skin/mucous membranes; rapidly invade bloodstream (4–7 days); disseminated spread (2–4 days). •  Invasion leads to transient fever, leuko­ cytosis, mild hemolysis and hemoglobinuria, albuminuria. •  Capillaries—endothelial cell damage. •  Liver—hepatic necrosis. •  Kidney—leptospiruria; Leptospira localize in damaged renal tubules; organism replicates in tubular epithelium. •  Serum antibodies appear as bacteremia decreases. •  Death— usually due to interstitial nephritis, vascular damage, renal failure; may result from septicemia, disseminated intravascular coagulopathy (DIC), respiratory failure. SYSTEMS AFFECTED •  Cardiovascular—endothelial cell damage, hemorrhage. •  Hepatobiliary—hepatitis, necrosis. •  Nervous—meningitis. •  Renal/ urologic—focal interstitial nephritis, hemo­ globinuric nephrosis, tubular damage/failure. •  Respiratory—vasculitis, interstitial pneumo­ nia, leptospiral pulmonary hemorrhage syndrome (LPHS).

and unvaccinated older dogs more likely to exhibit clincal disease. •  Dogs with adequate antibody titers seldom exhibit clinical disease unless exposed to serovar not in vaccine.

Predominant Sex

N/A

SIGNS General Comments

Historical Findings

•  Dogs—heartworm disease; hemolytic

Peracute to Subacute Disease

•  Fever. •  Sore muscles/stiffness. •  Weakness, lethargy. •  Anorexia, vomiting. •  Diarrhea— with/without blood. •  Icterus. •  Cough, dyspnea. •  Polyuria/polydipsia (PU/PD) progressing to anuria. •  Death.

Chronic Disease

•  No apparent illness. •  Fever. •  PU/PD.

Physical Examination Findings

Peracute to Acute Disease

•  Tachypnea. •  Tachycardia, weak pulses. •  Hematemesis. •  Hematochezia, melena. •  Epistaxis. •  Injected mucous membranes. •  Widespread petechial and ecchymotic hemorrhages. •  Reluctance to move, paraspinal hyperesthesia, stiff gait. •  Conjunctivitis. •  Rhinitis. •  Hematuria. •  Mild

lymphadenopathy.

CAUSES •  Dogs—L. canicola, L. icterohaemorrhagiae, L. pomona, L. grippotyphosa, L. copenhagenii, L. australis, L. autumnalis, L. ballum, and L. bataviae. •  Cats—L. canicola, L. grippotyphosa, L. pomona, and L. bataviae. RISK FACTORS

urologic—chronic kidney disease.

linked to feline stillbirth.

INCIDENCE/PREVALENCE •  Reported incidence (dogs)—falsely low due to inapparent and undiagnosed infections. •  Prevalence (dogs)—Increasing in urban dogs; hospital prevalence increasing since 1990s. GEOGRAPHIC DISTRIBUTION •  Worldwide, especially in warm, wet climates. •  Standing water, neutral or slightly alkaline soil promote presence in environ­ ment. •  L. canicola most common worldwide; L. icterohaemorrhagiae most common in Australia. •  L. bratislava has yet to be confirmed by culture as a serovar in dogs in the United States. SIGNALMENT Species

Dogs, rarely cats.

 DIAGNOSIS

Signs vary with age/immune status, virulence of infecting serovar, host response.

Transmission

•  Reproductive—abortion; weak puppies;

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DIFFERENTIAL DIAGNOSIS

Chronic Disease

•  Ophthalmic—anterior uveitis. •  Renal/

to 93–96°F (34–36°C). •  Organism survives best in stagnant water with neutral or slightly alkaline pH: ◦  180 days in wet soil; longer in standing water. •  Dense animal population— kennels or urban settings. •  Exposure to rodents, other wildlife (e.g., deer).

•  Direct—via urine, post-abortion discharge, fetus, sexual contact (semen). •  Indirect—

exposure (via urine) to contaminated environment (vegetation, soil, food, water, bedding). •  Disease in companion animals is often result of spillover from diseased wildlife maintenance hosts.

Host Factors

•  Vaccine—protection is serovar-specific; may

not prevent kidney colonization and urine shedding; new vaccines available of “subunit” type; newer panvalent antigen may crossprotect against many serovars. •  Outdoor animals, hunting dogs—exposure of abraded or water-softened skin increases risk of infection.

Environmental Factors

•  Warm, moist environment (low-lying areas,

rainy season of temperate regions).

•  Temperature range—44.6–50°F (7–10°C)

Subacute to Acute Disease

anemias; septicemia; viral infections (canine hepatitis, canine herpesvirus); neoplasia; trauma; lupus; tick-borne disease; toxoplas­ mosis; postrenal obstruction; renal toxins (e.g., ethylene glycol, aminoglycosides); causes of pulmonary interstitial/alveolar disease. •  Cats—hemotropic mycoplasmosis; toxins (e.g., acetaminophen); septicemia; feline immunodeficiency virus (FIV)- and feline leukemia virus (FeLV)-associated diseases; cholangitis; toxoplasmosis; feline infectious peritonitis (FIP); neoplasia; trauma; postrenal obstruction.

Reproductive/Neonatal Disease

•  Dogs—brucellosis, canine distemper, herpesviruses. •  Cats—FIP, FeLV,

panleukopenia, herpesvirus, toxoplasmosis, salmonellosis. CBC/BIOCHEMISTRY/URINALYSIS

•  CBC—leukocytosis with left shift;

leukopenia during leptospiremic phase; thrombocytopenia. Hematocrit variable with hemoconcentration, bleeding, or hemolysis. •  Chemistry— azotemia; electrolyte alterations—depend on degree of renal and gastrointestinal dysfunction (hyponatremia, hyper/hypokalemia, hypochloremia, hyperphosphatemia); hypoalbuminemia; elevated hepatic enzyme activities; hyperbilirubinemia. •  Prolonged prothrombin and partial thromboplastin times; increased d-dimer concentrations. •  Urinalysis—isosthenuria; proteinuria; glucosuria. OTHER LABORATORY TESTS Serology (Microscopic Agglutination Test [MAT])

•  Test serum in acute stage and 3–4 weeks later (convalescent). •  Unvaccinated

patients—titers initially low (1:100–1:200), higher in convalescent sample (1:800– 1:1,600 or higher) if homologous Leptospira serovar is tested; several serovars may cross-react in MAT test, especially if high titers to one serovar. •  Vaccinated patients— high titers for up to 12–16 weeks post vaccination, then drop to 500,000

cells/μL; typically small, mature lymphocytes. •  Larger size cells (intermediate-size or blasts) may be observed, especially with progression to blast crisis (advanced stage). •  Mild-tomoderate normocytic, normochromic anemia (nonregenerative). •  Normal-to-low platelet count (uncommon). •  Normal-to-low neutrophil count (uncommon). •  Normal-tomildly increased serum globulins. OTHER LABORATORY TESTS

•  Immunophenotyping by flow cytometry

(peripheral blood) is becoming more common practice for classification of leukemias (noninvasive)—affords prognostic information. •  Immunocytochemical staining (bone marrow samples), flow cytometry of bone marrow aspirates, or PCR for antigen receptor rearrangement (PARR) may be useful for classification of leukemias. •  Cytologic examination (bone marrow aspirate or core biopsy) may show high numbers of mature lymphocytes (especially B-cell chronic lymphocytic leukemia [CLL]); crowding out of normal cell lines in advanced stages. •  If hyperglobulinemia, serum protein electrophoresis to detect monoclonal gammopathy. •  Direct Coombs’ test may be positive with secondary

to blast crisis or becomes resistant to therapy. •  Median survival time with therapy approaches 18 months in dogs with B-cell CLL, and surpasses 24 months in dogs with T-cell CLL. •  Median survival time with therapy in cats was >14 months in one study.

DIAGNOSTIC PROCEDURES •  Bone marrow aspiration (cytology) or marrow biopsy (histopathology) may be used for immunophenotyping. •  Lymph node and spleen cytology or histopathology may help differentiate CLL from leukemic phase of lymphoma.

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ABBREVIATIONS •  CLL = chronic lymphocytic leukemia. •  PARR = PCR for antigen receptor rearrangement.

 TREATMENT

•  Usually outpatients treated with oral therapy.

•  Treatment should be instituted when patient demonstrates clinical signs of illness (including weight loss, lethargy), lymphadenomegaly or organomegaly, cytopenias, or with lymphocyte count above 50,000/μL. •  Consult a veterinary oncologist for updates in treatment options and regimens.

 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Lymphoma—may have a leukemic phase (stage V). •  Acute lymphoblastic leukemia. •  Immune-mediated hematologic diseases. •  Chronic antigenic stimulation (reactive lymphocytosis)—ehrlichiosis. •  Acute viral infection-associated lymphocytosis.

EXPECTED COURSE AND PROGNOSIS

•  Variable course, but eventually progressive

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 MEDICATIONS

DRUG(S) OF CHOICE •  Dogs—chlorambucil 6 mg/m2 PO q24h for 7–14 days; then 3 mg/m2 PO q24h; and eventually (maintenance) 2–4 mg/m2 q48h, adjusted based on response and chronic hematologic tolerability. •  Cats—chlorambucil 2 mg/patient regardless of body weight q2–4 days. •  Prednisone 2 mg/kg (up to maximum of 60 mg) PO q24h (dogs); 5–10 mg/cat q24h (cats; use prednisolone); in combination with chlorambucil; may be tapered or discontinued when lymphocyte count normalizes. •  Alternative chemotherapy agents and protocols to be considered when resistance or blast crisis develops over time— consult with an oncologist. CONTRAINDICATIONS/POSSIBLE INTERACTIONS Chemotherapy may have toxic side effects; seek advice with oncologist before starting treatment if you are unfamiliar with cytotoxic drugs.

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 FOLLOW-UP

PATIENT MONITORING Initially, examination of CBC every 2 weeks; response to treatment and disease progression. POSSIBLE COMPLICATIONS Chronic chemotherapy-induced myelosuppression; may need to alter dosage, depending on neutrophil and platelet counts.

 MISCELLANEOUS

­Suggested Reading

Adam F, Villiers E, Watson S, et al. Clinical pathological and epidemiological assessment of morphologically and immunologically confirmed canine leukemia. Vet Comp Onc 2009, 7:181–195. Bromberek JL, Rout ED, Agnew MR, et al. Breed distribution and clinical characteristics of B cell chronic lymphocytic leukemia in dogs. J Vet Intern Med 2016, 30:215–222. Campbell MW, Hess PR, Williams LE. Chronic lymphocytic leukaemia in the cat: 18 cases (2000–2010). Vet Comp Oncol 2013, 11:256–264. Comazzi S, Gelain ME, Martini V, et al. Immunophenotype predicts survival time in dogs with chronic lymphocytic leukemia. J Vet Intern Med 2011, 25:100–106. Workman HC, Vernau W. Chronic lymphocytic leukemia in dogs and cats: the veterinary perspective. Vet Clin North Am Small Anim Pract 2003, 33:1379–1399. Author Matthew R. Berry Consulting Editor Timothy M. Fan Acknowledgment The author and editors acknowledge the prior contribution of Louis-Philippe de Lorimier.



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Canine and Feline, Seventh Edition

Leukocytosis •  Increases in circulating leukocytes due to

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 BASICS

DEFINITION General term—white blood cell (WBC) count increased above reference interval; nonspecific to type of cell. Evaluation of individual leukocyte absolute numbers is needed to discern the cellular population(s) causing the overall increase in WBC count. Neutrophilia is the most common cause of a total WBC increase, and a left shift with toxic changes (e.g., Döhle bodies, cytoplasmic basophilia, foamy cytoplasmic vacuolation, and/or toxic granulation) may be present. PATHOPHYSIOLOGY One or more of the following mechanisms: •  Inflammation and increased tissue demand for leukocytes causing myeloid hyperplasia in the bone marrow. •  Translocation of cells from the marginating pool to the circulating pool of large vessels. •  Altered cytokine production resulting in increased release of cells from marrow storage pool. •  Decreased migration to tissues. •  Delayed apoptosis. SYSTEMS AFFECTED Chronic inflammation/leukocytosis may lead to nonspecific tissue damage and organ dysfunction. GENETICS Leukocyte adhesion deficiency (LAD) is an uncommon, autosomal recessive, primary immunodeficiency resulting in reduced neutrophil adhesion and inability to migrate to tissues. SIGNALMENT •  Nothing specific for generalized causes. •  LAD reported in Irish setters and a domestic longhair cat. •  Young and nervous/anxious animals with a physiologic response. •  Rottweilers, Alaskan Malamutes, Siberian huskies, and cats with eosinophil dysregulation diseases. SIGNS •  Animals with leukocytosis may exhibit fever, anorexia, weight loss, organomegaly, and other signs caused by the primary disease process. •  Affected animals with LAD can exhibit persistent marked leukocytosis/neutrophilia, impaired wound-healing, recurrent infections, and/or weight loss. CAUSES •  Etiologies resulting in increased inflammatory cytokine production include infectious or sterile causes, immune-mediated diseases, paraneoplastic or inflammatory disease. •  Shifting of neutrophils from the marginating pool to the circulating pool (measured) can be caused by stress or fear.

decreased margination to the tissues can be caused by excessive endogenous corticosteroid or in patients with LAD. •  Delayed apoptosis can lead to hypersegmentation of neutrophils. Neutrophilia

•  Mature neutrophil count above reference

interval.

•  Most common—stress/physiologic response

or inflammation caused by infectious or noninfectious conditions. •  Metabolic disease, corticosteroid excess (endogenous or exogenous). •  Physiologic (shift) or stress response. •  Tissue necrosis or trauma (surgical or other). •  Neoplasia—chronic myelogenous leukemia (primary) and secondary to histiocytic sarcoma; leiomyosarcoma; lymphoma; and mammary, pancreatic, squamous cell, bronchogenic, and hepatocellular carcinomas. Monocytosis

•  Monocyte count above reference interval,

usually accompanies a neutrophilia. •  Most common—corticosteroid-mediated stress response (dogs), or chronic inflammatory conditions (infectious and noninfectious). •  Metabolic disease, chemotherapeutic drugs. •  Recovery from acute marrow injury. •  Tissue necrosis or trauma. •  Acute or chronic myelomonocytic or monocytic leukemia. Lymphocytosis

•  Lymphocyte count above reference interval. •  Most common—physiologic response or

young (50,000/μL), sometimes referred to as a “leukemoid reaction.” •  Consider causes of severe inflammation first (e.g., pyometra, peritonitis) as chronic myeloid leukemia comprising mature neutrophils is rare in veterinary medicine. CBC/BIOCHEMISTRY/URINALYSIS

•  CBC with leukocyte differential and

absolute numbers with morphology review of a blood smear. •  Biochemical profile. •  Urinalysis with bacterial culture and sensitivity to evaluate for urinary tract infection, if indicated.

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Blackwell’s Five-Minute Veterinary Consult

Leukocytosis Factors That May Erroneously Alter Laboratory Results

Blood smear review may help exclude errors in automated cell counting that can occur in the presence of nucleated erythrocytes or parasites.

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OTHER LABORATORY TESTS •  Culture, serology, and/or PCR for infectious agents. •  ACTH stimulation test—if clinical concern for hyperadrenocorticism. •  Coombs’ test, saline agglutination test—if suspicion for immune-mediated anemia. •  Flow cytometry—if suspicion for hemic neoplasia, immune-mediated disease. •  PCR for antigen receptor rearrangement (PARR)—if suspicion for lymphoid neoplasia. IMAGING Radiography and ultrasonography can aid in identifying occult site(s) of infection or neoplasia. DIAGNOSTIC PROCEDURES

•  Bone marrow aspirate or biopsy if

indicated. •  Biopsy any masses. •  Organ evaluation, as indicated.

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 TREATMENT

APPROPRIATE HEALTH CARE •  Treatment should be based on the identified underlying etiology of the leukocytosis. •  Animals with infectious causes should receive appropriate antimicrobial medications. •  Suitable immunosuppression for immunemediated diseases. •  Patients with extreme leukocytosis >50,000/μL require intensive management,

(continued)

including the possibility of hospitalization due to increased risk of mortality.

SYNONYMS None SEE ALSO

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N/A

 MEDICATIONS

 FOLLOW-UP PATIENT MONITORING •  Determine if leukocytosis is persistent via repeat CBC to exclude physiologic response. •  In patients with extreme leukocytosis, serial CBCs every 24 hours, or as indicated, to assess the leukocyte response to medical therapy. EXPECTED COURSE AND PROGNOSIS •  Leukocyte counts decrease after treatment of the inciting cause. •  Resolution can vary from a few hours (e.g., lymphocytes post stress) to a few days or weeks (e.g., inflammatory neutrophilia). •  Extreme leukocytosis >50,000/μL is associated with a poor prognosis and high mortality rate; patients with fever and neoplasia have the shortest survival times.

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 MISCELLANEOUS

AGE-RELATED FACTORS Young animals (2 mm), and intrahepatic ducts; (2) gallbladder sediment with flukes (oval hypoechoic structures with echoic center), mildly thick gallbladder wall with a double-layered appearance (cholecystitis); (3) hypoechoic hepatic parenchyma with prominent hyperechoic portal areas (ducts) associated with cholangiohepatitis; dogs: heterogeneous parenchyma, ascites, spleno­ megaly, lymphadomegaly, thickened gastric and intestinal walls. DIAGNOSTIC PROCEDURES •  Fecal examination for trematode eggs. •  Cholecystocentesis—discloses fluke eggs in cats. •  Liver biopsy (cats and dogs)—reveals signs of infection, ova. PATHOLOGIC FINDINGS Cats

•  Gross—liver may appear large and

yellow-green with dilated bile ducts; may see flukes in bile ducts or gallbladder; increased size and tortuosity of bile ducts on cut section. •  Histologic lesions—depend on the number of flukes and duration of infestation; early stage (4–6 weeks): enlarged bile ducts and periductal areas infiltrated with inflammatory cells, especially eosinophils; mid-stage (4 months): severe adenomatous hyperplasia of bile duct epithelium and coincident periductal inflammation; late stage (6 months): extensive peribiliary fibrous connective tissue that may cause bile duct stenosis.

Dogs

•  Gross—ulcerative gastritis, submucosal

edema, red mucosal discoloration along intestinal tract, dystrophic mineralization of multiple organs. •  Histologic lesions— trematode eggs in multiple organs; granulomatous inflammation and fibrosis throughout multiple organs; dystrophic mineralization of multiple organs.

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 TREATMENT

Outpatient vs. inpatient—depends on severity of illness. Inpatient

•  Balanced polyionic fluids with

supplemental potassium chloride 20–40 mEq/L; as appropriate; based on serum electrolytes. •  Nutritional support—avoid development of hepatic lipidosis; feed high-protein calorically dense food and ensure food intake; use feeding tubes if needed to ensure adequate food intake in inappetent cats; rarely, severe clinical signs may require

parenteral nutrition; rarely hepatic enceph­ alopathy necessitates protein restriction. •  B vitamin supplementation—important for anorectic and ill cats on fluid therapy; 2 mL B-soluble vitamins/L fluids.

•  Hypercalcemia in dogs usually resolves

within 36–48 hours after praziquantel administration. •  Watch for signs of biliary tree occlusion after administration of praziquantel. •  Monitor fecal saline sedimentation for clearance of ova in dogs. PREVENTION/AVOIDANCE

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 MEDICATIONS

DRUG(S) OF CHOICE •  Praziquantel 20 mg/kg SC q24h for 3–5 days is treatment of choice for cats; eggs may pass in feces for up to 2 months after treat­ment. For dogs, varying dosages have been reported. Praziquantel at 30 mg/kg PO once and 50 mg/ kg SC once cleared a dog symptomatic for H. americana; more recently 25 mg/kg TID for 2 days and 3 days either orally or SQ, or 15–20 mg/kg PO q8h for 1–2 days is also reported. Some dogs were also treated concurrently with fenbendazole at 50 mg/kg PO q24h for 10 days. •  Prednisolone—initial dose for cats showing eosinophilia, significant inflammation on biopsy or having severe clinical signs: 1–2 mg/kg/day for 2–4 weeks; then tapered in 50% decrements every 2 weeks. •  Ursodeoxycholic acid 10–15 mg/kg q24h PO; tablet form and divided dose administered with feeding achieves best bioavailability; avoid if evidence of extrahepatic bile duct obstruction. •  Broadspectrum antibiotic coverage to protect against retrograde biliary tree infection with enteric organisms introduced by parasite; infection encouraged by fluke death in tissues. •  Antioxidant therapy—suggested by necro­ inflammatory tissue injury; vitamin E (10 IU/ kg day PO) and S-adenosyl-l-methionine (SAMe; Denosyl-SD4 has proven bioavailability in cats as a glutathione [GSH] donor): 20 mg/ kg PO daily, enteric coated tablets, until liver enzymes normalize. •  Antiemetic— metoclopramide (0.2–0.4 mg/kg PO, SC q6–8h or by constant rate infusion 1–2 mg/kg/ day); ondansetron (0.5 mg/kg q12h IV or PO 30 minutes before feeding); maropitant (1.0 mg/kg [5 mg/cat] IV, SC or PO once per day; maximum of 5 days). CONTRAINDICATIONS/POSSIBLE INTERACTIONS Pregnancy—use caution with drug use.

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 FOLLOW-UP

PATIENT MONITORING •  Monitor clinical signs, appetite, body condition and weight, liver enzymes, bilirubin, and fecal sedimentation.

•  Restrict outdoor access if endemic parasite. •  Praziquantel prophylaxis—every 3 months;

for outdoor cats in endemic, tropical climates. POSSIBLE COMPLICATIONS

•  Death from liver failure; untreated symptomatic disease. •  Biliary tree obstruction. •  Pancreatitis. •  Pancreatic

exocrine insufficiency—with chronic infection. •  Cholangitis/cholangiohepatitis (suppurative or nonsuppurative). EXPECTED COURSE AND PROGNOSIS Uncomplicated recovery with treatment expected in most patients.

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 MISCELLANEOUS

ZOONOTIC POTENTIAL None SEE ALSO •  Bile Duct Obstruction (Extrahepatic). •  Cholangitis/Cholangiohepatitis Syndrome. •  Hepatic Lipidosis. •  Hypercalcemia. ABBREVIATIONS

•  ALP = alkaline phosphatase. •  ALT = alanine aminotransferase. •  AST = aspartate aminotransferase. •  ATIII = antithrombin III. •  GSH = glutathione. •  PT = prothrombin time. •  PTH = parathyroid hormone. •  PTHrp = parathyroid-related hormone. •  PTT = partial thromboplastin time. •  PU/PD = polyuria/polydipsia. •  SAMe = S-adenosyl-l-methionine.

­Suggested Reading

Fabrick C, Bugbee A, Fosgate G. Clinical features and outcome of Heterobilharzia americana infections in dogs, J Vet Intern Med 2010, 24:140–144. Tams TR. Hepatobiliary parasites. In: Sherding RG, ed., The Cat: Disease and Management. Philadelphia, PA: Saunders, 1994, pp. 607–611. Author Kate Holan Consulting Editor Kate Holan Acknowledgment The author/editor acknowledges the prior contribution of Julie R. Pembleton-Corbett.

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Lower Urinary Tract Infection, Bacterial Breed Predilections

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 BASICS

DEFINITION •  Urinary tract infection (UTI)—bacterial adherence, replication, and persistence within the urinary tract associated with clinical signs and/or inflammation. •  Sporadic cystitis (uncomplicated UTI): lower UTI that occurs no more than once every 6 months. •  Recurrent UTI—UTI that occurs ≥3 times in a year, or ≥2 times in 6 months. Subcategories include: ◦  Persistent—UTI that fails to resolve after appropriate antimicrobial therapy. ◦  Relapse—UTI that appears to resolve; however, subsequent urine cultures confirm persistence of the original bacterial isolate. ◦  Reinfection—UTI resolves with appropriate therapy but abnormal urinary defenses allow for recolonization of different bacterial species. •  Subclinical bacteriuria (asymptomatic bacteriuria)—bacterial presence within the urinary tract not associated with detectable clinical signs and/or inflammation. PATHOPHYSIOLOGY UTI development is dependent on the interplay between bacterial virulence factors and impairment of the anatomical, functional, environmental, and immunologic competency of the host. Most commonly, uropathogenic bacteria originate from the enteric flora and ascend from the distal urogenital tract into the proximal urethra and urinary bladder. Colonization may elicit a mucosal inflammatory response resulting in dysuria, pollakiuria, pyuria, and hematuria. SYSTEMS AFFECTED Renal/urologic. INCIDENCE/PREVALENCE •  Bacteriuria is not equivalent to UTI. Current data identifies UTI prevalence given predisposing conditions. •  Prevalence of bacteriuria in dogs: ◦  With subclinical bacteriuria: 2.1–8.9%. ◦  With diabetes mellitus: 37%. ◦  With hyperadrenocorticism, at diagnosis: 46%. ◦  With thoracolumbar intervertebral disc extrusion: 20.0–38.5%. ◦  With indwelling urinary catheters: 63.8%. •  Prevalence of bacteriuria in cats: ◦ With subclinical bacteriuria: 0.9–28.8%. ◦ With lower urinary tract-associated clinical signs: 3.4–12.0%. ◦  With ureteral calculi: 8.4%. ◦  With chronic kidney disease: 16.9–29.1%. ◦  With diabetes mellitus: 12.2–12.8%. ◦  With perineal urethrostomies: 22%. GEOGRAPHIC DISTRIBUTION N/A SIGNALMENT Species

More common in dogs than cats.

Breed-associated conditions (hyperadreno­ corticism, urolithiasis, etc.) may promote bacteriuria. Mean Age and Range

•  UTIs occur at any age, but are more

common in older dogs and cats. •  Dogs— female: mean 7.7 ± 0.1 years; male: mean 8.0 ± 0.1 years. •  Cats—female: mean 11.8 ± 4.4 years; male: mean 9.8 ± 4.8 years.

Predominant Sex

•  Dogs—female dogs more commonly affected. •  Cats—female cats are slightly overrepresented.

SIGNS Historical Findings

•  Patients may be asymptomatic. •  Pollakiuria, dysuria, hematuria, stranguria, inappropriate elimination, and excessive licking at or discharge from the genitalia may be present. •  Systemic clinical signs (anorexia, fever) are infrequent and suggest complicating factors (e.g., pyelonephritis).

Physical Examination Findings

•  Unremarkable in most animals. •  Abnormalities

occasionally noted with urinary bladder palpation:

◦  Stimulation of micturition. ◦  Pain reactions.

CAUSES

•  Uropathogenic bacteria commonly

originate from enteric flora with rare hematogenous origins. •  Escherichia coli is the most common bacterial isolate in dogs (45–55%) and cats (37.3%). •  Eight species of bacteria (E. coli, Staphylococcus, Proteus, Streptococcus, Klebsiella, Enterococcus, Pseudomonas, and Corynebacterium) account for approximately 95% of UTIs. RISK FACTORS •  Immune dysfunction/suppression (e.g., hyperadrenocorticism, feline leukemia virus [FeLV], feline immunodeficiency virus [FIV]). •  Nidus for bacterial adherence and harboring (e.g., indwelling urinary catheters, uroliths). •  Altered urine composition (e.g., persistently dilute urine, glucosuria). •  Abnormal micturition/urine retention (e.g., loss of urethral tone, neurologic disease, urethral obstruction). •  Abnormal anatomy (e.g., ectopic ureters, hooded vulva). •  Disrupted urinary tract mucosal defenses (e.g., mucosal trauma).

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CBC/BIOCHEMISTRY/URINALYSIS

•  CBC and biochemistry are unremarkable. • Urinalysis: ◦  Proteinuria and hematuria indicate inflammation. ◦  Urine pH >7.5 may

indicate the presence of urease-producing bacteria (Proteus spp., Staphylococcus spp., Ureaplasma spp., or Corynebacterium spp.). ◦  Pyuria is present in most animals with UTI but is not synonymous with infection. ◦ Bacteriuria identification increases UTI suspicion. Using a modified Wright–Giemsa stain (Diff-Quik) or Gram stain can improve bacterial detection. OTHER LABORATORY TESTS

Urine Culture

•  Definitive diagnosis requires aerobic urine culture. •  In female dogs with limited antibiotic exposure forgoing a urine culture can be justified for uncomplicated UTI if the pathogen and local susceptibility patterns are known. In male dogs, cats, and animals with recurrent UTI urine culture is recommended. •  Cystocentesis is the gold standard method for collecting urine culture specimens. Bacterial growth >103 cfu/mL is diagnostic. •  Urine samples obtained by catheterization are often contaminated by the normal flora of the distal urethra. Bacterial growth >104 cfu/mL in male dogs, >105 cfu/mL in female dogs, and >103 cfu/mL in cats is diagnostic. Indwelling catheters may be colonized without concurrent UTI; therefore, sample collection from indwelling urinary catheters should be avoided. •  Culturing voided midstream urine samples should be avoided unless other urine collection techniques are contraindicated or not possible. •  Urine collected from nonsterile surfaces should not be cultured.

Antibiotic Sensitivity Testing

Antibiotic sensitivity is accurately predicted by use of the isolate’s “susceptible” vs. “resistant” profiles. IMAGING Rarely is imaging necessary for uncomplicated infections. Radiographs, contrast studies, and ultrasound may help to identify recurrent UTI-predisposing causes. DIAGNOSTIC PROCEDURES Cystoscopy is used in patients with recurrent UTI to visualize abnormalities within the urinary bladder and urethra including uroliths, masses, polyps, ectopic ureters, etc. PATHOLOGIC FINDINGS N/A

 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  UTI cannot be diagnosed or excluded based on the presence/absence of clinical signs. •  Dysuria, pollakiuria, hematuria, and stranguria occur with lower urinary tract diseases including cystolithiasis, urinary tract neoplasia, prostatitis, obstructive uropathy, and feline idiopathic cystitis.

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 TREATMENT

APPROPRIATE HEALTH CARE Outpatient treatment is appropriate; inpatient treatment may be necessary with UTI complications or associated conditions (e.g., acute pyelonephritis).





(continued)

Lower Urinary Tract Infection, Bacterial

NURSING CARE N/A

CONTRAINDICATIONS N/A

ACTIVITY Unrestricted

PRECAUTIONS Pyelonephritis or prostatitis necessitates therapies able to penetrate the respective tissues (see Pyelonephritis; Prostatitis and Prostatic Abscess).

DIET N/A CLIENT EDUCATION N/A SURGICAL CONSIDERATIONS Management of uroliths, polypoid cystitis, and infection niduses may require surgical intervention.

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POSSIBLE INTERACTIONS N/A ALTERNATE DRUGS Nonsteroidal anti-inflammatory drugs (NSAIDs) may be used cautiously to reduce clinical signs in dogs with cystitis while awaiting urine culture results. They should not be used in dehydrated patients.

 MEDICATIONS

DRUG(S) OF CHOICE •  Given the morbidity associated with sporadic cystitis, empiric antimicrobial treatment is commonly started before receiving urine culture results. •  When susceptibility data is available, the lowest tier antimicrobial should be selected. •  “Firstline” antimicrobials—should be selected when possible: ◦  Amoxicillin (11–15 mg/kg PO q8h). ◦ Trimethoprim-sulfadiazine (TMS) (15 mg/kg PO q12h). ◦ Amoxicillin/ clavulanic acid (12–25 mg/kg PO q12h). •  “Second-line” antimicrobials—reserved for resistant isolates based on culture and sensitivity or when patient factors prohibit the use of “first-line” therapies: ◦  Floroquinolones (e.g., marbofloxacin 2.7–5.5 mg/kg PO q24h; enrofloxacin; ciprofloxacin). ◦  Cefovecin (8 mg/kg SC). ◦  Nitrofurantoin (4.4–5.0 mg/kg PO q8h). •  “Third-line” antimicrobials—reserved for multidrug resistant infections necessitating therapeutic intervention: ◦  Amikacin (dogs 15–30 mg/kg IV or SC q24h; cats 10–14 mg/kg IV or SC q24h). ◦ Chloramphenicol (dogs 40–50 mg/kg PO q8h; cats 12.5–20 mg/kg [not exceeding 50 mg/cat] PO q12h). •  Antibiotic treatment of uncomplicated infections is recommended for 3–10 days. •  Recurrent UTI treatment requires a urine culture and sensitivity. •  Treatment durations are extended for persistent and relapse infections (up to 4 weeks). •  Reinfections are treated as multiple uncomplicated infections, however an attempt to identify an abnormality in host defenses should be pursued.

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 MISCELLANEOUS

ASSOCIATED CONDITIONS •  Struvite urolithiasis. •  Polypoid cystitis. • Pyelonephritis. • Prostatitis. •  Emphysematous cystitis. AGE-RELATED FACTORS Juvenile animals with recurrent UTIs should be evaluated for urolithiasis or urinary tract malformations. ZOONOTIC POTENTIAL N/A PREGNANCY/FERTILITY/BREEDING N/A SYNONYMS Bacterial cystitis.

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 FOLLOW-UP

PATIENT MONITORING •  For uncomplicated UTIs clinical improvement should occur within 48 hours. If clinical signs remain for >48 hours, complicating factors should be investigated. •  Complicated UTIs—continue therapy for 7–10 days beyond resolution of clinical signs, pyuria, and bacteriuria. Confirm resolution via urine culture 7–10 days after end of therapy. PREVENTION/AVOIDANCE

•  Diagnosis and control of predisposing

conditions is the most effective method for preventing UTIs. •  Ancillary therapies can be considered to prevent recurrence: ◦ Cranberry extract may inhibit E. coli attachment to the bladder mucosa. ◦ Methenamine—converted into formalin when urine pH is 50% are CD3+CD4+ in origin), while golden retrievers develop both B- and T-cell LSA in an ~50:50 ratio.

Median Age

Historically, 6–9 years. SIGNS History

•  Multicentric—from no clinical signs to anorexia, lethargy, vomiting, diarrhea, weight loss, fever, polydipsia and polyuria secondary to hypercalcemia. •  Gastrointestinal—­vomiting, diarrhea, anorexia, weight loss, malabsorption. •  Mediastinal—respiratory distress, pleural effusion, coughing, difficulty swallowing, caval syndrome. •  Skin: ◦ Cutaneous LSA—lesions usually generalized or multifocal: nodules, plaques, ulcers, focal alopecia and hypopig­ mentation. ◦ Mycosis fungoides—initial scaling, alopecia, pruritus progressing to thickened, ulcerated, exudative lesions. Later stages include proliferative plaques and nodules with progressive ulceration. Oral mucosa many times involved. •  Extranodal—vary with the anatomic site: ocular—photophobia and conjunctivitis; CNS—neurologic deficits, paresis, paralysis, seizures; hepatosplenic—lethargy, inappetance, weakness, icterus.

Physical Examination Findings

•  Multicentric—generalized, painless,

enlarged peripheral lymph node(s) with or without hepatosplenomegaly. •  Gastrointestinal—unremarkable to palpable thickened gut loops and/or abdominal mass, rectal mucosal irregularities, ascites. •  Mediastinal—dyspnea; tachypnea; muffled heart sounds secondary to pleural effusion, pitting edema of head, neck, forelimbs. •  Skin—raised plaques that may coalesce, patch lesions, and erythematous, exudative lesions. •  Extranodal—ocular—anterior uveitis, retinal hemorrhages, and hyphema; CNS—dementia, seizures, and paralysis. CAUSES Suggested causes include heritable breed risks, chromosomal aberrations, increased telomerase activity, germline and somatic genetic mutations, epigenetic changes, retroviral infection, Epstein–Barr virus infection, and environmental factors.

INCIDENCE/PREVALENCE

•  20–107 LSA cases per 100,000 dogs. •  LSA

comprises up to 24% of all canine neoplasms and 83% of all canine hematopoietic malignancies. SIGNALMENT Breed Predilections

•  Boxer, basset hound, golden retriever, Saint

Bernard, Scottish terrier, Airedale terrier, and bulldog—reported high-risk breeds.

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Multicentric—disseminated infections, metastatic disease, immune-mediated disorders, other hematopoietic tumors. •  Gastrointestinal—other GI tumors, foreign body, enteritis, GI ulceration, systemic

mycosis. •  Mediastinal—other tumors (thymoma, chemodectoma, ectopic thyroid), infectious disease. •  Skin—infectious dermatitis, pyoderma, immune-mediated dermatitis, histiocytic or mast cell disease. •  Extranodal—depends on affected site. CBC/BIOCHEMISTRY/URINALYSIS

•  Anemia of chronic disease, thrombocytopenia,

lymphocytosis, lymphopenia, neutrophilia, monocytosis, circulating blasts, hypoproteinemia (GI). •  Hypercalcemia, increased liver enzymes with hepatic involvement, increased creatinine or blood urea nitrogen with renal involvement. •  Urinalysis usually normal. OTHER LABORATORY TESTS

•  Immunohistochemistry (lymph node [LN]

biopsy/resection)—to determine immuno­ phenotype. •  Flow cytometry or PCR for antigen receptor rearrangements (PARR) (LN or affected organ fine-needle aspirates)—to determine immunophenotype. IMAGING

•  Thoracic radiography—sternal or tracheo­

bronchial lymphadenopathy, widened mediastinum, pulmonary densities, and pleural effusion. •  Abdominal ultrasonography— abdominal lymphadenopathy, hepatosplenic involvement, thickened bowel loops, other visceral organ involvement, ascites. DIAGNOSTIC PROCEDURES

•  Fine-needle aspirate cytology of enlarged

lymph nodes or other affected organs—for cytopathologic confirmation. •  LN biopsy or resection—for accurate histopathologic classification. •  Bone marrow cytology—for accurate prognosis. •  CSF analysis—if patient has neurologic signs. •  ECG—identify arrhythmias before doxorubicin administration. PATHOLOGIC FINDINGS •  Multicentric— effacement of LN parenchyma with large, neoplastic CD79a+ B-cells (high-grade DLBCL) or perifollicular proliferation of CD79a+ cells (MZL) or CD79a+ cell proliferation that maintains follicle architecture (FL). Effacement of LN parenchyma with large, neoplastic CD3+ T-cells (PTCL-NOS) or small, CD3+ cell proliferation between fading follicles (indolent TZL). •  Gastrointestinal—infiltration of neoplastic lymphocytes throughout mucosa and submucosa, with occasional transmural infiltration. •  Skin—CD79a+ B-cells infiltrating mucosa and submucosa, but sparing the epidermis (non-epitheliotrophic) LSA or CD3+ T-cells invading the epidermis: Pautrier’s microabscesses (mycosis fungoides). Hepatosplenic—sinusoidal infiltration of erythrophagocytic CD3+ T-cells. Staging

•  I—one enlarged LN. •  II—regionally enlarged LNs. •  III—generalized LN involvement. •  IV—visceral organ involvement.



Lymphoma—Dogs

(continued) •  V—blood or bone marrow involvement. •  Substage a—not sick. •  Substage b—sick.

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 TREATMENT

APPROPRIATE HEALTH CARE •  High-grade LSAs are exquisitely sensitive to both chemotherapy and radiation. •  Systemic multiagent chemotherapy—therapy of choice. •  Radiation therapy—for refractory lympha­ denopathy, large mediastinal masses, and solitary cutaneous areas. Half-body irradiation has been included into some chemotherapy protocols. •  Surgery—rarely used unless an acutely obstructive GI mass is identified or to remove a refractory lympha­ denopathy. •  Autologous and allogeneic bone marrow transplantation (BMT)—after total body irradiation can be considered. •  Fluid therapy—for advanced disease to treat clinically ill, azotemic, and/or dehydrated patients. Fluid therapy, steroids, ±calcitonin—to treat hypercalcemia. •  Consider aggressive fluid therapy—to prevent tumor lysis syndrome when inducing dogs with a high tumor burden or dogs with peripheral blood lymphoblasts. CLIENT EDUCATION

•  Canine LSA is a treatable, but rarely curable disease. •  Side effects of chemotherapy drugs

include reversible GI tract and bone marrow toxicities. •  Most dogs will not experience alopecia, but, dogs who need grooming will. •  The vast majority of dogs receiving chemo­ therapy enjoy an excellent quality of life.

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 MEDICATIONS

DRUG(S) OF CHOICE •  Consider combination chemotherapy protocols to treat intermediate and high-grade diseases and single-agent protocols to treat indolent diseases. •  Most multiagent protocols have superior remission and survival times when compared to single-agent protocols. •  Corticosteroids alone can induce significant multidrug resistance. Intermediate and High-Grade Lymphomas

•  L-CHOP—l-asparaginase 10,000 IU/m2,

vincristine (Onvcovin) 0.7 mg/m2 IV, cyclophosphamide (Cytoxan) 250 mg/m2 IV or PO, doxorubicin (Adriamycin) 30 mg/m2 IV, prednisone 30, 20, 10 mg/m2 PO q24h tapering for 3 weeks. Consult a veterinary oncologist concerning the treatment schedule. •  COP—vincristine 0.7 mg/m2 IV, cyclophosphamide (Cytoxan) 250 mg/m2 IV or PO, prednisone 30, 20, 10 mg/m2 PO q24h tapering for 3 weeks. Each drug given weekly.

Single Agent

•  Any drug of L-CHOP can be used as a

single agent, but expect shorter overall survival than multiagent. •  Doxorubicin (Adriamycin) 30 mg/m2 IV every 3 weeks (1 mg/kg for dog 5 years of age. •  Siamese cats tend to be diagnosed with

mammary tumors at a younger age (mean of 9 years). •  Male cats tend to be diagnosed with mammary tumors at an older age (mean of 12.8 years). Predominant Sex

•  Females predominate with only 1–5% of

mammary carcinomas occurring in male cats.

•  While being intact increases the risk of

mammary tumors (see Risk Factors), most cats diagnosed with mammary tumors are spayed. SIGNS

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Fibroepithelial hyperplasia—especially in young (7 years of age; median 9 years, range 11 weeks–14 years; a spinal meningeal sarcoma was diagnosed in an 11-week-old Rottweiler. •  Slight predominance for females. •  Cystic meningiomas reported.

• Domestic shorthair cats overrepresented. •  Most >9 years of age; mean 12 years, range 1–24 years; slight predominance for males. SIGNS General Comments

•  Vary with tumor location. •  Typically

chronic and insidiously progressive over weeks to months. •  May be acute if vascular invasion results in focal ischemia or if edema develops rapidly. •  Lateralizing deficits predominate. •  Elevated ICP, cerebral edema, or brain herniation may cause multifocal deficits, making localization of a focal mass/ lesion difficult based on clinical signs.

Historical Findings

May be prolonged history of vague signs until compensatory mechanisms (e.g., decreased cerebrospinal fluid [CSF] and blood volume) are overwhelmed, followed by rapid progression of clinical signs.

Intracranial

•  Dogs—late-onset seizures is the most

common presenting sign. •  Cats—abnormal behavior and mentation are the most common presenting signs. Nonspecific signs include lethargy, inappetence, and anorexia. Seizures less common than in dogs.

Intraspinal

•  Neck or back pain. •  Progressive

incoordination and weakness, which may worsen with exercise.

Physical Examination Findings

Intracranial

•  Cerebral disease is most common, causing

abnormal behavior and mentation; circling or head-pressing; contralateral hemi-neglect, hemianopsia, facial paresis, facial and thoracic hypesthesia and conscious proprioceptive deficits; seizures. •  Brainstem— alterations of consciousness; abnormal gait; ipsilateral proprioceptive and cranial nerve deficits in cranial nerves III to XII; central vestibular abnormalities. •  Cerebellum— ataxia and dysmetria; intention tremors; truncal sway; broad-based stance; lack of menace responses with normal vision, and pupillary light and palpebral reflexes. •  Orbital—exophthalmos, orbital swelling, prolapsed globe; blindness in the affected eye; fundic abnormalities.

Intraspinal

•  Paraspinal or radicular pain referable to the

region of spinal column affected. •  Ataxia and paresis caudal to the level of the lesion.

CAUSES •  Unknown. •  Documentation in young cats with mucopolysaccharidosis type I suggests a causal relationship.

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Metabolic or toxic encephalopathy—may also present with seizures or mentation changes and normal neurologic exam; differentiate with brain imaging. •  Other primary CNS (e.g., glioma, pituitary, nephroblastoma) or secondary (e.g., lymphoma, extensional, metastatic) tumors—may have more rapid onset and progression of signs; differentiate with brain or spinal imaging. •  Granulomatous meningoencephalitis—may cause progressive focal deficits in dogs; differentiate based on age and further diagnostics, such as imaging and CSF analysis. •  Nerve sheath tumors, gliomas, lymphoma, focal meningomyelitis, type II intervertebral disc disease, degenerative myelopathy—differentiate by spinal cord imaging. •  Cryptococcus granuloma— reported to have same appearance on CT as a meningioma in a cat. CBC/BIOCHEMISTRY/URINALYSIS Usually normal. IMAGING •  MRI—preferred imaging modality for intracranial and spinal disease. •  MRI—often hyperintense on T2-weighted images (T2WI), isointense on T1-weighted images (T1WI), and uniformly contrast-enhancing mass lesion of the brain or spinal cord; broad-based, with extra-axial attachment. A ‘dural tail’ is a characteristic feature. If present, ‘dural tail’ helps to differentiate an intraventricular meningioma from a choroid plexus tumor. Spinal cord swelling may make the distinction between intradural/extramedullary and intramedullary difficult. •  CT—often homogeneous contrast enhancement of well-circumscribed mass lesion. •  Skull radiography and CT—may reveal hyperostosis of the calvaria adjacent to the meningioma. Calcification of the mass causes increased tissue density. Hyperostosis may be seen in cats. •  Spinal radiography—usually normal with intraspinal meningioma; can be helpful to rule out bony lesions. •  Myelography—typically reveals an intradural–extramedullary mass and interruption of the normal flow of contrast at the tumor. ‘Golf tee’ appearance can be present with both nerve sheath tumor and meningioma. Differentiation requires biopsy. DIAGNOSTIC PROCEDURES •  CSF analysis—infrequently performed because diagnostic imaging is diagnostic. If performed, normal-to-high protein concentration with possible neutrophilic or mixed

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Meningioma—Cats and Dogs pleocytosis. Should not be considered unless CT or MRI have been performed. Contraindicated with increased ICP, as collection of CSF increases risk of brain herniation and consequent neurologic decompensation. •  Electroencephalography— reveals slow-wave, medium--to-high-voltage activity, indicating cortical depression. Paroxysmal waveforms characteristic of seizure activity may be evident. •  Biopsy—necessary for definitive diagnosis; perform intraoperatively or, for intracranial tumors, using a CT-guided stereotactic system.

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 TREATMENT

APPROPRIATE HEALTH CARE •  Inpatient—necessary if dehydration, anorexia, disequilibrium, and/or frequent or life-threatening seizures. •  Surgical excision— for definitive management; usually successful if the tumor is accessible. Incomplete excision is common, particularly for intracranial meningiomas in dogs, intraspinal meningiomas in cats, and in tumors ventral to the spinal cord. •  Fractionated conventional radiation therapy—15–20 treatments over 3–4 weeks, following incomplete excision, if excision not possible, or if a less invasive approach is desired. When combined with surgery, radiation is associated with prolonged survival time in canine intracranial and intraspinal meningiomas compared to surgery alone, and delays or prevents local recurrence of disease. Given the success of complete surgical excision of intracranial meningiomas in cats, radiation is rarely necessary. Feline intracranial meningiomas are likely radiation sensitive, but data are lacking. It should be considered when surgery is not an option •  Stereotactic radiosurgery (SRS)—high dose of radiation delivered to tumor with sub-millimeter accuracy. A steep dose-gradient limits exposure of normal tissue and reduces side effects of radiation. Can be conducted on an outpatient basis in 1–5 treatments delivered on consecutive days. The best candidates are those who are stable or able to be stabilized with steroids prior to the procedure. SRS significantly decreases tumor volume, but occurs slowly. SRS should be distinguished from intensity modulated radiation therapy (IMRT) delivered in 3–5 fractions (hypo­ fractionated IMRT), the former being more accurate. •  Chemotherapy—may be associated with prolonged survival after incomplete excision, post-radiation, or as sole agent. Hydroxyurea inhibits DNA synthesis, leading to cell death during the S

phase of the cell cycle. Hydroxyurea shows effectiveness in humans with intracranial meningiomas and is commonly used in veterinary medicine, but controlled studies are lacking. •  Medical management— antiepileptic drugs and corticosteroids are palliative, without effect on the primary disease process. Neither radiation or chemotherapy aid directly in control of edema or of neurologic signs such as seizures. NURSING CARE

•  Fluids—avoid overzealous fluid admini­

stration, as this may exacerbate cerebral edema and neurologic deficits. •  Use caution with jugular compression during venipuncture or when positioning for surgery to avoid increases in ICP.

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 MEDICATIONS

DRUG(S) OF CHOICE Cerebral Edema

•  Corticosteroids—improve neurologic deficits associated with vasogenic edema. •  Stuporous, severely ataxic, or showing signs of herniation—methylprednisolone sodium succinate 30 mg/kg IV or dexamethasone sodium phosphate 0.1 mg/ kg IV. •  Continued deterioration or no improvement—20% mannitol solution 0.5–1 g/kg IV over 15–20 minutes. Furosemide 2 mg/kg IV acts synergistically with mannitol and can be added if needed. Hypertonic saline 3–5 mL/kg may be used as an alternative or in addition to mannitol. Dexamethasone 0.05–0.1 mg/kg q24h IV. •  Once patient is stable—dexamethasone 0.05–0.1 mg/kg q24h or in divided daily doses PO or prednisone 0.25–0.5 mg/kg PO q12h; then taper to lowest effective dose.

Seizures

•  Antiepileptic drugs—mandatory if isolated

seizures >1/month, cluster seizures, or status; recommended if any seizure activity in animal with meningioma, and possibly prophylactically in animals with forebrain meningioma. •  Maintenance treatment—phenobarbital (first choice in dogs and cats) 2–3 mg/kg IV or PO q12h; or zonisamide 5–10 mg/kg q12h PO (dogs or cats); or levetiracetam 20–30 mg/kg q8h IV or PO as starting dose; if extended release levetiracetam q12h PO (dogs or cats). •  Cluster seizures or status— diazepam 0.25–5 mg/kg/h CRI; or phenobarbital 4 mg/kg IV q2–6h until 12–16 mg/kg total loading dose; or midazolam 0.2–0.4 mg/kg/h CRI; or levetiracetam 60 mg/kg IV.

(continued)

Chemotherapy

Hydroxyurea—150 mg/kg/week (dogs) and 75 mg/kg/week (cats).

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 FOLLOW-UP

PATIENT MONITORING •  Mannitol—monitor serum osmolality and electrolytes, particularly with repeated administration. Maintain osmolality at or below 320 mOsm/L to reduce risk of renal failure due to renal vasoconstriction. •  Corticosteroids—perform serial neurologic examinations; marked neurologic improvement is possible within 24–48 hours after initiation of treatment with corticosteroids. •  Antiepileptic drugs— evaluate serum pheno­barbital levels 3 weeks after initiation of therapy; evaluate liver enzymes every 6 months while on phenobarbital. •  Hydroxyurea—monitor CBC with platelet count before starting, at 2 weeks, 6 weeks then CBC, chemistry profile every 3–4 months. May lead to vomiting or diarrhea, stomatitis, sloughing of nails, alopecia, and dysuria; most serious effects are bone marrow depression and pulmonary fibrosis. EXPECTED COURSE AND PROGNOSIS Dogs

Intracranial

•  Surgical excision—outcome depends on surgical technique. Reported median survival time is 6.7 months (3 dogs). Survival increased with regional cerebral resection (16.5 months in 6 dogs), or with the use of a surgical aspirator (41.8 months in 17 dogs) or with endoscopyassisted tumor removal (70.1 months with forebrain and 23.4 months with caudal brain meningioma in 33 dogs). •  Surgical excision with postoperative fractionated radiation therapy—reported median survival times of 16.5 months–3 years. •  Radiation therapy alone—reported median survival times of 5–12.5 months with conventional radiation. •  Chemotherapy using hydroxyurea—reported mean survival time of 7–8 months. •  SRS (e.g., Frameless SRS, Varian Trilogy/TruBeam, Cyberknife)—reported mean survival time of 16.4 months in 38 dogs, and 19.8 months in 20 dogs. •  Medical management—reported median survival time of 3–4 months in dogs treated with palliative therapy alone.

Intraspinal

•  Surgical excision—reported mean survival

time of 19 months in 8 dogs. •  Surgical excision with postoperative radiation therapy—reported median survival time of 13.5 months in 6 dogs.



Canine and Feline, Seventh Edition

Meningioma—Cats and Dogs

(continued)

Cats

Intracranial

•  Surgical excision—good prognosis. Surgery

is curative in 75–80% of patients that undergo surgical excision. Reported mean survival time 22–27 months. Seizure activity may persist despite successful excision. Recurrence, if it occurs, is usually in same location. •  Medical management— neurologic deficits become more severe with time. Progression is often slow because meningiomas are slow growing.

Intraspinal

•  Surgical excision—survival time is shorter than that of cats with cerebral meningiomas: reported median survival times of 14.2 months in 16 cats and 17.3 months in 26 cats. •  Corticosteroids— palliative in the short term. Thoracolumbar disease progresses to paralysis and inability to control urination (urinary retention and possibly bladder atony and cystitis).

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 MISCELLANEOUS

AGE-RELATED FACTORS Brain tumor should be suspected in dogs and cats >5 years with recent onset of seizures and unremarkable extracranial diagnostic workup for seizures. ABBREVIATIONS •  CSF = cerebrospinal fluid. •  GI = gastrointestinal. •  ICP = intracranial pressure. •  IMRT = intensity modulated radiation therapy. •  SRS = stereotactic radiosurgery. •  T1WI = T1-weighted images. •  T2WI = T2-weighted images.

­Suggested Reading

Dewey CW, da Costa RC. A Practical Guide to Canine and Feline Neurology, 3rd ed.

Ames, IA: Wiley-Blackwell, 2016, pp. 183–191. Larue SM, Gordon IK. Radiation therapy. In: Withrow SJ, Vail DM, Page RL, eds., Withrow and MacEwen’s Small Animal Clinical Oncology, 5th ed. St. Louis, MO: W.B. Saunders, 2013, pp. 180–197. Motta L, Mandara MT, Skerritt GC. Canine and feline intracranial meningiomas: an updated review. Vet J 2012, 192(2):153–165. Petersen SA, Sturges BK, Dickinson PJ, et al. Canine intraspinal meningiomas: imaging features, histopathologic classification, and long-term outcome in 34 dogs. J Vet Intern Med 2008, 22:946–953. Sessums K, Mariani C. Intracranial meningioma in dogs and cats: a comparative review. Compend Cont Educ Vet 2009, 7:330–339. Authors Richard J. Joseph and Anne E. Buglione

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Meningitis/Meningoencephalitis/Meningomyelitis, Bacterial •  Vomiting. •  Bradycardia with systemic hypertension

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 BASICS

DEFINITION •  Meningitis—inflammation of the meninges. •  Meningoencephalitis—inflammation of the meninges and brain. •  Meningomyelitis—inflammation of the meninges and spinal cord.

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PATHOPHYSIOLOGY •  Bacterial infection of the CNS can occur by direct extension from an infected extraneural site or when bacteria are introduced by penetrating trauma or a migrating foreign body. •  Hematogenous spread of bacteria to the CNS from mucous membrane colonization or a distant pyogenic focus can occur. This is the most common cause in septicemic neonates and immunocompromised patients. •  Neurological deficits often develop from secondary inflammation but may be from bacterial invasion of the brain or spinal cord parenchyma. •  Inflammatory debris and adhesions can obstruct cerebrospinal fluid (CSF) flow, leading to secondary hydrocephalus. SYSTEMS AFFECTED •  Nervous—meninges, brain, or spinal cord. •  Multisystemic signs—may be present when the infection originates in an extraneural site or when the systemic inflammatory response is severe. INCIDENCE/PREVALENCE Rare SIGNALMENT Species

Dog and cat. Mean Age and Range

Any age.

Predominant Sex

Males and females affected equally. SIGNS General Comments

•  Patients are often systemically ill. •  Shock, hypotension, and disseminated

intravascular coagulation (DIC) are often found in septicemic patients. •  CNS signs may be profound and rapidly progressive. Physical Examination Findings

•  Pyrexia in approximately 50%. •  Cervical rigidity and hyperesthesia—

especially with meningitis.

•  Neurologic deficits—reflect the location of the

involved spinal cord or brain parenchyma (e.g., altered mentation, cranial nerve deficits, postural reaction deficits, ataxia, paresis, seizures). •  May find an extraneural site of underlying bacterial infection.

suggests increased intracranial pressure. CAUSES

•  Meningoencephalitis—can be secondary to

local extension from otitis media/interna or infection of the eye, retrobulbar space, sinuses, or nasal passages or due to direct inoculation by traumatic skull fractures or migrating foreign bodies. •  Meningomyelitis—can be secondary to discospondylitis or vertebral osteomyelitis. •  Hematogenous spread of bacterial infection to the CNS can occur in neonates with omphalophlebitis, immunocompromised patients, or in dogs with bacterial endocarditis, prostatitis, discospondylitis, pneumonia, urinary tract infections or severe gastroenteritis. •  The point of origin is not always found. RISK FACTORS

•  Untreated bacterial infection. •  Immunocompromised state. •  Injury involving the CNS or adjacent

structures.

acute cases, mononuclear cells may predominate in chronic cases. Negative bacterial culture. •  Serum and CSF IgA increased. •  Dramatic response to corticosteroid administration. Meningoencephalitis of Unknown Origin (MUO) •  Idiopathic noninfectious inflammatory

diseases of the brain, spinal cord, and meninges in dogs including granulomatous meningoencephalomyelitis (GME), necrotizing meningoencephalitis (NME), and necrotizing leukoencephalitis (NLE). A definitive diagnosis requires histopathology. •  Young adult (3–7 years), female, smallbreed dogs are most commonly affected. •  Neurologic abnormalities reflect the location of the lesion(s). •  MRI—usually multifocal parenchymal lesions with variable contrast enhancement. •  CSF— pleocytosis with >50% mono­ nuclear cells and increased protein concentrations. •  CSF culture—negative. Primary CNS Neoplasia

•  History protracted; neurologic signs

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS Infectious Meningitis (Nonbacterial) •  Canine distemper, toxoplasmosis,

neosporosis, cryptococcosis, blastomycosis, rickettsial organisms, West Nile virus, and feline infectious peritonitis all cause meningitis/meningoencephalitis that can be difficult to distinguish from bacterial disease. •  CSF—inflammatory with a variable lymphocytic, mixed mononuclear or neutrophilic pleocytosis depending on the specific infectious etiology. •  Antemortem diagnosis suspected based on typical clinical findings and identification of affected extraneural sites. •  Diagnosis is by identifying organisms in the CSF or in extraneural sites (using cytology, culture, or PCR) and by serology. Steroid-Responsive Meningitis–Arteritis (Aseptic Meningitis) •  Observed mainly in young (6–19 months)

adult large-breed dogs.

•  Beagles, boxers, Bernese mountain dogs,

German shorthaired pointers, Weimaraners, and Nova Scotia duck tolling retrievers are predisposed; any breed can be affected. •  Cervical pain without neurologic deficits is most common. •  Fever occurs in 60–80% of affected dogs. Signs may wax and wane initially. •  Affected dogs are systemically normal. •  CSF—increased nucleated cell count and protein. Neutrophilic pleocytosis in

limited to the CNS; standard laboratory tests normal. •  Diagnosis by CT, MRI, CSF analysis, and biopsy. CBC/BIOCHEMISTRY/URINALYSIS

•  Leukocytosis is common; left-shift or

toxicity may be seen. Thrombocytopenia may be present in septicemic patients. •  Biochemical changes are variable and often nonspecific. •  Pyuria and bacteriuria occur in patients with underlying urinary tract or prostatic infection and in some bacteremic animals. OTHER LABORATORY TESTS

•  Serologic tests—may differentiate bacterial

from other infectious diseases; in cats, toxoplasma titer may be positive without clinical disease. •  Cytology of infected tissues—skin, eyes, nasal discharge, lymph node, tracheal wash; helps identify nonbacterial causative organisms, especially in patients with fungal disease. •  Blood culture—positive in 30% of dogs with bacterial meningitis. IMAGING

•  Thorax radiography and abdominal

ultrasound—to identify underlying infection or other significant disease. •  Vertebral column radiography—disco­ spondylitis may be identified as a focus of infection. •  Head CT—may identify infected sinus, nasal cavity, or middle and inner ear as initiating site. Inflamed regions of brain parenchyma and meninges usually enhance with contrast.

(continued)

Meningitis/Meningoencephalitis/Meningomyelitis, Bacterial

•  Echocardiography—performed when

valvular endocarditis suspected based on murmur/arrhythmia. •  MRI with contrast—documents brain, spinal cord and meningeal inflammation and can identify extraneural sites of infection (sinus, nasal, ear). DIAGNOSTIC PROCEDURES CSF Analysis

•  Collection—a concern in animals with

altered mentation suggesting high intracranial pressure, because the procedure may precipitate brain herniation. Pretreat with mannitol. •  Analysis—neutrophilic pleocytosis with high protein concentration; neutrophils may appear toxic or degenerated and intracellular bacteria are occasionally seen; often difficult to differentiate aseptic from bacterial meningitis cytologically. •  Culture—aerobic or anaerobic; may be positive (75% of patients.

lipid-soluble drugs with small molecular size, low protein binding, and a low degree of ionization at physiologic pH recommended. •  Cultures—CSF, blood, urine, primary site; determine drug sensitivity; until cultures identify the organism choose a broadspectrum agent that penetrates the blood– brain barrier (BBB). •  Recommended drugs include third-generation cephalosporins (moxalactam, ceftriaxone, cefotaxime), fluoroquinolones, trimethoprimsulfonamides, doxycycline and metronidazole. •  Penicillin, ampicillin, amoxicillin-clavulanate, and carbapenems enter the CNS when there is inflammation and are a good choice to use in combination with another antibiotic that will continue to cross the BBB as inflammation resolves, such as trimethoprim-sulfonamides. Ampicillin may achieve high CSF concentrations even without inflammation. •  Metronidazole reaches high levels in CSF, brain parenchyma, and abscesses and demonstrates the best bactericidal activity against anaerobes. •  Clindamycin is lipid soluble but does not readily cross the BBB. Concentrations in brain and spinal cord are adequate for treatment of Toxoplasma and Neospora infections but insufficient for treating most CNS bacterial infections. •  Administer antibiotics intravenously for 3–5 days to achieve high CSF concentrations rapidly, then maintain on oral therapy. •  Immediate IV therapy can be based on cytology; penicillin for Gram-positive infections, fluoroquinolone or third-generation cephalosporin for Gram-negative infections. Antiepileptic Drugs

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 TREATMENT

APPROPRIATE HEALTH CARE Inpatient—treat aggressively; intensive care monitoring often necessary. NURSING CARE Fluid therapy and supportive care. CLIENT EDUCATION Inform client that rapid and aggressive treatment is important and that the prognosis for recovery is guarded.

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 MEDICATIONS

DRUG(S) OF CHOICE Antibiotics

•  Bactericidal agents that achieve therapeutic

concentrations within CSF are most desirable—

•  Indicated for seizures. •  Long-term use may be needed.

Corticosteroids

•  Most CNS dysfunction is due to

inflammation.

•  May administer dexamethasone 0.1 mg/kg

q24h for several days but use is somewhat controversial.

CONTRAINDICATIONS Aminoglycosides and first-generation cephalosporins—do not penetrate the BBB even in the presence of inflamed meninges.

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 FOLLOW-UP

PATIENT MONITORING Monitor for nervous system signs, fever, leukocytosis, and systemic signs.

PREVENTION/AVOIDANCE Treat local infections adjacent to the CNS (e.g., infections of the eyes, ears, sinuses, nose, and vertebral column) early and aggressively to prevent extension to the CNS. POSSIBLE COMPLICATIONS Damage to the brain and spinal cord may be irreversible. EXPECTED COURSE AND PROGNOSIS

•  Response to antibiotics—variable;

prognosis guarded.

•  Many patients die despite treatment •  Residual neurologic deficits are possible. •  Treatment for at least 4 weeks after

resolution of all signs is recommended.

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 MISCELLANEOUS

SEE ALSO •  Encephalitis. •  Meningoencephalomyelitis of Unknown Etiology (MUE). •  Steroid-Responsive Meningitis–Arteritis— Dogs. ABBREVIATIONS

•  BBB = blood–brain barrier. •  CSF = cerebrospinal fluid. •  DIC = disseminated intravascular

coagulation.

•  GME = granulomatous

meningoencephalomyelitis.

•  NLE = necrotizing leukoencephalitis. •  NME = necrotizing meningoencephalitis.

­Suggested Reading

Greene CE. Bacterial meningits. In: Sykes JE, ed., Canine and Feline Infectious Diseases. St. Louis, MO: Saunders Elsevier, 2014, pp. 886–892. Radaelli ST, Platt SR. Bacterial menigoencephalomyelitis in dogs: a retrospective study in 23 cases (1990– 1999). J Vet Intern Med 2002, 16:159–163. Tipold A, Stein VM. Inflammatory diseases of the spine in small animals. Vet Clin Small Anim 2010, 40:871–879. Authors Danielle Zwueste and Susan M. Taylor

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Meningoencephalomyelitis, Eosinophilic

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 BASICS

OVERVIEW Although eosinophilic meningoencephalomyelitis (EME) can be associated with meningitis, encephalitis, and myelitis as a result of CNS infection or parasitic migration, in most cases, no underlying cause can be found. Idiopathic EME occurs in young to middle-aged large-breed dogs and resolves in many cases following steroid treatment.

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SIGNALMENT •  Dog and rarely cat. •  Idiopathic EME— often larger dogs (>25 kg); Rottweilers and golden retrievers predisposed. •  Mean age—4 years (2 months–13 years). SIGNS •  Vary with CNS location and severity. •  Neurologic deficits—most frequently associated with cranium, infrequently with spinal cord and rarely with cranial nerve involvement. CAUSES & RISK FACTORS •  Idiopathic EME (unknown cause)— majority of reported cases. •  Infectious— Dirofilaria immitis and cuterebra myiasis in cats; Toxoplasma gondii, Neospora spp., Prototheca spp., Cryptococcus spp., and nematode migration with Baylisascaris procyonis in dogs. •  Angiostrongylus—dogs in Australia. •  Intervertebral disc disease probably as allergic response to disc material.

IMAGING •  Thoracic radiography and abdominal ultrasound—to rule out systemic involvement. •  MRI—variable; focal mass lesions, diffuse parenchymal abnormalities, postcontrast diffuse meningeal enhancement; abnormalities depend on cause and location of lesion. DIAGNOSTIC PROCEDURES CSF Analysis

•  Eosinophilic pleocytosis significant when >10%. •  Presence of eosinophilic pleocytosis by itself cannot differentiate idiopathic EME from infection causing CSF eosinophilic pleocytosis. •  Idiopathic EME—total nucleated cell count 4–3880 cells/μL (median 99 cells/mL; reference 10%, look for parasitic

and fungal disease. •  Test for heartworm, Neospora caninum, Toxoplasma gondii, and Cryptococcus neoformans. PATHOLOGIC FINDINGS

•  CSF eosinophilic pleocytosis does not

necessarily correlate with eosinophils observed in CNS parenchyma. •  Wide variety of pathologic findings may indicate multiple causes, or the same disease taken at different times.

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CBC/BIOCHEMISTRY/URINALYSIS

•  Peripheral eosinophilia—may or may not

be present. •  Biochemistry and urinalysis— usually normal with idiopathic disease; eosinophilia, liver enzyme activity, and creatine kinase may be elevated in infectious diseases. OTHER LABORATORY TESTS

•  Serology—to rule out suspected infectious

diseases. •  Fecal flotation and sedimentation— to rule out migratory parasite.

PREVENTION/AVOIDANCE Steroid treatment should not be stopped even if the animal is back to normal within a few days. A minimum of 8 weeks followed by tapering of the medication over as many weeks is mandatory. POSSIBLE COMPLICATIONS •  Recurrence may occur following cessation of medication. •  Ensure treatment dosage is adequate and reinstate for a longer period. EXPECTED COURSE AND PROGNOSIS

•  Idiopathic disease—good prognosis in most

cases with early treatment; improvement usually seen in the first 72 hours; full recovery in 2–6 months. Some patients continue to deteriorate despite steroids, and die. •  Protozoal and fungal diseases—poor-tograve prognosis. •  Larval migration— prognosis guarded to poor and depends on location of the lesion; signs may resolve, but larvae often continue to migrate and death may ensue. •  Degradation of eosinophils is toxic to nervous tissue; patient may have permanent deficits from not only the primary disease but also cell death.

 TREATMENT

 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Cannot be differentiated from other encephalitides solely on clinical signs; CSF analysis must be done. •  Idiopathic EME— negative serologic test results; marked CSF eosinophilic pleocytosis (20–95%); usually steroid-responsive. •  Infectious diseases— identified on presence of systemic signs, blood work, fecal sample, CSF, serum/CSF serology, and imaging.

 FOLLOW-UP

PATIENT MONITORING Inpatient—repeat neurologic examination every 6 hours to monitor progress.

•  Usually inpatient, because of severity of clinical

signs. •  Activity—as tolerated. •  Regular diet.

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 MEDICATIONS

DRUG(S) OF CHOICE •  Idiopathic disease—steroid administration; dexamethasone (0.2 mg/kg q24h for 1 day; then 0.15 mg/kg q24h for 6 days); follow with prednisone (0.5 mg/kg q24h for 8 weeks); then slowly wean patient off prednisone over 8 weeks–6 months depending on clinical response. •  Protozoal disease—clindamycin, sulfonamides, and pyrimethamine. •  Heartworm—microfilarial migration to the CNS is rare; no available treatment other than supportive. CONTRAINDICATIONS/POSSIBLE INTERACTIONS •  Important to differentiate idiopathic EME from infection as treatment greatly differs— immunosuppressive dose of steroids vs. anti-organism treatment. •  Steroid should be used with caution if diagnosis has not been substantiated.

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 MISCELLANEOUS

AGE-RELATED FACTORS Idiopathic EME is more frequent in young to middle-aged larger dog breeds (>25 kg). SEE ALSO Encephalitis ABBREVIATIONS •  EME = eosinophilic meningoencephomyelitis.

­Suggested Reading

Cardy TJA, Cornelis I. Clinical presentation and magnetic resonance imaging findings in 11 dogs with eosinophilic meningoencephalitis of unknown aetiology. J Small Anim Pract. 2018, 59(7):422–431. Williams JH, Köster LS, Naidoo V, et al. Review of idiopathic eosinophilic meningitis in dogs and cats, with a detailed description of two recent cases in dogs. J S Afr Vet Assoc 2008, 79(4):194–204. Windsor RC, Sturges BK, Vernau KM, et al. Cerebrospinal fluid eosinophilia in dogs. J Vet Intern Med 2009, 23(2):275–281. Author Joane M. Parent



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Meningoencephalomyelitis of Unknown Etiology (MUE)

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 BASICS

DEFINITION Meningoencephalomyelitis of unknown etiology (MUE) is a broad term used to describe inflammatory disorders that affect the CNS focally, diffusely, or multifocally. In the past, the majority of CNS inflammatory disorders were categorized as granulomatous meningoencephalomyelitis (GME). As a result, multiple less serious viral and idiopathic disorders were frequently erroneously diagnosed as GME. The appropriate clinical term to describe cases in which CNS inflammation is suspected is now considered MUE or meningioencephalitis of unknown etiology (MUO). PATHOPHYSIOLOGY •  Unknown. Although a specific etiologic agent is not recognized, in the majority of cases, viral and immune causes are strongly suspected. •  Three clinicopathologic forms are recognized: ocular, multifocal (brain or brain and spinal cord), and focal (single focus in the brain or spinal cord). SYSTEMS AFFECTED

•  Nervous. •  Ophthalmic.

GENETICS Not proven. INCIDENCE/PREVALENCE Unknown. Since brain biopsies are rarely obtained, a presumptive diagnosis is made in most cases. GEOGRAPHIC DISTRIBUTION Worldwide SIGNALMENT Breed Predilections

Any breed can develop MUE. Smaller toy breeds may be overrepresented and can be less responsive to therapy. However, the condition also occurs in medium and large-breed dogs. Mean Age and Range

•  Mean—5 years. •  Range—6 months–10

years.

Predominant Sex

Slightly higher prevalence in females. SIGNS •  Depend on the form of the disease and neuroanatomic localization. •  Cerebral form—frequently results in seizure activity. •  Ocular form—acute onset of blindness with dilated, unresponsive pupils. •  Focal form—cerebral lesion: disorientation, behavioral changes, seizures, cortical blindness, compulsive circling, head pressing; brainstem lesion: somnolence, cranial nerve deficits (most commonly facial and vestibular dysfunction), ipsilateral hemiparesis; spinal cord: neck pain, tetraparesis (C1–C5 or C6–T2 lesions) or

paraparesis (T3–L3 or L4–S2 lesions) and proprioceptive ataxia. In some patients the clinical signs can be unspecific and vague, delaying a prompt diagnosis and timely therapy. CAUSES Unknown RISK FACTORS •  Unknown. •  Some dogs develop clinical signs within 5–15 days of vaccination.

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  The combination of history, neurologic examination, CSF analysis, and MRI results usually lead to a presumptive diagnosis of inflammatory disease, but defining the cause of the inflammation can be problematic. •  It is possible that some dogs surviving inflammatory CNS disease have lesions compatible with GME, but post-mortem studies are not available to prove it. Alternatively, dogs who survive CNS inflammatory disease could have been suffering from other type of less serious viral or idiopathic inflammatory disease. Therefore the current accepted medical term to group these categories is MUE. •  Infectious inflammatory diseases—viral (distemper virus, other viruses); fungal (Blastomyces dermatitidis, Coccidioides spp., Cryptococcus neoformans); rickettsial (Rickettsia rickettsii); bacterial (Ehrlichia spp., E. coli, Streptococcus); protozoal (Neospora caninum, Toxoplasma gondii). •  Other inflammatory disease— necrotizing encephalitis of the Yorkshire terrier, Maltese, and pug; immune-mediated steroid-responsive meningitis (beagles, Bernese mountain dogs, Nova Scotia duck tolling retrievers, Weimaraners, boxers). •  Sudden acquired retinal degeneration. •  Brain tumor—meningioma, glioma, choroids plexus papilloma, lymphoma. •  Subatlantoaxial luxation. •  Caudo-occipital malformation syndrome (COMS). CBC/BIOCHEMISTRY/URINALYSIS Usually normal. OTHER LABORATORY TESTS Serologic testing to rule out infectious CNS diseases. IMAGING MRI—method of choice; abnormalities are variable and consist of solitary, multiple, or circumscribed mass lesions. Multiple areas of heterogeneous contrast enhancement are frequent in the multifocal form of the disease. Other findings include mass effect with midline shift, obstructive hydrocephalus, white matter edema, and effacement of the sulci. Usually MRI lesions are characterized as

hypointense in T1-weighted and hyperintense in T2-weighted images. Necrotic lesions are recognized by a center of hypointensity with a peripheral ring of enhancement. DIAGNOSTIC PROCEDURES CSF Analysis

•  Reference range—white cell count (0–3 cells/μL); protein concentration (0–30 mg/ dL). •  Helps confirm presence of inflammatory disease but rarely demonstrates a definitive cause. The following are only guidelines, as significant overlap exists regarding CSF cytology of different inflammatory disorders. •  Inflammatory diseases—white cell count and protein concentration usually increased. Even with a normal cell count, presence of an abnormal cell population (e.g., macrophages) should be taken into consideration as evidence of pathology. •  Usually, mononuclear pleocytosis; however, polymorphonuclear pleo­cytosis, or a normal CSF can be present. •  Bacterial (rare in dogs)—marked polymorphonuclear pleocytosis. •  Fungal, protozoal infections— mixed pleocytosis (mononuclear and polymorphonuclear); rarely a fungal organism (Cryptococcus neoformans or Blastomyces dermatitidis) is identified. •  Viral infections— mononuclear pleocytosis.

Brain Biopsy

Brain biopsy is the only procedure that can confirm conclusively a diagnosis of MUE. Due to morbidity, mortality, and cost associated with brain biopsy the test is not performed routinely. It is important to note that GME is not a clinical diagnosis but a term to describe findings at post-mortem. The term should not be used as clinical diagnosis, to avoid confusion. PATHOLOGIC FINDINGS •  Hallmark feature—dense perivascular distribution of mononuclear infiltrates (lymphocytes, monocytes, and plasma cells). •  Macroscopically, discoloration and softening of affected tissue sometimes evident.

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 TREATMENT

APPROPRIATE HEALTH CARE •  Stable patients can be discharged with recommended treatment. •  Inpatient—for severely affected dogs; monitor patient closely for progression of neurologic deficits. •  In severe cases, sequential assessment of pupil size and reaction to light, and mentation are helpful to determine risk of herniation. NURSING CARE

•  IV fluids for the anorexic patient. Take care

not to overhydrate to exacerbate cerebral edema. •  Provide a padded cage for dogs with vestibular ataxia, severe dementia, or seizure

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Meningoencephalomyelitis of Unknown Etiology (MUE) (continued) activity. •  Recumbent patients should be turned frequently (every 4 hours). ACTIVITY •  Depends on severity of disease and lesion localization. •  Ataxic patients should be confined to a padded cage to avoid injury. DIET Ensure adequate caloric intake.

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CLIENT EDUCATION •  Explain to the client that there is significant overlap of clinical signs among different inflammatory diseases. Insist on the importance of a diagnostic workup. •  Mortality rate is variable but clearly biased by older literature describing the severe cases that went to post-mortem as suffering from GME. Brain biopsies are rarely conducted. Clinical experience suggests that up to 70% of patients can respond to therapy, especially if initiated early in the course of the disease. However, treatment may be prolonged or could be required for life. •  Corticosteroid therapy may be necessary indefinitely.

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 MEDICATIONS

DRUG(S) OF CHOICE •  Dexamethasone 0.2 mg/kg IV or PO q24h for 4 days followed by prednisone 0.5–1.0 mg/ kg PO q24h for 2 weeks. Dose is adjusted according to response and side effects. The goal is to find dosage that keeps the clinical signs controlled with minimal side effects. If deterioration of clinical signs noted when tapering steroids, immediately go back to previous dose that controlled the signs or consider adding other immunosuppressant listed below. •  To prevent gastrointestinal ulceration, combine steroid therapy with omeprazole 0.5 mg/kg PO q24h, famotidine 0.5–1 mg/kg IV or PO q12h. •  Azathioprine 2 mg/kg PO q24h can be added if the patient is not tolerating the steroids well, to allow reduction of the prednisone dose. Usually, the dose of azathioprine is reduced to 1 mg/kg PO q 24 after 7 days of initiating the medication. •  Cytosine arabinoside 100 mg/m2 body surface area as a CRI over 12 hours. Alternatively 6 doses of cytosine arabinoside can be given q12h via SC injection. Repeat treatment every 3 weeks to 8 weeks pending clinical response. •  Mycophenolate mofetil has been recently advocated at a dose of 7–20 mg/ kg PO q12h for 3–4 weeks, then 10 mg/kg q24h. This medication can cause vomiting and diarrhea. •  If there is seizure activity— phenobarbital 2 mg/kg PO q12h, levetiracetam 20–30 mg/kg PO (ideally q8h but may be attempted q12h), or zonisamide 5–10 mg/kg PO q12h. •  Gabapentin 2–5 mg/kg PO q8–12h if compulsive circling is present.

CONTRAINDICATIONS •  Fungal, bacterial, and protozoal conditions can be exacerbated by the use of steroids. It is important to rule out these infectious disorders with proper diagnostic workup. •  Steroid should not be used in a patient treated or recently treated with nonsteroidal anti-inflammatory drugs (NSAIDs). PRECAUTIONS Reduction in corticosteroid therapy can result in recrudescence of clinical signs that may not be controlled again as initially. ALTERNATIVE DRUG(S)

•  Cyclosporine 3–7 mg/kg PO q12h.

•  Leflunomide 4 mg/kg PO q24h.

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 FOLLOW-UP

PATIENT MONITORING •  Repeat neurologic examination periodically (every 2–4 weeks). •  Evaluate CBC and biochemical profile regularly to monitor for leukopenia, thrombocytopenia, and liver and kidney function if alternative drugs are used. •  Monitor urine in patients on long-term steroid treatment—proteinuria or infection are frequent consequences. Patients receiving zonisamide may be at risk for keratoconjunctivitis sicca and immune-mediated conditions—hemolytic anemia, immune thrombocytopenia, and polyarthritis. POSSIBLE COMPLICATIONS

•  Deterioration of clinical signs despite

aggressive treatment. •  Status epilepticus, dementia, brain herniation, and death. EXPECTED COURSE AND PROGNOSIS

•  Not all patients with CNS inflammatory

disease have a poor prognosis. •  GME has been stereotyped as fatal without enough evidence. Uncertain if surviving dogs had GME as brain biopsies are rarely done.

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 MISCELLANEOUS

PREGNANCY/FERTILITY/BREEDING Corticosteroid therapy can affect gestation. SYNONYMS •  Granulomatous encephalitis. •  Granulomatous meningoencephalitis. •  Meningoencephalitis of unknown etiology. • Meningomyelitis. • Encephalitis. • Myelitis.

•  Steroid-Responsive Meningitis–Arteritis— Dogs. ABBREVIATIONS

•  COMS = caudo-occipital malformation

syndrome. •  GME = granulomatous meningoencephalomyelitis. •  MUE = meningoencephalomyelitis of unknown etiology. •  MUO = meningoencephalomyelitis of unknown origin. •  NSAID = nonsteroidal anti-inflammatory drug. INTERNET RESOURCES •  http://www.ivis.org •  http://www.vin.com

­Suggested Reading

Adamo PF, Rylaner H, Adams WM. Cyclosporine use in multi-drug therapy for meningoencephalomyelitis of unknown etiology in dogs. J Small Anim Pract 2007, 48(9):486–496. Coates JR, Jeffery ND. Perspectives on meningoencephalomyelitis of unknown origin. Vet Clin North Am Small Anim Pract 2014, 44:1157–1185. Demierre S, Tipold A, Griot-Wenk ME, et al. Correlation between the clinical course of granulomatous meningoencephalomyelitis in dogs and the extent of mast cell infiltration. Vet Record 2001, 148:467–472. Granger N, Smith PM, Jeffery ND. Clinical findings and treatment of non-infectious meningoencephalomyelitis in dogs: a systematic review of 457 published cases from 1962 to 2008. Vet J 2010, 184(3):290–297. Lowrie M, Thomson S, Smith P, Garosi L. Effect of a constant rate infusion of cytosine arabinoside on mortality in dogs with meningoencephalitis of unknown origin. Vet J 2016, 213:1–5. Smith PM, Stalin CE, Shaw D, et al. Comparison of two regimens for the treatment of meningoencephalomyelitis of unknown etiology. J Vet Intern Med 2009, 23(3):520–526. Talarico LR, Schatzberg SJ. Idiopathic granulomatous and necrotizing inflammatory disorders of the canine central nervous system: a review and future perspectives. J Small Anim Pract 2010, 51(3):138–149. Woolcock AD, Wang A, Haley A, et al. Treatment of canine meningoencephalomyelitis of unknown aetiology with mycophenolate mofetil and corticosteroids: 25 cases (2007– 2012). Vet Med Sci 2016, 10(2):125–135. Author Carolina Duque

SEE ALSO

•  Encephalitis. •  Encephalitis Secondary to

Parasitic Migration. •  Meningitis/ Meningoencephalitis/Meningomyelitis, Bacterial. •  Meningoencephalomyelitis, Eosinophilic. •  Necrotizing Encephalitis.

Client Education Handout available online



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Mesothelioma

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 BASICS

OVERVIEW •  Rare tumor in dogs and cats arising from the mesothelial cells of the serosal lining of the pleural, pericardial, or peritoneal cavities. •  Also has been reported in dogs to arise from the tunica vaginalis of the testes. SIGNALMENT •  Older animals—dog and cat. •  Sclerosing subtype more common in males. •  German shepherd dogs overrepresented.

are typically shed into effusions and can be highly reactive. •  Exploratory surgery (open or via thoraco­scopic or laparoscopic examination) with biopsies. •  Fibronectin levels in effusions—not specific for mesothelioma but typically elevated in neoplastic effusions.

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Garrett LD. Mesothelioma. In: Withrow SJ, Vail DM, Page RL, eds., Small Animal Clinical Oncology, 5th ed. Philadelphia, PA: Saunders, 2013, pp. 696–700. Author Rebecca G. Newman Consulting Editor Timothy M. Fan

 TREATMENT

•  Pericardiectomy or mass removal if possible. •  Symptomatic pericardiocentesis or

thoracocentesis.

 MISCELLANEOUS

It is not recommended to breed animals with cancer. Chemotherapy is teratogenic—do not give to pregnant animals.

­Suggested Reading

SIGNS

•  Pleural effusion—dyspnea, tachypnea,

exercise intolerance, coughing, gagging, cyanosis. •  Pericardial effusion—lethargy, anorexia, weakness, collapse, respiratory distress, exercise intolerance, distended abdomen, vomiting. •  Ascites—distended abdomen, anorexia, vomiting, lethargy, abdominal discomfort. •  Swollen testes. •  Sclerosing subtype signs are secondary to restriction around affected organs—vomiting, urinary issues. CAUSES & RISK FACTORS

•  Increased risk with asbestos exposure. •  Possible increased risk in golden retrievers with

idiopathic hemorrhagic pericardial effusion.

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS Other causes of effusions—hypoproteinemia, vasculitis, neoplasia (e.g., lymphoma, chemodectomas, hemangiosarcoma, carcinomatosis), idiopathic, congestive heart failure, liver disease, infectious/inflammatory. CBC/BIOCHEMISTRY/URINALYSIS N/A IMAGING •  Thoracic radiography—identification of pleural effusion, evaluation of cardiac silhouette (i.e., globoid heart consistent with pericardial effusion). •  Echocardiography—identification of pericardial effusion; rule out primary cardiac neoplasia. •  Thoracic and abdominal ultrasonography— evaluation of effusions. •  CT—identification of mass lesions and evaluation of lungs in the face of pleural effusion. DIAGNOSTIC PROCEDURES •  Cytology of effusions to rule out infectious causes or lymphoma—difficult to diagnose mesothelioma on cytology as mesothelial cells

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 MEDICATIONS

DRUG(S) OF CHOICE •  Intracavitary chemotherapy: ◦  Cisplatin (dog only) 50–70 mg/m2 every 3 weeks with saline diuresis. ◦  Carboplatin (cat) 180–200 mg/m2 every 3–4 weeks. ◦  Carboplatin (dog) 300 mg/m2 every 3 weeks. ◦  Mitoxantrone (dog) 5.0–5.5 mg/m2 every 3 weeks. •  IV chemotherapy—doxorubicin 30 mg/m2 (dog >10 kg) or 1 mg/kg (dog 3 years. ◦  Intracavitary carboplatin (cats) with piroxicam—6 months. ◦  Surgery and intracavitary cisplatin and IV doxorubicin—>27 months. ◦  Reported survival with surgery alone— 4–9 months.

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Metabolic, Nutritional, and Endocrine Bone Disorders

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 BASICS

DEFINITION •  Osteochoendrodysplasia, osteogenesis imperfecta (OI), and growth hormone (GH) anomalies include many metabolic, nutritional, and endocrine bone disorders. •  Osteochondrodysplasia (OCDP) is a growth and developmental abnormality resulting in the lack of normal bone growth and bone deformities. •  OI is a hereditary disease characterized by extremely fragile bones and teeth caused by defects in the structure of type I collagen. •  GH anomalies include, among others: ◦  Acromegaly (ACM)— results from excessive pituitary GH production or excessive production of female sex GH. ◦  Dwarfism (DW)—results from congenital lack of pituitary GH production. PATHOPHYSIOLOGY •  OCDP—genetic defect affecting all cartilage in the entire body. •  OI—genetic defect of type I collagen formation. Type I collagen is the most abundant structural component of skin, bone, cartilage, tendons, and ligaments. •  ACM—endogenous progesterone or exogenous progestins may give rise to GH hypersecretion of mammary origin. Mammary-derived (with or without mammary tumors) GH is biochemically identical to pituitary GH. Pituitary adenomarelated increased progesterone production is also possible. Hypothyroidism can also lead to ACM. •  DW—congenital GH deficiency. SYSTEMS AFFECTED

•  Cardiovascular. •  Endocrine/metabolic.

• Musculoskeletal. • Respiratory. • Skin/ exocrine. GENETICS

•  OCDP—autosomal dominant inheritance.

•  OI—autosomal recessive; collagen type I-encoding genes COL1A1 and COL1A2 are affected. •  ACM—abnormalities in the anterior pituitary gland; inherited in the Saint Bernard. •  DW—autosomal recessive inheritance. INCIDENCE/PREVALENCE All conditions discussed are rare. GEOGRAPHIC DISTRIBUTION N/A SIGNALMENT

Species

•  OCDP, ACM—dog and cat. •  OI—dog;

rare in cat. •  DW—dog.

Breed Predilections

•  OCPD—Scottish fold cat; great Pyrenees,

Alaskan Malamute, Samoyed, Scottish deerhound, Labrador retriever, basset hound,

and Norwegian elkhound. •  OI—golden retriever, collie, poodle, beagle, Bedlington terrier, wirehaired dachshund, Norwegian elkhound; domestic shorthair cats. •  ACM— Saint Bernard, cats. •  DW—German shepherd dogs. Mean Age and Range

•  OCDP—immature animals. •  OI—3–18

murmur secondary to a patent ductus arteriosus has been reported. CAUSES See Genetics. RISK FACTORS N/A for any discussed diseases; except ACM if exogenous progesterone is administered.

weeks. •  ACM—middle-aged to elderly females. •  DW—2–5 months.

Predominant Sex

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dogs: female; cats: male or female.

DIFFERENTIAL DIAGNOSIS •  OCDP, OI—metabolic disease, physical abuse, alimentary secondary hyperpara­ thyroidism, hypovitaminosis D, hypothyroidism. •  ACM—Pituitary gland tumor; long-term use of progesterone (older dogs, infertile bitches, aggressive dogs). •  DW—malnutrition.

•  OCPD—N/A. •  OI—N/A. •  ACM—

SIGNS •  OCDP—short, thickened, and hard, movable tail; short, buckled legs. Severity of the clinical signs most likely influenced by level of expression of dominant gene carrier of the mutation (homo- or heterozygous). •  OI—signs range from perinatal death to mild bone fragility, severe bone deformity, and innumerable fractures following minor trauma. •  ACM—soft tissue swelling of the face and abdomen; severe hypertrophy of soft tissues of the mouth, tongue, and pharynx (latter may cause stridor); polyuria; occasionally polyphagia. •  DW—proportionate growth retardation and an abnormally soft and woolly hair coat without guard hair. General Comments

Signs frequently reported by the owner: •  OCDP—difficult and decreased mobility, jumping, climbing, lameness; signs progressing. •  OI—sudden onset or progressive lameness. •  ACM, DW—similar to physical examination findings. Physical Examination Findings

•  OCDP: ◦  Cats—pain of long bones; unwillingness to rise. ◦  Dogs—larger than normal head, shorter jaw and resulting malaligned teeth, shortened bones, joint enlargement, lateral deviation of thoracic limbs, spinal deviation to either side. •  OI—pain and lameness secondary to fractures. Dentinogenesis imperfecta (secondary to abnormal collagen I) can be noted in addition to or as single entity: severe thinning of the dentine layer, leading to a translucent appearance, pink discoloration, and multiple tooth fractures. Sudden death due to rupture of chordae tendineae (also affected by abnormal cartilage), has been reported. •  ACM—inspiratory stridor, thick skin folds (mainly neck), prognathism, wide interdental spaces. Visceromegaly, if generalized, can result in abdominal enlargement. •  DW—profound dwarfism, retention of puppy hairs, lack of guard hairs. Hairs can be epilated easily. Gradual progressive truncal alopecia can be noted. Progressive dermal hyperpigmentation, scaly skin, and dermatitis is possible. In males, cryptorchidism is common; in females, persistent estrus is frequent. Continuous heart

 DIAGNOSIS

CBC/BIOCHEMISTRY/URINALYSIS

•  The following should be specifically

evaluated for all discussed diseases: serum concentrations of ionized calcium, phosphorus, vitamin D, and parathormone. •  OCDP, OI, DW—N/A. •  ACM—hyperglycemia, hyperphosphatemia, hypercholesterolemia, hyperproteinemia, increases in liver enzymes (specifically elevated alkaline phosphate), decreased thyroid hormone. •  DW—elevated plasma creatinine concentration. OTHER LABORATORY TESTS

•  OCDP, OI—N/A. •  ACM—prolactin,

cortisol, basal plasma GH levels elevated with disease progression. Elevated plasma insulin-like growth factor I (IGF-I) levels (however, increased GH and IGF can also be seen in healthy animals). Free thyroxine, thyroid-stimulating hormone (TSH), and adrenocorticotropic hormone (ACTH) stimulation tests recommended. GH test recommended to evaluate the pituitary gland function. Folliclestimulating hormone (FSH) and luteinizing hormone (LH) tests are recommended. Diabetes mellitus has been reported to develop secondary to insulin resistance, thus urinalysis with ACM can reveal glucosuria. •  DW—basal plasma concentrations of GH and IGF-I, prolactin, thyrotropin, and LH are low. With combined anterior pituitary function test, often no response of GH, TSH, and prolactin, but minor response of LH and FSH. IMAGING •  OCDP—radiographic changes more prominent in pelvic limbs (size and shape of the tarsal, carpal, metatarsal, metacarpal bones, phalanges), sacrum (articular spaces decreased), exostoses with diffuse osteopenia, zones of rarefication. Spine may show scoliosis, lordosis, or kyphosis. •  OI—radiographs reveal less opaque than normal long bone cortices, frequently pathologic fractures or evidence of chronic healing fractures.

(continued)

Metabolic, Nutritional, and Endocrine Bone Disorders

•  ACM—radiographs of thorax (in case of mammary tumor metastasis; also 85% cardiomegaly reported in cats); MRI of brain (pituitary); ultrasound of abdomen (assess organomegaly—specifically liver and kidneys). •  DW—MRI (brain), echocardiography. DIAGNOSTIC PROCEDURES •  OCDP—bone histology. •  OI—analysis of type I collagen obtained from cultured skin fibroblasts. •  ACM/DW—N/A. PATHOLOGIC FINDINGS •  OCDP, DW—N/A. •  OI—bone: absence of secondary spongiosa, irregular woven bone with absence of Haversian canals. •  ACM— pituitary or mammary gland changes depend on tumor. •  DW—aplasia of the hypophysis/ pituitary gland.

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 TREATMENT

NURSING CARE N/A ACTIVITY •  OCDP, OI—decrease activity to reduce discomfort. •  ACM—N/A. Rest 3 weeks if surgery (ovariohysterectomy) done. Specific care based on specialist’s recommendation following pituitary gland radiation. • DW—N/A. DIET OCDP, OI, ACM, DW—healthy diet. CLIENT EDUCATION

•  OCDP, OI—N/A; no cure. •  ACM,

DW—N/A.

SURGICAL CONSIDERATIONS •  OCDP—N/A; corrective osteotomies are not rewarding. •  OI—surgical treatment of fractures. •  ACM—withdrawal of exogenous progestagens and/or ovario(hyster)ectomy. If pituitary, consider hypophysectomy. Radiation of the hypophysis can also be considered. •  DW—N/A.

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 MEDICATIONS

DRUG(S) OF CHOICE •  OCDP—dogs: nonsteroidal antiinflammatory drugs (NSAIDs); cats: robenacoxib 1 mg/kg PO once a day for 3 days. •  OI—vitamin C 75 mg/kg PO once a day; bisphosphonate supplementation (alendronate sodium): dogs: 0.5–1 mg/kg PO once a day on empty stomach; cats: 10 mg/ cat PO on empty stomach once a week. Note: effectiveness of bisphosphonates to treat OI in dogs and cats has not been evaluated. • ACM: ◦  If progestagen-induced—

aglepristone (progesterone-receptor blocker) 15 mg/kg SQ on 2 consecutive days, repeat weekly until effect of progestagen ceases; surgery (see Surgical Considerations). ◦  If hypothyroidisminduced—levothyroxine sodium 0.02 mg/kg (dog) or 0.01 mg/kg (cat) PO once a day. Adjust dose based on the serum total thyroxine concentrations 4–6 hours post tablet admini­ stration, along with clinical response. •  DW— porcine GH 0.1–0.3 IU/kg SQ, 3 times a week. Thyroid hormone replacement if evidence of secondary hypothyroidism (see ACM dosing recommendation above). CONTRAINDICATIONS N/A PRECAUTIONS

•  OCDP, OI—N/A. If NSAIDs are used,

monitor for possible side effects as listed in package inserts. •  ACM—N/A.

POSSIBLE INTERACTIONS •  OCDP—must not use other NSAIDs. •  OI—none. •  ACM—theoretically, the following interactions may occur with aglepristone: efficacy of glucocorticoids and progestins might be reduced. Manufacturer states that despite lack of data, the following medications may interact with aglepristone: ketoconazole, itraconazole, erythromycin. Drug interactions when using levothyroxine sodium can include: amiodarone, antidepressants, antidiabetics, cholestyramine, corticosteroids, digoxin, ferrous sulfate, ketamine, phenobarbital, propylthiouracil, rifampin, sertraline, sucralfate, sympathicomimetic agents, warfarin. ALTERNATIVE DRUG(S) •  OCDP, OI—N/A. •  ACM—aglepristone; may be difficult to obtain in the United States.

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 FOLLOW-UP

PATIENT MONITORING •  OCDP—2 weeks, then as needed. Note that osteoarthritis can develop long term. •  OI—4–8 weeks for bone healing and improvement of bone density. •  ACM— initially weekly, then every month to monitor until stable. •  DW—weekly. PREVENTION/AVOIDANCE N/A POSSIBLE COMPLICATIONS

•  OCDP, DW—N/A. •  OI—other fractures.

•  ACM—if tumorous cause, metastasis and worsening of disease.

EXPECTED COURSE AND PROGNOSIS

•  OCDP—recurrence of signs and discom-

fort from arthritis. •  OI—development of other fractures. •  ACM—regression of clinical signs over time is expected; if GH did

not completely exhaust pancreatic beta cells, diabetes mellitus might resolve. •  DW—significant increase in body size often not seen (due to closure of epiphyseal plates); growth of primary hair is expected, while growth of guard hairs is variable.

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 MISCELLANEOUS

ASSOCIATED CONDITIONS •  OCDP—N/A. •  OI—can be accompanied by blue sclera, hearing loss, dwarfism, pulmonary pathology. •  ACM—diabetes mellitus, cardiac disease, decreased hepatic and renal function, peripheral neuropathies. •  DW—secondary bacterial dermatitis. Due to combined pituitary hormone deficiency, secondary hypothyroidism is frequent. GH administration might result in development of diabetes mellitus. PREGNANCY/FERTILITY/BREEDING Affected animals for all discussed topics are not to be used for breeding. To treat ACM, ovario(hyster)ectomy is often needed. ABBREVIATIONS

•  ACM = acromegaly. •  ACTH =

adrenocorticotropic hormone. •  DW = dwarfism. •  FSH = follicle-stimulating hormone. •  GH = growth hormone. •  IGF = insulin-like growth factor. •  LH = luteinizing hormone. •  OCDP = osteochondrodysplasia. •  OI = osteogenesis imperfecta. •  TSH = thyroid-stimulating hormone.

­Suggested Reading

Hazewinkel HAW. Metabolic, nutritional, and endocrine bone disorders. In: Bojrab MJ, Monnet E, eds., Mechanisms of Disease in Small Animal Surgery, 3rd ed. Jackson, WY: Teton NewMedia, 2010, pp. 601–610. Kooistra H.S. Acromegaly in dogs. In: Rand J., ed., Clinical Endocrinology of Companion Animals. Hoboken, NJ: Wiley-Blackwell, 2014, pp. 421–426. Montgomery R. Miscellaneous orthopedic diseases. In: Bojrab MJ, Monnet E., eds., Mechanisms of Disease in Small Animal Surgery, 3rd ed. Jackson, WY: Teton NewMedia, 2010, pp. 590–600. Seeliger F, Leeb T, Peters M, et al. Osteogenesis imperfecta in two litters of dachshunds. Vet Pathol 2003, 40:530–539. Von Pfeil DJF, DeCamp CE, Abood SK. The epiphyseal plate: nutritional and hormonal influences; hereditary and other disorders. Compend Contin Educ Vet 2009, 31(7):E1–E14. Author Dirsko J.F. von Pfeil Consulting Editor Mathieu M. Glassman

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Metaldehyde Toxicosis •  Delayed changes in hepatic or renal values

from uncontrolled hyperthermia/seizures.

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 BASICS

OVERVIEW •  Form of acetaldehyde; primarily affects the nervous system. •  Mainly found in slug and snail baits; sometimes in solid fuel for camp stoves. •  Crosses the blood–brain barrier and disrupts GABAergic inhibitory action, facilitating neuronal excitation and increasing potential for convulsions. •  Systems affected include: neuromuscular (seizures and muscle tremors), hepatobiliary (delayed hepatotoxicosis reported in dogs only), and multiple organ failure (secondary to seizures and hyperthermia). •  Incidence/prevalence—depends on presence and accessibility; weather resistant: persists in the environment for >14 days. •  More frequent in coastal, low-lying, temperate and subtropical regions of United States. Snails and slugs are common pests in those locations. SIGNALMENT Species

Dogs; much less often in cats. SIGNS •  Generally, within 3-4 hours but may occur in 1.5% of total hemoglobin. •  Methemoglobin differs from hemoglobin in that the iron moiety of heme groups has been oxidized from the ferrous (2+) to the ferric (3+) state. PATHOPHYSIOLOGY

•  About 3% of hemoglobin is oxidized to

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methemoglobin each day in normal animals as a result of autoxidation of hemoglobin or secondary to oxidants produced in normal metabolic reactions. •  Methemoglobin usually accounts for 50% of total hemoglobin), organs may suffer hypoxic injury. •  Hepatobiliary—in addition to hypoxic injury, the liver may be damaged directly by oxidant drugs that it metabolizes. •  Renal/urologic—in addition to hypoxic injury, the kidneys may be damaged if intravascular hemolysis occurs (pigmentary nephropathy). SIGNALMENT

•  Dogs and cats. •  Deficiency in RBC cytochrome b5 reductase

has been recognized in the Chihuahua, borzoi, English setter, mixed-breed dog, coonhound, poodle, corgi, Pomeranian, Staffordshire bull terrier, Parson Russell terrier, Australian shepherd dog, and American Eskimo dog, and in domestic shorthair cats. A defect in cytochrome b5 has been described in a mixed-breed dog. SIGNS Caused Directly

•  Possibly none in animals with mild to

moderate methemoglobinemia.

•  Cyanotic-appearing mucous membranes—

may be difficult to recognize in heavily pigmented animals. •  Lethargy, tachycardia, tachypnea, ataxia, and stupor caused by hypoxemia when methemoglobin content exceeds 50%.

Caused by Associated Diseases

•  Vomiting, anorexia, and diarrhea possible

in patients with drug toxicity. •  Hemoglobinuria secondary to severe intravascular hemolysis in some patients with Heinz body hemolytic anemia. •  Subcutaneous edema, especially involving the face, and salivation in animals with acetaminophen toxicity. CAUSES

•  Toxicity—acetaminophen, benzocaine,

phenazopyridine, and skunk musk cause Heinz body hemolytic anemia; excess nitrite in pet food and hydroxycarbamide toxicity are reported to cause methemoglobinemia without Heinz body hemolytic anemia. •  Deficiency in RBC cytochrome b5 reductase or a defect in RBC cytochrome b5. RISK FACTORS

•  Application of benzocaine or prilocaine to

traumatized skin or mucous membranes increases the likelihood of systemic absorption and methemoglobinemia. •  Cats are much more likely to develop clinically significant methemoglobinemia than are dogs after acetaminophen administration; this drug is not recommended for use in cats. •  Methemoglobinemia secondary to cyto­ chrome b5 reductase deficiency and a defect in cytochrome b are inherited disorders.

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Both low blood oxygen tension and methemoglobinemia can cause cyanoticappearing mucous membranes and darkcolored blood samples; hypoxemia is documented by measuring PaO2 24 hours to rule out inadvertent detection of the LH surge in the estrual bitch (should also have representative vaginal cytology with superficial cells predominating). If both are positive, then the bitch has been spayed. A negative test (14 hours of light/day. Note: exogenous estrogen exposure in a gonadectomized dog can cause the LH to become misleadingly negative. •  Anti-Müllerian hormone (AMH) testing: A positive test in a bitch or queen >6 months of age supports the presence of ovarian tissue (UC Davis Clinical Endocrinology Laboratory, Animal Health Diagnostic Center, Cornell University). In cases with a negative AMH but convincing clinical evidence supporting remnant syndrome, investigators advise obtaining a progesterone to identify persistent

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Blackwell’s Five-Minute Veterinary Consult

Ovarian Remnant Syndrome luteal structures lacking AMH. AMH differentiates exogenous estrogen exposure (negative) from the ovarian remnant (positive). •  Cytology of vulvar discharge can be suppurative if a uterine stump granuloma or pyometra exists. •  Provocative adrenal testing (pre- and postadrenocorticotropin [ACTH] administration). IMAGING Ultrasonography

•  Can be used to support a diagnosis of

O

ovarian remnant syndrome that is based on cytology and hormonal profiles; guides the surgical approach. •  Remnant ovarian tissue is most visible during the follicular phase (anechoic, cystic structures) or the luteal phase (hypo- or isoechoic cystic structures). •  Ultrasonographic imaging of ectopic ovarian tissue requires technical expertise and is best accomplished with a higher frequency, linear transducer (8–10 mHz). Ovarian remnants containing follicular or luteal structures often cause distal enhancement due to their fluid content; this can be used to locate them caudolateral to the ipsilateral kidney (see Web Figure 1). •  Evaluate the region dorsal to the bladder for a uterine remnant, which can enlarge under hormonal influence or with pathology (see Web Figure 2a,b). •  Evaluate the adrenal glands for normal size and shape. Normal canine adrenal glands are 10 ng/mL), implant should be removed. If not breeding, leave implant in place. ◦  In queens, cervical stimulation may be performed from initial induction several times daily for 24–48 hours.

•  Exogenous estrogen administration or

exposure.

CBC/BIOCHEMISTRY/URINALYSIS If estrogen toxicity—normocytic, normochromic anemia, thrombocytopenia, leukocytosis followed by leukopenia. OTHER LABORATORY TESTS

•  Serum progesterone concentration 1 cm considered cystic; enlarged ovaries may be neoplastic; anechoic structures with thickened walls may indicate luteinization (partial or complete) of follicular structures. Daily ultrasonography to document ovulation; color Doppler can assess ovarian follicular blood flow (increased with follicles, minimal with luteal structures). DIAGNOSTIC PROCEDURES Exploratory laparotomy to examine the ovaries or to obtain ovarian biopsies—the ovarian bursa must be opened to visualize the ovary.

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 FOLLOW-UP

•  Monitor progesterone concentrations

during pregnancy—luteal failure or hypoluteoidism more common with induced ovulation. •  Monitor progesterone after induction to confirm normal rise. •  Serial ultrasound exams (using color Doppler) may be useful to document ovulation.

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 MISCELLANEOUS

ASSOCIATED CONDITIONS Bilaterally symmetric nonpruritic alopecia (with prolonged estrus). PREGNANCY/FERTILITY/BREEDING •  Anovulation may be hereditary; discuss with owner prior to breeding. •  Subsequent cycles may be normal, necessi­ tating no treatment, or abnormal again. SEE ALSO •  Infertility, Female—Dogs. •  Sexual Development Disorders. ABBREVIATIONS

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N/A

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 TREATMENT

•  GnRH = gonadotropin-releasing hormone. •  hCG = human chorionic gonadotropin. •  LH = luteinizing hormone.

­Suggested Reading

 MEDICATIONS

DRUG(S) OF CHOICE •  Ovulation induction may be attempted once cytology reaches >70% anucleated cells and follicles are >4–5 mm (toy to small-breed canine), 5–7 mm (medium to large-breed canine), 7–10 mm (giant-breed canine), or 2–3 mm (feline). •  Ovulation-inducing agents: ◦  GnRH: 1.1–2.2 μg/kg IM or IV; 25 μg/ cat IM; may repeat daily for 1–3 days in bitches, single dose for queens. ◦  Human chorionic gonadotropin (hCG): 500–1,000 IU/dog IM; 500 IU/queen IM; may repeat in 2–3 days if ovulation does not occur.

Meyers-Wallen VN. Unusual and abnormal canine estrous cycles. Theriogenology 2007, 68:1205–1210. Author Cheryl Lopate Consulting Editor Erin E. Runcan



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Canine and Feline, Seventh Edition

Pain (Acute, Chronic, and Postoperative) endocrine markers of stress. Pain can result in a loss of function of affected tissues.

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 BASICS

DEFINITION •  Unpleasant sensory or emotional experience associated with actual or potential tissue damage (adaptive pain) or altered sensory neurobiology (chronic pain). •  The inability for the animal to communi­ cate does not negate presence of pain and the need for appropriate pain-relieving treatment. PATHOPHYSIOLOGY •  With physiologic pain, an application of a noxious stimulus activates specialized nerve endings called nociceptors; nociceptors transduce noxious chemical, mechanical, or thermal stimuli into electrochemical potentials that are transmitted via sensory nerves from the affected tissue to the spinal cord. •  In the dorsal horn of the spinal cord, the incoming first-order peripheral nerve synapses with ascending spinal neurons, which terminate in the brainstem. Incoming noxious information can be modulated in the dorsal horn by other incoming information, descending inhibitory nerve impulses, or pharmacologic inhibition by several classes of drugs. The ascending neurons synapse in the brainstem to form ascending tracts that end in the cortex, where sensation occurs. Neuroendocrine and physiologic responses (e.g., tachycardia, elevated cortisol) to noxious stimuli may originate from the brainstem and do not necessarily correlate with the perceived intensity of pain. •  Nociceptive processes (i.e., transduction, transmission, and modulation) appear to be similar anatomically and physiologically in most mammalian and many non-mammalian species. The perception of pain may vary between species and individuals of the same species since anatomic differences in cortical development exist and integration of past experiences and learned behaviors varies. •  Prolonged activity in nociceptive pathways (e.g., days, weeks, or months) from chronic injury or disease, or injury to nervous system tissues, may cause altered neuroprocessing resulting in sensitization of these pathways and hyperresponsiveness. This may cause an increased response to a stimulus not normally considered noxious (allodynia). SYSTEMS AFFECTED

•  Pain may originate from any tissue,

including the nervous system itself. In humans, certain pain syndromes may be associated with fear, anxiety, or depression in the absence of any observable injury. •  The physiologic response to pain can include decreased immune function, increased catabolism, and elevated neuro­

GENETICS Age, sex, breeding strain, and species can influence responses to noxious stimuli. Genes have been described that modify individual behavioral responses to noxious stimuli in several species. Genes may also be variably expressed depending on stimulus intensity and duration, which can lead to altered neuroprocessing and maladaptive or chronic pain. INCIDENCE/PREVALENCE

•  Evolutionarily, aversion to noxious stimuli

was protective to organisms, keeping them away from harm. •  While acute pain is beneficial to warn or teach an animal about potential harmful objects in its environment, persistent acute pain associated with surgery or injury does not benefit the patient and should be treated appropriately. •  Any form of chronic pain syndrome does not serve a protective function and should be treated. SIGNS •  Behavioral signs of pain and distress vary considerably among individuals. •  Experience, environment, age, species, and other factors can modify the intensity of the reaction to noxious stimuli or to an altered neurobiology associated with maladaptive or chronic pain. •  The most obvious clinical signs of distress in the dog and cat can include vocalization, agitation, abnormal posture or gait, thrashing, hyperesthesia, or hyperalgesia. •  More subtle signs shared by many conditions include trembling, lethargy, reduced appetite, stupor, and biting. •  Tachypnea, tachycardia, mydriasis, and hypertension are signs observed with the stress response that may also accompany pain; these are nonspecific and present in many nonpainful conditions. The stress response is often not associated with chronic pain due to adaptation. •  Clinical signs associated with chronically painful conditions may be very subtle or difficult to evaluate since homeostatic mechanisms tend to help the animal compensate. Chronically painful conditions are often associated with decreased activity, lameness, and/or depression. CAUSES •  Physiologic or adaptive pain can be caused by perceived or actual tissue disruption associated with trauma or surgery and also by chronic degenerative changes and inflammation associated with conditions such as osteoarthritis. •  Pain that extends beyond the initial tissue damage and healing processes is pathologic (maladaptive) and may indicate that the

initiation of altered nervous system processing has occurred. RISK FACTORS

•  All animals that experience surgical or

traumatic tissue damage or have recently altered behavior should be evaluated for the presence of pain. •  Due to the increasing prevalence of degenerative diseases in older patients, routine examination should include evaluation for pain. •  Pain intensity may not always correlate with the degree of tissue damage. However, more invasive soft tissue and orthopedic procedures or inflammatory disease progression in older patients are likely associated with greater pain.

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Identifying pain in veterinary patients is a diagnosis, and the medical record should reflect the veterinarian’s clinical diagnostic and treatment plan. •  Acute pain is almost always accompanied by tissue damage or disease, and diagnosis and treatment of the primary disorder should be done before or concomitantly with treatment of pain. The presence or absence of pain is sometimes used as a way of monitoring and diagnosing some conditions, and treatment should be in accordance with good medical practice. Pain should be differentiated from distress associated with other factors, such as restraint, restrictive bandaging, and separation from owners. Drugs used to treat pain, particularly opioids and dissociative anesthetics, may cause dysphoria, which often resembles and can be confused with signs of pain and distress. CBC/BIOCHEMISTRY/URINALYSIS

•  Cortisol release associated with acute pain

may appear as a stress leukogram.

•  Hyperglycemia may also be observed in

some patients, but can also be seen with anesthesia in the absence of tissue trauma. •  Normal laboratory test values do not rule out the presence of pain. OTHER LABORATORY TESTS N/A IMAGING

•  Many painful patients have underlying

changes in anatomic structures observable on ultrasound, radiography, CT or MRI. •  Chronic pathologic tissue changes such as the degree of osteophyte formation with osteoarthritis do not necessarily always correlate with the degree of pain and dysfunction experienced by the patient. Some patients can be painful without observable tissue or structural changes.

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Pain (Acute, Chronic, and Postoperative)

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DIAGNOSTIC PROCEDURES •  Review patient signalment, obtain a thorough history, and include pain assessment as part of every physical examination. The pain score should be recorded in the patient’s record along with temperature, pulse, and respiration. •  Thoroughly evaluate underlying conditions that may be contributing to pain and treat appropriately. •  Use a species-specific scoring tool for pain assessment to decrease subjectivity and observer bias. This will result in more effective pain management. Such tools are referred to as multifactorial clinical measurement instruments (CMIs) and are available for acute postoperative or chronic pain. •  CMIs for acute postoperative pain involve observing the patient without interaction; observing the patient while interacting with a caregiver; observing the patient’s response to palpation of the surgical site; and assigning a numerical score using a dynamic interactive visual analogue scale. The reevaluation interval will depend on the procedure, duration of intervention chosen, and previous pain score. •  CMIs for chronic pain primarily involve owner observations of their pets regarding exercise tolerance and general activity; ability to stand, walk, do stairs, jump, or rise; grooming behavior; and urination or defecation habits. •  Complete abolishment of pain may not be possible or desirable if analgesic administration results in excessive adverse effects. Therapy should aim to make pain tolerable.

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 TREATMENT

APPROPRIATE HEALTH CARE •  Analgesic drug selection depends on species, pain intensity, and underlying cause. •  Treat the underlying cause at the same time if possible. •  Acupuncture, prescribed activity (e.g., physical therapy), mesenchymal stromal cell or platelet-rich plasma injection, and physical manipulation (massage, trigger point manipulation, chiropractic) may be useful adjunctive treatment modalities for certain types of painful musculoskeletal conditions. •  If the patient’s quality of life is not acceptable after all reasonable therapeutic options have been explored, euthanasia may be the most humane option. NURSING CARE

•  General good nursing practices. •  Nonpharmacologic, including bandaging

and hydrotherapy, may be appropriate. ACTIVITY

•  Rehabilitation medicine and weight loss is a

useful adjunct for some musculoskeletal conditions.

•  Cage rest or limited activity may be useful

for certain types of pain. DIET

•  Dietary changes to help treat the underlying

condition (e.g., weight reduction for hip dysplasia) may be beneficial. •  Many supplements have been marketed that may have beneficial effects on articular cartilage or modify inflammatory disease progression. •  Commercial veterinary diets are marketed specifically for animals with mobility issues. CLIENT EDUCATION

•  When pain medication is dispensed,

educate clients on what to look for with effective treatment, as well as adverse effects. Use caution when dispensing opioids to clients for at-home administration and ensure they understand requirements for safe storage and disposal. •  Inform the client that analgesic effectiveness varies and several drugs may need to be tried before an effective treatment is found. Pain management must be individualized because of the neurobiologic complexity of pain perception. •  Clients should be asked to participate in evaluation of their pet’s pain, especially chronic pain. Species-specific CMIs are available and can help document treatment effectiveness. SURGICAL CONSIDERATIONS

•  Surgical treatment of the underlying

condition causing pain may be the best treatment in some circumstances. •  Ablative procedures (neurectomy) to halt pain transmission is not always associated with positive results and may result in worsening of the painful condition. These procedures are rarely performed in veterinary patients.

­

 MEDICATIONS

DRUG(S) OF CHOICE (SEE ALSO APPENDIX VII) •  Opioids, alone or in combination with other classes of drugs, such as sedative/tranquilizers or nonsteroidal anti-inflammatory drugs (NSAIDs), are widely used for the manage­ ment of acute postoperative pain. •  Full μ-opioid receptor agonists, such as morphine, hydromorphone, and fentanyl, are usually effective for moderate to severe pain. Partial agonist or agonist–antagonist drugs, such as buprenorphine and butorphanol, are usually reserved for mild to moderate pain. •  Opioids generally have poor oral bioavail­ ability, and oral doses should be adjusted accordingly. •  Full μ-opioid receptor agonists can be used safely in cats; however, doses are usually reduced relative to dog doses.

(continued)

•  An SC injectable formulation of

buprenorphine has been approved for 24-hour postoperative pain control in cats. •  Should dysphoria develop after opioid administration, tranquilization with an α2-agonist or acepromazine may be beneficial. •  NSAIDs are used most commonly for the chronic treatment of painful conditions in dogs. They can be safe when administered chronically, but gastrointestinal (GI), hepatic, and renal adverse effects are possible. The best strategy appears to be reducing the dose to the lowest effective dose in an individual. If chronic administration is anticipated serum chemistries should be considered to monitor for hepatic and renal adverse effects. •  Veterinary-approved NSAIDs for dogs and cats have demonstrated acceptable safety profiles; however, there is no strong indication that any particular veterinary-approved NSAID is associated with a greater or lesser incidence or prevalence of adverse events. •  Long-term use of low-dose meloxicam is approved in cats in many countries other than the United States. •  Grapiprant is a non-cyclooxygenase (COX)-inhibiting NSAID that targets prostaglandin E2 (EP4 receptors) approved for osteoarthritic pain and inflammation in dogs. •  Liposome-encapsulated bupivacaine is approved for peri-incisional infiltration in dogs undergoing cranial cruciate ligament surgery and for peripheral nerve block in cats. Gradually released local anesthetic can provide analgesia for up to 72 hours. Extralabel use is also encountered frequently for other types of procedures. •  Additional information is available for many drugs and should be referred to when considering extralabel use. Owners should be informed of the risks of analgesic drug therapy in their pet before consenting to treatment. Neuropathic Pain

Treatment of neuropathic pain is a subcategory of pathologic pain. It may originate from brain or spinal masses, injury (such as with intervertebral disc disease), inflammation, or the repetitive stimulation of the pain transmission system by a chronic injury outside the CNS. Classic signs that accompany neuropathic pain are allodynia and hyperalgesia. Neuropathic pain does not always respond well to traditional analgesics, such as NSAIDs and opioids, although these drugs are usually tried initially (except for NSAIDs when neurosurgery is imminent). Tricyclic anti­ depressants, antiepileptic drugs (e.g., gabapentin), N-methyl-d-aspartate (NMDA) receptor antagonists, and other alternative (complementary) therapies may be effective. Most of these treatments consist of extra- or off-label use of human medications and require careful client communication and approval.



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Canine and Feline, Seventh Edition (continued)

CONTRAINDICATIONS •  Opioids may be associated with severe respiratory depression in human patients, but in most dogs and cats cause only minimal respiratory depression. In patients with severe respiratory compromise or intracranial hypertension, opioids may be contraindicated. Most μ-opioid receptor agonists can also alter GI and urinary tract motility, resulting in constipation, urinary retention, and vomiting. •  NSAIDs can cause GI ulceration, hepato­ pathies, and impaired renal function. Preexisting GI, hepatic, or renal disease may be a contraindication to their use. Concomitant glucocorticoid therapy, severe stress, or anorexia may predispose many animals to adverse effects. NSAIDs that significantly inhibit COX-1 may also alter platelet function and may result in increased surgical blood loss. Acetaminophen or acetaminophencontaining analgesics should not be used in cats. PRECAUTIONS

•  Carefully monitor patients for adverse

effects and clinical effectiveness following administration of analgesic drugs. •  Opioid-induced hyperthermia has been reported in feline patients, most commonly after fentanyl patch application or hydro­ morphone administration. •  Opioid administration may result in altered GI motility (constipation), inappetence, and urine retention. These signs usually appear soon after initiation of opioid therapy and should resolve within 12–36 hours of stopping opioid administration. In the interim supportive care such as passing a urinary catheter may be necessary. •  In consultation with the pet owner, the veterinarian may feel the need to prescribe NSAIDs to a particular patient even if the risk for adverse events is deemed increased due to disease or preexisting conditions. The veterinarian should strive to ethically balance the long-term therapeutic risk of drugs such as NSAIDs against the benefit of improved quality of life. •  Opioid abuse has affected all health professions including veterinary medicine and veterinarians must play active roles in combating abuse and misuse of opioids. With new opioid prescribing guidelines now published in many jurisdictions, veterinarians must remain up to date on all relevant regulations. POSSIBLE INTERACTIONS •  Opioids can reduce the anesthetic requirements for most species, especially when combined with α2-agonists or acepromazine as a premedication before anesthesia. In humans the combination of certain opioids such as meperidine with serotonin-altering drugs may result in toxicity (e.g., l-deprenyl, amitriptyline, tramadol,

Pain (Acute, Chronic, and Postoperative) trazadone) and are occasionally prescribed to veterinary patients. •  Concurrent glucocorticoid therapy may enhance NSAID toxicity. •  Other drugs that predispose animals to GI or renal impairment, such as aminoglycoside antimicrobials, should be used with caution when NSAIDs are also being administered. ALTERNATIVE DRUG(S) •  Adjunctive analgesic drugs (e.g., gabapentin, amantadine, amitriptyline, tramadol) may be beneficial for patients that have altered neuroprocessing associated with chronic disease changes or nervous system injury. To select and administer an adjuvant analgesic properly, the veterinarian should be aware of the drug’s clinical pharmacology. The following information about the drug is necessary: (1) approved indication, (2) unapproved indication (e.g., as an analgesic) widely accepted in veterinary medical practice, (3) common side effects and potentially serious adverse effects, (4) pharmacokinetic features, and (5) specific dosing guidelines for pain (see Appendix VII). •  Nontraditional medical treatments are common, but should be evaluated for safety and effectiveness before recommendation. •  A number of alternative treatments for chronic pain in dogs and/or cats are in various stages of development and marketing including mesenchymal stem cell therapy and anti-nerve growth factor (anti-NGF) mono­ clonal drugs. •  Potential novel approaches to chronic pain currently being investigated include cannabidiol (CBD) which is available commercially and from marijuana dispensaries in jurisdictions where allowed. The FDA has decided to regulate CBD as a food additive and the legality of recommending and producing CBD for veterinary patients is unclear at this time. More research is needed before such therapies can be routinely recommended. •  Low-level laser therapy has gained popularity as an adjunctive technique to manage postoperative pain and facilitate earlier return to function following cruciate surgery in dogs. While this therapy may prove beneficial in individual cases, controlled studies using force plate analysis have not documented efficacy to date.

­

 FOLLOW-UP

PATIENT MONITORING •  Frequent evaluation of analgesic drug effectiveness should be performed.

•  Patients receiving chronic analgesic

medication, especially NSAIDs, should be evaluated periodically to monitor GI, liver, and renal function. •  It is the responsibility of the veterinarian to ensure that information about the effects of prescribed drugs is disseminated to clients. PREVENTION/AVOIDANCE Although some degree of pain is usually an unavoidable consequence of surgery or trauma, when possible, the preemptive administration of analgesic drugs may provide better pain control and reduce the potential for CNS wind-up. Use of proper anesthetic techniques incorporating analgesic premedications and local and regional analgesic techniques where appropriate, are effective ways of practicing preemptive analgesia. EXPECTED COURSE AND PROGNOSIS Acute pain associated with surgery or trauma usually resolves with tissue healing. Opioids may be most effective for the 12–24 hours following surgery, whereas NSAIDs may be better after that period. Some NSAIDs are effective analgesics immediately after surgery. When pain signs persist beyond the normal course of a few days to weeks, suspect persistent disease, injury, or CNS changes and consult an anesthesiologist or a board-certified specialist trained in pain management for suggestions about appropriate therapy.

­

 MISCELLANEOUS

PREGNANCY/FERTILITY/BREEDING •  Opioids may cause fetal respiratory depression following delivery. NSAIDs may alter maternal or fetal prostaglandin production, resulting in pregnancy complications. •  The effects on the fetus of many of the analgesic drugs approved for use in dogs and cats are not widely reported. ABBREVIATIONS

•  CBD = cannabidiol. •  CMI = multifactorial clinical measurement

instrument.

•  COX = cyclooxygenase. •  GI = gastrointestinal. •  NGF = nerve growth factor. •  NMDA = N-methyl-d-aspartate. •  NSAID = nonsteroidal anti-inflammatory drug.

INTERNET RESOURCES

•  American College of Veterinary Anesthesia

and Analgesia’s position paper on treatment of pain in animals: http://acvaa.org/docs/ Pain_Treatment

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Blackwell’s Five-Minute Veterinary Consult

Pain (Acute, Chronic, and Postoperative) •  International Veterinary Academy of Pain

Management: http://www.ivapm.org •  World Small Animal Veterinary Association (WSAVA) Global Pain Council Guidelines: https://wsava.org/global-guidelines/ global-pain-council-guidelines/

­Suggested Reading

Epstein M, Rodan I, Griffenhagen G, et al. AAHA/AAFP pain management guidelines for dogs and cats. J Am Anim Hosp Assoc 2015, 51(2):67–84.

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Grimm KA, Tranquilli WJ, Lamont LA, et al. Veterinary Anesthesia and Analgesia: The Fifth Edition of Lumb and Jones. Ames, IA: Wiley-Blackwell, 2015. Renwick SM, Renwick AI, Brodbelt DC, et al. Influence of class IV laser therapy on the outcomes of tibial plateau leveling osteotomy in dogs. Vet Surg 2018, 47(4):507–515.

(continued)

Steagall P, Robertson SA, Taylor P. Feline Anesthesia and Pain Management, Ames, IA: Wiley-Blackwell, 2017. Authors Leigh A. Lamont, Kurt A. Grimm, and William J. Tranquilli  Client Education Handout available online



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Canine and Feline, Seventh Edition

Palatal Defects Historical Findings

­

 BASICS

DEFINITION Communication between the nasal and oral cavities. PATHOPHYSIOLOGY •  Secondary to congenital cleft of the secondary palate to include the hard and/or soft palate. •  Secondary to a traumatic injury causing disruption of the lateral maxilla and/or hard palate. •  Secondary to resective surgery for neoplasms of the lateral maxilla and/or hard palate. •  Secondary to extraction of maxillary canine and rostral premolar teeth (see Oronasal Fistula). SYSTEMS AFFECTED •  Gastrointestinal (oral cavity). •  Respiratory. GENETICS May be inherited or secondary to intrauterine abnormality. INCIDENCE/PREVALENCE •  Primary cleft palate is an abnormality of the lip and premaxilla and is rarely associated with a palatal defect communicating with the nasal cavity. •  Brachycephalic breeds are predisposed to primary cleft palate. •  Breed predilection for congenital cleft of the secondary palate. SIGNALMENT Species

Dogs more common than cats. Breed Predilections

Brachycephalic breeds, miniature schnauzer, beagle, cocker spaniel, dachshund, and Siamese cats. Mean Age and Range

At birth in dogs with primary or secondary cleft palate. Predominant Sex

N/A

SIGNS •  Difficulty nursing. •  Regurgitation. •  Nasal discharge; often mucopurulent. •  Sneezing. •  Gagging when drinking water or eating. •  Poor growth. •  Lethargy and depression in chronic cases with severe secondary rhinitis. •  Cough in cases of secondary aspiration pneumonia. General Comments

Dogs with primary or secondary cleft palate should be neutered since the condition is considered to be inherited.

Signs reported by the owner as above; or following trauma or oncologic surgery. Physical Examination Findings

­

 TREATMENT

•  Hard and/or soft plate defect

APPROPRIATE HEALTH CARE Inpatient

•  Nasal discharge. •  Thoracic auscultation for aspiration

NURSING CARE Supportive preoperative care.

communicating with the nasal cavity. pneumonia.

•  Patient is “poor doer.” •  Check for other congenital abnormalities.

CAUSES •  Failure of the palatine shelves to fuse during development at 25–28 days of gestation. •  Foreign body, vehicular, or bite trauma. •  Oncologic surgery for neoplasms of the hard palate and/or lateral maxilla. •  Wound dehiscence following maxillofacial reconstructive surgery. RISK FACTORS

•  Inherited (recessive or irregular dominant,

polygenic).

•  Nutritional. •  Hormonal (steroids). •  In utero abnormality. •  Viral.

­

 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS Fungal or bacterial rhinitis. CBC/BIOCHEMISTRY/URINALYSIS •  Recommended as preoperative database. •  CBC may reflect secondary chronic rhinitis and/or secondary aspiration pneumonia. OTHER LABORATORY TESTS Consider aerobic bacterial culture and sensitivity of nasal tissue in cases of chronic rhinitis. IMAGING

•  Thoracic radiographs are recommended to

rule out aspiration pneumonia.

•  MRI or CT imaging is recommended prior

to oncologic surgery for imaging of the maxillary/palatal lesion. •  Three-view thoracic radiographs are recommended to check for distant metastasis before operating patients with neoplasms. DIAGNOSTIC PROCEDURES Sedated oral examination. PATHOLOGIC FINDINGS

•  Secondary rhinitis is usually self-limiting

and resolves following surgical repair.

•  Long-term (4–6 weeks) antimicrobial

therapy based on culture and sensitivity may be necessary to treat the chronic rhinitis.

ACTIVITY N/A DIET •  Preoperative diet should be small-dog food “meatballs” fed by hand or a diet with a consistency that does not cause potential aspiration pneumonia. •  Postoperative diet should be a thick liquid consistency for the first 2 weeks. CLIENT EDUCATION

•  A palatal defect requires surgery for repair. •  Multiple surgeries may be required to repair

the palatal defect.

•  Medical management is ineffective and is

only indicated when multiple surgical attempts to repair the palatal defect have failed. •  There is a higher surgical success rate in older puppies. •  Tube feeding may be required for the neonate patient until surgery, or until the patient can eat a diet of appropriate consistency. •  Secondary rhinitis is expected and self-limiting with clinical signs more of a nuisance than pathologic. SURGICAL CONSIDERATIONS

•  The surgical goal is to provide a soft tissue

barrier or layer to reestablish and segregate the oral and nasal cavities. •  Congenital secondary cleft palate— recommend using a sliding bipedicle flap repair technique or an overlapping flap repair technique. •  Traumatic palatal defect—recommend either a buccal mucosal flap repair technique or hard palate mucoperiosteal flap repair technique. •  Palatal defect following oncologic surgery— recommend either a buccal mucosal flap repair technique and/or hard palate mucoperiosteal flap repair technique. •  Palatal defect following maxillofacial reconstruction dehiscence—recommend either a buccal mucosal flap repair technique and/or hard palate mucoperiosteal flap repair technique. •  Lavage the nasal cavity before surgery to remove any foreign material or debris that may have accumulated in the nose. •  A permanent silastic obturator may used to occlude small palatal defects in refractory cases where surgery has failed multiple times.

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Blackwell’s Five-Minute Veterinary Consult

Palatal Defects

(continued)

POSSIBLE COMPLICATIONS

•  Wound dehiscence and failure to repair the

­

 MEDICATIONS

DRUG(S) OF CHOICE N/A unless treating preoperative rhinitis. PRECAUTIONS N/A POSSIBLE INTERACTIONS N/A ALTERNATIVE DRUGS N/A

 FOLLOW-UP PATIENT MONITORING Recommend 2- and 4-week postoperative examinations to determine success of the surgical procedure.

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PREVENTION/AVOIDANCE •  Diet should be a thick liquid consistency for 2 weeks postoperatively. •  Chew toys and other objects are prohibited for the first 8 weeks postoperatively.

palatal defect.

•  Chronic, preexisting rhinitis may require

extended postoperative antimicrobial therapy.

EXPECTED COURSE AND PROGNOSIS •  Surgery is usually successful, however multiple surgical procedures may be required. •  The overall prognosis is “good.”

PREGNANCY/FERTILITY/BREEDING Congenital cleft palate defects are considered inherited and affected dogs should be neutered. SYNONYMS N/A INTERNET RESOURCES Search oronasal communication, oronasal fistula, cleft palate.

­Suggested Reading

­

 MISCELLANEOUS

ASSOCIATED CONDITIONS •  Rhinitis. •  Aspiration pneumonia. AGE-RELATED FACTORS

•  There is a higher surgical success rate in

older puppies.

•  Tube feeding may be required for the neonate

patient until surgery, or until the patient can eat a diet of appropriate consistency. •  Initial dietary management and feeding by the owner is labor intensive. ZOONOTIC POTENTIAL N/A

Hedlund CS. Surgery of the oral cavity and oropharynx. In: Fossum TW, Hedlund CS, Hulse DA, et al., eds., Small Animal Surgery. St. Louis, MO: Mosby, 1997, pp. 210–215. Manfra Marretta S, Grove TK, Grillo JF. Split palatal U-flap: a new technique for repair of caudal hard palate defects. J Vet Dent 1991, 8:5–8. Smith MM. Island mucoperiosteal flap for repair of oronasal fistula in a dog. J Vet Dent 2001, 18:140–144. Smith MM, Rockhill AD. Prosthodontic appliance for repair of oronasal fistula in a cat. J Am Vet Med Assoc 1996, 208:1410–1412. Author Mark M. Smith Consulting Editor Heidi B. Lobprise



Canine and Feline, Seventh Edition

1027

Pancreatitis—Cats SIGNALMENT Species

­

 BASICS

Cat

DEFINITION •  Inflammation of the pancreas most often of unknown cause(s). •  Acute pancreatitis— inflammation of the pancreas that occurs abruptly with little or no permanent patho­ logic change. •  Chronic pancreatitis— continuing inflammatory disease that is accompanied by irreversible morphologic change such as fibrosis.

Breed Predilections

PATHOPHYSIOLOGY

Historical Findings

•  Host defense mechanisms normally prevent

pancreatic autodigestion by pancreatic enzymes, but under select circumstances these natural defenses fail; autodigestion occurs when these digestive enzymes are activated within acinar cells. •  Local and systemic tissue injury is due to the activity of released pancreatic enzymes and a variety of inflammatory mediators such as kinins, free radicals, and complement factors that are released by infiltrating neutrophils and macrophages. The most common pathologies involving the feline pancreas include acute necrotizing pancreatitis (ANP), acute suppurative pancreatitis, and chronic nonsuppurative pancreatitis. SYSTEMS AFFECTED

•  Gastrointestinal (GI)—altered GI motility

(ileus) due to regional chemical peritonitis; local or generalized peritonitis due to enhanced vascular permeability; concurrent inflammatory bowel disease (IBD) may be seen in some cats. •  Hepatobiliary—lesions due to shock, pancreatic enzyme injury, inflammatory cellular infiltrates, hepatic lipidosis, and intra/extrahepatic cholestasis. Feline GI inflammatory disease (concurrent cholangitis ± IBD) may be seen in some cats. •  Respiratory—pulmonary edema or pleural effusion. •  Cardiovascular—cardiac arrhythmias may result from release of myocardial depressant factor. •  Hematologic—activation of the coagulation cascade and systemic consumptive coagulopathy (disseminated intravascular coagulation [DIC]) may occur. GENETICS No genetic basis for disease pathogenesis in cats has been identified. INCIDENCE/PREVALENCE

•  True prevalence is unknown but this is a

relatively common clinical disorder in cats. •  Necropsy surveys suggest an increased prevalence in cats with cholangitis, and IBD. The unique feline pancreaticobiliary anatomy and intestinal microbiota likely contribute to multiorgan inflammatory disease in this species. GEOGRAPHIC DISTRIBUTION Worldwide

Siamese cats.

Mean Age and Range

Mean age for acute pancreatitis is 7.3 years; any age may be affected. Predominant Sex

None

SIGNS •  Vague, nonspecific, and nonlocalizing signs. •  Anorexia, lethargy, and vomiting are reported most frequently. •  Weakness. •  Abdominal pain. •  Diarrhea—small bowel

and large bowel diarrhea and fever are less common in cats than in dogs. Physical Examination Findings

•  Severe lethargy. •  Inappetance. •  Dehydration—common; due to GI losses. •  Abdominal pain—recognized much less frequently in cats than dogs. •  Mass lesions may be palpable. •  Fever—observed in 25%

of cats.

CAUSES Etiology is most often unknown; possibilities include: •  Hepatobiliary disease—both inflammatory and degenerative (hepatic lipidosis). •  Pancreatic trauma/ischemia. •  Duodenal reflux. •  Drugs/toxins (organo­ phosphates). •  Pancreatic duct obstruction. •  Hypercalcemia. •  Inflammatory GI disease. •  Nutrition—excessively lean body mass is associated with ANP. RISK FACTORS

•  Breed? •  Obesity? •  Organophosphate poisoning. •  Concurrent hepatic/intestinal

inflammatory disease.

­

 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  GI disease (obstruction, foreign body, perforation, infectious gastroenteritis, ulcer disease)—exclude with CBC/biochemistry/ urinalysis, diagnostic imaging, and paracentesis. •  GI or hepatic neoplasia— exclude with tissue biopsy. •  Urogenital disease (pyelonephritis, prostatitis or abscessation, pyometra, urinary tract rupture or obstruction, acute renal failure)—exclude with CBC/biochemistry/urinalysis, urine culture/sensitivity, and imaging. •  Hepatobiliary disease (cholangitis and extrahepatic biliary obstruction [EHBO])—exclude with CBC/ biochemistry/urinalysis, bile acids, imaging, and liver biopsy. •  Abdominal neoplasia— exclude with imaging and cytology or biopsy.

CBC/BIOCHEMISTRY/URINALYSIS

•  CBC—often reveals nonregenerative anemia

(40%), leukocytosis (38%), and/or leukopenia (15%). •  Serum biochemistries—often show prerenal azotemia; liver enzyme activities (alanine aminotransferase, alkaline phosphatase) are often elevated because of hepatic ischemia or exposure to pancreatic enzymes; hyperbilirubinemia with intra/extrahepatic biliary obstruction; hyperglycemia with necrotizing pancreatitis due to hyper­ glucagonemia; hypoalbuminemia, hyper­ cholesterolemia, and hypertriglyceridemia are common. Hypocalcemia is more common in cats than dogs, and a low ionized calcium concentration is a negative prognostic indicator in cats. •  Urinalysis—increased urine specific gravity associated with dehydration or can be unremarkable. OTHER LABORATORY TESTS •  Serum amylase and lipase activities are unreliable serologic markers—may be elevated, but are nonspecific; can also increase with hepatic, renal, or neoplastic disease in the absence of pancreatitis. •  Serum pancreatic lipase immunoreactivity (fPL) is a highly sensitive and specific serologic marker of acute pancreatic inflammation. A cage-side fPL assay (SNAP fPL) has been developed as a useful screening tool. Elevation in SNAP fPL should be followed up by laboratory measurement of serum Spec fPL to quantitate the degree of elevation. IMAGING •  Abdominal radiographs—may include increased soft tissue opacity in the right cranial abdominal compartment; loss of visceral detail (“ground glass appearance”) due to abdominal effusion; static gas pattern in the proximal duodenum. •  Abdominal ultrasound— nonhomogeneous solid or cystic mass lesions suggest pancreatic abscess; may be a pancreatic mass or altered echogenicity (hypoechoic) in the area of the pancreas; pancreas is usually enlarged with irregular borders, surrounding mesentery may be hyperechoic due to focal peritonitis, may see peritoneal effusion and extrahepatic biliary obstruction. •  fPL assay and pancreatic ultrasound in combination have the highest specificity for an antemortem diagnosis of acute pancreatitis. DIAGNOSTIC PROCEDURES

•  Ultrasound-guided needle aspiration may

confirm inflammation (cytology), abscess, or cyst. •  Laparoscopy with pancreatic forceps biopsy for histologic diagnosis. •  Histopathologic evaluation may miss focal or segmental pancreatic inflammation and results should be interpreted with caution. PATHOLOGIC FINDINGS •  Gross findings (acute pancreatitis)—mild swelling with edematous pancreatitis. •  Gross findings (chronic pancreatitis)—pancreas is reduced in size, firm, gray, and irregular; may contain extensive adhesions to surrounding

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Pancreatitis—Cats viscera. •  Microscopic changes (acute pancreatitis)—include edema, parenchymal necrosis, hemorrhage, and neutrophilic cellular infiltrate with acute lesions. •  Microscopic changes (chronic pancreatitis)— pancreatic fibrosis around ducts, ductal epithelial hyperplasia, atrophy, and mononuclear cellular infiltrate.

­

 TREATMENT

APPROPRIATE HEALTH CARE •  Eliminate the inciting cause (if possible). •  Supportive care is most important. NURSING CARE

•  Aggressive IV fluid therapy. Fluid therapy

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goals—correct hypovolemia and maintain pancreatic microcirculation. •  An isotonic crystalloid such as lactated Ringer’s solution or Normosol-R® is the first-choice rehydration fluid. •  Correct initial dehydration (mL = % dehydration × weight in kg × 1000) and give over 4–6 hours. •  May need colloids to improve pancreatic circulatory needs and prevent ischemia. •  Following replacement of deficits, give additional fluids to match maintenance requirements (2.5 × weight in kg = mL/kg/h) and ongoing losses (estimated). •  Potassium chloride (KCl) supplementation usually needed because of potassium loss in the vomitus; base potassium supplementation on measured serum levels (use 20 mEq of KCl/L of IV fluid if serum potassium levels are not known; do not administer faster than 0.5 mEq/kg/h). ACTIVITY Restrict DIET •  Continue to feed orally unless vomiting is intractable; feeding maintains intestinal epithelial integrity and minimizes bacterial translocation. •  Initiate enteral feeding via esophagostomy, gastrostomy enteral feeding device, or nasoesophageal tube placement. •  NPO in animals with persistent vomiting for the shortest time possible; when there has been no vomiting for 12 hours, offer small volumes of water; if tolerated, begin small, frequent feedings of a diet that does not contain excessive amounts of dietary fat. Most nutritionists agree that excessive dietary fat restriction is not necessary in cats with pancreatitis. CLIENT EDUCATION

•  Discuss the need for extended hospitalization. •  Discuss the expense of diagnosis and treatment. •  Discuss possible short-term and

long-term complications (see Associated Conditions). SURGICAL CONSIDERATIONS

•  May need surgery to remove pseudocysts,

abscesses, or devitalized tissue seen with

(continued)

necrotizing pancreatitis. •  May need laparotomy and pancreatic biopsy to confirm pancreatitis and/or rule out other, nonpancreatic diseases such as cholangitis, lipidosis, and/or IBD. •  EHBO from pancreatitis may require ductal decompression with surgical correction.

­

 MEDICATIONS

DRUG(S) OF CHOICE •  Animals with intermittent vomiting should be treated with antiemetics. Maropitant 1 mg/kg SQ or PO q24h or ondansetron 0.1–0.5 mg/kg slow IV q8–12h are good first-choice options. •  Analgesics to relieve abdominal pain, e.g., butorphanol 0.1– 0.4 mg/kg SQ q6h, buprenorphine 0.005– 0.015 mg/kg IM or IV q6–12h or fentanyl CRI 2–4 μg/kg/h as needed. •  Antibiotics only if evidence of sepsis from bacterial translocation and to prevent pancreatic infection. CONTRAINDICATIONS Drugs reported to cause or exacerbate pancreatitis: •  Anticholinergics (e.g., atropine). •  Azathioprine. •  Chlorothiazide. •  Estrogens. •  Furosemide. •  Tetracycline. •  l-Asparaginase. PRECAUTIONS Only use antibiotics if a clear clinical condition exists, such as infection.

POSSIBLE COMPLICATIONS •  Failed response to supportive therapy. •  Associated conditions such as EPI, diabetes mellitus, and hepatic lipidosis. •  Progression of acute pancreatitis to chronic pancreatitis. EXPECTED COURSE AND PROGNOSIS

•  Guarded for most patients with ANP; cats

with multiorgan inflammation may be less responsive to treatment. •  More guarded to poor for patients with severe necrotizing pancreatitis, decreased ionized calcium fraction, hyperkalemia, fPL >20 μg/L, and systemic conditions.

­

 MISCELLANEOUS

ASSOCIATED CONDITIONS Life-Threatening

•  Pulmonary edema (e.g., adult respiratory distress syndrome). •  Cardiac arrhythmias. •  Peritonitis. •  DIC.

Non-Life-Threatening

•  Diabetes mellitus. •  EPI. •  Chronic pancreatitis. •  Cholangitis and hepatic lipidosis. •  IBD.

SEE ALSO

•  Acute Abdomen. •  Cholangitis/ Cholangiohepatitis Syndrome. •  Exocrine Pancreatic Insufficiency. •  Inflammatory

Bowel Disease.

ABBREVIATIONS

­

 FOLLOW-UP

PATIENT MONITORING •  Evaluate hydration status closely during first 24 hours of therapy; twice daily check physical examination, body weight, hematocrit, total plasma protein, BUN, and urine output. Evaluate the effectiveness of fluid therapy after 24 hours and adjust flow rates and fluid composition accordingly; repeat biochemistries to assess electrolyte/ acid–base status. •  Watch closely for systemic complications involving a variety of organ systems; perform appropriate diagnostic tests as needed (see Associated Conditions). •  Gradually taper fluids down to maintenance requirements if possible. Maintain oral alimentation or enteral nutrition as described above, being careful to feed diets that do not contain excessive amounts of dietary fat. •  Monitor for clinical evidence of IBD and treat accordingly. •  Monitor for progression to diabetes mellitus, exocrine pancreatic insufficiency (EPI), and/or hepatic lipidosis in cats with ANP. PREVENTION/AVOIDANCE

•  Weight reduction if obese. •  Avoid high-fat

diets.

•  ANP = acute necrotizing pancreatitis. •  DIC = disseminated intravascular coagulation. •  EHBO = extrahepatic biliary obstruction. •  EPI = exocrine pancreatic insufficiency. •  fPL = feline pancreatic lipase immunoreactivity. •  GI = gastrointestinal. •  IBD = inflammatory bowel disease.

INTERNET RESOURCES Veterinary Information Network: http:// www.vin.com/VIN.plx

­Suggested Reading

Simpson KS. Pancreatitis and triaditis in cats: causes and treatment. J Small Anim Pract 2015, 56(1):40–49. Stockhaus C, Teske E, Schellenberger K, et al. Serial serum feline pancreatic lipase immunoreactivity concentrations and prognostic variables in 33 cats with pancreatitis. J Am Vet Med Assoc 2013, 243:1713–1718. Xenoulis PG. Diagnosis of pancreatitis in dogs and cats. J Small Anim Pract 2015, 56(1):13–26. Author Albert E. Jergens Consulting Editor Mark P. Rondeau  Client Education Handout available online



Canine and Feline, Seventh Edition

1029

Pancreatitis—Dogs Mean Age and Range

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 BASICS

DEFINITION Inflammation of the pancreas, which may occur abruptly with little or no permanent pathologic change (acute pancreatitis) or occur continuously or intermittently with irreversible morphologic change such as fibrosis and atrophy (chronic pancreatitis). PATHOPHYSIOLOGY •  Premature intrapancreatic activation of zymogens results in local inflammation, edema, and necrosis of the pancreas and peripancreatic fat. •  Pancreatic enzymes and inflammatory cytokines result in local (abdominal pain, vomiting) and possibly systemic effects (pyrexia, systemic inflamma­ tory response syndrome [SIRS], multiple organ dysfunction syndrome [MODS], and acute kidney injury [AKI]). •  An autoimmune mechanism is suspected in English cocker spaniels, but remains unproven. SYSTEMS AFFECTED •  Gastrointestinal (GI)—altered GI motility (ileus) due to regional chemical peritonitis; local or generalized peritonitis due to enhanced vascular permeability. •  Cardiovascular—cardiac arrhythmias may result from release of myocardial depressant factor. •  Hemic/lymphatic/immune— circulating proinflammatory cytokines and altered endothelial cell function can result in complications such as SIRS and/or disseminated intravascular coagulation (DIC). •  Hepatobiliary—hepatocellular damage can occur secondary to regional inflammation. Inflammation of the pancreas can also result in extrahepatic bile duct obstruction. •  Renal/ urologic—AKI can occur as a consequence of MODS. •  Respiratory—regional vasculitis can cause pulmonary edema and/or pleural effusion. In severe cases, life-threatening acute respiratory distress syndrome can develop. GENETICS A possible genetic basis has been reported in miniature schnauzers where mutations in the SPINK1 gene may confer increased susceptibility. INCIDENCE/PREVALENCE

•  Unknown, but it is a relatively common clinical disorder. •  Up to 1% of normal dogs

Acute pancreatitis is most common in middle-aged and older (>7 years) dogs. Predominant Sex

Females overrepresented in some reports. SIGNS Historical Findings

•  Duration and severity of clinical signs can

be variable, depending on the form of disease (acute vs. chronic). •  Lethargy/anorexia. •  Vomiting. •  Weakness. •  Abdominal pain (may be absent in chronic disease). •  Diarrhea—small or large bowel type. Physical Examination Findings

•  Lethargy. •  Dehydration—common; due to GI losses. •  Abdominal pain—may adopt a “prayer position.” •  Mass lesions may be palpable. •  Fever—common with more severe acute pancreatitis. •  Less common—respiratory

distress, bleeding, and cardiac arrhythmias.

CAUSES Etiology is most often unknown; possibilities include: •  Nutritional factors (e.g., dietary indiscretion, hyperlipoproteinemia). •  Pancreatic trauma/ischemia. •  Duodenal reflux. •  Drugs/toxins. •  Pancreatic duct obstruction. •  Hypercalcemia. •  Infectious agents—babesiosis. RISK FACTORS •  Breed—miniature schnauzers, terriers. •  Obesity. •  Prior GI disease. •  Endocrine disease. •  Dietary indiscretion—access to garbage or fatty foods. •  Hypertriglyceridemia— while an association exists between hyper­ triglyceridemia and pancreatitis, a causative link remains unclear. •  Infectious—vectorborne diseases (babesiosis, ehrlichiosis, and leishmaniasis) have been identified in some cases of acute pancreatitis. •  Drugs/ toxins—idiosyncratic reactions to certain drugs (l-asparaginase, azathioprine, chlorpromazine, clomipramine, potassium bromide) have been described. Zinc toxicosis, mainly from ingestion of pennies minted after 1982, may cause pancreatitis. •  Hypercalcemia—not specifically documented in dogs, but shown in multiple species. •  Surgery—possible; secondary to hypoperfusion or traumatic manipulation of the pancreas.

may have histologic evidence of pancreatitis. GEOGRAPHIC DISTRIBUTION Worldwide SIGNALMENT

Species

Dog

Breed Predilections

•  Acute—miniature schnauzer, Yorkshire terrier, other terriers. •  Chronic—cocker

spaniel and cavalier King Charles spaniel.

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  GI (obstruction, septic peritonitis, ulcer, neoplasia)—differentiate via abdominal imaging. •  Hepatobiliary (cholangiohepatitis, copper hepatopathy, mucocele, neoplasia, toxicity)—abdominal imaging showing significant gallbladder pathology, liver histopathology, hepatic copper quantification.

•  Genitourinary (AKI, pyelonephritis, leptospirosis, uroabdomen, pyometra, prostatitis)—azotemia, hyperphosphatemia, hyperkalemia, isosthenuric urine, active urinary sediment; positive urine culture; leptospiral microscopic agglutination titers. Abdominal imaging showing uterine, prostatic or urinary bladder pathology. •  Other: ◦ Hypoadrenocorticism—concurrent hyponatremia and hyperkalemia, lack of a stress leukogram, post adrenocorticotropic hormone stimulation cortisol of 3.6 kg. ◦  Meloxicam—load 0.2 mg/kg PO, then 0.1 mg/kg PO q24h—liquid. ◦  Tepoxalin—load 20 mg/kg, then 10 mg/ kg PO q24h. •  Glucocorticoids: ◦  May give anti-inflammatory dosage— prednisone 0.5–1 mg/kg PO. ◦  Potential side effects well documented. ◦  Goal for chronic use—low-dose and alternate-day therapy. PRECAUTIONS NSAIDs—can cause gastrointestinal tract ulceration, hepatotoxicity, or nephrotoxicity. POSSIBLE INTERACTIONS NSAIDs—do not use in conjunction with glucocorticoids; risk of gastrointestinal tract ulceration; consider appropriate washout times when switching from one NSAID to another. ALTERNATIVE DRUG(S) N/A

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 FOLLOW-UP

PATIENT MONITORING Recheck lameness every 2–4 weeks to detect more serious concurrent orthopedic problems.

PREVENTION/AVOIDANCE N/A POSSIBLE COMPLICATIONS N/A EXPECTED COURSE AND PROGNOSIS

•  Self-limiting disease. •  Treatment is symptomatic and appears to

have no influence on duration of clinical signs. •  Multiple limb involvement is common. •  Lameness typically lasts from a few days to several weeks; may persist for months; may recur. •  Occasional case has unrelenting pain and lameness that is unresponsive to therapy. Euthanasia has been recommended in these dogs.

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 MISCELLANEOUS

ASSOCIATED CONDITIONS N/A AGE-RELATED FACTORS Typically affects immature and young dogs ZOONOTIC POTENTIAL N/A PREGNANCY/FERTILITY/BREEDING Females reported to be more susceptible to panosteitis during estrus; no proven relationship to reproductive hormones or pregnancy. SYNONYMS •  Enostosis. •  Eosinophilic panosteitis. •  Fibrous osteodystrophy. •  Juvenile osteomyelitis.

ABBREVIATIONS •  NSAID = nonsteroidal anti-inflammatory drug.

­Suggested Reading

Halliwell WH. Tumorlike lesions of bone. In: Bojrab MJ, ed., Disease Mechanisms in Small Animal Surgery, 2nd ed. Philadelphia, PA: Saunders, 1993, pp. 932–933. LaFond E, Bruer GJ, Austin CC. Breed susceptibility for developmental diseases in dogs. J Am Anim Hosp Assoc 2002, 38:467–477. Muir P, Dubielzig RR, Johnson KA. Panosteitis. Compend Contin Educ Pract Vet 1996, 18:29–33. Piermattei DL, Flo GL, DeCamp CE. Miscellaneous conditions of the musculoskeletal system. In: Handbook of Small Animal Orthopedics and Fracture Repair, 4th ed. Philadelphia, PA: Saunders, 2006, pp. 775–778. Schwarz T, Johnson VS, Voute L, Sullivan M. Bone scintigraphy in the investigation of occult lameness in the dog. J Small Anim Pract 2004, 45:232–237. Trostel CT, Pool RR, McLaughlin RM. Canine lameness caused by developmental orthopedic diseases: Panosteitis, Legg-CalvéPerthes disease, and hypertophic osteodystrophy. Compend Contin Educ Pract Vet 2003, 25(4):282–292. Author Laura A. Barbur Consulting Editor Mathieu M. Glassman Acknowledgment The author and editors acknowledge the prior contribution of Larry Carpenter.  Client Education Handout available online

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Blackwell’s Five-Minute Veterinary Consult

Panting and Tachypnea •  Pleural space disease—diminished breath

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 BASICS

DEFINITION •  Tachypnea—increased respiratory rate. •  Panting—rapid, shallow, open-mouth breathing that is usually not associated with gas exchange issues. PATHOPHYSIOLOGY

•  Respiratory rate, rhythm, and effort are

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controlled by the respiratory center in the brainstem in response to numerous afferent pathways, both central and peripheral in origin. These include the cerebral cortex, central chemoreceptors, peripheral chemo­ receptors, stimulation of mechano­receptors in the airways that sense lung inflation and deflation, stimulation of irritant receptors of the airways, stimulation of C-fibers in the alveoli and pulmonary blood vessels that sense interstitial congestion, and baroreceptors that sense changes in blood pressure. •  Tachypnea and panting can occur in response to stimulation of any of the above receptor pathways. SYSTEMS AFFECTED Respiratory SIGNALMENT

•  Dog and cat; no age, or sex predilection. •  Older, large-breed dogs predisposed to

panting associated with laryngeal paralysis.

•  Brachycephalic dogs prone to panting due

to upper airway obstruction. SIGNS

Historical Findings

•  Patients with primary respiratory or cardiac

disease usually have associated coughing or exercise intolerance. •  Nonrespiratory causes—clinical complaints associated with the primary disease, e.g., polyuria, polydipsia, polyphagia (PU/PD/PP) with hyperadrenocorticism, intermittent signs of systemic hypertension with pheochromocytoma. Physical Examination Findings

•  Brachycephalic syndrome (stenotic nares,

stertorous respirations associated with soft palate elongation or saccular eversion) may be observed. •  Stridor can be evident with upper airway diseases. •  Lower airway disease—cough, expiratory wheezes on auscultation, abdominal effort. •  Pulmonary parenchymal disease—may have crackles on auscultation; harsh or moist lung sounds common, may be normal. •  Cardiogenic pulmonary edema—heart murmur or arrhythmia, tachycardia, gallop sound, hypothermia, pale mucous membranes, poor capillary refill time.

sounds: ventrally—fluid; dorsally—air; unilaterally—space-occupying lesions, pyothorax, chylothorax. •  Thoracic wall disease—can have paradoxical respiratory pattern, visible and/or palpable trauma. •  Nonrespiratory diseases—findings will depend on the other diseases, e.g., pale mucous membranes if anemic, hepatomegaly with hyperadrenocorticism. •  Other signs could indicate trauma. CAUSES Panting

•  Pain, anxiety, hyperthermia, fever. •  Brachycephalic airway syndrome. •  Laryngeal disease. •  CNS disease causing abnormal ventilatory

control.

•  Cardiovascular compromise (shock),

hypertension, arrhythmia.

•  Drug therapy (opioids) •  Metabolic acidosis. •  Hyperadrenocorticism, corticosteroid therapy. •  Pheochromocytoma. •  Hyperthyroidism. •  Hypocalcemia. •  Can be a normal behavioral pattern in some

dogs.

Tachypnea

•  Hypoxemia, hypercapnia, hypotension,

hyperthermia/fever, anemia, acidosis, systemic inflammatory response syndrome (SIRS)/ sepsis, brainstem disease. •  Upper airway/larynx—elongated soft palate, laryngeal paralysis, edema, collapse, foreign body, neoplasia, granuloma, stenosis, inflammation, trauma, webbing. •  Trachea—collapse, stenosis, trauma, foreign body, neoplasia, parasites, extraluminal compression (lymphadenopathy, enlarged left atrium, heart-base tumors). •  Lower airway disease—allergic disease, inflammation, infection (Mycoplasma), parasites, neoplasia. •  Pulmonary parenchymal disease—edema (cardiogenic or noncardiogenic), pneumonia or pneumonitis, neoplasia (primary or metastatic), hemorrhage, fibrosis, lung lobe torsion, atelectasis. •  Pulmonary thromboembolism associated with—immune-mediated hemolytic anemia (IMHA), hyperadrenocorticism, pulmonary thromboembolism (PLE), protein-losing nephropathy (PLN), cardiac disease, neoplasia, heartworm disease. •  Pleural space disease—pleural effusion or pneumothorax, neoplasia, diaphragmatic hernia. •  Abdominal distention—organomegaly; neoplasia, pregnancy; obesity; ascites; gastric dilatation, torsion. •  CNS disease—compression or infarct near the respiratory center.

•  Metabolic acidosis—diabetic ketoacidosis,

lactic acidosis, uremia, renal tubular acidosis, diarrhea.

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Tachypnea without respiratory distress— may be a nonrespiratory problem. •  Stertor and stridor are features of upper airway disease—auscultation over the trachea can help delineate upper airway noises from lower airway noises. •  Thoracic auscultation and percussion— most useful for distinguishing pleural disease (dampened lung sounds, dull percussion) from parenchymal disease (normal, harsh or moist lung sounds, crackles on auscultation). •  Wheezes on auscultation are suggestive of narrowed lower airway (bronchi, bronchioles). •  Crackles on auscultation are features of pulmonary parenchymal diseases. •  Congestive heart failure—murmur, tachycardia, poor pulse quality, jugular pulses, hypothermia. CBC/BIOCHEMISTRY/URINALYSIS

•  Anemia—can cause nonrespiratory tachypnea. •  Polycythemia—chronic hypoxia. •  Inflammatory leukogram—pneumonia,

pneumonitis, pyothorax, or nonrespiratory causes (SIRS, sepsis). •  Eosinophilia—hypersensitivity or parasitic airway disease. •  Thrombocytosis—hyperadrenocorticism predisposes to pulmonary thromboembolism (PTE); alternatively, could indicate irondeficiency anemia. •  Sodium:potassium ratio 40 mL/kg/day). •  Polydipsia (PD)—increased water consumption (dogs, >90 mL/kg/day; cats, >45 mL/kg/day). PATHOPHYSIOLOGY

•  The volumes of urine produced and water

idiopathic, traumatic, neoplastic, or congenital CDI; some drugs (e.g., alcohol and phenytoin). •  Primary PD—behavioral, pyrexia, pain, organic disease of the anterior hypothalamic thirst center of neoplastic, traumatic, or inflammatory origin. RISK FACTORS

•  Kidney, liver and/or endocrine disease. •  Administration of diuretics, corticosteroids,

anticonvulsants.

consumed are controlled by interactions between the kidneys, pituitary gland, and hypothalamus through monitoring of plasma osmolality. Volume receptors within the atria and aortic arch also influence thirst and urine production. PU may occur when the quantity of functional antidiuretic hormone (ADH) synthesized in the hypothalamus or released from the posterior pituitary is limited, or when the kidneys fail to respond normally to ADH. PD occurs when the thirst center in the anterior hypothalamus is stimulated. •  In most PU patients, plasma becomes relatively hypertonic and activates thirst mechanisms; the PD maintains hydration as a compensatory response. Occasionally PD is the primary process and PU is compensatory. In this case, the patient’s plasma becomes relatively hypotonic because of excessive water intake, ADH secretion is reduced, resulting in PU.

•  Low-protein diets.

SYSTEMS AFFECTED •  Urologic—full bladder. •  Cardiovascular—circulating volume. •  Endocrine/metabolic—pituitary gland, hypothalamus play a role in compensation to PU or PD.

Differentiating Causes

SIGNALMENT

•  Dog and cat. •  Congenital diseases in many breeds (e.g.,

central diabetes insipidus [CDI], nephrogenic diabetes insipidus [NDI], portovascular anomaly, kidney disease). •  Kidney disease, hyperadrenocorticism (HAC), hyperthyroidism, neoplasia affecting the pituitary or hypothalamus predominantly affect middle-aged and older animals. CAUSES

•  Primary PU due to impaired kidney

response to ADH—kidney disease, HAC, hyperthyroidism, pyelonephritis, leptospirosis, pyometra, hepatic failure, hypercalcemia, hypokalemia, kidney medullary solute washout, dietary protein restriction, drugs, congenital NDI. •  Primary PU caused by osmotic diuresis— diabetes mellitus (DM), primary kidney glucosuria, postobstructive diuresis, some diuretics (e.g., mannitol and furosemide), ingestion or administration of large quantities of solute (e.g., sodium chloride or glucose), and hypersomatotropism.

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS Differentiating Similar Signs

•  Differentiate PU from pollakiuria.

Pollakiuria: often associated with dysuria, stranguria, hematuria. Patients with PU void large quantities of urine; patients with pollakiuria frequently void small quantities of urine. Confirm PU/PD by measuring 24-hour water intake and urine output (3- to 5-day collection period preferred). •  Urine specific gravity (USG) measurement may provide evidence of hypersthenuria (dogs, >1.030; cats, >1.035), ruling out persistent PU/PD. •  Kidney disease, HAC, DM,

hyperthyroidism.

•  Progressive weight loss—consider chronic

kidney disease, DM, hyperthyroidism, hepatic failure, pyometra, pyelonephritis, hypoadrenocorticism, malignancy-induced hypercalcemia. •  Decreased appetite—consider kidney disease, pyelonephritis, malignancy-induced hypercalcemia, hepatic disease, hypoadrenocorticism. •  Polyphagia—consider DM, hyperthyroidism, HAC, acromegaly. •  Bilateral alopecia or other cutaneous problems—consider HAC, endocrinologic disorders •  Uremic breath and stomatitis—consider advanced kidney disease. •  Vomiting—consider kidney disease, hypoadrenocorticism, pyelonephritis, hepatic failure, hypercalcemia, hypokalemia, hyper­ thyroidism, DM. •  Malaise and/or weakness—kidney disease, hypoadrenocorticism, pyometra, hyper­ calcemia, DM, hepatic disease, hypokalemia, HAC. •  Palpable thyroid nodule—consider hyperthyroidism. •  Hypertensive retinopathy—consider chronic kidney disease (CKD), hyperthyroidism, DM, HAC.

•  Recent estrus (previous 2 months) in a

middle-aged intact female—consider pyometra. •  Abdominal distention—consider hepatic failure, HAC, pyometra, nephrotic syndrome. •  Lymphadenopathy, anal sac mass or other neoplastic process—consider hypercalcemia of malignancy. •  Behavioral or neurologic disorder— consider hepatic failure, primary PD, CDI. •  Marked PD (patients almost continuously seek and consume water)—consider primary PD, CDI, NDI. •  Consider drug-induced (steroids, diuretics, anticonvulsants) PU/PD. •  Consequence of urolith prevention/ dissolution or high salt diet. Key point: PU/PD may be the first symptom of many diseases. CBC/BIOCHEMISTRY/URINALYSIS

•  Urinalysis is useful to confirm PU,

discriminate water diuresis from solute diuresis, and identify urinary tract infection (UTI). •  Serum sodium concentration or osmolality may help differentiate primary PU from PD. Measuring serum osmolality is preferred; calculated serum osmolality is not an acceptable alternative. •  Relative hypernatremia or high serum osmolarity suggests primary PU. •  Hyponatremia or low serum osmolarity suggests primary PD, except in animals with hypoadrenocorticism, which have hypo­ natremia and primary PU. •  Azotemia is typical of kidney causes for PU/PD, but may also indicate dehydration resulting from inadequate compensatory PD. •  Unexpectedly low BUN concentrations suggest hepatic failure. •  With high hepatic enzymes, consider HAC, hyperthyroidism, hepatic failure, pyometra, DM, or administration of drugs (e.g., anti­ convulsants and corticosteroids). •  Persistent hyperglycemia suggests DM. •  Hyperkalemia, particularly if associated with hyponatremia, suggests hypoadreno­ corticism or therapy with potassium-sparing diuretics. •  Hypercalcemia induces PU only when it results from increased ionized calcium (not protein-bound calcium) concentration. •  Hypoalbuminemia supports kidney or hepatic causes of PU/PD. •  Neutrophilia is consistent with pyelonephritis, pyometra, HAC, corticosteroid administration. •  USG values 1.001–1.003 suggest primary PD, CDI, and congenital NDI. •  Glucosuria supports a diagnosis of DM or kidney glucosuria. •  Pyuria, white blood cell casts, and/or bacteriuria should prompt consideration of pyelonephritis.

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1114

Blackwell’s Five-Minute Veterinary Consult

Polyuria and Polydipsia OTHER LABORATORY TESTS •  ACTH stimulation or dexamethasone suppression tests rule out HAC. •  Thyroxine concentration to rule out hyperthyroidism. •  Bile acids (fasting and postprandial) to rule out portosystemic shunt or hepatic failure. •  Urine culture—chronic pyelonephritis cannot be conclusively excluded by absence of pyuria or bacteriuria. •  Cytology from lymph node aspirate may diagnose lymphoma, which induces PU by hypercalcemic nephrotoxicity or direct infiltration of kidney tissues. •  Paired Leptospira titer to rule out leptospirosis. •  ADH response test to rule out CDI. •  Water deprivation testing (see Diagnostic Procedures) is controversial due to dehydration risk; use selectively.

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IMAGING Abdominal survey radiography, ultrasono­ graphy: may provide evidence of kidney, hepatic, adrenal, or uterine disorders that can cause PU/PD. DIAGNOSTIC PROCEDURES Modified Water Deprivation with ADH Response Test •  Differentiates CDI from primary PD and

NDI. Rule out other causes for PU/PD before performing this test. Controversial, some suggest omitting water deprivation and proceeding directly to ADH administration to rule in CDI, however administration of ADH to patients with primary PD may be dangerous. •  Contraindicated in dehydrated and azotemic patients; ADH response testing may be performed safely in these patients. •  Patients that concentrate urine adequately in response to water deprivation have adequate ADH production and kidney response to ADH. If other causes have been ruled out, primary PD is presumed to be present. •  Failure to concentrate urine adequately in response to properly designed water deprivation tests, but forming concentrated urine in response to administration of exogenous ADH = CDI. •  Failure to concentrate urine adequately in response to water deprivation and also failure to further concentrate urine in response to administration of exogenous ADH = NDI.

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 TREATMENT

•  Serious medical consequences are rare if

patient has free access to water and is able to

drink. Until the mechanism of PU is understood, discourage owners from limiting access to water. Direct treatment at the underlying cause. •  Provide PU patients with free access to water unless they are vomiting. If vomiting, give replacement maintenance fluids parenterally after appropriate samples have been collected for initial diagnostics. Provide fluids parenterally when other conditions limit oral intake or dehydration persists despite PD. •  Base fluid selection on the underlying cause for fluid loss; lactated Ringer’s solution is acceptable for most patients. •  When dehydration has resulted from withholding water, or when urine is hyposthenuric, providing oral water or parenteral administration of dextrose 5% in water may be preferred to lactated Ringer’s solution. •  Primary PD—treat by gradually limiting water intake to a normal daily volume. May be necessary to reduce water intake over days–weeks to avoid undesirable behavior such as barking, urine consumption, or other bizarre behavior. Monitor patient closely to avoid iatrogenic dehydration. Salt (1 g/30 kg q12h) or sodium bicarbonate (0.6 g/30 kg q12h) may be given orally to help reestablish kidney medullary solute gradient. Consider behavior modification if water restriction alone is unsuccessful. CLIENT EDUCATION Do not withhold water from patients with PU because potentially dangerous dehydration may result.

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 MEDICATIONS

DRUG(S) OF CHOICE Varies with underlying cause. CONTRAINDICATIONS Do not administer ADH to patients with primary PD due to risk of inducing water intoxication (hyponatremia, hypo­ osmolality, and neurologic complications). PRECAUTIONS Until kidney disease and hepatic failure have been excluded as potential causes for PU/PD, use caution in administering any drug eliminated via these pathways.

(continued)

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 FOLLOW-UP

PATIENT MONITORING •  Hydration status—assessment of hydration, serial evaluation of body weight. •  Fluid intake and urine output provide a useful baseline for assessing response to therapy. POSSIBLE COMPLICATIONS Dehydration, hypovolemic shock, hypernatremia.

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 MISCELLANEOUS

ASSOCIATED CONDITIONS •  Bacterial UTI. •  Urinary incontinence may develop in dogs with concurrent urethral sphincter dysfunction, presumably because of increased bladder filling associated with PD. SEE ALSO

•  Acute Kidney Injury. •  Chronic Kidney Disease. •  Congenital and Developmental Renal

Diseases.

•  Diabetes Insipidus. •  Diabetes Mellitus. •  Fanconi Syndrome. •  Hepatic Failure, Acute. •  Hyperadrenocorticism. •  Hypercalcemia. •  Hyperthyroidism. •  Hypoadrenocorticism (Addison’s Disease). •  Hypokalemia. •  Leptospirosis. •  Pyelonephritis. •  Pyometra. •  Urinary Tract Obstruction.

ABBREVIATIONS

•  ACTH = adrenocorticotropic hormone. •  ADH = antidiuretic hormone. •  CDI = central diabetes insipidus. •  CKD = chronic kidney disease. •  DM = diabetes mellitus. •  HAC = hyperadrenocorticism. •  NDI = nephrogenic diabetes insipidus. •  PU/PD = polyuria/polydipsia. •  USG = urine specific gravity. •  UTI = urinary tract infection.

Author David J. Polzin Consulting Editor J.D. Foster

 Client Education Handout available online



Canine and Feline, Seventh Edition

1115

Portosystemic Shunting, Acquired

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 BASICS

OVERVIEW •  Acquired portosystemic shunts (APSS)— develop subsequent to portal hypertension (PH) and involve complex physiology aberrations and adaptations; experimentally form 5–14 weeks after onset of PH. •  Prehepatic PH—compromised perfusion through abdominal portion of the portal vein. •  Intrahepatic PH—classified as presinusoidal, sinusoidal, postsinusoidal causes. •  Posthepatic PH—rostral to hepatic vein; cardiac, pericardial, or major vein causes. •  APSS evolve from preexisting remnant vessels and the process of angiogenesis. •  APSS common in dogs and cats but differ in location from the clinically symptomatic esophageal APSS common in humans; common APSS in dogs and cats involve communications between left gonadal remnants vessels, the left renal vein, and splenic veins with the caudal vena cava. SIGNALMENT

•  Most common—in dogs with chronic

necroinflammatory liver disease.

•  Less common—in dogs with ductal plate

malformations (DPM, congenital hepatic fibrosis [CHF] phenotype), rare noncirrhotic portal hypertension (NCPH), recovery from severe panlobular necrosis, dogs with porto­ systemic vascular anomaly (PSVA) intolerant to surgical shunt attenuation, or dogs simply with severe portal vein hypoplasia/atresia. •  APSS in cats—DPM with CHF phenotype, severe CCHS (rare), or PSVA intolerant to surgical shunt attenuation (severe portal hypoplasia) or rarely just severe portal vein atresia. •  Extrahepatic bile duct obstruction (EHBDO) >6 weeks. •  Certain disorders—have age or breed incidence (see Ductal Plate Malformation (Congenital Hepatic Fibrosis); Cirrhosis and Fibrosis of the Liver; Hepatitis, Chronic). •  Breeds—DPM more common in domestic longhair, Persian and Himalayan cats, boxer dogs but may affect any pure- or mixed-breed dog. SIGNS •  Clinical signs—sequelae of PH, impaired hepatic perfusion, and hepatofugal circulation (hepatofugal = splanchnic portal circulation away from the liver) with or without or reduced hepatic function depending on cause. •  Ascites—common but variable; often fluctuates in severity. •  APSS may associate with episodic hepatic encephalopathy (HE)— may manifest as neurobehavioral or neurocognitive abnormali­ ties, amaurotic blindness, polyuria/polydipsia (PU/PD), anorexia, lethargy, vomiting; neurologic signs may localize to cerebrum, brainstem, or suggest transverse myelopathy.

•  PH leads to hypertensive splanchnic vasculopathy—may provoke gastroduodenal bleeding/ulceration because of thin-walled dilated arterials; may progress to perforation and septic peritonitis, life-endangering blood loss if coexistent coagulopathy; can provoke severe HE; causes anorexia, vomiting, diarrhea, abdominal pain, anemia, and sometimes iron deficiency (if chronic blood loss). •  Urogenital—obstructive uropathy due to ammonium biurate urolithiasis, gross or microscopic hematuria, pollakiuria, dysuria, rare severe hematuria (ureteral APSS varices).

CAUSES & RISK FACTORS

•  Multiple tortuous vessels—represent

acquired vasculature interconnecting portal and systemic venous circulations. •  Lack of valves in main portal vein structure allows blood to follow “a path of least resistance” through APSS to vena cava (systemic circulation). Valves in portal tributaries influence hepatofugal circula­ tory routes. •  PH—results from many disease processes. •  Common causes of PH—diffuse hepatic fibrosis with or without cirrhosis; chronic unresolved EHBDO (>6 weeks); portal venous thromboembolism (TE), hepatic sinusoidal occlusion syndrome (zone 3, injury causing regional parenchymal collapse or vascular damage to hepatic venules, veins). •  Less common causes of PH involve idiopathic PH or NCPH (obliteration of tertiary portal venules), blockade of large hepatic veins or prehepatic vena cava (Budd– Chiari syndrome) by thrombi, neoplasia or vascular “kinking”; disorders constraining splanchnic portal circulation: vascular stricture or strangulation, severe portal vein atresia rare congenital or acquired hepatic AV malformation(s) causing arterialization of the portal circulation, or severe intrahepatic portal vein atresia. •  Episodic HE. •  Ammonium urate urolithiasis.

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  CNS signs—infectious disorders (e.g., FIP, FeLV- or FIV-related infections or conditions, canine distemper, toxoplasmosis, other); toxicities (e.g., lead, mushrooms, drugs, acute hepatic failure); hydrocephalus; idiopathic epilepsy; metabolic disorders (e.g., severe hypoglycemia, hypo- or hyperkalemia, hypocalcemia, severe hypophosphatemia). •  Gastrointestinal signs—bowel obstruction; dietary indiscretion; foreign body ingestion; inflammatory bowel disease. •  Urinary tract signs—bacterial urinary tract infection; urolithiasis; obstructive uropathy.

•  PU/PD—disorders of urine concentration

(diabetes insipidus, diabetes mellitus, adrenal hyperplasia, hypercalcemia), primary PD, congenital or acquired renal disease. •  Causes of abdominal effusion— cardiopulmonary disorders causing rightsided heart failure; pericardial disease; primary inflammatory hepatopathies; infiltrative hepatic disease (e.g., neoplasia, amyloid); liver lobe torsion; nonhepatic abdominal disorders associated with effusions (e.g., splenic torsion, visceral neoplasia, carcinomatosis, pancreatitis); or peritonitis: chemical (e.g., bile, urine, chyle) or septic. CBC/BIOCHEMISTRY/URINALYSIS

•  CBC—microcytosis (reflects portosystemic

shunting or iron deficiency); mild nonregenerative anemia common; poikilocytes (cats) and target cells (dogs). •  Biochemistry—low BUN, low to lownormal creatinine, glucose, albumin, and cholesterol are common; variable liver enzyme activity (ALP usually high in young animals), ALP induction by inflammatory cytokines or cholestasis, ALT normal or elevated; bilirubin variable; features depend on underlying cause and chronicity. •  Urinalysis—variable urine concentration; ammonium biurate crystalluria, hematuria, pyuria, and proteinuria reflect urolithiasis or infection. OTHER LABORATORY TESTS

•  Total serum bile acids (TSBA)—sensitive

indicator of PSS; variable pre- with markedly increased post-meal values (>100 μmol/L); “shunting pattern” implicated by relatively low pre- and markedly increased post-meal values; however, 10–20% dogs and cats have higher pre- than post-meal TSBA reflecting slow gastric or enteric transit or delayed gallbladder contraction. •  Blood ammonia—fasting, sensitive but inconsistent indicator of HE and shunting; ammonium biurate crystalluria infers high blood ammonia (evaluate 3 urine specimens, 4–8 hours after eating); ammonia tolerance testing—(oral or rectal NHCl4) best test for ammonia intolerance; caution: may induce HE. •  Coagulation tests—prolonged PT, aPTT, reflect severity of liver dysfunction, synthetic failure, DIC, or vitamin K1 adequacy; low protein C activity reflects PSVA or APSS, enteric or renal losses or consumption. •  Abdominal effusion—usually pure or modified transudate. IMAGING Abdominal Radiography

•  Liver size depends on underlying cause;

microhepatia common in dogs with chronic liver disease with APSS, PSVA, or severe portal vein atresia. Some disorders associate with large liver size or large liver lobes: AV malformations, some DPM (cystic lesions).

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Portosystemic Shunting, Acquired •  Abdominal effusion—impairs visualization

of visceral margins; ascites associated with severe portal atresia, some PSVA after surgical attenuation, some animals with DPM (CHF phenotype) with APSS, chronic liver disease with APSS, and other causes of PH. •  Ammonium biurate calculi—radiolucent unless radiodense mineral shell (infection). •  Size of post-hepatic vena cava may reflect pericardial or cardiac causes (distended vein). Radiographic Portovenography

Demonstrates multiple APSS; not recommended due to complicating risks, see alternatives. Abdominal Ultrasonography

Tru-Cut samples may not provide adequate tissue for definitive diagnosis. PATHOLOGIC FINDINGS

•  Gross—small, irregularly contoured liver

with chronic liver disease (cirrhosis, fibrosis).

•  Normal to large liver in early venous outflow

obstruction: Budd–Chiari, sinusoidal occlusion syndrome. •  Isolated large liver lobe—intrahepatic AV malformation. •  Normal to small liver—DPM (CHF phenotype), NCPH, portal TE, portal atresia, PSVA. •  Normal to large liver in some cats with DPM.

•  Liver size depends on underlying cause.

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May disclose change in size or absence of specific liver lobes or gallbladder in DPM or AV malformations. •  May disclose disease-related hepatic parenchymal or biliary changes. •  APSS—characterized by hepatofugal portal flow (unreliable US detection) and APSS using color-flow Doppler; tortuous APSS varices have turbulent blood flow; APSS often situated adjacent to left kidney or associated with splenic vasculature. •  Intrahepatic AV communication/fistula— pulsating arterialized vascular within enlarged liver lobe, abdominal effusion and APSS. •  Other causes of PH and APSS are detected using US color-flow Doppler: portal venous thrombi or stricture, hypoplastic portal vein at porta hepatis, diminished hepatic venule/ vein filling (venoocclusive syndrome), or Budd–Chiari hepatic vein outflow obstruction. •  Abdominal effusion—common. •  Uroliths—renal pelvis, urinary bladder; rare ureteral.

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 TREATMENT

Appropriate Health Care

Inpatient—severe signs of HE or tense abdominal effusion requiring therapeutic abdominocentesis and critical care. Diet

•  Nutritional support—essential to maintain

DIAGNOSTIC PROCEDURES

body condition to optimize control of hyperammonemia-associated HE; speciesspecific balanced, restricted-protein diet (avoid red meat, organ meat, fish in dogs); protein allowance optimized to tolerance (see Hepatic Encephalopathy). Cats have different protein requirements compared to dogs. •  Protein allowance titrated to response with adjunctive treatment modulating production and absorption of enteric toxins contributing to HE (colonic products mainly); use commercial diets formulated for liver disease or moderate renal insufficiency as a baseline diet. •  Dogs—commercial liver diets provide 2.2–2.5 g protein/kg body weight when fed to meet energy requirements; titrate protein using 0.25 g/kg additional allocations q5–7 days until optimized tolerance determined: dairy and soy protein are best sources for dogs; if necessary white meat chicken can be introduced in small amounts to stimulate appetite. •  Cats—pure carnivores require meat-derived protein; use diets for renal insufficiency. •  Parenteral nutrition rarely used—see Hepatic Encephalopathy. •  Sodium restriction important in dogs with ascites; 50–100 mg sodium/100 kcal or 5 years if managed successfully during symptomatic illnesses.

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 MISCELLANEOUS

ASSOCIATED CONDITIONS •  Ammonium urate urolithiasis. •  Ascites. •  Coagulopathy. •  Hepatic encephalopathy. •  Enteric bleeding/ulceration. •  Obstructive uropathy. SEE ALSO

•  Ascites. •  Cirrhosis and Fibrosis of the Liver. •  Coagulopathy of Liver Disease. •  Ductal Plate Malformation (Congenital

Hepatic Fibrosis).

•  Hepatic Encephalopathy. •  Hepatitis, Chronic. •  Portal Hypertension. •  Portosystemic Vascular Anomaly,

Congenital.

ABBREVIATIONS

•  APSS = acquired portosystemic shunt. •  AV = arteriovenous. •  CCHS = cholangitis/cholangiohepatitis

syndrome.

•  CHF = congenital hepatic fibrosis. •  CRS = colorectal scintigraphy. •  DPM = ductal plate malformation. •  EHBDO = extrahepatic bile duct

obstruction.

•  HE = hepatic encephalopathy. •  NCPH = noncirrhotic portal hypertension. •  NSAID = nonsteroidal anti-inflammatory

drug.

•  PH = portal hypertension. •  PSVA = portosystemic vascular anomaly. •  PU/PD = polyuria/polydipsia. •  SPS = splenoportal scintigraphy. •  TE = thromboembolism. •  TSBA = total serum bile acids.

­Suggested Reading

Buob S, Johnston AN, Webster CR. Portal hypertension: pathophysiology, diagnosis, and treatment. J Vet Intern Med 2011, 25:169–186. Iwakiri Y. Pathophysiology of portal hypertension. Clin Liver Dis. 2014, 18(2):281–291. Simonetto DA, Liu M, Kamath PS. Portal hypertension and related complications: diagnosis and management. Mayo Clinic Proc 2019, 94:714–726. Author Sharon A. Center Consulting Editor Kate Holan

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Portosystemic Vascular Anomaly, Congenital INCIDENCE/PREVALENCE 0.2–0.6% of large referral clinic.

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 BASICS

DEFINITION •  Aberrant venous connections between the portal and systemic circulations; macroscopic shunts permit portal hepatofugal circulation (flow away from or around the liver). •  May be extrahepatic portosystemic vascular anomaly (E-PSVA) or intrahepatic (I-PSVA). •  Most are single vessels; occasionally two shunts may be identified. •  Most small-breed dogs with PSVA also have microscopic vascular abnormalities (see Hepatoportal Microvascular Dysplasia).

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PATHOPHYSIOLOGY •  Clinical signs—reflect hepatofugal circulation that prohibits hepatic cleansing of enteric toxins, food-derived nitrogenous toxins, and other noxious colonic substances from portal blood. •  Microhepatia—deprivation of splanchnic hepatotrophic factors (e.g., insulin) causes hepatic atrophy. •  Episodic hepatic encephalopathy (HE)— associated with consumption of high-protein foods, gastrointestinal bleeding, other causes of increased heme turnover (blood transfusions, hemolysis), dehydration, azotemia, alkalosis, hypokalemia, infections, constipation, catabolism, and certain drugs. •  Ammonium biurate crystalluria/urolithiasis— reflect hyperammonemia and impaired conversion of uric acid to water-soluble allantoin; may be a presenting problem. •  Severity of clinical signs reflect the magnitude of macroscopic shunting. SYSTEMS AFFECTED

•  Nervous—episodic HE in most but not all. •  Gastrointestinal—intermittent inappetence;

vomiting; diarrhea; pica; ptyalism (cats).

•  Urogenital— “plump” kidneys; ammonium

urate urolithiasis; 50% male dogs cryptorchid in one retrospective report. •  Asymptomatic—up to 20% of dogs with PSVA. GENETICS

•  E-PSVA—most common in small-breed

dogs (e.g., Yorkshire terrier, Cairn terrier, Maltese, Tibetan spaniel, miniature schnauzer, Norfolk terrier, pug, shih tzu, Havanese, papillon. •  I-PSVA—most common in large-breed dogs (e.g., Irish wolfhound, Labrador retriever, Old English sheepdog, golden retrievers). •  Autosomal dominant complex polygenic inheritance suspected to cause PSVA/micro­ vascular dysplasia (MVD) trait in small-breed dogs; MVD most common phenotype. •  I-PSVA—appears heritable in Irish wolfhounds patent ductus venosus type I-PSVA and kindred of Labrador retrievers, Old English sheepdogs, golden retrievers.

GEOGRAPHIC DISTRIBUTION Reported worldwide.

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 DIAGNOSIS

•  Stunted growth—common. •  Signs often initiate with weaning of puppy

DIFFERENTIAL DIAGNOSES •  CNS signs—infectious disorders (FIP-, FeLV- or FIV-related infections in cats, canine distemper, toxoplasmosis); toxicities (lead, mushrooms, recreational drugs); congenital CNS malformations (hydrocephalus); congenital storage disorders; idiopathic epilepsy; metabolic disorders (severe hypoglycemia, hypokalemia, hyperkalemia, hypocalcemia); necrotizing meningoencephalitis or granulomatous meningoencephalitis—idiopathic inflammatory CNS syndromes in small-breed dogs (e.g., pug, Maltese, Yorkshire terriers). •  Gastrointestinal signs—bowel obstruction; dietary indiscretion; foreign body ingestion; inflammatory bowel disease. •  Urinary tract signs—bacterial urinary tract infection or other forms of urolithiasis. •  PU/PD—disorders of urine concentration (diabetes insipidus, diabetes mellitus, abnormal adrenal function, hypercalcemia), primary polydipsia. •  Primary liver disease. •  MVD—in asymptomatic PSVA animals.

•  Gastrointestinal signs—inappetence,

•  CBC—microcytosis; mild non-regenerative

SIGNALMENT Species

Dog and cat; most common in small-breed dogs. Breed Predilections

Higher risk—purebred and mixed small “terrier” type dogs; cats—domestic shorthair, fewer pure breeds. Mean Age and Range

•  Usually identified in juveniles; some

asymptomatic dogs as old as 13 years at initial diagnosis. •  Asymptomatic animals present older; miniature schnauzers and dogs with porto­ azygous shunts. Predominant Sex

N/A

SIGNS Historical Findings

or kitten to commercial growth foods. vomiting, diarrhea, pica.

•  Cats—ptyalism. •  Episodic HE—most dramatic and

predominating sign in many dogs, improves with fluids, broad-spectrum antibiotics, and lactulose. •  CNS signs—weakness, propulsive circling or pacing, vocalization, apparent hallucinations, ataxia, disorientation, head pressing, signs consistent with transverse myelopathy, vague hyperpathia, amaurotic blindness, behavioral changes (aggression in cats), twitching or trembling, focal or generalized seizures, or progressive obtundation to coma. •  Urinary signs—polyuria/polydipsia (PU/PD); ammonium biurate crystalluria: pollakiuria, dysuria; hematuria; urethral/ ureteral ammonium biurate urolith obstruction. •  Asymptomatic—up to 20% of dogs. •  Affected bitches may produce viable litters. Physical Examination Findings

•  Normal appearance, but most have stunted

stature; microhepatia; HE; copper-colored irises in non-blue-eyed cats (note: Persian, Russian blue, some others normally have copper-colored iris; iris color does not change with PSVA ligation). •  Neurologic signs. CAUSES Congenital developmental vascular malformations.

CBC/BIOCHEMISTRY/URINALYSIS

anemia; poikilocytosis (cats); target cells (dogs). •  Biochemistry—inconsistent low BUN, creatinine, cholesterol; hypoglycemia—in young tiny toy breeds, variable liver enzyme activity (ALP high in young patients), ALT normal or elevated; bilirubin normal; hypoalbuminemia inconsistent and mild. •  Urinalysis—normally concentrated or dilute urine; ammonium biurate crystalluria; hematuria, pyuria, and proteinuria: with urolithiasis or infection. OTHER LABORATORY TESTS

•  Total serum bile acid (TSBA)—sensitive

indicator of portosystemic shunting (PSS); random fasting values may be within reference intervals; 2 hours post-meal values usually markedly high (>100 μmol/L); always use paired samples around confirmed meal ingestion; no need to fast before testing. TSBA often remain abnormal in small-breed dogs after PSVA attenuation due to concurrent MVD. Important TSBA testing strategy—food-initiated enterohepatic bile acid challenge essential; verify meal consumption; feed typical size meal; feed dog’s regular diet for testing. •  Blood ammonia—fasting, sensitive but inconsistent indicator of HE and shunting; ammonia tolerance testing—oral or rectal NHCl4 administration; may cause transient HE. •  Coagulation tests—prolonged clotting times compared to healthy dogs but not clinically significant; are not associated with increased risk for bleeding.



Canine and Feline, Seventh Edition



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Portosystemic Vascular Anomaly, Congenital

•  Protein C—low values help differentiate PSVA from MVD; usually 70% in MVD, may be ≥70% in asymptomatic PSVA. Test reflects magnitude of macroscopic shunting. Protein C especially useful for postoperative assessment after PSVA ligation if initial activity subnormal; normali­ zation coordinates with good surgical outcome despite sustained high TSBA values. Protein C is not similarly applicable in cats.

IMAGING Abdominal Radiography

•  Microhepatia—dogs > cats. •  Renomegaly—some dogs. •  Ammonium urate urolithiasis—radiolucent

unless combined with radiodense mineral shell. Radiographic Portovenography

•  Mesenteric portography—old gold standard

for PSVA diagnosis.

•  Currently used as intraoperative assessment

of hepatic portal perfusion via fluoroscopy, accurate PSVA localization and assesses postligation liver perfusion.

Abdominal Ultrasonography

•  Subjective assessment of microhepatia and

vascular profiles; difficult to identify some PSVA (portoazygos, splenophrenic, gastro­ phrenic); US identification of PSVA is highly operator dependent. •  Color-flow Doppler—assists in US PSVA verification. •  I-PSVA—usually more easily imaged with US than E-PSVA. •  Other US features—renomegaly, uroliths: bladder, renal pelvis, rare ureteral. •  US microbubble study—can confirm PSS; splenic injection of agitated heparinized blood (microbubbles). Colorectal (CRS) or Splenoportal (SPS) Scintigraphy •  Tc99m pertechnetate CRS or SPS measures

shunt fraction; normal dog shunt fraction ≤15%; PSVA shunt fraction usually >60% but depends on severity of macroscopic shunting; shunt fraction in MVD is usually mildly increased above normal. •  CRS—sensitive noninvasive test confirming macroscopic shunting; cannot differentiate PSVA from acquired PSS (APSS) or E-PSVA from I-PSVA. •  SPS—may miss caudal PSVA; details insufficient to differentiate type of shunt (APSS vs. PSVA or I-PSVA, E-PSVA). Multisector CT

Gold standard imaging modality defining arterial and venous circulations; definitively demonstrates PSVA and APSS. DIAGNOSTIC PROCEDURES •  Vascular imaging provides definitive diagnosis of PSVA. •  Fine-needle aspiration cytology—cannot diagnose PSVA or MVD.

•  Liver biopsy—required for definitive diagnosis of portal venous hypoperfusion; rules out most acquired hepatobiliary disorders causing increased TSBA except splanchnic portal thromboembolism (TE), noncirrhotic portal hypertension (NCPH) and cannot usually differentiate MVD from PSVA. •  Open surgical wedge or laparoscopic liver biopsies preferred with samples collected from several (n = 3) liver lobes; avoid sampling caudate lobe. •  Needle core samples may be inadequate for definitive diagnosis of portal venous hypo­perfusion.

PATHOLOGIC FINDINGS

•  Gross—small, smooth-surfaced liver; PSVA

may be difficult to verify at autopsy due to collapse of portal vasculature. •  Histologic features—cannot discriminate MVD, PSVA, NCPH, or extrahepatic portal venous TE/occlusion without history, clinical findings, and imaging details. Note: dogs with MVD lacking PSVA have histologic features identical to PSVA but lack macro­ scopic shunting. •  Portal venous hypoplasia—invalid histologic diagnosis as failure to identify perfused portal veins can reflect any cause of portal venous hypoperfusion. •  Note: dogs ≤4 months of age demonstrate increased juvenile or small portal triads.

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 TREATMENT

APPROPRIATE HEALTH CARE Inpatient—severe signs of HE; medical intervention prior to liver biopsy and PSVA ligation. NURSING CARE See Hepatic Encephalopathy. DIET •  Nutritional support—essential to maintain body condition and muscle mass. •  Species-specific balanced protein-restricted diet—use commercial canine liver diet for dogs and feline renal diet for cats as a baseline diet. To these diets, additional protein allocations are titrated based on patient response, in combination with treatments ameliorating HE. •  Dogs—as tolerated, add an additional 0.25 g up to 1.0 g protein/kg body weight using dairy quality protein (e.g., cottage cheese, cheddar cheese, yogurt, scrambled eggs); incrementally adjust observing over 5–7 day intervals (see Hepatic Encephalopathy). •  Cats—as tolerated, additional white meat chicken may be used. •  Avoid organ meats, fish, and red meat as protein sources.

•  Asymptomatic or minimally symptomatic

animals can survive well with dietary and medical interventions. CLIENT EDUCATION

•  Explain therapeutic options: medical vs.

surgical and risks of each managerial strategy.

•  Surgical ligation—has potential to cure;

expect improvement in all symptomatic dogs that tolerate some degree of shunt attenuation. •  Postoperative clinical signs—may persist despite PSVA attenuation requiring chronic nutritional and medical management; some dogs can have medical and dietary inter­ ventions withdrawn. •  Clinical improvement may occur after surgical ligation despite persistent high TSBA values. •  Surgical/anesthetic risks—influenced by surgeon skill and experience, hospital, supportive critical care, type of PSVA, and histologic liver features. •  Monitoring protein C—can document improved portal perfusion in dogs with sustained high TSBA values; protein C activity will increase and may normalize with successful surgery (if low preoperatively); retest 2–6 months after surgery. This test is useful in cats for this purpose. •  If surgery not pursued or ligation not tolerated: remain vigilant for ammonium biurate obstructive uropathy; urethral obstruction (males) may require permanent urethrostomy. SURGICAL CONSIDERATIONS

•  HE—should be mitigated with medical

management before anesthesia and surgery.

•  ICU monitoring—recommended post­

operatively for 72–96 hours.

•  Surgical PSVA ligation—optimal goal of

complete ligation; may not be tolerated leading to APSS. APSS may develop with any method of shunt attenuation: direct silk ligation, ameroid device, cellophane banding, or IV coiling (I-PSVA). •  Partial PSVA ligation—improves patient health in most cases. •  Degree of tolerated PSVA closure judged at surgery—physiologic responses to temporary shunt occlusion but intraoperative assessments can still be inaccurate or misleading. •  Intraoperative portography advised— verifies correct PSVA identification and evaluates immediate change in hepatic portal perfusion as a real-time assessment. •  Ameroid constrictor, cellophane banding, IV coiling—gradual PSVA attenuation, reduce immediate postoperative surgical risk; caution: may later result in APSS in some patients, degree of PSVA attenuation is unknown with these methods without follow-up vascular imaging. •  Intrahepatic PSVA—more difficult to ligate than E-PSVA; right-sided I-PSVA most difficult, left-sided I-PSVA consistent with

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Portosystemic Vascular Anomaly, Congenital patent DV easiest; IV coiling an alternative method but may require multiple procedures for optimal response, is expensive, requires interventional training. •  Ammonium biurate urolith removal— bladder stones most common, ensure urethra is free of uroliths by retrograde catheterization/ flushing. •  Occasional male dog may require permanent urethrostomy. Postoperative Complications

•  Prolonged postoperative recovery—small

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patients developing intraoperative hypothermia. •  Acute severe PH—may reflect intolerance to PSVA ligation, flipping of ameroid constrictor, portal vein thrombi; mesenteric ischemia characterized by acute enteric hemorrhage, abdominal pain, tachycardia, hyper- or hypothermia, pancreatitis, endotoxemia, sepsis, acute renal failure and hypovolemic shock. •  Seizures—usually develop within 96 hours of PSVA ligation; risk factors remain unclarified with no demonstrated association with presence or absence of preoperative seizures, type of PSVA, method or degree of shunt attenuation, or patient age. Postoperative seizure prevalence—recent large multihospital study of dogs with seizures within 7 days of surgery: 6.7% of 524 dogs without preoperative levetiracetam treatment and 8.3–11.2% of 416 dogs receiving different pre- and postoperative levetiracetam protocols. One study implicates greater risk for pugs. Postoperative seizures reported in ~22% of cats undergoing PSVA ligation. •  Management of postligation seizures—often unsuccessful with persistent neurologic deficits in survivors, especially cats. Treatment remains anecdotal and requires consideration of cerebral edema if protracted seizure activity and intensive supportive care; successful management protocols (dogs and cats) include: IM phenobarbital (4–6 mg/kg IM q12h) combined with propofol CRI (0.3–0.6 mg/kg/minute titrated to achieve heavy sedation to drug-induced coma), and in one dog additional medetomidine (CRI (0.016 μg/kg/min). Initial treatment with IV levetiracetam has variable short-term response; flumazenil has no effect. Follow-up at-home treatments with phenobarbital, KBr, and/or levetiracetam have been successfully used. •  Abdominal effusion—typically transient after shunt ligation resolving within 7 days; alone, does not indicate intolerable PSVA attenuation; serious PH indicated by signs of mesenteric ischemia; monitor girth and body weight postoperatively to evaluate effusion. •  Administration of hetastarch can increase perioperative bleeding. •  Blood component therapy containing acid citrate dextrose may provoke hypocalcemia

and coagulopathy (hypercitratemia) in patients 8–9) or when the dipstick is immersed in the urine for a prolonged time. •  Low concentrations of Bence Jones proteins or gamma globulins may not be detected by urine dipstick. •  SSA turbidometric test results are falsely increased by radiographic contrast media, penicillins, sulfisoxazole, or the urine preservative thymol. •  SSA test results are falsely decreased by very alkaline urine and increased by uncentrifuged urine. •  If proteinuria is detected by these methods, the urine sediment should be evaluated for hematuria, pyuria, and/or bacteriuria. Hematuria alone typically does not increase urine albumin content above the negligible range (i.e., >1 mg/dL) or the UP:C above 0.4



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Canine and Feline, Seventh Edition

Proteinuria

(continued)

until there is a color change in the urine. 81% of dogs with pyuria had normal UP:C. •  To determine persistence, repeat the urine protein screening test in proteinuric patients that initially have a normal urine sediment or have been treated for urinary tract inflammation or hemorrhage. If proteinuria is transient and the urine sediment is normal, consider functional proteinuria or false-positive test results. •  Although not all animals with glomerular disease are hypoalbuminemic, glomerular proteinuria should be suspected when proteinuria and hypoalbuminemia are concurrent. As disease progresses, clinico­ pathologic changes consistent with glomerular disease may develop. OTHER LABORATORY TESTS

•  Urine protein should be quantified in dogs

and cats that have hypoalbuminemia and/or repeatedly positive urine dipstick or SSA tests in absence of LUT hemorrhage or inflammation. The UP:C is the preferred because more is known about use of this test and it is technically easier to perform than 24-hour urine collections. •  MA is detected in dogs using a point-ofcare immunoassay or quantitation using an immunoassay. MA is an early predictor of proteinuria. If repeatedly positive, and if the concentration is increasing, the patient may be at risk for glomerular disease. •  Thoroughly evaluate an animal for an underlying disease when persistent proteinuria is believed to be of glomerular origin. •  Urine and serum protein electrophoresis may identify pre-glomerular proteinuria in patients with monoclonal gammopathies or urinary immunoglobulin light chains (Bence Jones proteins). IMAGING Ultrasound and radiographs may reveal an underlying infectious, inflammatory, or neoplastic disease process or evidence of LUT disease. Ultrasound may show structural changes suggesting primary renal disease (e.g., loss of corticomedullary distinction, hyper­ echogenicity, and irregular surface margin) or evidence in support of LUT disease.

nephritis, amyloidosis, podocyopathy, focal segmental glomerulosclerosis, glomerulosclerosis. •  Animals with tubular proteinuria most often have a degree of tubulointerstitial nephritis. •  Postrenal proteinuria would be expected to have inflammatory, neoplastic, or polypoid lesions.

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 TREATMENT

APPROPRIATE HEALTH CARE Most can be managed as outpatients. Inpatient care may be required during select diagnostic evaluation (renal biopsy) or when there are complications associated with uremia, thromboembolism or edema in patients with glomerular proteinuria. NURSING CARE Physical therapy and exercise may limit formation of edema in patients with glomerular proteinuria and hypoalbuminemia. ACTIVITY Activity should not be restricted in animals with proteinuria. DIET If glomerular disease is suspected, feed a diet formulated for kidney disease. CLIENT EDUCATION It is important to determine the cause of persistent proteinuria, which may indicate the presence of kidney disease. Renal proteinuria is a risk factor for progressive kidney disease, thromboembolism, and edema. SURGICAL CONSIDERATIONS Animals with severe hypoalbuminemia (i.e., 3–4 mg/kg may cause vomiting, lethargy or hyperactivity, hypertension, and tachycardia. •  Head-bobbing, DIC, or myoglobinuria indicate serious intoxication and a more guarded prognosis.

­

 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS Other CNS stimulants and sympathomimetics—amphetamines, cocaine,

•  Acepromazine 0.05–1.0 mg/kg IM or IV;

start low and titrate up as needed.

CBC/BIOCHEMISTRY/URINALYSIS

•  Chlorpromazine 0.5–1.0 mg/kg IV or IM;

expected in most cases.

•  Cyproheptadine 1.1 mg/kg PO or per

•  No specific clinical pathology alterations are •  In severe cases DIC, myoglobinemia,

myoglobinuria, or azotemia may occur. OTHER LABORATORY TESTS Urine or serum from patients with pseudo­ ephedrine toxicosis may give a positive test for amphetamine in OTC drug test kits or human hospital drug screens.

­

 TREATMENT

•  Manage severe or life-threatening signs first. •  Control CNS stimulation, then manage

cardiovascular (CV) stimulation, as blood pressure and heart rate may decrease significantly once CNS signs are managed. •  For seizures, use propofol, pentobarbital, or phenobarbital; consider gas anesthetic for refractory cases. •  For agitation, hyperactivity, or other CNS stimulation, use acepromazine or chlorpromazine. •  Cyproheptadine has been used with some success to manage dysphoria, vocalization, and hyperthermia. •  Propranolol (or other beta-blocker) may be considered in patients with sustained tachycardia. •  External cooling measures may be required for hyperthermic patients. •  IV fluid administration assists in stabilization of CV effects, support of kidney function, and excretion of pseudoephedrine and its metabolites. •  Monitor heart rate/rhythm, body temperature, and blood pressure. In severely affected patients, monitor renal function, coagulation parameters, hydration, and electrolytes. •  Gastrointestinal decontamination (induction of emesis, administration of activated charcoal) may be considered in patients that have ingested >1 mg/kg of pseudoephedrine and are not displaying significant clinical signs.

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 MEDICATIONS

DRUG(S) OF CHOICE •  Propofol 0.1–0.6 mg/kg/min IV. •  Pentobarbital 30 mg/kg IV to effect. •  Phenobarbital 3–4 mg/kg IV.

start low and titrate up as needed.

rectum q6h (dogs); 2–4 mg PO or per rectum (cats). •  Propranolol 0.02–0.06 mg/kg IV q6–8h PRN. •  Emetics—Dogs: 3% hydrogen peroxide 2.2 mL/kg PO, maximum 45 mL, may repeat once if first dose unsuccessful; apomorphine crushed and diluted with sterile saline and instilled in conjunctival sac, rinse eye after emesis, or 0.03 mg/kg IV; ropinirole hydrochloride 3.75 mg/m2 as directed by product label. Cats: dexmedetomidine 6–18 µg/kg IM; xylazine 0.44 mg/kg IM; hydromorphone 0.1 mg/kg SC. •  Activated charcoal 1–3 g/kg suspended in 50–200 mL of water. CONTRAINDICATIONS/POSSIBLE INTERACTIONS The use of diazepam to control CNS stimulation should be avoided, as diazepam may induce a dysphoric effect in these patients and worsen the CNS excitation.

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 FOLLOW-UP

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 MISCELLANEOUS

Renal insufficiency resulting from myoglobinuria may require long-term follow-up and care.

ABBREVIATIONS •  CV = cardiovascular. •  DIC = disseminated intravascular coagulation. •  OTC = over-the-counter.

­Suggested Reading

Means C. Dietary supplements and herbs. In: Poppenga RH, Gwaltney-Brant SM, eds. Small Animal Toxicology Essentials. Chichester: Wiley-Blackwell, 2011, pp. 161–169. Means C. Ma huang: all natural but not always innocuous. Vet Med 1999, 94:511–512. Author Sharon Gwaltney-Brant Consulting Editor Lynn R. Hovda



Canine and Feline, Seventh Edition

1145

Pseudomacrothrombocytopenia (Inherited Macrothrombocytopenia)

­

 BASICS

OVERVIEW •  A common cause of thrombocytopenia and increased mean platelet volume (MPV) in cavalier King Charles spaniels (CKCS), and infrequently in other breeds. •  Caused by an inherited mutation that impairs platelet maturation, resulting in the early release of platelets from the bone marrow. The released platelets are significantly larger than normal. •  Overall platelet mass (product of platelet number and average size) is unaffected, therefore clinical signs of hypocoagulability are not seen. SIGNALMENT

•  Dogs—primarily CKCS with infrequent

reports in Norfolk terriers, Cairn terriers, English toy spaniels, and Jack Russell terriers; other breeds also sporadically affected. •  A similar condition is also reported in Akitas, although a specific mutation has not yet been identified in this breed. •  The condition is present from birth, but is often not detected until a CBC is performed. The mutation is autosomal, therefore there is no sex predilection. SIGNS Not associated with clinical signs; often incidentally noted on a CBC performed for other reasons. CAUSES & RISK FACTORS

•  Caused by point mutations in the gene

encoding β1-tubulin, which is involved in platelet formation. The mutations impair the formation of microtubules in the megakaryocyte (platelet precursor) and result in the release of lower numbers of platelets that are larger than normal. •  The condition is inherited in an autosomal fashion, with homozygotes exhibiting moderate to marked thrombocytopenia and moderate to marked increases in MPV. Heterozygotes are less severely affected and may have a mild thrombocytopenia and/or mild increase in MPV. •  In the United States, it has been estimated that approximately 47% of CKCS are homozygous for the mutation and 45% are heterozygous.

­

 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Must be differentiated from causes of pathologic thrombocytopenia such as immune-mediated thrombocytopenia, disseminated intravascular coagulation, infectious diseases (especially tick-borne

diseases), and causes of decreased platelet production (i.e., bone marrow disease). •  Breed (especially CKCS), absence of clinical signs, and a normal plateletcrit (PCT) (see CBC/Biochemistry/Urinalysis) are strongly suggestive of inherited macrothrombocytopenia. •  Blood smear evaluation is also recommended to rule out in vitro platelet clumping, which artifactually induces a decreased platelet count and increased MPV. CBC/BIOCHEMISTRY/URINALYSIS

•  CBC—moderate to marked thrombo­

cytopenia (40,000–200,000/μL) with significantly increased MPV; PCT expected to be within reference interval (RI = 0.129–0.403%). •  PCT—a numeric representation of overall platelet mass (product of platelet number and average size). Some automated analyzers calculate the value automatically. If not provided, PCT can be calculated using the following formula: PCT = (PLT × MPV)/10,000 where PLT is platelet count and MPV is mean platelet volume. OTHER LABORATORY TESTS If definitive diagnosis is desired, genetic testing to confirm the presence of the mutation can be performed; currently, this is available through the Auburn University Hemostasis Laboratory.

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 TREATMENT

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 MEDICATIONS

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 FOLLOW-UP

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 MISCELLANEOUS

None required—nonpathogenic condition without clinical signs.

N/A

Once affected individuals are identified, platelet mass in these patients should be evaluated via PCT; if this value falls below the reference interval, a concurrent pathologic thrombocytopenia may be present.

ABBREVIATIONS •  CKCS = cavalier King Charles spaniel. •  MPV = mean platelet volume. •  PCT = plateletcrit. •  PLT = platelet count.

INTERNET RESOURCES https://www.vetmed.auburn.edu/academicdepartments/dept-of-pathobiology/ diagnostic-services/

­Suggested Reading

Davis B, Toivio-Kinnucan M, Schuller S, Boudreaux MK. Mutation in beta1-tubulin correlates with macrothrombocytopenia in Cavalier King Charles Spaniels. J Vet Intern Med 2008, 22:540–545. Author Megan N. Caudill Consulting Editor Melinda S. Camus

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1146

Blackwell’s Five-Minute Veterinary Consult

Ptyalism

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 BASICS

DEFINITION •  Excessive production and secretion of saliva (see Web Figure 1). •  Pseudoptyalism is the excessive release of saliva that has accumulated in the oral cavity due to inability to swallow. PATHOPHYSIOLOGY

•  Saliva is constantly produced and

secreted into the oral cavity from the salivary glands. •  Saliva production increases when salivary nuclei in the brainstem are stimulated. •  Higher centers in the CNS can excite or inhibit salivary nuclei. •  Taste and tactile stimuli in the oral cavity increase saliva production. •  Physiologic hypersalivation may occur with: anticipation of eating, hyperthermia and purring (cats). •  Saliva production may be increased with gastro­ intestinal (GI) or CNS disorders.

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SYSTEMS AFFECTED Skin—may cause salivary staining. GENETICS N/A INCIDENCE/PREVALENCE Variable GEOGRAPHIC DISTRIBUTION Worldwide SIGNALMENT Species

Dog and cat. Breed Predilections

•  Congenital portosystemic shunts—

Yorkshire terrier, Maltese, Australian cattle dog, miniature schnauzer, and Irish wolfhound. •  Congenital megaesophagus— wirehaired fox terrier and miniature schnauzer; familial predispositions have been reported in German shepherd dog, Newfoundland, Great Dane, Irish setter, Chinese Shar-Pei, greyhound, retriever breeds, and Siamese cats. •  Congenital hiatal hernia—Chinese Shar-Pei. •  Lip conformation—giant breeds, such as Saint Bernard, Great Dane, and mastiff. •  Brachycephalic airway syndrome—pug, English and French bulldog. Mean Age and Range

Young animals are more likely to have congenital abnormalities and to ingest foreign materials. SIGNS Historical Findings

•  Anorexia—with oral lesions, GI disease, and systemic disease. •  Eating behavior changes— with oral disease or cranial nerve (CN) dysfunction: may refuse hard food, chew only on the unaffected side (if unilateral lesion), maintain an unusual head/neck position, or

drop food. •  Other behavioral changes— irritability, aggressiveness, and reclusiveness, especially if painful. •  Dysphagia. •  Nausea. •  Regurgitation—with esophageal disease. •  Vomiting—with GI or systemic disease. •  Weight loss. •  Pawing at the face or muzzle—with oral discomfort. •  Neurologic signs—with exposure to caustic drugs or toxins, hepatic encephalopathy, seizure disorders or other intracranial disease. Physical Examination Findings

•  Periodontal disease. •  Gingivitis/stomatitis—

with toxins, infection, immune-mediated disease or nutritional deficiency. •  Oral mass •  Glossitis—with ulceration, mass or foreign body. •  Oropharyngeal inflammation, ulceration, mass, or foreign body. •  Blood in the saliva—with bleeding from the oral cavity, pharynx, or esophagus. •  Halitosis—with oral disease (most common), or esophageal and gastric disease. •  Facial pain. •  Dysphagia. •  CN deficits—trigeminal nerve (CN V) lesions can cause drooling due to inability to close the mouth; facial nerve palsy (CN VII) can cause drooling from the affected side; glossopharyngeal (CN IX), vagus (CN X), and hypoglossal (CN XII) nerve lesions can cause a loss of the gag reflex or inability to swallow. •  Cheilitis or acne—persistent drooling can lead to dermatologic lesions. CAUSES Conformational Disorder of the Lips

Neurologic

•  Rabies—decreased swallowing causes increased drooling. •  Pseudorabies in dogs. •  Botulism. •  Tetanus. •  Dysautonomia. •  Disorders causing dysphagia. •  Disorders causing facial nerve palsy or a dropped jaw. •  Seizures—during a seizure, ptyalism may occur because of autonomic discharge or reduced swallowing of saliva, and may be exacerbated by chomping of the jaws. •  Nausea associated with vestibular disease. •  Anxiety.

Drugs and Toxins

•  Caustic substances (e.g., household cleaning products). •  Anesthesia may induce reflux esophagitis. Drugs used for premedication may induce nausea, vomiting or ptyalism. •  Oral, otic or ophthalmic medications that are poorly palatable (especially in cats). •  Those that induce hypersalivation, including organophosphate compounds, cholinergic drugs, insecticides containing boric acid, pyrethrin and pyrethroid insecticides, ivermectin (dogs), fluids containing benzoic acid derivatives (cats), clozapine (a tricyclic dibenzodiazepine), caffeine, and illicit drugs such as amphetamines, cocaine, and opiates. Has also been reported with capromorelin administration in dogs and cats. •  Animal venom (e.g., black widow spider, Gila monster, and North American scorpion). •  Toad and newt secretions. •  Plant consumption or prehension (e.g., poinsettia, Christmas trees, Amanita mushrooms) may cause increased salivation.

Most common in giant-breed dogs. Oral and Pharyngeal

•  Oral trauma. •  Foreign body (e.g., stick, foxtail, or sewing needle). •  Neoplasm. •  Abscess. •  Gingivitis or stomatitis—

secondary to periodontal disease, bacterial, viral (e.g., feline leukemia virus [FeLV] or feline immunodeficiency virus [FIV]) or fungal infection, immune-mediated disease (e.g., lymphoplasmacytic stomatitis, pemphigus vulgaris), uremia, ingestion of a caustic agent, poisonous plants, effects of radiation therapy to the oral cavity or burns (e.g., biting on an electrical cord). •  Swallowing disorders.

Salivary Gland

•  Sialoadenitis. •  Sialolithiasis. •  Sialadenosis (idiopathic enlargement). •  Mucocele. •  Fistula. •  Foreign body. •  Neoplasm. •  Infarct. •  Immune-mediated disease (rare).

Esophageal or GI

•  Esophageal foreign body. •  Esophageal neoplasm. •  Esophageal stricture. •  Esophagitis. •  Gastroesophageal reflux disease (GERD). •  Infection (e.g., spirocercosis, pythosis). •  Hiatal hernia. •  Megaesophagus. •  Esophageal dysmotility. •  Gastric distension/volvulus. •  Gastric ulcer. •  Gastroenteritis.

Metabolic

•  Hepatic encephalopathy (especially in cats). •  Hyperthermia. •  Uremia.

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Differentiating causes of ptyalism and pseudoptyalism requires a thorough history, including vaccination status, current medications, possible toxin exposure, and duration of ptyalism. •  May be able to distinguish salivation associated with nausea (signs of depression, lip smacking, and retching) from dysphagia by observing the patient. •  Complete physical examination (with special attention to the oral cavity and neck) and neurologic examination are critical; wear examination gloves when rabies exposure is possible. CBC/BIOCHEMISTRY/URINALYSIS •  CBC—often unremarkable; leukocytosis in patients with immune-mediated, inflammatory or infectious disease. •  Stress leukogram— common in animals that have ingested a caustic agent or organophosphate. •  FeLV-infected cats may have leukopenia and nonregenerative anemia. •  Serum creatine kinase activity should be evaluated in all dysphagic patients. •  Possible microcytosis with portosystemic shunts. •  Biochemical analysis—usually unremarkable except in patients with renal disease (azotemia, hyperphosphatemia), and hepatic encephalo­ pathy (possibly elevated hepatic enzyme activities, decreased BUN, hypoalbuminemia,



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Canine and Feline, Seventh Edition

Ptyalism

(continued)

hypocholesterolemia, hyperbilirubinemia, and hypoglycemia). •  Marked ptyalism can result in hypokalemia and acidosis from the loss of potassium and bicarbonate-rich saliva. •  Urinalysis—often normal; decreased urine specific gravity with renal or hepatic disease. •  Urate urolithiasis may be noted in patients with portosystemic shunts. OTHER LABORATORY TESTS •  Fasting and postprandial bile acids and/or fasting ammonia when hepatic encephalopathy is suspected. •  Serologic FeLV and FIV testing in cats with oral lesions. •  Acetylcholine receptor antibody titer if focal myasthenia gravis is suspected. •  Serum cholinesterase level if organophosphate toxicosis is suspected. •  Post-mortem fluorescent antibody testing of brain tissue if rabies is suspected. IMAGING •  Survey radiography of the oral cavity, neck, and thorax when foreign body, structural abnormality, or neoplasm is suspected. •  Abdominal radiographs ± abdominal ultrasound may help diagnose cause of vomiting; may also help diagnose hepatic or renal disease. •  Ultrasonographic evaluation, CT angiography, portal venography, or portal scintigraphy may help diagnose a portosystemic shunt. •  Fluoroscopic evaluation of swallowing may be useful in dysphagic patients to evaluate esophageal function and motility; use caution during barium administration in animals that are dysphagic. •  MRI or CT for suspected intracranial lesions. •  CT of head is more sensitive than radiographs, especially when foreign body or neoplasia is suspected. DIAGNOSTIC PROCEDURES •  Biopsy and histopathology of mucocutaneous lesions—possibly including immunofluorescence testing when immune-mediated disease (e.g., pemphigus vulgaris) is suspected. •  Fine-needle aspiration of oral lesions and regional lymph nodes. •  Biopsy and histopathology of oral lesion, salivary gland, or mass. •  Consider esophagoscopy or gastroscopy if lesions distal to the oral cavity are suspected; endoscopic removal of foreign bodies may be possible. PATHOLOGIC FINDINGS Varies as to the underlying condition.

NURSING CARE

•  Petroleum jelly can be applied to areas of

the face constantly wet from saliva to help prevent moist dermatitis. •  Astringent solutions applied for 10 minutes q8–12h can be used to treat areas of moist dermatitis. ACTIVITY N/A DIET •  Enteral nutritional support (esophagostomy, gastrostomy tubes, etc.) may be needed in patients with ptyalism and anorexia secondary to severe oral, GI, or metabolic causes. •  Reduced protein diets may be recommended for patients with hepatic encephalopathy, but are not necessarily warranted in animals with portosystemic shunts that are not encephalopathic. CLIENT EDUCATION Client education will depend on the underlying disease process. SURGICAL CONSIDERATIONS

•  Surgical procedures will vary depending on

underlying cause; ligation of parotid salivary duct has been described. •  Corrective surgery for brachycephalic airway surgery may result in improved GI signs.

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 MEDICATIONS

DRUG(S) OF CHOICE •  Anticholinergic medications may be given symptomatically to reduce the flow of saliva; atropine 0.05 mg/kg SC PRN or glycopyrrolate 0.01 mg/kg SC PRN. However, this is typically unnecessary as treatment should focus on underlying disease. •  Antiemetics for nausea (see Acute Vomiting, for list of antiemetics and dosages). •  Crystalloid fluids may be given IV or SC to treat dehydration caused by prolonged or severe ptyalism. •  Antacid therapy may be useful for treatment of GERD (e.g., proton pump inhibitors—omeprazole 1 mg/kg PO q12h). •  Phenobarbital 2 mg/kg PO q12h has been effective in treating idiopathic hypersialosis. •  Anticonvulsant therapy is indicated for seizure activity. CONTRAINDICATIONS N/A PRECAUTIONS Depends on underlying cause.

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 TREATMENT

APPROPRIATE HEALTH CARE •  Treat the underlying cause (refer to sections pertaining to specific conditions). •  Symptomatic treatment to reduce the flow of saliva—generally unnecessary, may be of little value to the patient, and may mask other signs of the underlying cause and thus delay diagnosis; only recommended when hypersalivation is prolonged and severe and, if possible, after the underlying condition has been diagnosed.

ALTERNATIVE DRUG(S) •  Some clinicians have anecdotally used levetiracetam for idiopathic hypersialosis. •  Other acid-reducing agents may be used.

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 FOLLOW-UP

PATIENT MONITORING •  Depends on the underlying cause. •  Continually monitor hydration, body

weight, serum electrolytes, and nutritional status, especially in dysphagic or anorexic animals. PREVENTION/AVOIDANCE Depends on underlying cause. POSSIBLE COMPLICATIONS •  Metabolic acidosis. •  Dehydration. •  Hypokalemia. •  Moist dermatitis. •  Aspiration pneumonia. EXPECTED COURSE AND PROGNOSIS Depends on underlying cause. If underlying cause is correctable, prognosis for resolution may be more favorable.

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 MISCELLANEOUS

ASSOCIATED CONDITIONS N/A ZOONOTIC POTENTIAL Rabies PREGNANCY/FERTILITY/BREEDING N/A SYNONYMS •  Drooling. •  Hypersalivation. •  Sialism. •  Sialorrhea. •  Sialosis. SEE ALSO •  Dysphagia. •  Esophagitis. •  Hepatic Encephalopathy. •  Megaesophagus. •  Periodontal Disease. •  Stomatitis and Oral Ulceration. ABBREVIATIONS •  CN = cranial nerve. •  FeLV = feline leukemia virus. •  FIV = feline immunodeficiency virus. •  GERD = gastroesophageal reflux disease. •  GI = gastrointestinal.

­Suggested Reading

Claude AK, Dedeaux A, Chiavaccini L, Hinz S. Effects of maropitant citrate or acepromazine on the incidence of adverse effects associated with hydromorphone premedication in dogs. J Vet Intern Med 2014, 8:1414–1417. Kaye BM, Rutherford L, Perridge DJ, Haar GT. Relationship between brachycephalic airway syndrome and gastrointestinal signs in three breeds of dog. J Small Anim Pract 2018, 59:670–673. Niemiec BA. Ptyalism. In: Ettinger SJ, Feldman EC, eds., Textbook of Veterinary Internal Medicine, 7th ed. St. Louis, MO: Elsevier, 2010, pp. 185–188. van der Merwe LL, Christie J, Clift SJ, Dvir E. Salivary gland enlargement and sialorrhoea in dogs with spirocercosis: a retrospective and prospective study of 298 cases. J S Afr Vet Assoc 2012, 83(1):920. Author Valerie J. Parker Consulting Editor Mark P. Rondeau

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Blackwell’s Five-Minute Veterinary Consult

Pulmonary Contusions

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 BASICS

OVERVIEW •  Hemorrhage in the lung parenchyma caused by tearing and crushing from direct thoracic trauma. •  Relatively small volumes of blood in the parenchyma markedly compromise lung function. •  Fluid resuscitation for treatment of shock can exacerbate lung dysfunction from secondary edema. SIGNALMENT Dog and cat. SIGNS

•  History of trauma. •  Tachypnea. •  Abnormal respiratory effort. •  Postural adaptations to respiratory distress. •  Cyanotic or pale mucous membranes. •  Auscultation

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of harsh bronchovesicular sounds or crackles. •  Expectoration of blood or blood-tinged fluid. •  Additional injuries secondary to trauma and shock can also be noted. CAUSES & RISK FACTORS

•  Blunt trauma. •  Motor vehicle accidents. •  Falls from a height. •  Abuse.

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Hemothorax—auscult dull lung sounds ventrally. •  Pneumothorax—auscult dull lung sounds dorsally. •  Diaphragmatic hernia—distinguished radiographically. •  Coagulopathy can result in pulmonary hemorrhage; identified by abnormal coagulation tests or platelet count. •  Acute onset of pulmonary hemorrhage—can be seen with neoplasia or pulmonary infarction from bacterial endocarditis or heartworm disease. •  Expectoration of bloody fluid (not frank hemorrhage) can occur in animals with acute respiratory distress syndrome (ARDS) or congestive heart failure. •  If no known history of trauma, pneumonia or edema (cardiogenic and noncardiogenic) are possible differentials. CBC/BIOCHEMISTRY/URINALYSIS

•  CBC—can reveal anemia or mature neutrophilia. •  Biochemistry profile—can

Thoracic Focused Assessment with Sonography for Trauma (TFAST®) and Focused Lung Ultrasound •  Point-of-care emergency ultrasound helps

identify intrathoracic trauma during initial triage. •  Increased lung rockets (B-lines) indicative of contusions or edema. •  Absence of a glide sign dorsally indicative of pneumothorax. •  Pleural effusion noted indicative of hemothorax. DIAGNOSTIC PROCEDURES •  Coagulation tests for coagulopathy or disseminated intravascular coagulation. •  Pulse oximetry or arterial blood gas analysis—can confirm hypoxemia. •  Examination of tracheal wash cytology—can show excessive numbers of erythrocytes and macrophages.

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 TREATMENT

•  Usually inpatient for stabilization. •  Support

respiratory function, stabilize cardiovascular function. •  If pneumothorax suspected, thoracocentesis should be performed. •  Assess and treat injuries to other organ systems. •  Restrict activity, minimize stress, and monitor carefully for deterioration. •  Respiratory support—oxygen supplementation for hypoxemia; intubation and positive-pressure ventilation if severe. •  Shock— fluids generally required; judicious fluid therapy to avoid exacerbation of pulmonary edema. •  Blood or plasma transfusion—consider if anemia or coagulopathy. •  Nutritional support—as needed to maintain body condition and immune status.

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 MEDICATIONS

DRUG(S) OF CHOICE •  Oxygen supplementation if dyspnea or hypoxemia. •  Analgesics administered as warranted. •  Low-dose diuretics— contraindicated unless suspected volume overload and respiratory distress is severe. CONTRAINDICATIONS/POSSIBLE INTERACTIONS Diuretics—no value in the early stages of pulmonary contusions and potentially harmful; decrease intravascular volume, which is contraindicated for shock.

demonstrate hypoproteinemia (blood loss); can reveal damage to other organ systems. IMAGING

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Thoracic Radiography

PATIENT MONITORING •  Monitor respiratory rate and effort, mucous membrane color, heart rate, pulse quality, and lung sounds. •  Measure serial packed cell volume (PCV) and total solids and perform pulse oximetry and/or arterial blood gas analysis as needed for the first 24 hours. •  Monitor ECG frequently to detect ventricular arrhythmias associated

•  Usually a patchy alveolar pattern—focal or

asymmetrical, but can be generalized.

•  Contusions generally worse in the area of rib fractures if present. •  Always perform

thoracic radiographs in trauma patients after stabilization to rule out hemothorax, pneumothorax, and diaphragmatic hernia.

 FOLLOW-UP

with hypoxemia or traumatic myocarditis.

•  Radiographs—repeated if clinically indicated.

PREVENTION/AVOIDANCE Appropriate restriction of the animal to prevent trauma. POSSIBLE COMPLICATIONS •  Bacterial pneumonia (uncommon)—owing to systemic immunosuppression from trauma, shock, and reduced pulmonary defenses. •  Development of a moist productive cough and failure to improve within 48 hours— suspect pneumonia. •  Patients with severe shock can develop ARDS (less common). EXPECTED COURSE AND PROGNOSIS •  Respiratory function can deteriorate during the initial 12–24 hours and then should gradually improve. •  Clinical improvement within 48 hours with radiographic resolution likely in 7–10 days. •  If patient fails to improve clinically after 48 hours, evaluate for complications or concurrent disease.

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 MISCELLANEOUS

ASSOCIATED CONDITIONS •  Pneumothorax. •  Fractured ribs. •  Flail chest. •  Ruptured trachea, bronchi, or esophagus. •  Cardiac arrhythmias—ventricular. •  Other possible complications of trauma. SEE ALSO Pneumothorax ABBREVIATIONS •  ARDS = acute respiratory distress syndrome. •  PCV = packed cell volume. •  TFAST® = Thoracic Focused Assessment with Sonography for Trauma.

­Suggested Reading

Boysen SR, Lisciandro GR. The use of ultrasound for dogs and cats in the emergency room: AFAST and TFAST. Vet Clin North Am Small Anim Pract 2013, 43(4):773–797. Campbell VL, King LG. Pulmonary function, ventilator management and outcome of dogs with thoracic trauma and pulmonary contusions: 10 cases (1994–1998). J Am Vet Med Assoc 2000, 217:1505–1509. Holowaychuk MK, Marks SL, Hansen BG, DeFrancesco T. Pulmonary contusions. Stand Care Emerg Crit Care Med 2006, 8(10):1–6. Powell LL, Rozanski EA, Tidwell AS, Rush JE. A retrospective analysis of pulmonary contusion secondary to motor vehicular accidents in 143 dogs: 1994–1997. J Vet Emerg Crit Care 1999, 9:127–136. Vnuk D, Pirkic B, Maticic D, et al. Feline high-rise syndrome: 119 cases (1998–2001). J Feline Med Surg 2004, 6:5, 305–312. Author Cassandra O. Janson Consulting Editor Elizabeth Rozanski Acknowledgment The author and editors acknowledge the prior contribution of Lesley G. King.



Canine and Feline, Seventh Edition

1149

Pulmonary Edema, Noncardiogenic Mean Age and Range

•  Higher incidence in pediatrics—associated

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 BASICS

DEFINITION Accumulation of edema fluid in the pulmonary interstitium and alveoli, in the absence of heart disease. PATHOPHYSIOLOGY •  Associated with increased pulmonary vascular permeability and leakage of fluid into the interstitium and alveoli; if severe, can be accompanied by an inflammatory response and accumulation of neutrophils and macrophages. •  Several mechanisms contribute to changes in pulmonary vascular permeability. •  Stimulation of brainstem (medulla) vasomotor centers can lead to a reflex systemic release of catecholamines resulting in systemic vasoconstriction and temporary shunting of blood into the pulmonary circulation resulting in transient pulmonary circulatory overload and endothelial damage—likely pathogenesis in patients with neurogenic edema, electrocution, and upper airway obstruction. •  In patients with upper airway obstruction, negative intrathoracic pressure from inspiratory attempts against an airway obstruction also contributes to edema formation. •  Increased vascular permeability can be part of a generalized inflammatory response that develops in patients with systemic inflamm­atory response syndrome (SIRS), sepsis, or pancreatitis. •  The inciting insult can trigger a cascade inflammatory response that often worsens over 24 hours following the initial episode. •  Severity of clinical manifestation varies, ranging from mild to severe; the most seriously affected patients can progress from normal to death rapidly after the incident.

with strangulation, head trauma, and electric cord bites. •  Older—associated with laryngeal obstruction and neoplasia. SIGNS General Comments

Vary, depending on underlying cause and severity. Historical Findings

•  Predisposing causes—airway obstruction;

electric cord bite; seizures; head trauma; near drowning; smoke exposure; adverse drug effects. •  Acute onset of dyspnea.

Physical Examination Findings

•  Mild to severe dyspnea. •  Increased respiratory rate and effort; open-mouthed breathing. •  Postural adaptations to respiratory distress (if severe)- orthopnea, unwillingness to lie down. •  Pale or cyanotic mucous membranes (severe). •  Harsh lung sounds (early, mild) or generalized crackles (late, severe) on auscultation. •  Expectoration of pink froth or bubbles; can have large volumes of bloody fluid flowing out of endotracheal tube in severely affected intubated animals. •  Normal cardiac auscultation; can detect arrhythmias; tachycardia common. •  Oral ulceration or burns if electrocution. •  Cranial nervous system abnormalities or other indications of neurologic disease. •  Stridor over the upper airway in cases of brachycephalic syndrome, airway masses/abscesses, or foreign bodies. •  Smokey odor or burns indicative of smoke exposure.

CAUSES

•  Upper airway obstruction—laryngeal

paralysis; choke-chain injury; mass; abscess.

•  Electrocution. •  Acute neurologic disease—

GENETICS Unknown

head trauma; intra­-cranial hypertension, prolonged seizures. •  Smoke inhalation. •  Aspiration pneumonia. •  Systemic inflammatory response syndrome—sepsis; endotoxemia; pancreatitis. •  Anaphylaxis (cats). •  Near drowning. •  Adverse drug reactions including certain anesthetic drugs (ketamine), thiazides, or certain antineoplastics (vincristine, cisplatin in cats). •  Transfusionrelated acute lung injury—limited evidence in veterinary medicine. •  Vasculitis.

INCIDENCE/PREVALENCE Uncommon

•  Hypoproteinemia. •  Crystalloid fluid

SYSTEMS AFFECTED •  Respiratory. •  Cardiovascular— hypotension, tachycardia, and shock. •  Hemic/lymphatic/immune— if severe and causing respiratory failure, can be associated with disseminated intravascular coagulation (DIC). •  Renal/urologic—acute renal failure.

SIGNALMENT

RISK FACTORS resuscitation.

Species

Dog and cat. Breed Predilections

None specific; brachycephalic dogs are more prone to airway obstruction, older large-breed dogs—laryngeal paralysis, small-breed dogs— tracheal collapse.

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Cardiogenic pulmonary edema. •  Pulmonary infection—bacterial, viral, or fungal pneumonia. •  Pulmonary neoplasia.

•  Pulmonary hemorrhage (e.g., anticoagulant rodenticide exposure). •  Pulmonary

thromboembolism.

CBC/BIOCHEMISTRY/URINALYSIS

•  Leukocytosis common, leukopenia and

thrombocytopenia possible due to neutrophil sequestration in the lung and platelet consumption. •  Biochemistries—usually normal; may note hypoalbuminemia owing to pulmonary protein loss; mild stress-related hyperglycemia. •  Urinalysis—usually normal.

OTHER LABORATORY TESTS Coagulation testing—mild to moderate prolongation of prothrombin time/partial thromboplastin time (PT/PTT) in animals with consumption and DIC. Severe coagulopathy may indicate hemorrhage as true cause for respiratory signs. IMAGING

•  Thoracic radiographs—vital; can reveal

prominent interstitial pattern with mild or early disease; alveolar infiltrates with moderate or severe disease; infiltrates commonly but not always in dorsocaudal lung, sometimes asymmetrical and predominantly right-sided. Cardiac silhouette generally normal. •  Echocardiography—rule out cardiogenic pulmonary edema. •  Pointof-care thoracic ultrasound—increased lung rockets (B-lines) may indicate pulmonary edema, increased left atrial:aortic ratio more indicative of cardiogenic edema and underlying heart disease. DIAGNOSTIC PROCEDURES

•  Cytology of airway fluid—inflammatory:

neutrophils and some alveolar macrophages. Fluid tends to have high protein values >3 g/ dL. Culture negative unless concurrent bacterial pneumonia. •  Edema fluid to plasma ratio (EF:PL) compares protein in the edema fluid to plasma protein. An increased ratio (>0.65) is indicative of noncardio­genic pulmonary edema. •  Pulse oximetry— noninvasive, continuous monitoring of arterial hemoglobin saturation with oxygen and arterial blood gas analysis. Demonstrates mild to severe hypoxemia and hypocapnia; not specific but indicates the severity of pulmonary dysfunction. •  B-type natriuretic peptide (NT-proBNP) testing in cats and dogs can suggest underlying heart disease and supports a diagnosis of cardiogenic edema. PATHOLOGIC FINDINGS

•  Gross—lungs usually heavy, red, or congested;

fail to collapse; often exhibit a wet cut surface; can ooze foam from major airways. •  Histopathology—depends on severity of the insult; early, mild: may note eosinophilic amorphous material filling the alveoli or can be near normal because fluid removed in processing; severe: alveolar hyaline membranes, alveolitis, and interstitial inflammatory infiltrates with neutrophils and macrophages evident and

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Blackwell’s Five-Minute Veterinary Consult

Pulmonary Edema, Noncardiogenic accompanied by atelectasis, vascular congestion, and hemorrhage; lesions can be found within hours of a severe insult.

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 TREATMENT

APPROPRIATE HEALTH CARE •  Inpatient vs. outpatient—depends on the severity of respiratory dysfunction and the underlying cause (e.g., airway obstruction or seizures generally require hospitalization). •  Make every effort to resolve and treat the underlying cause. •  Mild to moderate— patients generally improve within 24–48 hours; cardiovascular and respiratory support while the lung repairs. •  Severe—difficult to treat; usually requires positive-pressure ventilation (PPV) due to respiratory failure; many patients die despite treatment.

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NURSING CARE •  Oxygen therapy—vital in moderate to severe disease; administer via mask or hood, nasal catheter, or oxygen cage; inspired oxygen concentration depends on the severity of disease; most patients do well on 40–50% oxygen, but severe disease can require 80–100% to maintain stability. •  Severe— can require PPV and positive end-expiratory pressure (PEEP). •  Judicious fluid therapy with a balanced electrolyte solution as replacement solution for dehydration or shock; use cautious fluid administration and avoid fluid overload. •  Plasma, albumin, or synthetic colloids—consider with severe hypoproteinemia or low colloid osmotic pressure; improved oncotic pressure may minimize movement of fluid into lungs.

drugs. •  Furosemide—diuresis not indicated as edema due to permeability changes, not high hydrostatic pressure. May act as bronchodilator and decrease pulmonary shunting, though evidence is limited. Can consider cautious boluses (0.5–2 mg/kg IV, IM) or nebulization, particularly early in course of disease. •  Corticosteroids—for reduction of airway swelling in patients with upper airway obstruction; generally ineffective for pulmonary inflammatory response; if used, recommend anti-inflammatory dosage (e.g., dexamethasone SP at 0.05–0.1 mg/kg IV). •  The use of beta-adrenergic agonists such as terbutaline may increase clearance of alveolar fluid. •  Sedatives—use cautiously if anxiety is contributing to respiratory distress or airway obstruction. Sedation can decrease central respiratory drive, contributing to progression of respiratory failure. •  Additional therapy as indicated by underlying cause—anticonvulsants, analgesia for oral ulcerations. PRECAUTIONS •  Diuretics (e.g., furosemide)—can cause dehydration and decrease in intravascular volume, exacerbating cardiovascular collapse or shock with minimal effect on edema. •  Corticosteroids—can predispose patients to infectious complications (e.g., pneumonia).

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 FOLLOW-UP

disease progressing rapidly to fulminant pulmonary edema and respiratory failure is associated with a very poor prognosis.

PATIENT MONITORING •  Monitor respiratory rate, pattern and auscultation (every 2–4 hours) for the first 24–48 hours, depending on severity of disease. •  Assess pulmonary function by pulse oximetry or arterial blood gas analysis (initially every 2–4 hours), depending on severity of disease. •  Assess packed call volume (PCV) and total solids. Evaluate mucous membranes, pulse quality, heart rate, blood pressure, and urine output every 2–4 hours to assess cardiovascular status and possible progression to shock.

SURGICAL CONSIDERATIONS Relevant only for treating the underlying cause.

•  Avoid contact with electric wire. •  Correct and avoid airway obstruction. •  Manage

ACTIVITY Exercise restriction and minimal stress to decrease oxygen requirements. CLIENT EDUCATION

•  Warn client that the condition can worsen before improving. •  Inform client that severe

PREVENTION/AVOIDANCE

seizures and neurologic disease.

­

 MEDICATIONS

DRUG(S) OF CHOICE •  Damaged endothelium in the pulmonary vasculature—no specific treatment available. •  Inflammatory response—generated by a variety of mediators and cascades; cannot effectively be blocked by anti-inflammatory

POSSIBLE COMPLICATIONS Usually none if patient recovers from the acute crisis. EXPECTED COURSE AND PROGNOSIS •  Mild to moderate—resolution of signs in 24–72 hours with supportive care. •  Severe— difficult to treat; can require PPV if respiratory failure. •  Overall survival rates—

(continued)

80–90%. •  Long-term prognosis—excellent if responsive to therapy.

­

 MISCELLANEOUS

ASSOCIATED CONDITIONS Acute respiratory distress syndrome. SYNONYMS •  Acute alveolar failure. •  Acute lung injury. •  Capillary leak syndrome. •  Congestive atelectasis. •  Hemorrhagic lung syndrome. •  Progressive respiratory distress. •  Shock lung. •  Traumatic wet lung. SEE ALSO Acute Respiratory Distress Syndrome. ABBREVIATIONS

•  DIC = disseminated intravascular

coagulation. •  NT-ProBNP = B-type natriuretic peptide. •  PCV = packed cell volume. •  PEEP = positive end-expiratory pressure. •  PPV = positive-pressure ventilation. •  PT = prothrombin time. •  PTT = partial thromboplastin time. •  SIRS = systemic inflammatory response syndrome.

­Suggested Reading

Drobatz KJ, Saunders HM, Pugh C, Hendricks JC. Noncardiogenic pulmonary edema: 26 cases (1987–1993). J Am Vet Med Assoc 1995, 206:1732–1736. Kerr LY. Pulmonary edema secondary to upper airway obstruction in the dog: A review of nine cases. J Am Anim Hosp Assoc 1989, 25:207–212. Kolata RJ, Burrows CF. The clinical features of injury by chewing electrical cords in dogs and cats. J Am Anim Hosp Assoc 1981,17:219–222. Rozanski EA, Dhupa N, Rush JR, Murtaugh RJ. Differentiation of the etiology of pulmonary edema by measurement of the protein content. Proc Int Vet Emerg Crit Care Symp VI 1998:844. Ward JL, Lisciandro GR, Ware WA, Viall AK, et al. Evaluation of point-of-care thoracic ultrasound and NT-proBNP for the diagnosis of congestive heart failure in cats with respiratory distress. J Vet Intern Med 2018, 32:1530–1540. Author Cassandra O. Janson Consulting Editors Elizabeth Rozanski Acknowledgment The author and editors acknowledge the prior contribution of Lesley G. King.



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Pulmonary Thromboembolism

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 BASICS

DEFINITION Develops when a thrombus lodges in the pulmonary arterial (PA) tree, occluding blood flow to the portion of lung supplied by that artery. PATHOPHYSIOLOGY •  Pulmonary thromboembolism (PTE) associated with heartworm disease (HWD) occurs in situ in the pulmonary vessels; in most other instances, thrombus origin is unclear. •  Potential sites of origin include right atrium, venae cavae, and jugular, femoral or mesenteric veins; thrombi are carried in the venous circulation to the lungs, and lodge in the pulmonary arteries. •  Abnormal blood flow (stasis), vascular endothelial damage, and hypercoagulability are believed to predispose to thrombus formation. •  Often a complication of another primary disease process.

•  Tachycardia, weak pulses, jugular vein distension, pale or cyanotic mucous membranes, delayed capillary refill time, right-sided heart murmur, and split or loud S2 in severe cases.

CAUSES •  HWD. •  Neoplasia. •  Hyperadrenocorticism (Cushing’s disease) or corticosteroid administration. •  Proteinlosing nephropathy or enteropathy. •  Immune-mediated hemolytic anemia (IMHA). •  Pancreatitis. •  Pulmonary hypertension (PH). •  Orthopedic trauma or surgery. •  Sepsis. •  Disseminated intra­ vascular coagulation. •  Liver disease. RISK FACTORS •  Coagulopathy, especially any hypercoagulable state. •  Diseases listed under Causes are associated. •  Estrogen administration, immobility, and air travel may be causative in humans.

SYSTEMS AFFECTED

•  Cardiovascular—pulmonary hypertension

(PH) may result, leading to right ventricular enlargement, right ventricular failure (cor pulmonale), and reduced cardiac output. •  Respiratory—diminished pulmonary blood flow leads to arterial hypoxemia and dyspnea. GENETICS N/A INCIDENCE/PREVALENCE

•  Unknown—likelihood of PTE increases with

abnormal coagulation or severe systemic disease. •  Uncommon in the dog and cat; likely underdiagnosed due to nonspecific clinical signs, lack of clinical suspicion, and paucity of noninvasive, definitive diagnostic tests. GEOGRAPHIC DISTRIBUTION N/A SIGNALMENT Species

Dog and cat. Breed Predilections

N/A

Mean Age and Range

•  More frequently seen in middle-aged to older dogs. •  Bimodal age distribution

reported in cats; peak occurrence 10 years of age.

Predominant Sex

N/A

SIGNS Historical Findings

•  Often reflect the primary disease process. •  May include peracute dyspnea, anorexia,

syncope, collapse, cough, hemoptysis, weakness, exercise intolerance, and inability to sleep or get comfortable.

Physical Examination Findings

•  Tachypnea and dyspnea in most animals; adventitious lung sounds in some animals.

­

 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Other diseases that cause clinically important dyspnea and hypoxemia without profound radiographic findings include upper airway obstruction, laryngeal paralysis, and diffuse airway disease processes (e.g., toxin inhalation and interstitial lung disease). •  Upper airway obstruction often manifests as inspiratory dyspnea; breath sounds often loudest over trachea or larynx. •  PTE should be a leading diagnostic consideration in a patient with acute onset of dyspnea or collapse and a known associated disease. CBC/BIOCHEMISTRY/URINALYSIS CBC—may be normal; thrombocytopenia may be seen in up to 50% of dogs with PTE; leukocytosis may develop. Biochemistry— results often reflect underlying disease. Urinalysis—results often reflect underlying disease; evaluate for proteinuria. OTHER LABORATORY TESTS •  Arterial blood gases often show arterial hypoxemia (Pao2 often 10 years of age.

Predominant Sex

UTI affects females more commonly than males. SIGNS General Comments

Differentiation between pyelonephritis, subclinical bacteriuria, and lower UTI may be difficult in some patients. Historical Findings

•  Polyuria/polydipsia.

­

 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Clinical diagnosis of pyelonephritis is usually presumptive, based on results from CBC, biochemical analysis, urinalysis, urine culture, and diagnostic imaging; definitive diagnosis is not usually required for planning treatment. •  Since many lack specific symptoms attributable to pyelonephritis, any patient with UTI could potentially have pyelo­ nephritis; the best methods for differentiating between upper and lower UTI are ultrasonography or excretory urography. •  Consider pyelonephritis as a rule-out for fever of unknown origin, polyuria/polydipsia, acute decline in renal function, and/or lumbar/abdominal pain. CBC/BIOCHEMISTRY/URINALYSIS

•  CBC—results often normal with chronic

pyelonephritis; leukocytosis and immature neutrophilia may be detected in some patients.

•  Biochemistry—values usually normal

unless chronic pyelonephritis leads to CKD (azotemia with inappropriate urine specific gravity). •  Urinalysis may reveal hematuria, pyuria, proteinuria, bacteriuria, and leukocyte casts. Leukocyte casts are diagnostic for renal inflammation, but unfortunately are very uncommon. Observe dilute urine specific gravity in patients with nephrogenic diabetes insipidus, which may occur secondary to pyelonephritis from Gram-negative bacteria. Absence of these abnormalities does not rule out pyelonephritis. OTHER LABORATORY TESTS

•  Quantitative urine culture to confirm UTI;

see Lower Urinary Tract Infection chapters for interpretation. •  Dogs with chronic pyelonephritis may have a negative urine culture and may require multiple urine cultures to confirm UTI. IMAGING

•  Ultrasonography and excretory urography

are the best methods for presumptively differentiating between upper and lower UTI. Ultrasonography is more sensitive than excretory urography for identification of mild-to-moderate acute pyelonephritis. •  Ultrasonographic findings supporting pyelonephritis include dilation of the renal pelvis and proximal ureter and a hyperechoic mucosal margin line within the renal pelvis and/or proximal ureter. •  IV urography may reveal decreased opacity of the nephrogram phase, dilation and blunting of the renal pelvis with lack of filling of the collecting diverticula, decreased opacity of contrast media in the collecting system, and dilation of the proximal ureter. •  In patients with acute pyelonephritis, the kidneys may be large; in patients with chronic pyelonephritis, the kidneys may be small, with an irregular surface contour. •  Concomitant nephroliths detected in some patients by survey radiography or ultrasonography. DIAGNOSTIC PROCEDURES Definitive diagnosis requires urine cultures obtained from the renal pelvis. Pyelocentesis can be performed percutaneously using ultrasound guidance or during exploratory surgery. Urine cultures from the renal pelvis usually are similar to cultures from the bladder unless obstruction is present. PATHOLOGIC FINDINGS

•  Kidneys affected by chronic pyelonephritis

may have areas of infarction and scarring on the capsular surface. The renal pelvis and collecting diverticula may be dilated and distorted from chronic infection and inflammation. Purulent exudate is occasionally observed in the renal pelvis.



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Pyelonephritis

(continued)

•  Light microscopic findings include

papillitis, pyelitis, interstitial nephritis, and leukocyte casts in tubular lumens.

­

 TREATMENT

APPROPRIATE HEALTH CARE Outpatient treatment with oral antibiotics if the animal is clinically well. Hospitalized care if patient is dehydrated, has decreased renal function or if sepsis is suspected. ACTIVITY Unlimited DIET Renal therapeutic diets are recommended for concomitant CKD. CLIENT EDUCATION •  Recurrent pyelonephritis may be asympt­ omatic. Unresolved chronic pyelonephritis may lead to progression of CKD; diagnostic follow-up is important to document resolution or progression of pyelonephritis. •  In patients with infected nephroliths, resolution of pyelonephritis is unlikely unless the nephroliths are removed. SURGICAL CONSIDERATIONS •  Complete obstruction of the upper urinary tract of a patient with pyelonephritis may rapidly progress to septicemia and therefore should be regarded as a medical emergency. The cause of the obstruction should be corrected by endoscopic or surgical ureteral stent placement. •  Infected nephroliths—remove surgically, medically dissolve (struvite), or fragment by extracorporeal shock wave lithotripsy; use periprocedural antibiotics to reduce the risk of urosepsis when manipulating infected nephroliths. •  Unilateral nephrectomy is usually not effective for elimination of suspected unilateral pyelonephritis.

­

 MEDICATIONS

DRUG(S) OF CHOICE •  Base antibiotic selection on urine culture and susceptibility testing. Initiate antibiotics pending culture results. •  Antibiotics should be bactericidal, achieve good serum and urine concentrations, and not be nephrotoxic.

•  High serum and urinary antibiotic

concentrations do not necessarily ensure high tissue concentrations in the renal medulla; thus, chronic pyelonephritis may be difficult to eradicate. •  If systemically ill or azotemic, administer IV antibiotics for initial 48 hours. •  Give orally administered antibiotics at full therapeutic dosages for 2–6 weeks. Duration of antibiotics required for resolution of pyelonephritis is not definitively known. •  Do not use drugs that achieve good concentrations in urine but poor concen­ trations in serum (e.g., nitrofurantoin). CONTRAINDICATIONS Do not use aminoglycosides unless no other alternatives exist on the basis of urine culture and susceptibility testing. PRECAUTIONS Trimethoprim-sulfa combinations can cause side effects (keratoconjunctivitis sicca, blood dyscrasias, and polyarthritis) when administered for more than 4 weeks.

­

 FOLLOW-UP

PATIENT MONITORING Perform urine cultures and urinalysis during antibiotic administration (∼5–7 days into treatment) and 1 and 4 weeks after antibiotics are finished. PREVENTION/AVOIDANCE Eliminate factors predisposing to UTI; correct ectopic ureters. POSSIBLE COMPLICATIONS Progressive CKD, recurrent pyelonephritis, struvite nephroliths, septicemia, septic shock, metastatic infection (e.g., endocarditis, polyarthritis). EXPECTED COURSE AND PROGNOSIS •  Patients with acute or subacute pyelo­ nephritis—fair to good, with a return to normal health unless the patient also has nephroliths, CKD, or some other underlying cause for UTI (e.g., obstruction or neoplasia). •  Established chronic infection of the renal medulla may be difficult to resolve because of poor tissue penetration of antibiotics. •  Patients with CKD caused by pyelo­ nephritis—prognosis determined by the severity and rate of progression of the CKD.

•  Recurrent pyelonephritis is likely if infected

nephroliths are not removed.

­

 MISCELLANEOUS

ASSOCIATED CONDITIONS Hyperadrenocorticism, exogenous glucocorticoid administration, CKD, hyperthyroidism (cats), and diabetes mellitus are associated with lower UTI, which can ascend into the ureters and kidneys. PREGNANCY/FERTILITY/BREEDING Use antibiotics that are safe for the pregnant bitch or queen. SYNONYMS Upper UTI, pyelitis. SEE ALSO •  Chronic Kidney Disease. •  Lower Urinary Tract Infection, Bacterial. •  Lower Urinary Tract Infection, Fungal. •  Nephrolithiasis. •  Urinary Tract Obstruction. •  Urolithiasis, Struvite—Dogs. ABBREVIATIONS

•  CKD = chronic kidney disease. •  UTI = urinary tract infection.

­Suggested Reading

Bouillon J, Snead E, Casswell J, et al. Pyelonephritis in dogs: retrospective study of 47 histologically diagnosed cases (2005–2015). J Vet Intern Med 2018, 32:249–259. Etedali NM, Reetz JA, Foster JD. Complications and clinical utility of ultrasonographically guided pyelocentesis and antegrade pyelography in cats and dogs: 49 cases (2007–2015). J Am Vet Med Assoc 2019, 254:826–834. Foster JD, Krishnan H, Cole S. Characterization of subclinical bacteriuria, bacterial cystitis and pyelonephritis in dogs with chronic kidney disease. J Am Vet Med Assoc 2018, 252:1257–1262. Author Larry G. Adams Consulting Editor J.D. Foster Acknowledgment The author and editors acknowledge the prior contribution of Carl A. Osborne.  Client Education Handout available online

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Pyoderma •  Variable pruritus—typically pruritic; the

­

 BASICS

DEFINITION •  Bacterial infection of the skin. •  Surface bacterial infections—often referred to as a “hot spot;” represents an acute moist dermatitis involving the surface of the skin. •  Superficial pyoderma—involves the epidermis and the intact hair follicle; includes mucocutaneous pyoderma. •  Deep pyoderma—involves the dermis and possibly subcutis; furunculosis is often present; patients can be systemically ill. PATHOPHYSIOLOGY

•  Skin infections occur when the surface

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barrier of the skin has been broken, the skin has become macerated by chronic exposure to moisture, the population of resident bacterial flora has been altered, circulation has been impaired, and/or immunocompetency of the patient has been negatively impacted by systemic illness or immunosuppressive therapy. •  Pyoderma is usually secondary to an underlying cause; the primary, underlying cause should be identified and managed to reduce the frequency and recurrence of skin infections. SYSTEMS AFFECTED Skin/exocrine. GENETICS N/A INCIDENCE/PREVALENCE

•  Dogs—very common. •  Cats—uncommon.

SIGNALMENT Species

Dog and cat. Breed Predilections

•  Dog—short-coated breeds, especially those

with excessive skin folds.

•  German shepherd dog—severe, inflamm­

atory and deep pyoderma that responds to antibiotics; frequently relapses.

Mean Age and Range

Age of onset is usually directly related to the underlying cause. Predominant Sex

underlying cause may be pruritic or the staphylococcal infection itself may be pruritic; may not be pruritic if associated with hyper­cortisolemia.

Physical Examination Findings

•  Papules. •  Pustules. •  Crusted papules. •  Crusts. •  Epidermal collarettes. •  Circular erythematous or hyperpigmented

patches (macules).

•  Alopecia; moth-eaten hair coat. •  Hemorrhagic bullae. •  Scaling. •  Lichenification. •  Erosions. •  Ulcerations. •  Target lesions. •  Abscess. •  Furunculosis, cellulitis.

CAUSES

•  Staphylococcus pseudintermedius—most

frequent dogs and cats.

•  Pasteurella multocida—cats. •  Deep bacterial skin infections may be

complicated by Gram-negative organisms (e.g., Escherichia coli, Proteus spp., Pseudomonas spp.). •  Rarely caused by higher bacteria (e.g., Actinomyces, Nocardia, Mycobacteria, Actinobacillus). RISK FACTORS

•  Hypersensitivity—flea allergic dermatitis;

atopic dermatitis; cutaneous adverse reaction to food; contact allergic dermatitis. •  Parasites—especially Demodex spp. •  Fungal infection—dermatophytosis (Microsporum canis, Microsporum gypseum, or Trichophyton mentagrophytes) most common. •  Endocrine diseases—hypothyroidism; hyperadrenocorticism; sex hormone imbalance. •  Immunosuppression—excessive cortico­ steroid administration; young animals. •  Seborrhea—chin acne; schnauzer comedo syndrome. •  Conformation—short coat; skin folds; redundant interdigital skin. •  Trauma—pressure points; grooming; scratching; rooting behavior; irritants. •  Foreign body—foxtail; grass awn.

extent of lesions may be obscured by hair coat. •  Deep—often affects the chin, dorsal muzzle, pressure points, and feet; may be generalized and associated with symptoms of systemic illness, such as pyrexia and/or pain. Historical Findings

•  Acute or gradual onset.

OTHER LABORATORY TESTS N/A DIAGNOSTIC PROCEDURES

•  Multiple skin scrapings—demodicosis. •  Direct smear from intact pustule—

neutrophils with intracellular bacteria, typically cocci. •  Cytology from underneath a crust or edge of an epidermal collarette; help differentiate pemphigus foliaceus (acantholytic keratinocytes) and deep fungal infections (blastomycosis, cryptococcosis) from pyoderma; tissue grains may identify filamentous organisms characteristic of higher bacteria. •  Trichograms—dermatophytosis, follicular abnormalities. •  Dermatophyte culture—dermatophytosis. •  Surface or papule/pustule cytology— pemphigus foliaceus. •  Intradermal allergy testing—atopy. •  Elimination diet trial—food hypersensitivity. •  Endocrine tests—hypothyroidism, hyperadrenocorticism. •  Skin biopsy is rarely useful unless the infection is deep in nature; utilized to obtain tissue sample for macerated tissue culture. •  Recommended in recurrent cases and/or

SIGNS •  Superficial—usually involves the trunk;

CBC/BIOCHEMISTRY/URINALYSIS •  Superficial pyoderma—normal or may reflect underlying cause (e.g., anemia due to hypothyroidism; stress leukogram and high serum alkaline phosphatase due to hyperadrenocorticism; eosinophilia due to parasitism). •  Generalized, deep pyoderma—may demonstrate leukocytosis with a regenerative left shift and hyperglobulinemia; abnormalities related to an underlying cause may be present.

Culture and Susceptibility Testing

None

General Comments

pyoderma; may be associated with systemic symptoms. •  Pustular diseases—dermatophytosis; demodicosis; pemphigus foliaceus; and subcorneal pustular dermatosis. •  Deep furunculosis—higher bacterial infection; demodicosis; dermatophytosis; opportunistic fungal infections; deep fungal infections; panniculitis; and zinc-responsive dermatosis. •  Superficial pyoderma in short-coated breeds often misdiagnosed as urticaria due to acute onset of pruritic papules and follicular tufting.

­

 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Hypersensitivity—pruritus precedes lesions; persists with resolution of pyoderma. •  Flea allergic dermatitis or atopic dermatitis— may be seasonal. •  Endocrinopathy—relapsing pyoderma; consider if not associated with pruritus or pruritus resolves with resolution of the

failure to respond to empiric antibiotics.

•  Often positive for S. pseudintermedius. •  Other organisms besides staphylococci and

higher bacteria may be cultured from lesions of deep pyoderma. •  Contents of an intact pustule—most reliable results for superficial infections. •  Punch biopsy obtained utilizing sterile technique for macerated tissue culture; especially and removal of the epidermis for



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Canine and Feline, Seventh Edition

Pyoderma

(continued)

deep pyoderma; more likely false-negative results with superficial pyoderma. •  Freshly expressed exudate from a draining tract or from beneath a crust—may yield the pathogen or a contaminant if the lesion is not intact. PATHOLOGIC FINDINGS

•  Subcorneal pustules. •  Intraepidermal neutrophilic microabscesses. •  Perifolliculitis. •  Folliculitis. •  Furunculosis. •  Nodular to diffuse dermatitis. •  Panniculitis. •  Inflammatory reaction—suppurative or

pyogranulomatous.

•  Tissue grains within pyogranulomas—

observed most often with Actinomyces, Actinobacillus, and Nocardia. •  Special stains—used to identify Gramnegative bacteria or acid-fast organisms.

­

 TREATMENT

APPROPRIATE HEALTH CARE Usually outpatient, except for severe, generalized deep pyoderma. NURSING CARE •  Severe, generalized, deep pyoderma—may require IV fluids, parenteral antibiotics, and/ or daily whirlpool baths. •  Benzoyl peroxide or chlorhexidine shampoos—remove surface debris. •  Frequent topical therapy can help reduce the severity and frequency of recurrence. •  Whirlpool baths—deep pyoderma; remove crusted exudate; encourage drainage; decrease inflammation and improve tissue oxygenation. DIET Novel protein or hydrolysate diet if secondary to cutaneous adverse reaction to food. SURGICAL CONSIDERATIONS Fold pyoderma may require surgical correction to prevent recurrence.

•  Amoxicillin–clavulanate—most isolates of

Staphylococcus and P. multocida susceptible; generally effective for skin infections in cats. •  Superficial pyoderma—initially treated empirically with one of the antibiotics listed above. •  Recurrent, resistant, or deep infections— choose antibiotic therapy based upon culture and susceptibility testing (e.g., chloramphenicol). •  Multiple organisms with different antibiotic susceptibilities—select antibiotic on basis of the staphylococcal susceptibility. CONTRAINDICATIONS Corticosteroids—mask inflammation causing therapy to be discontinued prematurely and resulting in selection for resistant organisms; if used concurrently, therapy should be extended and the patient should be reevaluated before discontinuing antibiotic therapy. PRECAUTIONS •  Cephalosporins, erythromycin, lincomycin, and clindamycin—vomiting; administer with food. •  Aminoglycosides—renal toxicity usually precludes prolonged systemic use. •  Trimethoprim–sulfamethoxazole—kerato­ conjunctivitis sicca, fever, hepatotoxicity, polyarthritis, and hematologic abnormalities, especially neutropenia; not recommended for use in Doberman pinschers. •  Chloramphenicol—use with caution in cats; mild, reversible anemia in dogs (uncommon); associated with aplastic anemia in humans; rear temporary limb muscle weakness is a possible side effect. POSSIBLE INTERACTIONS Trimethoprim-sulfamethoxazole—falsely decreased thyroid hormone test results. ALTERNATIVE DRUG(S) Bacterin (Staphage Lysate, Delmont Laboratories), staphoid AB, or autogenous injections—may improve antibiotic efficacy and decrease infection recurrence.

 MEDICATIONS

DRUG(S) OF CHOICE •  S. pseudintermedius isolates—usually susceptible to cephalosporins, amoxicillin– clavulanate, erythromycin, clindamycin, and trimethoprim–sulfamethoxazole; somewhat less responsive to lincomycin; frequently resistant to amoxicillin, ampicillin, penicillin.

pyoderma; also consider causes for poor wound healing including hypothyroidism. •  Topical benzoyl peroxide gel or mupirocin 2% ointment may be helpful adjunct therapies—chin acne, fold pyoderma, respectively. •  Identification and management of the underlying cause is crucial to prevent recurrence. POSSIBLE COMPLICATIONS Bacteremia and septicemia. EXPECTED COURSE AND PROGNOSIS Likely to be recurrent or nonresponsive if underlying cause is not identified and effectively managed.

­

 MISCELLANEOUS

ASSOCIATED CONDITIONS N/A AGE-RELATED FACTORS •  Impetigo—affects young dogs before puberty; can be associated with poor husbandry; often requires only topical therapy. •  Superficial pustular dermatitis—occurs in kittens; associated with overzealous “mouthing” by the queen. •  Pyoderma secondary to atopic dermatitis— usually begins between 1 and 3 years of age. •  Pyoderma secondary to endocrine disorders— usually begins in middle adulthood. ZOONOTIC POTENTIAL

•  Cutaneous tuberculosis—rare. •  Feline leprosy—unknown.

PREGNANCY/FERTILITY/BREEDING N/A SEE ALSO

•  Acne—Cats. •  Acne—Dogs. •  Perianal Fistula. •  Pododermatitis.

­Suggested Reading

­ ­

•  Padded bedding—may ease pressure point

 FOLLOW-UP

PATIENT MONITORING Administer oral antibiotics for a minimum of 7–10 days beyond clinical cure; approx­ imately 3–4 weeks for superficial pyoderma; 6–10 weeks for deep pyoderma. PREVENTION/AVOIDANCE •  Routine bathing with benzoyl peroxide or chlorhexidine shampoos—may help prevent recurrences.

Helton Rhodes KA, Werner A. Blackwell’s Five-Minute Veterinary Consult: Clinical Companion: Small Animal Dermatology, 3rd ed. Hoboken, NJ: Wiley-Blackwell, 2018. Author Elizabeth R. Drake Consulting Editor Alexander H. Werner Resnick  Client Education Handout available online

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Blackwell’s Five-Minute Veterinary Consult

Pyoderma—Methicillin-Resistant

­

 BASICS

OVERVIEW •  Staphylococcal bacterial skin infection resistant to all β-lactam antibiotics. •  Most often caused by Staphylococcus pseudintermedius; rarely Staphylococcus aureus. SIGNALMENT Dogs and Cats

•  More common with chronic, primary skin

conditions; associated with exposure to one or more courses of antibiotic therapy. •  Pyoderma less common in cats. SIGNS

Dogs and Cats

•  Papules. •  Pustules. •  Crusts. •  Crusted

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papules. •  Epidermal collarettes. •  Furunculosis, cellulitis if deep. •  Circular erythematous or hyperpigmented spots (macules). •  Alopecia, moth-eaten hair coat, especially in short-coated breeds. •  Hemorrhagic bullae. •  Scale. • Lichenification. • Abscess. • Pyoderma that persists despite appropriate empiric therapy. CAUSES & RISK FACTORS

•  Hypersensitivity—flea allergic dermatitis;

atopic dermatitis; cutaneous adverse reaction to food; contact allergic dermatitis. • Parasites—especially Demodex spp. •  Endocrine—hypothyroidism; hyperadreno­ corticism (especially if nonpruritic). •  Immunosuppression—iatrogenic due to chronic glucocorticoid therapy; young animals. •  Seborrhea—chin acne; schnauzer comedo syndrome. •  Additional—short coat; skin folds; redundant interdigital skin; trauma of pressure points, especially in hypothyroid dogs; excessive grooming; scratching; rooting behavior; irritants; foreign bodies (foxtail; grass awn).

­

 DIAGNOSIS

CBC/BIOCHEMISTRY/URINALYSIS Generalized, deep pyoderma—may demonstrate leukocytosis with regenerative left shift and hyperglobulinemia; in addition, may reflect underlying cause; sepsis is a concern, especially if patient is immunosuppressed. DIAGNOSTIC PROCEDURES •  Culture and susceptibility testing—essential when methicillin-resistant infection is suspected; should be performed when there is inadequate response to empiric treatment with antibiotics or in cases with a history of methicillin-resistant S. pseudintermedius (MRSP). •  Multiple skin scrapings— demodicosis. •  Direct smear from intact pustule—neutrophils with intracellular bacteria. •  Cytology—from underneath crust or edge of epidermal.collarette. •  Skin biopsy—rarely useful unless infection deep; used to obtain tissue sample for macerated tissue culture. •  Dermatophyte culture— fungal infection. •  Intradermal allergy testing—atopic dermatitis. •  Elimination diet trial—cutaneous adverse reaction to food. •  Endocrine tests—hypothyroidism, hyper­adrenocorticism.

Cats

•  Dermatophytosis. •  Flea-allergic dermatitis.

•  Demodicosis. •  Pemphigus foliaceus. •  Methicillin-sensitive pyoderma. •  Epitheliotropic lymphoma in older animals.

 FOLLOW-UP

PATIENT MONITORING Regular reevaluation of patient while still receiving treatment aids in decision regarding continuation of therapy or need for additional diagnostic tests. PREVENTION/AVOIDANCE •  Choose antibiotic therapy from culture and susceptibility data—treatment failure occurs when antibiotic changes made without evidence. •  Successful management of underlying disease. •  Handwashing before and after handling patient. EXPECTED COURSE AND PROGNOSIS

•  Good if antibiotic choice is based on

culture and susceptibility data and underlying cause is managed. •  Methicillin-resistant infections not more virulent, but fewer antibiotic choices available for treatment.

PATHOLOGIC FINDINGS

neutrophilic microabscesses. •  Perifolliculitis. • Folliculitis. • Furunculosis—deep infection. •  Nodular to diffuse dermatitis. •  Panniculitis—deep infection. •  Inflammatory reaction—suppurative; pyogranulomatous with deep infections.

­

 TREATMENT

•  Topical therapy essential—chlorhexidine

shampoo or spray, dilute bleach bathing, mupirocin ointment, for localized disease. •  Some cases resolve with topical therapy only—must be consistent/frequent. •  Generalized, deep pyoderma—hospitali­ zation, IV fluids, IV antibiotics, whirlpool baths, depending on severity and risk for sepsis.

­

 MISCELLANEOUS

ZOONOTIC POTENTIAL •  Exposure of humans and animals to methicillin-resistant S. aureus (MRSA) and MRSP is common. •  MRSP infections in humans are rare. •  MRSP is not MRSA— MRSA infections in animals are rare and most associated with exposure to humans with MRSA infection. SEE ALSO

•  Pododermatitis. •  Pyoderma.

ABBREVIATIONS

•  MRSA = methicillin-resistant S. aureus.

• MRSP = methicillin-resistant S. pseudintermedius.

INTERNET RESOURCES Weese SJ: www.wormsandgermsblog.com

­Suggested Reading

Dogs

•  Methicillin-sensitive pyoderma. •  Pemphigus foliaceus. •  Systemic lupus erythematosus. •  Other primary causes for pyoderma. •  Epitheliotropic lymphoma (older animals).

­

•  Subcorneal pustules. •  Intraepidermal

DIFFERENTIAL DIAGNOSIS •  Demodicosis. •  Dermatophytosis.

may suppress immune system function and delay resolution.

­

 MEDICATIONS

DRUG(S) OF CHOICE •  Antibiotic therapy must be based on culture and susceptibility data. •  Appropriate anti­biotics must be administered long enough to resolve infection. CONTRAINDICATIONS/POSSIBLE INTERACTIONS Corticosteroid steroids—masks inflammation and suppresses immune system function; therapy should be discontinued. Oclacitinib—

Helton Rhodes KA, Werner A. Blackwell’s Five-Minute Veterinary Consult: Clinical Companion: Small Animal Dermatology, 3rd ed. Hoboken, NJ: Wiley-Blackwell, 2018. Author Elizabeth R. Drake Consulting Editor Alexander H. Werner Resnick



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Pyometra SIGNS

•  Elevated alanine aminotransferase and

Historical Findings

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 BASICS

DEFINITION Pyometra is a bacterial suppurative inflammation of the endometrium leading to intraluminal accumulation of purulent exudate within the uterus.

•  Dogs—usually within 12 weeks of last estrus. •  Cats—usually within 4 weeks of last estrus. •  History of treatment with estrogens and/or

progestogens.

Physical Examination Findings

•  Uterus—may be enlarged on abdominal

palpation.

PATHOPHYSIOLOGY •  Incompletely understood and multifactorial. •  Classic theory—repeated exposure of endometrium to high concentrations of estrogen during proestrus and estrus followed by high concentrations of progesterone during diestrus without pregnancy leads to development of cystic endometrial hyperplasia (CEH), which predisposes uterus to ascending bacterial infections. •  Strains of Escherichia coli with uropathogenic virulence factors that allow adhesion to the endometrium and establish­ ment of an infection without CEH enter uterus during proestrus and estrus and act as a mucosal irritant stimulating development of CEH under the influence of progesterone. Uterine secretions may act as a growth medium for ascending bacteria. •  Regardless of underlying cause, pyometra does not occur in absence of progesterone (endogeneous or exogeneous).

•  Systemic illness—depends on duration and

SYSTEMS AFFECTED •  Reproductive. •  Hemic/lymphatic/immune.

•  No correlation with pseudopregnancy in

GENETICS •  Genetic predisposition suspected in some related bitches. •  Suggested breed predisposition in Bernese mountain dog, Rottweiler, rough-coated collie, oriental cat breeds. INCIDENCE/PREVALENCE Accurate assessment difficult because most dogs and cats in the United States undergo elective ovariohysterectomy (OHE). A recent Swedish study reported overall incidence of pyometra in bitches as 199 per 10,000 dogs at risk and in queens as 17 per 10,000 cats at risk. Lower incidence in queens because they are induced ovulators. SIGNALMENT Species

Dog and cat. Mean Age and Range

Usually >6 years old; range 4 months to 16 years; mean 7.25 years. Predominant Sex

•  Female—ovary intact. •  Spayed bitches and queens with ovarian

remnant syndrome may develop a stump pyometra.

severity. •  Open cervix—bloody, purulent vaginal discharge, may not be noticed in queens. •  Closed cervix—systemically ill from endotoxemia and bacteremia: polyuria, polydipsia, lethargy, inappetence/anorexia, vomiting, abdominal distension, dehydration, shock. •  Pyrexia.

alkaline phosphatase enzyme activities.

•  Electrolyte disturbances. •  Urinalysis—isosthenuria, bacteriuria,

glucosuria, and proteinuria possible. Collect sample by catheterization of urinary bladder to avoid risk of uterine puncture with cystocentesis. Midstream urine sample may be contaminated by vaginal discharge. OTHER LABORATORY TESTS

•  Cytologic examination of vulvar discharge—

dogs.

degenerate neutrophils, phagocytized bacteria; may be indistinguishable from purulent discharge associated with vaginal disease (e.g., vaginitis, vaginal mass, foreign object). Vaginoscopy can confirm origin and rule out other causes of discharge. •  Bacterial culture and sensitivity—vulvar discharge sample to be taken directly from the uterus transcervically or cranial vagina with the aid of a vaginal speculum and guarded swab. A free-catch urine sample can also be useful as the causative agent in the pyometra is often located in the bladder. •  Serologic testing for Brucella canis—rapid slide agglutination test as a screen; sensitive but not specific. If positive, recheck by an agar gel immunodiffusion test or bacterial culture of whole blood, lymph node aspirate, or vulvar discharge. •  Hormone assay—in most cases, progesterone concentration will be >2 ng/mL; important to measure in animals that present in anestrus, as treatment with a progesterone receptor antagonist will be ineffective.

progestagens (for estrus prevention) in both queens and bitches.

Radiography

CAUSES

•  Dogs—repeated exposure of endometrium

to estrogen followed by prolonged exposure to progesterone without pregnancy. •  Cats—may be the result of estrogen at estrus followed by a progestational (pseudo­ pregnancy) phase caused by spontaneous ovulation or ovulation induction. RISK FACTORS

•  Middle-aged to older, nulliparous ovary-

intact females may be predisposed.

•  Pharmacologic use of estrogen (mismate

shot) during midestrus to early diestrus.

•  Long-term and high-dose use of

IMAGING •  Enlarged, distended uterus (see Web Figure 1). •  Rule out pregnancy— fetal skeletal

ossification occurs 45 days after ovulation.

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Pregnancy. •  Vaginitis. •  Metritis and retained fetal membranes (associated within first days post partum). •  Hydrometra (serous intrauterine discharge); mucometra (mucoid intrauterine discharge); hematometra (hemorrhagic intrauterine discharge). •  Other causes of polyuria/polydipsia— diabetes mellitus, hyperadrenocorticism, renal disease. CBC/BIOCHEMISTRY/URINALYSIS

•  Neutrophilia or neutropenia with left shift ±

toxic change; more severe with closed cervix. •  Normocytic, normochromic anemia. •  Hyperglobulinemia, hyperproteinemia, hypoalbuminemia, hypercholesterolemia, elevated C-reactive protein concentration. •  Azotemia.

Ultrasonography

•  Uterine horns distended with intraluminal

fluid, with or without flocculation. Uterine wall thickened with irregular edges and small hypoechoic areas consistent with cystic change (CEH) (see Web Figure 2), uterine wall can appear thin if severely distended; monitoring of the volume of uterine fluid is necessary during medical therapy; presence of severe CEH and/or ovarian cysts associated with poorer prognosis for medical manage­ ment and fertility. •  Rule out pregnancy—20–24 days after ovulation. •  Pyometra may rarely occur with pregnancy in dogs. DIAGNOSTIC PROCEDURES Vaginoscopy—indicated in dogs with purulent vulvar discharge and no apparent uterine enlargement; allows determination of site of origin of the discharge; not possible in cats.

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Pyometra PATHOLOGIC FINDINGS •  Endometrium (dogs and cats)— cobblestone appearance (see Web Figure 3). •  Cystic endometrial surface—covered by malodorous, mucopurulent exudate; thickened by increased endometrial gland size and cystic gland distension.

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 TREATMENT

APPROPRIATE HEALTH CARE •  Inpatient; life-threatening condition if the cervix is closed, resulting in endotoxemia, bacteremia, and sepsis. Resuscitation requires immediate IV fluid administration and broad-spectrum antibiotics to stabilize for anesthesia and surgery. •  Open-cervix pyometra may be a candidate for medical therapy. NURSING CARE Supportive care.

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CLIENT EDUCATION •  Medical treatment only recommended for valuable, young (4 years), bitches with evidence of chronic CEH changes and/or ovarian follicular cysts, bitches that present systemically unwell and require immediate emergency care and stabilization. •  Patients should be systemically stabilized prior to anesthesia for surgery (correction of any acid–base derangements, dehydration, hypotension, shock, electrolyte abnormalities, arrythmias) and administered IV fluids and IV broad-spectrum antibiotics. •  Closed-cervix pyometra—exercise great care in handling the enlarged and friable uterus (see Web Figure 4). •  Place saline-soaked laparotomy sponges in abdomen to prevent leakage of purulent material into peritoneal cavity.

(continued)

Cloprostenol

•  Synthetic PGF2α analogue; longer action

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 MEDICATIONS

DRUG(S) OF CHOICE Antibiotics

•  Empirical, pending results of bacterial

culture and sensitivity: ◦◦ Broad-spectrum—ampicillin 22 mg/kg PO, IV q8h; amoxicillin and clavulonic acid 22 mg/kg, PO, q12h; ampicillin and sulbactam 22–30 mg/kg IV q8–12h or cefazolin 22 mg/kg IV, IM q8h combined with enrofloxacin 5–10 mg/kg PO q24h. ◦◦ Continue for at least 14 days after resolution of vulvar discharge and fluid in uterine lumen. •  Rationale of medical therapy—remove progesterone and its effects on uterus, eliminate bacteria from uterus, promote cervical dilation and drainage of pus from the uterus. Aglepristone

•  Progesterone receptor antagonist;

competitively binds to progesterone receptor with greater affinity than natural progesterone, preventing biological effect of progesterone. Will not lower progesterone levels. •  Dose—10 mg/kg SC, days 1, 2, 8, and if not cured day 14 and 28 in bitches. An additional injection at day 5 has been associated with an improved treatment success rate. In queens, 15 mg/kg SC is recommended. Minimal side effects. Excellent choice for closed pyometras as it dilates the cervix with minimal uterine contractions. Evacuation of uterus may be improved by adding prostaglandin. Aglepristone is not registered or approved by FDA in United States and not suitable for use in bitches with poor liver or kidney function. Prostaglandins (PGF2α)

•  Doses listed here for native compound only

(dinoprost tromethamine; Lutalyse®); has both luteolytic and ecobolic actions. •  Lower doses minimize side effects and ecobolic effect, especially in closed pyometras. Once the cervix is fully dilated the dose can be gradually increased if tolerated. •  Animals should be monitored in hospital for at least 1 hour after each treatment. If animal is systemically well, may be managed as outpatient. •  Side effects (dose-dependent)—tachypnea, vomiting, diarrhea, urination, anxiety; seen 20 minutes after administration and last for 15–30 minutes. Use of PGF2α in brachy­ cephalic breeds is contraindicated due to their predisposition to bronchospasm. •  Dogs and cats—10 μg/kg SC q5-6h day 1, then increase to 20–25 μg/kg q5–6h if tolerated for 1–2 days; then increase to 50 μg/ kg q5–6h for 3–4 days. Queens are more resistant to PGF2α than bitches; often higher doses for longer periods are required.

(>30 hours) than natural form of PGF2α.

•  Dogs—1 μg/kg SC q24h for 7–14 days;

convenience of once a day or every 2–3 days treatment but greater side effects, stimulates less uterine contractions and prolonged time to resolution compared to natural form of PGF2α.

Dopamine Agonists

Cabergoline (5 μg/kg PO q24h for 7–14 days) or bromocriptine (10–20 μg/kg PO q8h); both given with food to reduce risk of vomiting; cabergoline has fewer side effects. Prolactin antagonists (e.g., have luteolytic action); best used in combination with PGF2α—should see cervical opening within 24–48 hours. Only effective after 25 days post ovulation. CONTRAINDICATIONS High-dose PGF2α and cloprostenol cause strong uterine contractions that may cause uterine rupture or force purulent exudate through the oviducts if used with closedcervix pyometra. ALTERNATIVE DRUG(S) Misoprostol—synthetic PGE1 analogue (10 μg/kg PO or 200 μg tablet in 20 kg bitch intravaginally). Side effects minimal, facilitates cervical relaxation. Best used in combination with aglepristone and PGF2α (PGE1 does not induce luteolysis).

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 FOLLOW-UP

PATIENT MONITORING •  OHE—For patients not responding to medical treatment within 5 days or those refractory to medical treatment. •  Clinical improvement should be seen within 48 hours after initiation of treatment: ◦◦ Vaginal discharge—should reduce in volume and character over 5 days. ◦◦ Ultrasonography—to assess response to treatment; reduction in uterine wall thickness and intraluminal fluid should be seen within 3 days after start of treatment; fluid in lumen should be absent within 5–7 days. •  Serum progesterone concentrations decline within 48 hours of treatment with PGF2α and should be 6.0); rule out ureasepositive urinary tract infection. OTHER LABORATORY TESTS Venous blood gas and serum electrolyte analysis indicates hyperchloremic normal anion gap metabolic acidosis. Urine pH is >6.0 in distal RTA vs. 6.0). •  Ammonium chloride tolerance test— administer 200 mg/kg PO; measure urine pH before and hourly for 5 hours; empty the bladder hourly. Urine pH in normal dogs decreases to 3 or 3.5 times the length of the L2 vertebra in cats or dogs, respectively. •  Excretory urography or CT to confirm renomegaly, hydronephrosis, and spaceoccupying masses. •  Antegrade pyelography may exclude ureteral obstruction. •  Thoracic radiography indicated to detect metastases. Ultrasonographic Findings

•  Distinguish between PKD, perinephric

pseudocysts, hydronephrosis, neoplasia, abscess, and subcapsular hematoma. •  Acute inflammation may be associated with increased cortical echogenicity, perinephric effusion, or a medullary band of increased echogenicity. DIAGNOSTIC PROCEDURES

•  Cytologic examination of fine-needle

aspirate can confirm renal cyst, abscess, or neoplasia. Due to potential for seeding of neoplastic cells in the abdominal wall, fine-needle aspiration should be avoided if some renal tumors (e.g., renal carcinoma) are suspected. •  If renal aspirate is nondiagnostic, biopsy may be indicated.

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 TREATMENT

•  Diagnose and treat underlying cause of

renomegaly.

•  Outpatient unless dehydration or

decompensated renal failure exist.

•  Therapeutic renal diet is indicated to

prolong survival time for CKD when serum creatinine exceeds 2 mg/dL. •  Administer balanced electrolyte solution intravenously or subcutaneously to maintain hydration as needed.



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Renomegaly

(continued)

•  If the patient has dehydration or continuing

fluid losses such as vomiting or diarrhea, administer fluids intravenously to correct hydration deficits, maintain daily fluid need, and replace ongoing losses.

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blood pressure measurements are indicated depending on the underlying cause. POSSIBLE COMPLICATIONS CKD, depending on underlying cause of renomegaly.

CONTRAINDICATIONS/POSSIBLE INTERACTIONS Avoid nephrotoxic drugs.

 FOLLOW-UP

PATIENT MONITORING •  Perform physical examination and weigh patient to assess hydration.

•  Polycystic Kidney Disease. •  Urinary Tract Obstruction.

ABBREVIATIONS

•  CKD = chronic kidney disease. •  FeLV = feline leukemia virus. •  FIP = feline infectious peritonitis. •  PKD = polycystic kidney disease.

­Suggested Reading

 MEDICATIONS

DRUG(S) OF CHOICE Vary with the cause.

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•  CBC, serum chemistries, urinalysis,

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 MISCELLANEOUS

ZOONOTIC POTENTIAL Leptospirosis can be spread by contact with infected urine. SEE ALSO •  Ethylene Glycol Toxicosis. •  Feline Infectious Peritonitis (FIP). •  Hydronephrosis. •  Leptospirosis. •  Lymphoma—Cats. •  Perirenal Pseudocysts.

Cuypers MD, Grooters AM, Williams J, et al. Renomegaly in dogs and cats. Part I: Differential diagnosis. Compend Contin Educ Pract Vet 1997, 19:1019–1033. Author Cathy E. Langston Consulting Editor J.D. Foster Acknowledgment The authors and editors acknowledge the prior contribution of Allyson C. Berent.

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Respiratory Parasites Physical Examination Findings

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 BASICS

DEFINITION Helminths, arthropods, and protozoa that reside in the respiratory tract or pulmonary vessels of dogs and cats. PATHOPHYSIOLOGY Infestation with parasites causes rhinitis, bronchitis, pneumonitis, or arteritis, depending on the location of the organism within the respiratory system. Eosinophilic inflammation usually results from invasion of the parasite. SYSTEMS AFFECTED •  Respiratory. •  Cardiovascular. •  Hepatic— with hepatopulmonary migration of some parasites (Toxocara spp.). •  Neurologic—with migration of parasites to the brain (Cuterebra) or cerebral hemorrhage (Angiostrongylus). GENETICS There is no genetic basis. INCIDENCE/PREVALENCE Depends on parasite.

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GEOGRAPHIC DISTRIBUTION •  Pneumonyssoides caninum, Aelurostrongylus abstrusus, Linguatula serrata, Oslerus (Filaroides) osleri, Crenosoma vulpis, Eucoleus (Capillaria) aerophilus, Toxoplasma gondii, Toxocara spp.—worldwide. •  Eucoleus boehmi, Cuterebra spp., Filaroides hirthi, Paragonimus kellicotti—primarily North America. •  Andersonstrongylus (Filaroides) milksi— North America, Europe. •  Angiostrongylus vasorum—various countries of Europe, Africa, South America, North America. SIGNALMENT Species

Dog and cat. SIGNS General Comments

•  Upper respiratory—similar to historical findings; variable. •  Lower respiratory and

parenchyma—cough elicited on tracheal palpation; occasionally harsh lung sounds. •  Vascular—may present with signs of pulmonary disease, right-sided heart failure, anemia, coagulopathy, neurologic signs. CAUSES

•  Upper respiratory (nasal cavity and

sinuses)—Pneumonyssoides caninum, Eucoleus boehmi, Linguatula serrata, Cuterebra spp. •  Lower airway (trachea and bronchi)—dogs and cats: Eucoleus (Capillaria) aerophilus (rare in cats); dogs: Oslerus osleri, Filaroides hirthi, Andersonstrongylus milksi, Crenosoma vulpis. Cuterebra spp. in the trachea. •  Pulmonary parenchyma—dogs and cats: Paragonimus kellicotti, Toxoplasma gondii; dogs: Filaroides hirthi, Andersonstrongylus milksi; cats: Aelurostrongylus abstrusus, Troglostrongylus brevior, Troglostrongylus subcrenatus. •  Vascular—dogs and cats: Dirofilaria immitis, larval migration of Toxocara canis and T. cati; dogs: Angiostrongylus vasorum. RISK FACTORS •  Depends on the specific parasite—some have intermediate or paratenic hosts that must be ingested by the definitive host, putting hunting or scavenging animals at higher risk. •  Crenosoma vulpis—snails. •  Paragonimus kellicotti—snails, crabs, shellfish. •  Aelurostrongylus abstrusus—snails and slugs; transport hosts: rodents, frogs, lizards, birds. •  Linguatula serrata—ingestion of sheep offal. •  Toxoplasma gondii—ingestion of infected small mammals and birds or less commonly by ingesting sporulated oocysts in soil or water. •  Multi-animal households with unhygienic living conditions—allows fecal– oral or direct-contact transmission. •  Angiostrongylus vasorum—gastropods (slugs/ snails) or frogs are the intermediate host. Frogs can also serve as paratenic hosts.

•  Four basic categories—upper airway (nasal

cavity and sinuses), lower respiratory (trachea and bronchi), pulmonary parenchyma, and vascular; based on location and lifestyle of parasite. •  Often insidious and chronic, with few clinical signs. •  Respiratory compromise often not severe.

Historical Findings

•  Upper respiratory—sneezing; nasal

discharge (serous, sanguinous); reverse sneezing; nasal irritation or rubbing; neurologic signs with Cuterebra spp. •  Lower respiratory and parenchyma—may have no clinical signs, variable coughing, tachypnea, or altered respiratory pattern. •  Vascular— can have weight loss, lethargy, coughing, exercise intolerance. Acute onset of respiratory distress if embolization or hemorrhage occurs.

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Upper respiratory—other causes of epistaxis, rhinitis, or sinusitis (see specific chapters). •  Lower respiratory—acute bronchitis (nonparasitic); chronic bronchitis; infectious tracheobronchitis. •  Pulmonary parenchyma— eosinophilic lung disease; bronchopneumonia; granulomatous pneumonia; pulmonary granulomatosis. •  Vascular—other causes of coagulopathy, right-sided heart failure, or pulmonary artery disease. CBC/BIOCHEMISTRY/URINALYSIS •  CBC—variable; may note eosinophilia, basophilia, neutrophilia, and monocytosis; can see anemia with Angiostrongylus vasorum.

•  Biochemistry—often normal; high liver

enzyme activity with some parasites during early stages as a result of hepatic migration if burden is substantial. •  Urinalysis—normal.

OTHER LABORATORY TESTS Coagulopathy with Angiostrongylus vasorum or severe cases of heartworm disease (disseminated intravascular coagulation). IMAGING Thoracic Radiography

•  Often nonspecific findings—generalized

interstitial pattern; peribronchiolar infiltrates, nodular to alveolar pattern. •  Oslerus—soft tissue nodular densities within the trachea at the level of the carina. •  Paragonimus—can see bullae, cystic lesions or pneumothorax due to bulla or cyst rupture. •  Dirofilaria—rightsided heart enlargement, tortuous and truncated pulmonary arteries, pulmonary infiltrates (dogs). Few cardiac changes in cats, large pulmonary arteries possible. DIAGNOSTIC PROCEDURES

Sputum Examination

May reveal eggs or larvae (L-1). Fecal Examination

•  Multiple examinations often necessary; negative results do not rule out infection. •  Direct fecal smear: Angiostrongylus (larvae). •  Standard fecal flotation: Eucoleus aerophilus (eggs), Eucoleus boehmi (eggs). •  Zinc sulfate centrifugation: Aelurostrongylus (larvae), Oslerus osleri, Andersonstrongylus milksi, Filaroides hirthi (larvae, larvated eggs), Angiostrongylus vasorum (larvae). •  Baermann: Aelurostrongylus (larvae), Oslerus osleri, Andersonstrongylus milksi, Filaroides hirthi (larvae, eggs), Crenosoma (larvae, larvated eggs), Angiostrongylus (larvae). •  Sedimentation: Paragonimus (eggs).

Rhinoscopy

•  Upper respiratory—examination via

retrograde pharyngoscopy or rhinoscopy with antegrade flushing of anesthetic gas can allow visualization of nasal mites; retrograde nasal lavage and cytologic examination of fluid can be helpful. •  Eucoleus boehmi—histopathology can reveal eggs deep within the epithelium. •  Linguatula serrata—diagnosis made by observation of eggs in nasal secretions or around the nares. Bronchoscopy

•  Lower respiratory and parenchyma—rarely can see tracheal and bronchial parasites and parasitic nodules; occasionally can be removed for definitive identification. •  Tracheal wash or bronchoalveolar lavage can allow identification of larvae (Oslerus osleri, Aelurostrongylus, Crenosoma, Filaroides hirthi, Andersonstrongylus milksi, Angiostrongylus); eggs (Eucoleus aerophilus, Paragonimus); organisms (Toxoplasma). •  Oslerus osleri—can also be diagnosed by brushings or histopathology of nodules at the carina.





Respiratory Parasites

(continued)

PATHOLOGIC FINDINGS •  Upper respiratory—may find nasal mites or worms in epithelium of sinuses and nasal cavity. •  Lower respiratory and parenchyma— can see pulmonary nodules containing parasites throughout the parenchyma or within bronchi. •  Vascular—changes include thrombi and intimal proliferation of the vascular walls. •  Cuterebra spp. can be found in brain sections when associated with neurologic signs.

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 TREATMENT

APPROPRIATE HEALTH CARE Most commonly outpatient—upper and lower respiratory parasites; may need repeated examinations to monitor response. NURSING CARE Supportive care and oxygen therapy can be needed depending on the severity of disease. ACTIVITY Strict cage rest if severe pulmonary dysfunction occurs with upper or lower respiratory parasites; also with vascular parasite infection or bullous lung disease associated with Paragonimus. ­DIET No special restrictions. CLIENT EDUCATION •  Explain that treatment duration and response depend on the type of parasite. •  Warn client of the risk of recurrence in animals that maintain lifestyles conducive to transmission of the parasites (e.g., hunting, sporting dogs, multidog households, outdoor cats). SURGICAL CONSIDERATIONS Ruptured Paragonimus cysts generally require surgical excision.

25–50 mg/kg q12h for 10–14 days; very difficult to clear. •  Oslerus osleri—efficacious therapy not fully determined. Consider ivermectin 400 μg/kg SC or PO q3 weeks for four doses. •  Crenosoma vulpis—levamisole 7.5 mg/kg SC q48h (two doses); fenbendazole 50 mg/kg PO q24h for 7 days; milbemycin oxime 0.5 mg/kg PO once. •  Aelurostrongylus abstrusus—fenbendazole 25–50 mg/kg PO q24h for 10 days; ivermectin 400 μg/kg SC, selamectin spot-on formula 45 mg/cat, two doses, 23 days apart. •  Filaroides hirthi, Andersonstrongylus milksi—fenbendazole 50 mg/kg PO q24h for 14 days; albendazole 50 mg/kg PO q12h for 5 days, repeat in 3 weeks. •  Paragonimus kellicotti—praziquantel 25 mg/kg PO, SC q8h for 3 days; fenbendazole 25–50 mg/kg PO q12h for 14 days. •  Toxoplasma— clindamycin 12.5 mg/kg PO q12h for 28 days. •  Angiostrongylus vasorum— fenbendazole 20–50 mg/kg PO q24h for 5–21 days; milbemycin oxime 0.5 mg/kg PO weekly for 4 weeks; single topical application of moxidectin 2.5 mL/kg. •  Toxocara spp. larval migration—fenbendazole 50 mg/kg PO q24h for 10 days. •  Anti-inflammatory agents— recommendations for concurrent use of steroids vary. CONTRAINDICATIONS Ivermectin—not labeled for use in dogs or cats other than for heartworm prophylaxis; contraindicated at dosages >100 μg/kg in breeds with known sensitivity (collies, collie breeds, and Australian shepherd dogs). PRECAUTIONS None ALTERNATIVE DRUG(S) None

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 MEDICATIONS

DRUG(S) OF CHOICE •  Anthelmintics—few studies confirm efficacy; most data anecdotal. For treatment of Dirofilaria, see chapters on Heartworm Disease. •  Pneumonyssoides caninum— selamectin 6–24 mg/kg applied every 2 weeks for three treatments. milbemycin oxime 0.5–1 mg/kg PO weekly for 3 weeks, ivermectin 200 μg/kg SC or PO for two treatments 3 weeks apart; note: not labeled for use in dogs at this dosage. •  Cuterebra— ivermectin 300 μg/kg SC or PO every other day for three doses combined with a tapering dose of corticosteroids. •  Linguatula serrata— physical removal of organisms from the sinuses. •  Eucoleus aerophilus, E, boehmi— ivermectin 200 μg/kg PO once; fenbendazole

 FOLLOW-UP

PATIENT MONITORING •  Serial fecal Baermann larval extractions or examination for eggs—some anthelmintics can suppress egg or larval production in some species and intermittent shedding reduces value of repeated fecal exams. •  Resolution of clinical signs—suggests response to treatment; does not indicate complete clearance of parasites. •  Peripheral eosinophilia, if noted initially, may subside with treatment. •  Repeat bronchoscopic examination—can help assess efficacy of treatment for Oslerus osleri. PREVENTION/AVOIDANCE

•  Avoid activity that predisposes to infestations (often not practical). •  Avoid

contact with wildlife reservoirs (especially wild canids and felids). •  Consider prophylactic treatment for heartworm.

POSSIBLE COMPLICATIONS

•  Chronic pulmonary damage—possible with

persistent and heavy lower respiratory parasite burdens. •  Infestations generally not fatal; however, severe pulmonary damage can result with some species; Cuterebra spp. and Angiostrongylus can cause fatal neurologic complications. •  Pneumonyssoides caninum has been associated with gastric dilation and volvulus. EXPECTED COURSE AND PROGNOSIS •  With aggressive management—prognosis usually fair to excellent; variable. •  Return to performance—depends on chronicity of disease and level of chronic pulmonary damage by lower respiratory parasites. •  Recurrence possible.

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 MISCELLANEOUS

ZONOTIC POTENTIAL None SYNONYMS •  Lungworm infestation—Aelurostrongylus, Eucoleus (Capillaria) aerophilus, Crenosoma, Oslerus osleri, Filaroides hirthi, Andersonstrongylus milksi. •  Nasal mite infestation—Pneumonyssoides caninum, Pneumonyssus caninum. •  French heartworm—Angiostrongylus vasorum. SEE ALSO •  Heartworm Disease—Cats. •  Heartworm Disease—Dogs. •  Pneumonia, Eosinophilic. INTERNET RESOURCES Bowman DD. Respiratory system parasites of the dog and cat, Part I: Nasal mucosa and sinuses, and respiratory parenchyma and Part II: Trachea and bronchi, and pulmonary vessels: http://www.ivis.org/advances/ Parasit_Bowman/ddb_resp/ivis.pdf

­Suggested Reading

Lacorcia L, Gaser R, Anderson BA, Beveridge I. Comparison of bronchoalveolar lavage fluid examination and other diagnostic techniques with the Baermann technique for detection of naturally occurring Aelurostrongylus abstrusus infection in cats. J Am Vet Med Assoc 2009, 235(1):43–49. Marks SL, Moore MP, Rishniw M. Pneumonyssus caninum: the canine nasal mite. Compend Contin Educ Pract Vet 1994, 16:577–582. Author Elizabeth Rozanski Consulting Editor Elizabeth Rozanski Acknowledgment The author/editor acknowledges the prior contribution of Jill S. Pomrantz.  Client Education Handout available online

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Retained Placenta

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 BASICS

OVERVIEW •  Dogs—placenta retained beyond the immediate postpartum period; placentas usually passed within 15 minutes of birth of a puppy; may develop acute metritis secondary to retained placenta. •  Cats—may retain placentas for days without signs of illness. •  Extremely uncommon. SIGNALMENT •  Dog—rare, most common in toy dog breeds. •  Cat—rare. SIGNS Historical Findings

•  Recent parturition. •  Continued vulvar discharge of lochia. •  Owner may note number of placentas

passed, although this information is frequently unreliable.

Physical Examination Findings

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•  Green lochia vulvar discharge. •  Palpation of firm mass in uterus—not

always possible.

•  Concurrent clinical signs of postpartum

metritis.

CAUSES & RISK FACTORS

•  Toy breed. •  Large litter size. •  Dystocia.

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Postpartum metritis—physical examination and vaginal cytologic examination show no signs of infection with uncomplicated retained placenta; metritis may develop concurrently. •  Retained fetus—differentiated by radiography or ultrasonography. CBC/BIOCHEMISTRY/URINALYSIS Usually normal when uncomplicated. OTHER LABORATORY TESTS Vaginal cytologic examination—parabasal epithelial cells; may note erythrocytes; biliverdin clumps.

IMAGING Ultrasonography—echogenic but nonfetal mass within the uterus. DIAGNOSTIC PROCEDURES Celiotomy or hysterotomy—may be required for diagnosis.

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 TREATMENT

•  Outpatient for healthy bitch or queen. •  Instruct owner to monitor rectal

temperature and observe for signs of systemic illness. •  Ovariohysterectomy—curative; recommended if future breeding is not a consideration. •  Surgical removal—indicated if medical treatment is unsuccessful and the bitch develops metritis.

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 MEDICATIONS

DRUG(S) OF CHOICE •  Oxytocin—known or suspected condition in otherwise healthy cats and dogs; dogs: 0.5 IU/kg IM, up to 5 IU total dose; cats: 0.5–1 IU IM. Oxytocin may be ineffective after 48 hours postpartum. •  Can precede oxytocin treatment with calcium gluconate (10%); dogs and cats, 0.5–1.5 mL/kg IV slowly over 15 minutes; monitor for bradycardia during injection. •  Metritis—treat accordingly (see Metritis). CONTRAINDICATIONS/POSSIBLE INTERACTIONS Do not give progestational drugs.

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 FOLLOW-UP

•  Monitor temperature and physical

condition.

•  Acute metritis (dogs)—may develop if the

placenta is not passed; fair to good prognosis for recovery with treatment. •  Prognosis for future reproduction—good without metritis; fair to poor with metritis.

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 MISCELLANEOUS

SEE ALSO Metritis

­Suggested Reading

Feldman EC, Nelson RW. Periparturient diseases. In: Feldman EC, Nelson RW, eds., Canine and Feline Endocrinology and Reproduction, 3rd ed. Philadelphia, PA: Saunders, 2004, pp. 808–834. Grundy SG, Davidson AP. Theriogenology question of the month. Acute metritis secondary to retained fetal membranes and a retained nonviable fetus. J Am Vet Med Assoc 2004, 224(6):844–847. Author Joni L. Freshman Consulting Editor Erin E. Runcan



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Retinal Degeneration

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 BASICS

DEFINITION •  Degeneration of the retina from inherited or acquired causes. •  Inherited—generalized progressive retinal atrophy (PRA); a group of progressive retinal diseases; may be subdivided into photoreceptor dysplasias (begin before retina fully develops 4–6 years. •  Cone degeneration disease—3–4 months. •  SARDS—middle-aged to old.

Predominant Sex

•  Storage disease—mucopolysaccharidosis,

gangliosidosis, mannosidosis, fucosidisis (English springer spaniel). •  Ornithine aminotransferase deficiency—progressive and total atrophy of choroid and retina; older cats.

•  PRA—X-linked recessive condition in Siberian husky and Samoyed, therefore primarily males. •  SARDS—70% female.

Neoplastic

SIGNS

Nutritional

Historical Findings

and cats)—may cause partial or complete degeneration. •  Taurine deficiency (cats)— retinal degeneration, dilated cardiomyopathy.

•  PRA (dog)— gradually progressing

nyctalopia that ultimately affects vision in bright light; may note dilated pupils or brighttapetal reflex; may appear acutely blind. Dysplasias have early onset and blindness by 2 years. Degenerations are later onset and blind in later life. •  Hemeralopia or cone degeneration disease—rare. Between 8 and 12 weeks of age puppies show photophobia and trouble navigating in bright light. Progresses to total day blindness. Night vision remains normal. •  Central PRA (dogs)—rare in United States; central vision lost; may never become completely blind. •  SARDS—vision lost in 1–4 weeks; polyuria, polydipsia, and polyphagia common. Physical Examination Findings

•  If severe—direct and consensual pupillary

Neoplastic infiltrate may lead to scars from previous retinal detachment if treated. •  Severe deficiency of vitamin E or A (dogs

Infectious/Immune

•  Retina will degenerate from inflammation; may be focal, multifocal, or generalized. SARDS— some cases are immune-mediated retinitis.

Idiopathic

SARDS—dogs; post-inflammatory—dogs and cats. Toxic

•  Idiosyncratic reaction to griseofulvin or enrofloxacin (cats). •  Radiation—dogs or cats

treated for nasal or CNS neoplasia.

•  Phototoxicity—operating microscopes,

welding light exposure. RISK FACTORS

light reflexes impaired or nearly abolished.

•  Ocular disease—cataracts, panuveitis,

depigmentation or mottled hyperpig­ mentation; retinal blood vessel attenuation and optic nerve atrophy. •  PRA (dogs)— cataracts and vitreous degeneration can occur. •  SARDS (dogs)—obesity; may note slow or absent pupillary light reflexes (PLR). Chromatic PLR testing (melan 100), reduced or no red PLR, normal blue PLR. •  Borzoi chorioretinopathy—multifocal chorioretinal lesions (hyperpigmented and hyperreflective). •  Taurine-deficient retinopathy (cats)— begins as a spot in area centralis; then horizontal band forms superior to optic

•  Cats—enrofloxacin dose should not exceed

•  Tapetal hyperreflectivity and nontapetal

chorioretinitis, retinal detachment, glaucoma.

5 mg/kg/day. Toxicity noted at lower doses in compromised animals (i.e., renal disease).

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Acute vision loss, PLR slow or absent— SARDS, optic neuritis, retinal detachment, unrecognized PRA, or glaucoma; PLR normal—rapidly developing diabetic cataracts

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Retinal Degeneration or visual cortex disease. •  Slowly progressive visual loss—PRA, cataracts, severe corneal disease (e.g., pigmentation, scarring, or edema), chronic retinitis, chorioretinitis, vitreal inflammation. CBC/BIOCHEMISTRY/URINALYSIS

•  Usually normal, unless systemic disease. •  SARDS (dogs)—may suggest hyperadreno-

­corticism.

OTHER LABORATORY TESTS

•  Test for hyperadreoncorticism, evaluate sex

hormone levels, check blood pressure, evaluate for proteinuria with SARDS. •  Taurine concentration (cats)—especially with dilated cardiomyopathy. •  Serum and urine ornithine concentrations (cats)— elevated with ornithine aminotransferase deficiency. •  Genetic testing - many tests are available from many different companies; VetGen, Animal Genetics, Animal Labs, Embark Vet are examples. May identify affected, non-affected and carriers. IMAGING

•  Thoracic radiographs and cardiac

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ultrasound—in cats with suspected taurine deficiency. •  CT or MRI—investigate causes of central blindness. DIAGNOSTIC PROCEDURES

•  Ophthalmic examination. •  Electroretinography—localizes cause of

blindness when retina not visible or appears normal. •  Chromatic PLR (Melan 100)— differentiates outer retinal layer problems (red reduced) vs. inner retina layers (absent blue). Definitive diagnosis requires electroretinogram as interpretation can be confounded by iris atrophy and stress-induced mydriasis. •  Cerebrospinal fluid tap—for cases of suspected optic neuritis. PATHOLOGIC FINDINGS

•  Thin retina. •  Edges of focal retinal scars— sharply delineated. •  Hyperpigmented areas—

associated with postinflammatory scars or central PRA. •  End-stage degenerations— marked photoreceptor atrophy and reduction in retinal cell density. •  Lipopigment accumulated in neuroepithelium—central PRA, ceroid lipofuscinosis, congenital stationary night blindness. •  Lysosome storage diseases—accumulation in neuronal/retinal layers/cornea.

(continued)

CLIENT EDUCATION

•  Most blind animals function well in stable environment. •  Blind dogs should

be supervised if outside, in unfenced yards or in an area with a pool. •  Suggest playing with toys that make sounds. •  Older blind animals with hearing loss or senility may not adapt well. •  Some blind animals experience behavioral changes such as aggression or reduced activity. •  Animals with only one blind eye can function normally. •  Blind cats should be kept indoors. SURGICAL CONSIDERATIONS Not indicated unless painful.

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 MEDICATIONS

DRUG(S) OF CHOICE •  None currently effective. •  Pyridoxine— for ornithine aminotransferase deficiency (cats). •  Adequate dietary taurine—halt progression of taurine-deficient retinopathy. •  SARDS—if autoimmune retinitis, immune suppressive treatment may preserve/ restore some vision. GENE THERAPY Experimental—retinal pigment epithelium dystrophy in briard. CONTRAINDICATIONS N/A PRECAUTIONS Cataract surgery—not recommended if retinal degeneration is severe; perform preoperative electroretinogram.

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 FOLLOW-UP

PATIENT MONITORING •  Serial fundic examinations—signs of degeneration over weeks with SARDS; months with PRA. •  Cataract formation— with PRA or SARDS. PREVENTION/AVOIDANCE

•  Do not breed known or suspected carriers of PRA or other heritable diseases. •  Genetic

testing on breeding animals.

POSSIBLE COMPLICATIONS

•  Cataracts. •  Glaucoma. •  Uveitis. •  Ocular

trauma (result of visual impairment).

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 TREATMENT

DIET •  Cats—food should contain 500–750 ppm taurine. •  Dogs—balanced diet, avoid those high in polyunsaturated fats.

•  Obesity (reduced activity).

EXPECTED COURSE AND  PROGNOSIS •  Inherited PRA—progresses to blindness; slow progression allows patient to adapt to

visual loss. •  Degeneration from inflamm­ ation—usually does not progress unless persistent or recurrent inflammation. •  SARDS—irreversible blindness. •  Taurine deficiency (cats)—degeneration may halt at any stage.

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 MISCELLANEOUS

ASSOCIATED CONDITIONS SARDS—hyperadrenocorticism, proteinuria, hypertension, elevated sex hormones. AGE-RELATED FACTORS N/A ZOONOTIC POTENTIAL N/A PREGNANCY/FERTILITY/BREEDING N/A SYNONYMS •  PRA—progressive rod-cone degeneration; retinal atrophy. •  Taurine-deficient retinopathy—feline central retinal degeneration. SEE ALSO

•  Blind Quiet Eye. •  Chorioretinitis. •  Lysosomal Storage Diseases. •  Retinal Detachment.

ABBREVIATIONS

•  PLR = pupillary light reflex. •  PRA = progressive retinal atrophy. •  SARDS = sudden acquired retinal

degeneration syndrome.

­Suggested Reading

Narfström K, Petersen-Jones S. Diseases of the canine ocular fundus. In: Veterinary Ophthalmology, 5th ed. Ames, IA: Blackwell, 2013, pp. 2087–2235. Author Patricia J. Smith Consulting Editor Kathern E. Myrna  Client Education Handout available online



1195

Canine and Feline, Seventh Edition

Retinal Detachment Breed Predilections

•  Depends on cause. •  Terrier breeds—

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 BASICS

DEFINITION Separation of the neural retina from the retinal pigment epithelium (RPE). PATHOPHYSIOLOGY •  Subretinal space—a potential space between RPE and neural retina in which fluid or exudates accumulate. •  Etiopathogenesis is one or a combination of rhegmatogenous (retinal tear), subretinal exudation, or traction. Rhegmatogenous Retinal Detachment (RRD)

A tear or hole in retina related to age, cataracts, traction from inflammatory debris or vitreal degeneration, trauma, or retinal degeneration. Vitreous fluid moves into the subretinal space, resulting in detachment. Probably the predominant type occurring in association with cataracts and after cataract or lens surgery. Exudative

•  Fluid accumulates in the subretinal space

because of breakdown of blood–retinal barrier. •  Subretinal fluid—serous, hemorrhagic, or exudative. •  Hematogenous/ systemic pathogenetic factors—common. •  Vasculitis, hypertension, and hyperviscosity— may cause serous detachment with or without hemorrhage. Traction

•  Fibrous or fibrovascular tissue; detaches

retina and/or may cause retinal tear.

•  Associated with trauma, intraocular foreign

bodies, or any cause of severe vitreal inflammation. SYSTEMS AFFECTED

•  Nervous. •  Ophthalmic. •  May be

manifestation of systemic disease or neoplasia. GENETICS Depends on cause—dogs with hereditary cataracts or lens luxation may develop RRD. Some breeds may develop RRD from primary vitreous abnormalities (shih tzu), colobomas of optic nerve (collie), or severe retinal dysplasia inducing retinal tears or traction. INCIDENCE/PREVALENCE •  Exudative—most common in dogs and cats. •  RRD—uncommon. More common in dogs because of the greater prevalence of severe vitreal degeneration, cataracts, and cataract surgery. GEOGRAPHIC DISTRIBUTION Varies with the distribution of infectious etiologies. SIGNALMENT Species

Dog and cat.

predisposed to primary lens luxation, may contribute to RRD. •  Breeds that develop cataracts. •  Shih-tzu, Boston terrier, Italian greyhound, Chihuahua, corgi—predisposed to spontaneous RRD owing to abnormal liquefied vitreous. •  Dogs with merle coat color (Australian shepherd dog, Shetland sheepdog, Great Dane, collie) may have severe retinal dysplasia and optic nerve or scleral colobomas, leading to RRD. •  Breeds with severe retinal dysplasia: English springer spaniel, Labrador retriever, Bedlington terrier. •  Breeds with serous retinopathy (also known as RPE dysplasia, canine multifocal retinopathy): Great Pyrenees, mastiff, coton de Tulear. Mean Age and Range

•  Depends on cause. •  Older patients—

cataracts and systemic diseases (e.g., hyper­tension, neoplasia, immune-mediated disease). •  Young dogs—retinal dysplasia, canine multifocal retinopathy, uveodermatologic syndrome. SIGNS •  Blindness or reduced vision in affected eye. •  Dilated pupil with slow or no pupillary light response (PLR). PLR may be near normal if detachment is acute. •  Blood vessels or a “membrane” may be observed easily through the pupil just behind the lens. •  Vitreous abnormalities—floaters, hemorrhage, or syneresis (liquefaction); common. •  Interruption or alteration of course of blood vessels due to retinal elevation. •  With clear subretinal fluid— vessels may cast shadows. •  With exudative fluid or blood, tapetum/RPE may not be visible. •  Other signs related to underlying systemic disease or inflammation (see Chorioretinitis). •  Canine multifocal retinopathy—multifocal gray to tan elevated lesions (focal detachments) of various size. Starts around 11 weeks, progresses with time. CAUSES Bilateral—suggests a systemic problem, except in breeds with a predisposition to severe vitreal degeneration (e.g., shih tzu). Degenerative

End-stage progressive retinal degeneration— may lead to RRD if retina tears. Anomalous

•  Colobomas—collie eye anomaly; abnormal

retina around colobomatous optic nerve or large choroidal staphylomas may lead to RRD (merle ocular dysgenesis). •  Severe retinal dysplasia, or oculoskeletal dysplasia (Labrador retrievers, Samoyeds). •  Canine multifocal retinopathy. •  Multiple ocular anomalies.

Metabolic

•  Hyperviscosity (e.g., due to hyperprotein­ emia from multiple myeloma or other causes).

•  Polycythemia. •  Shock. •  Dogs—systemic hypertension, hypothyroidism, hypercho­ lesterolemia . •  Cats—systemic hypertension (usually related to hyperthyroidism, chronic renal disease).

Neoplastic

•  Primary or metastatic. •  Multiple myeloma,

lymphoma, and intraocular masses (e.g., ciliary body adenocarcinoma or melanoma). •  Pheochromocytoma may cause hypertension. Infectious

•  Infectious retinitis or chorioretinitis may cause focal or diffuse detachment. •  Infection

may extend from or to the CNS.

Immune-Mediated/Inflammatory

•  Immune complex disease—vasculitis or

inflammation can result in exudative detachment: ◦  Dogs—systemic lupus erythematosus (SLE); uveodermatologic syndrome, meningoencephalitis of unknown etiology. ◦  Cats—periarteritis nodosa; SLE.

Idiopathic

•  If all other causes are ruled out, including retinal tears. •  Idiopathic steroid-responsive

detachment—reported in giant-breed dogs; may occur in any breed.

Trauma and Toxic

•  Penetrating injury or foreign body. •  Severe

blunt trauma with inflammation or hemorrhage, usually unilateral. •  Surgical trauma—if lens or vitreous disturbed (e.g., cataract surgery), can lead to RRD. •  Toxic— drug reactions (e.g., trimethoprim-sulfa, ethyelene glycol, griseofulvin [cats]). RISK FACTORS

•  Systemic hypertension. •  Old age—retinal

thinning, severe vitreal degeneration. •  Hypermature, intumescent cataracts that may rupture (e.g., diabetic cataracts). •  Luxated lenses. •  Lens extraction. •  Hereditary—young dogs that have more severe retinal dysplasia and/or multiple ocular anomalies.

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Blindness or impaired vision—optic neuritis, glaucoma, cataracts, progressive retinal atrophy, sudden acquired retinal degeneration syndrome (SARDS; see Retinal Degeneration), CNS disease. •  Dilated pupil with slow or absent pupillary light reflexes— glaucoma, oculomotor nerve lesion, optic neuritis, progressive retinal atrophy, SARDS. •  Membrane or vessels associated with or behind lens—persistent tunica vasculosa lentis, persistent pupillary membranes, fibrovascular membrane due to intraocular neoplasia or inflammation.

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Retinal Detachment CBC/BIOCHEMISTRY/URINALYSIS Typically normal, unless systemic disease present. OTHER LABORATORY TESTS •  Depends on suspected systemic problem. •  Protein electrophoresis or documentation of Bence Jones proteinuria. •  Coagulation profile. •  Bacterial culture of ocular or body fluids. •  Thyroid hormone measurement. •  Serologic or PCR testing for infectious diseases. IMAGING •  Thoracic and abdominal radiographs, ultrasound, and/or CT. •  Spinal radiographs may reveal bony changes consistent with multiple myeloma. •  Ocular ultrasound—if ocular media is opaque, can identify retinal detachments or intraocular masses. DIAGNOSTIC PROCEDURES

•  Ophthalmic examination. •  Serial blood

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pressure measurement—normal systolic arterial pressure 6.0 mg/dL). Hypercalcemia is immediate (2–3 hours) and transient (will decline to normal within 24 hours post ingestion) with calcipotriol ingestion. In cholecalciferol rodenticide toxicity, hypercalcemia is evident 12 hours post ingestion and persists for weeks if not treated. •  Hyperphosphatemia (>8 mg/dL) may precede hypercalcemia. •  Hypokalemia. •  Azotemia. •  Hyposthenuria, proteinuria, and glucosuria. •  Metabolic acidosis. OTHER LABORATORY TESTS

•  In acute, one‐time ingestions, serum 25‐

hydroxy vitamin D concentration is increased at least 10 times normal (normal ranges: dogs, 60–215 nmol/L; cats, 65–170 nmol/L) in cholecalciferol toxicosis. •  In chronic intoxications, serum 25‐hydroxy vitamin D concentrations can increase from 1.5 to 5 times above normal values. •  Serum 1,25-dihydroxy vitamin D is only transiently increased and is of limited diagnostic value. •  The total calcium‐to‐total phosphorus ratio in renal cortex of deceased dogs is in the range of 0.4–0.9 (normal 80 nmol/L supports a diagnosis of cholecalciferol toxicosis. •  Biliary 25‐hydroxy vitamin D concentration >100 nmol/L supports a diagnosis of cholecalciferol toxicosis. •  Decreased intact parathyroid hormone (iPTH) (normal in dogs is 3–17 pmol/L and for cats is 0–4 pmol/L). •  Normal Na/K ratio. IMAGING Ultrasonography—renal, gastric wall, lung hyperechogenicity. DIAGNOSTIC PROCEDURES

•  Electrocardiogram—may show bradycardia,

sinus tachycardia, ventricular premature complexes. •  Endoscopy—may reveal erosive/hemorrhagic gastric mucosa. PATHOLOGIC FINDINGS

•  Diffuse mineralization of gastric wall and

intestines; hemorrhage in gastric mucosa; mineralization of the soft palate, salivary glands, other soft tissues.

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Blackwell’s Five-Minute Veterinary Consult

Rodenticide Toxicosis—Cholecalciferol •  Necrosis and mineralization of myocardium

(especially the atria) and large blood vessels; myocardial degeneration. •  Mineralization of glomerular mesangium and capsule, and renal tubular basement membranes. •  Tubular necrosis. •  Mineralization of lungs.

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 TREATMENT

APPROPRIATE HEALTH CARE •  Cholecalciferol—once clinical signs show (usually 24–36 hours post ingestion), gastric decontamination is not worth while. •  Hospitalization with close observation in all cases for at least 48 hours post ingestion.

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NURSING CARE •  Correct dehydration and electrolyte imbalances (hypokalemia). •  Enhance calciuresis with fluid therapy— strongly recommended for all patients. •  Peritoneal dialysis with a calcium‐free dialysate—for severe azotemia and hypercalcemia. •  Blood transfusion—if anemia is severe or in case of hypovolemia. •  Antibiotic therapy—as needed. •  Parenteral alimentation—recommended to rest the gut and to overcome anorexia. DIET Offer low‐calcium, low‐phosphorus diets. CLIENT EDUCATION •  Caution client to keep all rodenticide products in places that are inaccessible to pets. •  Warn client that vitamin D toxicity is a severe and costly disease to treat with prolonged therapy and hospitalization.

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 MEDICATIONS

DRUG(S) OF CHOICE •  Pamidronate disodium—to treat hypercalcemia. •  Salmon calcitonin—to treat hypercalcemia. Decontamination of Gastrointestinal Tract

•  Within 2 hours of vitamin D ingestion. •  Emetic and activated charcoal followed by

osmotic cathartics.

•  Dogs—apomorphine 0.02–0.04 mg/kg IV,

IM, SC, or subconjunctivally.

•  Cats—xylazine 0.4–0.5 mg/kg IV. •  Activated charcoal powder (1–4 g/kg)

combined with a saline cathartic (magnesium or sodium sulfate, 250 mg/kg)—PO or by gastric tube.

Hypercalcemia Reduction

•  Pamidronate disodium 1.3–2.0 mg/kg in

0.9% sodium chloride slow IV over 2–4 hours; repeat once in 3–4 days for large ingestions; do not combine with salmon calcitonin. •  Salmon calcitonin 4–6 IU IM or SC every 6 hours till calcium concentration stabilizes; rarely used as limited efficacy and patients may become refractory. •  IV fluids: 0.9% sodium chloride or 5% dextrose with 0.45% sodium chloride fluids to begin; change as needed. •  Prednisolone—dogs and cats: 2–6 mg/kg IM or PO q12h. •  Furosemide—dogs, 2–6 mg/kg; cats, 1–4 mg/kg SC, IV, or IM q8–12h.

(continued) •  Cholecalciferol‐induced hypercalcemia is

persistent, requiring long‐term management and supportive care (2–4 weeks). PREVENTION/AVOIDANCE Keep rodenticides out of reach of pets. POSSIBLE COMPLICATIONS

•  Chronic renal failure—inability to

concentrate urine.

•  Subclinical renal, cardiovascular, and

gastrointestinal sequelae—due to mineralization. EXPECTED COURSE AND PROGNOSIS Cholecalciferol—depends on severity and duration of hypercalcemia; if hypercalcemia is unresponsive or severe mineralization occurs before therapy is initiated, prognosis is poor.

Seizure Control

•  Diazepam 0.5–1 mg/kg IV, repeat as

necessary.

Control of Clinically Significant Ventricular Arrhythmias

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 MISCELLANEOUS

•  Lidocaine—dogs, 2–4 mg/kg IV over 1

AGE‐RELATED FACTORS Distinguish from normal juvenile hypercalcemia.

Gastrointestinal Protection

PREGNANCY/FERTILITY/BREEDING Vitamin D has antiproliferative effects and the potential for teratogenesis.

minute, repeat up to 8 mg/kg; cats, use cautiously at 0.25–0.5 mg/kg IV slowly.

•  Sucralfate 0.25–1 g PO q6–8h. •  Famotidine 0.5–1 mg/kg IV, IM, PO q12h.

Antiemetics

•  Maropitant 1 mg/kg SQ, IV or PO q24h.

PRECAUTIONS

•  Supratherapeutic doses of pamidronate

disodium may worsen renal failure.

•  Salmon calcitonin—associated with side

effects: anorexia, anaphylaxis, and emesis. Rarely used. •  Xylazine—may aggravate respiratory depression and result in vagal‐mediated slowing of the heart rate. •  Prolonged prednisolone therapy may result in adrenocortical suppression; taper doses gradually over a 2‐ to 4‐week treatment period.

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 FOLLOW‐UP

PATIENT MONITORING •  Following pamidronate therapy—serum calcium and BUN at 24, 48, and 72 hours following exposure; if hypercalcemia still present, repeat pamidronate infusion 72 or 96 hours after the first infusion and monitor serum calcium and BUN q48h. •  Following calcitonin therapy—serum calcium and BUN; monitor q24h and continue adjusting dose until calcium returns to normal (24–48 hours for calcipotriol, or 2–4 weeks for cholecalciferol).

SYNONYMS N/A ABBREVIATIONS •  iPTH = intact parathyroid hormone. •  NSAID = nonsteroidal anti‐inflammatory drug.

­Suggested Reading

Bates N. Vitamin D toxicosis. Compan Anim 2017, 22(12):700–706. DeClementi C, Sobczak BR. Common rodenticide toxicoses in small animals. Vet Clin North Am Small Anim Pract 2018, 48(6):1027–1038. Peterson ME, Fluegenman K. Cholecalciferol. Top Compan Anim Med 2013, 28(1): 24–27. Rumbeiha WK. Cholecalciferol. In: Peterson ME, Talcott PA, eds., Small Animal Toxicology, 3rd ed. St. Louis, MO: Saunders, 2013, pp. 489–498. Rumbeiha WK, Braselton WE, Nachreiner R, et al. The post‐mortem diagnosis of cholecalciferol toxicosis: A novel approach and differentiation from ethylene glycol toxicosis. J Vet Diagn Invest 2000, 12:426–432. Rumbeiha WK, Fitzgerald SD, Kruger JM, et al. Use of pamidronate disodium to reduce cholecalciferol‐induced toxicosis in dogs. Am J Vet Res 2000, 61:9–13. Author Wilson K. Rumbeiha Consulting Editor Lynn R. Hovda



1211

Canine and Feline, Seventh Edition

Rodenticide Toxicosis—Phosphides •  Tremorgenic mycotoxins. •  Acute GI

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 BASICS

OVERVIEW •  Used as a rodenticide since the early 1930s at various concentrations (2–10%) in a powder, pellet, or paste formulation. Available as zinc, aluminum, and magnesium salts. •  Distinctive odor, often described as acetylene, rotten fish, or garlic. •  Most common route of exposure is ingestion; however, toxicosis can occur via inhalation and absorption through broken skin. •  Hydrolysis leads to phosphine gas production. Phosphine gas has corrosive and irritant effects on the gastrointestinal (GI) mucosa, which leads to vomiting, hematemesis, or melena. The gas is rapidly absorbed and systemically distributed leading to effects on other organ systems. •  Phosphine leads to the production of free radicals and oxidative stress, causing direct cellular damage and may inhibit cellular respiration. •  Toxic exposure is reported to be 20–40 mg/kg; however, the gastric pH is reported to affect toxicity. SIGNALMENT No known age, breed, or sex predilection. SIGNS •  Within 15 minutes to 4 hours but can be delayed up to 18 hours. •  GI—anorexia, vomiting, and melena. •  Cardiovascular— direct myocardial damage, arrhythmias, decreased inotropy, hypotension. •  Respiratory—pulmonary edema, pleural effusion. •  Hemic/lymphatic/immune— methemoglobinemia, Heinz body production. •  Nervous—ataxia, weakness, tremors, hyperesthesia, and seizures. •  Renal/urologic— azotemia, acute renal failure. •  Hepatobiliary— increased alanine transaminase (ALT), aspartate transferase (AST), and total bilirubin. •  Endocrine/metabolic—metabolic acidosis, electrolyte imbalance. •  Musculoskeletal— weakness, ataxia. CAUSES & RISK FACTORS •  Increased hydrolysis in a moist, acidic environment; thus, recent food ingestion lowers gastric pH and increases hydrolysis. Owner should be instructed not to feed their pet. •  Owners and veterinary staff are at risk for inhalation exposure if the animal vomits in a poorly ventilated area. Owners should be told to lower their windows on the way to the clinic.

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Organophosphate. •  Metaldehyde. •  Serotonin syndrome. •  Nonsteroidal anti-inflammatory drug (NSAID) toxicosis.

disease (hemorrhagic gastroenteritis [HGE], gastroenteritis, parvovirus). •  Congestive heart failure. •  Respiratory disease (noncardiogenic pulmonary edema— secondary to electrocution, near drowning, seizures, or acute respiratory distress syndrome [ARDS]). •  Metabolic disease (renal, hepatic, pancreatitis).

18 mg/kg PO q24h, silymarin/milk thistle 50–250 mg/day PO q24h. If associated coagulopathy—vitamin K1 2–3 mg/kg PO q12–24h. •  Oxidative damage or for methemoglobinemia—N-acetylcysteine. •  Painful—opioids (hydromorphone 0.05–0.1 mg/kg IV) or tramadol 2–4 mg/kg PO q8–12h. Avoid NSAIDs.

CBC/BIOCHEMISTRY/URINALYSIS

•  May see increased liver enzymes (ALT, AST,

and total bilirubin); can be delayed 3–5 days.

•  Electrolyte alterations (decreased potassium or magnesium). •  Methemoglobinemia,

Heinz body formation, and subsequent hemolysis. OTHER LABORATORY TESTS

•  Confirmation through gas chromatography

or a Dräger detection tube (referral laboratory testing). •  Post-mortem samples from the liver, kidney. IMAGING If respiratory signs, thoracic radiographs to assess for pulmonary edema. PATHOLOGIC FINDINGS Are nonspecific.

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 FOLLOW-UP

Varies on a case basis.

PATIENT MONITORING Several organ systems may be affected; vitals, heart rhythm, blood pressure, and CNS should be monitored for 18 hours. PREVENTION/AVOIDANCE Have owners remove all baits from environment. POSSIBLE COMPLICATIONS Liver or renal failure. EXPECTED COURSE AND PROGNOSIS •  Asymptomatic patients should be monitored for up to 12–18 hours. •  Symptomatic patients should be monitored for at least 48 hours or until life-threatening signs have resolved.

 TREATMENT

•  No antidote. •  The goal of treatment with

recent, asymptomatic patients is to safely decontaminate. •  Administration of a liquid antacid such as magnesium hydroxide, aluminum hydroxide, calcium carbonate, or even a 5% sodium bicarbonate solution may help to increase the gastric pH and thus decrease phosphine gas production. •  Emesis induction with apomorphine, hydrogen peroxide, or gastric lavage for gastric emptying. •  Activated charcoal may help decrease toxicity but should be given only if the patient’s clinical status allows. •  IV fluid therapy with monitoring for any clinical signs or progression of signs for at least 18 hours. •  Supplemental oxygen for hypoxemia.

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 MEDICATIONS

•  GI protectants—famotidine 0.5–1 mg/kg

IV/PO q12–24h, omeprazole 0.5–1 mg/kg PO q12–24h, sucralfate 0.25–1 g PO q8–12h, or possibly misoprostol 2–5 μg/kg PO q8h. •  Tremors—methocarbamol 44–220 mg/kg IV or to effect; do not exceed 330 mg/kg/day. •  Seizures—diazepam 0.5–1 mg/kg IV, phenobarbital 4–16 mg/kg IV to effect, levetiracetam 30–60 mg/kg IV, or propofol 1–8 mg/kg or to effect, followed by a CRI at 0.1–0.6 mg/kg/h. •  Liver effects— hepatoprotectants (S-adenosylmethionine

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 MISCELLANEOUS

ABBREVIATIONS •  ALT = alanine transaminase. •  ARDS = acute respiratory distress syndrome. •  AST = aspartate transferase. •  GI = gastrointestinal. •  HGE = hemorrhagic gastroenteritis. •  NSAID = nonsteroidal anti-inflammatory drug. INTERNET RESOURCES https://www.avma.org/KB/Resources/ Reference/Pages/Phosphine-productprecautions.aspx

­Suggested Reading

Gray SL, Lee JA, Hovda LR, et al. Potential zinc phosphide rodenticide toxicosis in dogs: 362 cases (2004–2009). J Am Vet Med Assoc 2011, 239:646–651. Knight MW. Zinc phosphide. In: Peterson ME, Talcott PA, eds., Small Animal Toxicology, 3rd ed. St. Louis, MO: Elsevier Saunders, 2013, pp. 853–864. Author Sarah L. Gray Consulting Editor Lynn R. Hovda  Client Education Handout available online

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1212

Blackwell’s Five-Minute Veterinary Consult

Roundworms (Ascariasis)

 BASICS

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OVERVIEW •  Ascariasis caused by Toxocara canis (dogs), T. cati (cats), and Toxascaris leonina (dogs, cats); Baylisascaris (raccoons) can infect dogs and causes neural larval migrans in people. •  Transplacental transmission of T. canis larvae from bitch to pups causes prenatal infection; transmammary transmission of larvae occurs with both Toxocara spp.; no transplacental or transmammary transmission with Toxascaris. •  In first month of life, infected neonatal pups may develop abdominal pain and rapidly deteriorate before Toxocara eggs appear in feces. •  Older pups and kittens can acquire by ingesting eggs spread by dams with postgestational infection; dams can be infected by ingesting immature worm stages in pups’ feces or vomitus or by predation on vertebrate transport hosts. •  Adult ascarids occur in lumen of small intestine; larval stages of Toxocara spp. may migrate in liver and lungs. •  If numerous, ascarids (up to 10–12 cm long) can distend intestine and cause colic, interference with gut motility, inability to utilize food, intestinal rupture. SIGNALMENT

•  Dog and cat. •  Important in puppies/kittens

due to in utero/transmammary transmission.

SIGNS •  Abdominal distension; often with palpable intestinal distension. •  Colic. •  Weakness, loss of condition, cachexia; poor nursing or appetite; scant feces. •  Coughing due to larval lung migration. •  Entire litter may be affected.

weakness, lethargy, pallor, enteritis) or Strongyloides (diarrhea); coccidiosis, giardiasis; examine feces for eggs or larvae. •  Physaloptera. CBC/BIOCHEMISTRY/URINALYSIS Usually normal. OTHER LABORATORY TESTS N/A IMAGING N/A DIAGNOSTIC PROCEDURES •  Fecal flotation to detect eggs: ◦  Toxocara eggs spherical pitted outer shell membrane, single dark cell filling interior, 80–85 μm (T. canis), ~75 μm (T. cati). ◦  Baylisascaris eggs similar to T. canis eggs but smaller (~76 × 60 μm), more finely pitted shell. ◦  Toxascaris eggs ovoid, smooth exterior shell membrane, 1–2 cells with light-colored cytoplasm; cells do not fill interior of egg; 80 × 70 μm in diameter. •  Necropsy of siblings—identify ascarids by size, appearance. •  Fecal ELISA—commercial test detects antigen produced by adult and immature roundworms of both sexes; can detect prepatent infection.

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 TREATMENT

infection reservoir for puppies during gestation; queen becomes infected during late pregnancy or lactation and transfers to kittens via transmammary route. •  Access to infected transport hosts. •  Concurrent enteric infections. •  Toxocara larvae undergo extensive migration and can cause granulomatous inflammation (visceral larva migrans). Visceral larva migrans caused by ascarids is cause of human morbidity. •  Somatically arrested larvae in small vertebrates are source of infection for dogs/cats that hunt.

treated as inpatients; provide parenteral fluids. •  Alert client to possibility of sudden death or chronic debilitation. •  Treat dam with adulticide/larvicide anthelmintic to remove intestinal stages and limit transmission to subsequent litters.

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 MEDICATIONS

DRUG(S) OF CHOICE Adulticide/Larvicide Anthelmintics

•  Fenbendazole 50 mg/kg PO q24h for 3 days. •  Milbemycin oxime 0.5 mg/kg

(dogs) or 2 mg/kg (cats) PO q30 days.

•  Moxidectin (dogs) 2.5 mg/kg, topically, q30 days. •  Moxidectin (in combination

with imidacloprid) 10 mg/kg, topically, q30 days. •  Emodepside 3 mg/kg, or praziquantel 12 mg/kg, topically once for cats ≥8 weeks old; repeat in 30 days if cat is reinfected.

Adulticide Anthelmintics

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Transmammary perinatal infection of neonates with hookworms (anemia, melena,

CONTRAINDICATIONS/POSSIBLE INTERACTIONS N/A

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 FOLLOW-UP

PATIENT MONITORING Repeat post-treatment fecal exams on puppies/kittens and/or repeat anthelmintic treatment every 2–3 weeks until old enough for monthly anthelmintic product. PREVENTION/AVOIDANCE •  Minimize environmental contamination, treat infected dogs/cats with anthelmintic, dispose of feces promptly. •  Prevent dogs/cats from hunting or ingesting transport hosts. •  Extra-label treatment of dam with adulticide/ larvicide anthelmintic to remove intestinal stages and decrease vertical transmission. POSSIBLE COMPLICATIONS Transplacental transmission of large numbers of larvae can result in fetal death or birth of weak, nonviable offspring. EXPECTED COURSE AND PROGNOSIS Prognosis good after anthelmintic treatment; guarded with severe prenatal T. canis infection.

•  Generally outpatient. •  Acute severe cases

CAUSES & RISK FACTORS

•  Dormant Toxocara larvae in dam’s tissues is

dogs. •  Selamectin 6 mg/kg, topically, once (T. cati, cats): dogs, extra-label.

•  Pyrantel pamoate 5 mg/kg PO (dogs) or

10–20 mg/kg PO (cats, extra-label).

•  Pyrantel/praziquantel, label dose for cats. •  Febantel/praziquantel/pyrantel, label dose for dogs. •  Ivermectin/pyrantel, label dose for

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 MISCELLANEOUS

AGE-RELATED FACTORS Greater concern in neonates. ZOONOTIC POTENTIAL •  Visceral larva migrans, ocular larva migrans, neural larva migrans, chronic abdominal or cutaneous problems may follow ingestion of infective Toxocara spp. or Baylisascaris eggs by humans; advise clients to practice good hygiene after handling feces. •  Most likely cause of neural larva migrans is Baylisascaris; virtually all raccoons become infected with Baylisascaris and therefore extreme caution should be exercised with clients having raccoons as “pets.” INTERNET RESOURCES

•  http://www.capcvet.org •  http://www.cdc.gov

­Suggested Reading

Bowman DD. Georgis’ Parasitology for Veterinarians, 9th ed. St. Louis, MO: Saunders, 2009, pp. 197–198, 201–208. Authors Matt Brewer and Jeba R.J. Jesudoss Chelladurai Consulting Editor Amie Koenig



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Canine and Feline, Seventh Edition

Sago Palm Toxicosis

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 BASICS

OVERVIEW •  Cycad palms, also called sago palms, belong in the family Cycadaceae. •  Native to tropical and subtropical regions but have become popular ornamental plants in the United States. •  Cycas revoluta, Cycas circinalis, and Zamia floridana are the most common species. •  Contain the toxins cycasin, betamethylamino-lalanine, and an unidentified high-molecularweight compound. •  Toxins present in all parts of the plant; highest concentrations in seeds. •  Cycasin is metabolized by the intestinal flora to the active hepatotoxic, carcinogenic, mutagenic, teratogenic, and neurotoxic compound methylazoxymethanol (MAM). •  Cycad toxicosis has been documented in several animal species (dogs and ruminants) and humans. •  In dogs, gastrointestinal (GI) disturbances and hepatic damage predominate; nervous system involvement is less common. SIGNALMENT

•  Dogs—no breed, sex, or age predilection. •  Cats—no cases reported.

CBC/BIOCHEMISTRY/URINALYSIS •  Anemia. •  Elevated serum liver enzymes (alanine transaminase, aspartate transaminase, alkaline phosphatase, bilirubin). •  Hypoalbuminemia. •  Hypoglycemia. •  Glucosuria, hemoglobinuria, myoglobinuria, bilirubinuria, proteinuria, and increased urine specific gravity.

sago palm toxicosis available. Can be given for supportive therapy. •  N-Acetylcysteine— antioxidant; no data on efficacy in sago palm toxicosis available. A glutathione precursor that can be included in the treatment regimen for acute fulminant hepatic failure at 140 mg/ kg IV load, followed by 70 mg/kg IV q6h for 7 treatments.

OTHER LABORATORY TESTS •  Ammonia tolerance test—hyperammonemia. •  Prolonged prothrombin time/partial thromboplastin time.

CONTRAINDICATIONS/POSSIBLE INTERACTIONS N/A

IMAGING N/A DIAGNOSTIC PROCEDURES

•  History of cycad palm ingestion and presence of appropriate clinical signs. •  Identification of plant in ingesta or feces. •  Biopsy and histo­

pathology of liver—hepatic necrosis. •  Necropsy—hepatic centrilobular necrosis.

PATHOLOGIC FINDINGS •  Detection of cycad palm material in GI tract and/or in feces. •  Gross detection of liver enlargement. •  Histologic detection of centrilobular and midzonal coagulative hepatocellular necrosis.

SIGNS

•  GI disturbances such as vomiting, diarrhea, and abdominal pain. •  Signs associated with

hepatic damage (ecchymoses, petechiae, hemorrhage, edema, etc.). •  Gait abnormalities; paresis/paralysis; tremors. •  Depression, coma, and death. CAUSES & RISK FACTORS Access to and ingestion of cycad palm.

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 TREATMENT

•  No antidote available. •  GI decontamination

with activated charcoal can be attempted but efficacy is unknown. •  Supportive care including close monitoring and, depending on the severity of clinical signs, IV fluids, correction of electrolyte imbalances and hypoglycemia, vitamin K1, and plasma transfusions.

 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS Other Causes of Acute GI Upset

•  Infectious. •  Metabolic. •  Toxic. •  Dietary.

Other Causes of Acute Liver Failure

•  Microcystins (hepatotoxic blue-green algal

toxins)—access to water with algal bloom, algal material on legs or in stomach contents, detection of microcystins in stomach contents. •  Amanitin—access to mushrooms (Amanita, Galerina, and Lepiota spp.), GI signs between 6 and 24 hours after ingestion. •  Cocklebur (Xanthium spp.)—access to cocklebur (only seeds and two-leaf cotyledon stage are toxic). •  Aflatoxins—access to moldy food. •  Acetaminophen overdose. •  Xylitol—access to xylitol-containing products (sugar-free gum, chewable vitamins, baked goods); initial hypoglycemia. •  Severe acute pancreatitis.

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 FOLLOW-UP

PATIENT MONITORING •  Liver enzymes/function. •  Coagulation status. PREVENTION/AVOIDANCE Deny access to sago palms. POSSIBLE COMPLICATIONS

•  Hepatic encephalopathy. •  Disseminated intravascular coagulation. •  Renal failure.

EXPECTED COURSE AND PROGNOSIS

•  Dogs develop vomiting within minutes, followed by further GI upset. •  Changes in

clinical laboratory values occur after 24–48 hours. •  Nadir serum albumin levels and nadir platelet counts are important prognostic indicators. •  Liver failure within a few days. •  Prognosis is poor to guarded.

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 MISCELLANEOUS

ABBREVIATIONS •  GI = gastrointestinal. •  MAM = methylazoxymethanol. INTERNET RESOURCES

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 MEDICATIONS

DRUG(S) OF CHOICE •  Activated charcoal—multi-dose activated charcoal at 1–4 g/kg PO q4–6h for 2–3 days post ingestion. Mix activated charcoal in water at 1 g/5−10 mL of water. •  IV fluids— maintain hydration, induce diuresis, correct hypoglycemia. •  Dextrose—50% dextrose 1 mL/kg IV slow bolus (1–3 minutes). •  Vitamin K1—0.5–1.5 mg/kg SC or IM q12h; 1 mg/kg PO q24h. •  Blood products— dependent on hemostatic test results. ALTERNATIVE DRUG(S)

•  S-Adenosylmethionine—antioxidant and

hepatoprotectant; no data on efficacy in sago palm toxicosis available. Dose 20 mg/kg PO q24h. •  Ascorbic acid and cimetidine— hepatocyte protectors; no data on efficacy in

•  http://www.petpoisonhelpline.com/poison/ sago-palm/ •  http://www.aspca.org/pet-care/

animal-poison-control/toxic-and-non-toxicplants/fern-palm

­Suggested Reading

Albretsen JC, Khan SA, Richardson JA. Cycad palm toxicosis in dogs: 60 cases (1987–1997). J Am Vet Med Assoc 1998, 213(1):99–101. Clarke C, Burney D. Cycad palm toxicosis in 14 dogs from Texas. J Am Anim Hosp Assoc 2017, 53:159–166. Ferguson D, Crowe M, McLaughlin L, et al. Survival and prognostic indicators for cycad intoxication in dogs. J Vet Intern Med 2011, 25(4):831–837. Authors Adrienne C. Bautista and Birgit Puschner Consulting Editor Lynn R. Hovda

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1214

Blackwell’s Five-Minute Veterinary Consult

Salivary Mucocele

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 BASICS

OVERVIEW •  Salivary mucoceles (sialoceles) are nonepitheliallined cavities filled with saliva that has leaked from a damaged salivary gland or duct; they are surrounded by granulation tissue that forms secondary to inflammation caused by the free saliva. •  There are four major pairs of salivary glands: parotid, mandibular, sublingual, and zygomatic. Smaller salivary glands are located in the soft palate, lips, cheeks, and tongue. •  Types of mucoceles are listed in Table 1. The most common type occurs with injury to the sublingual gland or its duct. SYSTEMS AFFECTED Gastrointestinal SIGNALMENT

•  Three times more frequent in dogs than in

cats.

•  Commonly affected breeds include

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miniature poodle, German shepherd dog, dachshund, and Australian silky terrier. •  Slight predisposition of males compared to females. •  No age predisposition. SIGNS Cervical Sialocele

•  Soft, fluctuant, minimally painful or

nonpainful, gradually developing cervical mass. •  Pain is usually manifested only during the acute-manifestation phase of the sialocele. Sublingual Sialocele

•  Soft, sublingual swelling (also called ranula;

from Latin: rana, frog). •  Often blood-tinged saliva secondary to self-trauma while eating. •  Abnormal tongue movement, tongue displaced, dysphagia. Pharyngeal Sialocele

•  Swelling in pharyngeal wall. •  Dysphagia and respiratory distress when

very large.

Zygomatic Sialocele

•  Periorbital swelling. •  Exophthalmos and protrusion of third

eyelid.

•  Divergent strabismus. •  Periocular pain. •  Pressure-related neuropathy of the optic

nerve.

CAUSES & RISK FACTORS The cause is rarely identified. Suspected causes: •  Blunt trauma to the head and neck (choke chains).

•  Bite wound. •  Penetrating foreign body. •  Ear canal surgery, parotid duct

transposition, maxillectomy.

•  Sialoliths. •  Dirofilariasis.

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 DIAGNOSIS

•  Cytologic evaluation (Wright’s stain) reveals

diffuse or irregular clumps of pink to violet-staining mucin, large phagocytic cells with small, round nuclei and foamy cytoplasm, intermixed salivary gland epithelial cells, and nondegenerate neutrophils in small numbers. •  Stain with a mucus-specific stain (e.g., periodic acid–Schiff ) for definitive diagnosis.

•  Diagnosis is based on history, visual

examination, and paracentesis of the fluidfilled swelling. •  Determine the site of origin with help of oral examination, palpation, sialography, or exploration of the sialocele. DIFFERENTIAL DIAGNOSIS •  Sialoadenitis (second most common salivary gland disease; usually involving the zygomatic gland; often concurrent with sialoliths and other ductal foreign bodies). •  Sialadenosis (nonpainful, noninflammatory salivary gland swelling; usually mandibular gland). •  Necrotizing sialometaplasia (painful salivary gland swelling; squamous metaplasia with ischemic necrosis; usually mandibular gland). •  Salivary neoplasia (rare; mandibular and parotid glands most commonly involved; usually adenocarcinomas). •  Sialoliths (calcium phosphate or carbonate). •  Cervical abscess. •  Foreign body. •  Hematoma. •  Abscessed or neoplastic lymph nodes. CBC/BIOCHEMISTRY/URINALYSIS Laboratory abnormalities are rarely seen. OTHER LABORATORY TESTS N/A

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 TREATMENT

•  Patients with acute respiratory distress

(pharyngeal sialoceles) might need to be intubated or have a temporary tracheostomy performed. Transoral drainage via stab incision may be required prior to intubation. •  Complete surgical excision of the involved gland–duct complex and drainage of the sialocele is the treatment of choice. Permanent drainage may be achieved with marsupialization of sublingual and pharyngeal sialoceles.

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 MEDICATIONS

DRUG(S) OF CHOICE Antibiotics based on bacteriologic evaluation, if concurrent abscessation or sialadenitis. CONTRAINDICATIONS Nonsurgical treatment with repeated drainage or injection of cauterizing or antiinflammatory agents is not curative and will complicate subsequent surgery by causing abscessation or fibrosis.

IMAGING

•  Ideally CT or MRI with contrast. •  Skull and upper neck radiography only

helpful to identify sialoliths, foreign bodies, or neoplasia. •  Sialography (injection of iodinated, water-soluble contrast agent into the salivary duct) reserved for patients with trauma, previous surgeries, or fistulous draining tracts and can be helpful to determine the size and source of sialoceles. •  Retrobulbar ultrasound. DIAGNOSTIC PROCEDURES Aseptic Paracentesis

•  Differentiates sialoceles from neoplasia and

abscess.

•  Aspirated fluid is viscous, clear, or pink,

yellow, brown or black (blood-tinged) with a low cell count; surrounding soft tissue may show low-grade chronic plasmacyticlymphocytic inflammation.

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 FOLLOW-UP

PATIENT MONITORING Penrose drains placed after sialadenectomy are usually removed 24–72 hours following surgery. POSSIBLE COMPLICATIONS •  Seroma formation (after excessive tissue dissection, insufficient dead space manage­ ment, and when Penrose drains are not used following sialadenectomy). •  Infection. •  Sialocele recurrence (1 week. •  Untreated—often fatal.

PATHOLOGIC FINDINGS

•  Lymphoid tissue enlargement—tissues

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•  Petechial hemorrhages. •  Gastrointestinal tract thickening with white

ASSOCIATED CONDITIONS Infection with N. salmincola does not itself cause severe clinical disease.

yellowish with prominent white foci. nodules.

•  Intestinal contents—frequently contain free

blood; flukes may not be grossly visible. •  Histopathology—depletion of lymph node follicles; infiltration of lymphoid tissues and intestinal submucosa by histiocytes; cytoplasm contains numerous lymphoid follicles; flukes may be found embedded in gastrointestinal mucosa.

 MISCELLANEOUS

ZOONOTIC POTENTIAL N. salmincola can cause gastrointestinal disturbances and eosinophilia in humans; N. helminthoeca does not cause human disease. INTERNET RESOURCES https://www.vetmed.wsu.edu/outreach/ Pet-Health-Topics/categories/diseases/ salmon-poisoning

­Suggested Reading

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Lymphoma. •  Toxicosis. •  Canine parvovirus type 2 infection. •  Ehrlichia canis infection.

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 TREATMENT

•  Inpatient—acutely ill patients. •  Supportive therapy—IV fluids with

electrolytes; colloids or packed red blood cell transfusions may be needed; consider antiemetics and parenteral nutrition.

Sykes JE. Salmon poisoning disease. In: Sykes JE, ed., Canine and Feline Infectious Diseases. St. Louis, MO: Elsevier Saunders, 2014, pp. 311–319. Author Jane E. Sykes Consulting Editor Amie Koenig



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Canine and Feline, Seventh Edition

Salmonellosis Mean Age and Range

•  Dogs—neonatal/immature puppies,

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 BASICS

DEFINITION Infection caused by many different serotypes of Salmonella, causing enteritis, septicemia, and abortions. PATHOPHYSIOLOGY •  Salmonella—Gram-negative bacterium; colonizes small intestine (ileum); adheres to and invades enterocytes; enters and multiplies in lamina propria and local mesenteric lymph nodes; cytotoxin and enterotoxin are produced; inflammation and prostaglandin synthesis ensue; results in secretory diarrhea, mucosal sloughing. •  Uncomplicated gastroenteritis—organisms are stopped at the mesenteric lymph node stage; patient has only diarrhea, vomiting, dehydration. •  Bacteremia and septicemia following gastroenteritis—more serious; focal extra­ intestinal infections (abortion, joint disease) or endotoxemia may result; may cause thrombosis, disseminated intravascular coagulation (DIC), death. •  Some patients recover from septicemia but have prolonged recovery. SYSTEMS AFFECTED

•  Gastrointestinal—enterocolitis; inflammation,

mucosal sloughing, secretory diarrhea. •  Systemic disease (e.g., bacteremia, focal infections, septicemia)—multiorgan infarction, thrombosis, abscesses, meningitis, osteomyelitis, abortion. GENETICS N/A INCIDENCE/PREVALENCE

•  True incidence unknown; prevalence in

healthy dogs/cats similar to diarrheic animals. •  Most infections subclinical. •  Dogs—clinical disease most often seen in the young and pregnant bitches. Common in racing greyhounds and sled dogs due to raw meat diets; presence of Salmonella in feces does not necessarily imply infection. •  Cats—natural resistance; stressed, hospitalized, and shelter cats at risk. Pandemics of salmonellosis in migrating songbirds (usually Salmonella Typhimurium) in spring lead to epidemics in bird-hunting cats. •  Raw meat diet (especially chicken) risks—Campylobacter spp. in addition to Salmonella spp. and Listeria spp. Outbreaks linked to pet foods/treats common. GEOGRAPHIC DISTRIBUTION Worldwide SIGNALMENT Species

Dog and cat.

pregnant bitches. Most adult carrier dogs clinically normal. •  Cats—adults highly resistant unless treated with an antimicrobial prior to exposure.

Environmental Factors

•  Diet: ◦◦ Raw food diet is major risk factor. ◦◦ Contaminated dog treats (e.g., pig ears). ◦◦ Dehydrated (dry) pet food; semi-moist

foods usually not as risky.

SIGNS

•  Coprophagia. •  Grooming habits—can contaminate

General Comments

•  Dense population—colonies, boarding

Disease severity—subclinical (carrier state, more common) to severe clinical cases in neonatal and stressed adult animals. Historical Findings

•  Diarrhea, can be hemorrhagic. •  Vomiting. •  Fever. •  Malaise. •  Anorexia. •  Vaginal discharge/abortion—dogs. •  Chronic febrile illness—persistent fever,

anorexia, malaise without diarrhea.

Physical Examination Findings

•  Asymptomatic carrier states—no clinical

signs.

•  Gastroenteritis—fever (102–104°F/39–

40°C), diarrhea with mucus and/or blood, dehydration, abdominal pain, tenesmus, pale mucous membranes, weight loss. •  Gastroenteritis with bacteremia, septic shock, or endotoxemia—brick-red mucous membranes, tachycardia, bounding pulses, rapid capillary refill time (unless decompensatory shock), tachypnea, abdominal pain, weakness. •  Focal extraintestinal infections—conjunctivitis, cellulitis, pyothorax, diskospondylitis. •  Cats—chronic febrile illness, vague, nonspecific clinical signs. •  Recovering patients—chronic intermittent diarrhea for 3–4 weeks (may shed Salmonella in stool >6 weeks). CAUSES

•  Any one of more than 2,000 serotypes of

salmonellae.

•  Two or more simultaneous serotypes in host

animal can occur: ◦◦ Most common serotypes—Newport, Typhimurium, Albany, 4,5,12:i:, Dublin, Heidelberg.

RISK FACTORS Disease Agent

•  Salmonella serotype determines virulence,

infectious dose, and route of exposure.

•  Host factors that increase susceptibility: ◦◦ Age—neonatal/young dogs and cats;

immature immune system. ◦◦ Health—debilitated young animals (immature gastrointestinal tract, poorly developed normal microbial flora) or adults with concurrent disease. ◦◦ Disrupted gastrointestinal flora (adult cats)—antimicrobial treatment; exposure to salmonellae during hospitalization.

environment, feed and water dishes.

facilities, shelters: ◦◦ Build up of Salmonella in environment, more efficient fecal–oral cycling. ◦◦ Stress. ◦◦ Exposure to infected (or carrier) animals. •  Unsanitary environment. Hospitalized Animals

Nosocomial exposure (plus stress) or activation (by stress) of preexisting asymptomatic (carrier) Salmonella infection, especially in animals treated with antimicrobial drugs. Vaccinated Cats

Death reported in kittens (likely to be subclinically infected by Salmonella) post vaccination, with high titers of modified live panleukopenia vaccine.

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Acute gastroenteritis—infectious, foreign body, neoplasia: ◦◦ Viral gastroenteritis—canine enteric coronavirus, canine parvovirus, rotavirus, canine distemper. ◦◦ Bacterial gastroenteritis—Escherichia coli, Campylobacter jejuni, Yersinia enterocolitica. •  Bacterial overgrowth syndrome— Clostridium difficile, C. perfringens. •  Parasites—helminths, protozoa (Giardia, Coccidia, Cryptosporidia), salmon poisoning. •  Acute gastritis—erosions or ulcers. •  Diet-related—allergy or food intolerance. •  Drug- or toxin-induced distress. •  Extraintestinal disorders (metabolic disease). CBC/BIOCHEMISTRY/URINALYSIS

•  CBC—variable; depends on stage of illness:

initially neutropenia, left-shifted neutrophils, lymphopenia, thrombocytopenia, non-regenerative anemia. •  Hypoalbuminemia, electrolyte abnormalities related to gastrointestinal losses. DIAGNOSTIC PROCEDURES

•  Fecal/rectal bacterial culture—special media

needed: ◦◦ Subclinical carriers may have intermittent positive fecal culture (>6 weeks). ◦◦ Use of antimicrobials before sampling may yield false-negative culture. ◦◦ Serotyping of cultured organisms— helpful to define outbreak.

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Blackwell’s Five-Minute Veterinary Consult

Salmonellosis •  Cultures of blood and joint fluid, ileum,

mesenteric lymph node, liver/spleen, bone marrow. •  Fecal cytology—leukocytes present. •  Fecal Salmonella PCR. •  Abdominal ultrasound (clinical gastroenteritis)—lymphadenomegaly, enterocolitis, typhlitis, peritonitis. PATHOLOGIC FINDINGS Lymphoplasmacytic, neutrophilic typhlitis/ enteritis with ulceration, crypt abscessation, lymphoid hyperplasia, pyogranulomas; lymphadenitis.

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 TREATMENT

APPROPRIATE HEALTH CARE •  Outpatient—uncomplicated gastroenteritis. •  Inpatient—with bacteremia/septicemia, gastroenteritis in neonatal/immature animals (rapidly debilitated). NURSING CARE

•  Varies according to severity of illness—

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assess dehydration, body weight, ongoing fluid loss, shock, hematocrit, albumin, electrolytes, acid–base status. •  Supportive care—fluid and electrolyte replacement: ◦◦ Parenteral, balanced, polyionic isotonic replacement solution (lactated Ringer’s). ◦◦ Oral fluids—hypertonic glucose solutions; for secretory diarrhea. •  Plasma transfusions—if serum albumin 170 mEq/L, dogs; >175 mEq/L, cats) may cause neurologic signs including lethargy, behavioral changes, ataxia, muscle tremors, and seizures. Coma and death may occur. •  LD50 (dogs) = 4 g NaCl/kg, 180 mEq/L is consistent with salt toxicosis. IMAGING

•  Thoracic radiography if respiratory signs to

evaluate for hypervolemia and signs of fluid overload and pulmonary edema. •  MRI or CT—evaluate for subarachnoid or cerebral hemorrhage. DIAGNOSTIC PROCEDURES CSF tap for sodium concentration (rarely performed) and rule out other causes for neurologic signs. PATHOLOGIC FINDINGS

•  Hemorrhage of stomach, small intestine,

and colon.

•  Cerebral edema, perivascular hemorrhage

and fibrinous exudate.

•  Pulmonary edema. •  Acute renal and hepatic necrosis.

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 TREATMENT

APPROPRIATE HEALTH CARE Hospitalization recommended for electrolyte monitoring. NURSING CARE Asymptomatic

•  Decontamination with emesis if appropriate

time frame.

•  Monitor Na level in the hospital for 6 hours

post exposure.

•  If asymptomatic and Na remains normal,

discharge patient to be monitored at home.

Symptomatic

•  Stabilize neurologic signs as needed. •  Decontamination with emesis if indicated. •  IV fluids for rehydration. May need to

match fluid Na content to patient serum Na depending on chronicity and degree of hypernatremia. •  Calculate free water replacement for hypernatremia: ◦  IV use D5W or 0.45% NaCl + 2.5% dextrose; use with caution in patients with hyperglycemia. ◦  Water oral or via nasoesophageal tube— use for stable patients that are not vomiting or those with underlying cardiac disease/ failure or evidence of fluid overload. Can be used with IV therapy. ◦  Acute toxicity (24 hours) or unknown time frame—lower Na slowly, not to exceed 12 mEq/day (0.5 mEq/h).

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Blackwell’s Five-Minute Veterinary Consult

Salt Toxicosis •  Free water deficit calculation:

[(patient Na ÷ normal Na) − 1] × (0.6 × body  weight kg) × 1000 = Free water deficit in  milliliters DIET Oral water can be offered to lower Na. Water intake should be regulated so that Na level does not drop too rapidly. CLIENT EDUCATION Outdoor pets may be susceptible to decreased intake with frozen or empty water containers or if they become trapped in a garage or shed. Heated water bowls and multiple water sources should be available. SURGICAL CONSIDERATIONS Gastrotomy may be needed to remove homemade playdough or ornament dough if unable to remove with emesis or gastric lavage.

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(continued) •  Furosemide 1–4 mg/kg IV q2–8h or a CRI

0.1–0.5 mg/kg/h IV titrated to effect for hypervolemia or pulmonary edema until signs resolve. CONTRAINDICATIONS Activated charcoal—will worsen hypernatremia. PRECAUTIONS

•  Mannitol, hypertonic saline, and sodium

bicarbonate should be used with caution as they may worsen hypernatremia. •  Diuretics such as furosemide may be helpful for Na excretion via the kidney but hydration status needs to be monitored carefully. •  Hyponatremia or rapid correction of chronic hypernatremia (due to idiogenic osmole formation) during treatment can cause cerebral edema formation and worsening or reoccurrence of neurologic signs. ALTERNATIVE DRUG(S) N/A

 MEDICATIONS

DRUG(S) OF CHOICE •  Antiemetic for vomiting—maropitant 1 mg/kg SC or IV q24h. •  Proton pump inhibitor if signs of stomach mucosal irritation: ◦  Pantoprazole 1 mg/kg IV slowly q24h. ◦  Omeprazole 1 mg/kg PO q24h. •  Methocarbamol 55–220 mg/kg IV slowly, to effect for muscle tremors; do not exceed 330 mg/kg/day. •  Anticonvulsant such as diazepam 0.5–2 mg/kg IV for seizures.

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 FOLLOW-UP

PATIENT MONITORING •  Sodium level should be monitored during treatment; frequency depends on severity of signs and chronicity of hypernatremia but generally every 2–4 hours. •  Hydration status monitored every 4–6 hours. PREVENTION/AVOIDANCE Salt should not be recommended or given as an emetic.

POSSIBLE COMPLICATIONS Persistent neurologic impairment with severe toxicity. EXPECTED COURSE AND PROGNOSIS •  Neurologic signs should improve with improvement of Na level. •  Prognosis is generally good. Guarded to poor prognosis with severe neurologic signs and poor response to treatment.

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 MISCELLANEOUS

PREGNANCY/FERTILITY/BREEDING N/A SYNONYMS Hypernatremia

­Suggested Reading

Barr JM, Khan SA, Safdar A, et al. Hypernatremia secondary to homemade play dough ingestion in dogs: a review of 14 cases from 1998–2001. J Vet Emerg Crit Care 2013, 14(3):196–202. DiBartola SP. Disorders of sodium and water: hypernatremia and hyponatremia. In: Fluid, Electrolyte and Acid-Base Disorders in Small Animal Practice, 4th ed. St. Louis, MO: Elsevier- Saunders, 2012, pp. 45–79. Guillaumin J, DiBartola SP. Disorders of sodium and water homeostasis. Vet Clin Small Anim 2017, 47:293–312. Author Katherine L. Peterson Consulting Editor Lynn R. Hovda



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Canine and Feline, Seventh Edition

Sarcoptic Mange DIAGNOSTIC PROCEDURES

•  Pinnal–pedal reflex—rubbing the ear

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 BASICS

OVERVIEW A nonseasonal, intensely pruritic, highly contagious parasitic skin disease of dogs and other mammalian species caused by Sarcoptes scabiei var. canis mites. PATHOPHYSIOLOGY Burrowing mites induce hypersensitivity, causing intense pruritus. SYSTEMS AFFECTED Skin/exocrine SIGNALMENT •  All in-contact dogs usually affected. •  Transient pruritus of in-contact other species: cats, humans. SIGNS •  Nonseasonal, progressively worsening intense pruritus. •  Pruritus develops within 4–6 weeks of exposure. •  Seroconversion 3 weeks after clinical signs develop. •  Rare individuals do not seroconvert and therefore may not develop severe pruritus. •  Elbows, pinnal margins, ventrum, and hocks affected first. •  Crusted papules leading to generalized alopecia, crusting, and excoriations; lichenification and thickening with chronicity. •  Poor response to antihistamines and anti-inflammatory doses of steroids. •  Mite numbers often low. •  Immunocompromised individuals may harbor larger numbers of mites. CAUSES & RISK FACTORS

•  Close contact with other dogs in animal

shelters, boarding kennels, groomers, dog parks, and veterinary offices. •  Exposure to fox or coyote.

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Hypersensitivity dermatitis. •  Bacterial folliculitis. •  Parasitic dermatitis (demodicosis, Pelodera, Otodectes, Cheyletiella, Trombicula, Dirofilaria). •  Dermatophytosis. •  Malassezia dermatitis. •  Zinc-responsive dermatosis. •  Ear margin seborrhea. •  Pemphigus foliaceus. OTHER LABORATORY TESTS ELISA—available in some countries to identify Sarcoptes-infested dogs: False positives due to crossreactivity with other mites.

margin between the thumb and forefinger induces the dog to scratch with its hind leg. •  Superficial skin scrapings—positive in 20–50% of scabies cases; false-negative results are common. •  Fecal flotation—may reveal mites or ova. •  Response to scabicidal treatment—most common method for diagnosing scabies.

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 TREATMENT

•  All in-contact dogs must be treated. •  Resolution of pruritis may take several weeks

due to hypersensitivity reaction to the mite.

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 FOLLOW-UP

•  Response to therapy may require 4–6

weeks.

•  Topical scabicidal treatments are more

prone to failure because of incomplete application of the treatment solution. •  Immunity or tolerance does not develop: reinfection may occur with subsequent contact with infected animals. •  Approximately 30% of dogs with Sarcoptes infections will also react to house dust mite antigens on intradermal tests. House dust mite allergy may be a sequela to scabies infection.

•  Sarcoptes mites usually die quickly in the

environment; however, mites have been reported to survive for up to 3 weeks. Thorough cleaning of the dog’s environment is recommended in crowded conditions.

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 MEDICATIONS

DRUG(S) OF CHOICE •  Selamectin—labeled application every 30 days, or application every 2 weeks for at least three treatments. •  Isoxazoline parasiticides (afoxalaner, lotilaner, fluralaner or sarolaner)-at labeled dosage/ frequency. •  Ivermectin 0.2–0.4 mg/kg SC or PO every 1–2 weeks. •  Milbemycin 2 mg/kg PO every 1–2 weeks. •  Doramectin 0.2–0.6 mg/kg SC or PO weekly. •  Moxidectin 0.2–0.3 mg/kg SC or PO weekly; with imidacloprid topical at labeled frequency. •  Lime sulfur 2–4% applied weekly for 4–6 weeks. •  Fipronil spray applied to entire skin surface every 2 weeks for three treatments. •  Topical antiseborrheic therapy in conjunction with scabicidal therapy. •  Systemic antibiotics—may be needed to resolve secondary pyoderma. •  Prednisolone 1 mg/kg for 5–7 days or longer if necessary to relieve pruritus and self-mutilation. CONTRAINDICATIONS/POSSIBLE INTERACTIONS •  Ivermectin—do not use/use with caution in ABCB1 mutant dogs; increased risk of avermectin toxicity in herding breeds: Shetland sheepdogs, Old English sheepdogs, Australian shepherd dogs, and their crosses. •  Potential increased risk of neurotoxicosis with concurrent use of spinosad, macrocyclic lactone, or systemic azole medications. •  Isoxazoline parasiticides—potential for neurologic adverse events in dogs and cats reported.

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 MISCELLANEOUS

ZOONOTIC POTENTIAL •  Sarcoptic mange is zoonotic. People in close contact with an affected dog may develop a pruritic, papular rash on body areas in frequent contact with dogs. •  Lesions resolve spontaneously when the affected animals are treated. ABBREVIATIONS

•  ELISA = enzyme-linked immunosorbent

assay.

­Suggested Reading

Becskei C, De Bock F, Illambas J, Cherni JA et al. Efficacy and safety of novel oral isoxazoline, sarolaner (Simparica™) for the treatment of sarcoptic mange in dogs. Vet Parasitol 2016, 222:56–61. Beugnet F, de Vos C, Liebenberg J, Halos H, et al. Efficacy of afoxolaner in a clinical field study in dogs naturally infested with Sarcoptes scabiei. Parasite 2016, 23:26. Fourie LJ, Heine J, Horak IG. The efficacy of an imidacloprid/moxidectin combination against naturally acquired Sarcoptes scabiei on dogs. Australian Vet J 2006, 84:17–21. Lower KS, Medleau L, Hnilica KA. Evaluation of an enzyme-linked immunosorbent assay (ELISA) for the serological diagnosis of sarcoptic mange in dogs. Vet Dermatol 2001, 12:315–320. Romero C, Heredia R, Pineda J, et al. Efficacy of fluralaner in 17 dogs with sarcoptic mange. Vet Dermatol 2016, 27(5):353–e88. Author Liora Waldman Consulting Editor Alexander H. Werner Resnick

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1222

Blackwell’s Five-Minute Veterinary Consult

Schiff–Sherrington Phenomenon •  Vascular myelopathies (e.g., fibrocartilaginous embolism, coagulopathies, etc.).

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 BASICS

OVERVIEW •  Thoracic limb extension associated with pelvic limb paralysis or paresis after acute and usually severe spinal cord lesion caudal to the cervical intumescence, best observed when the patient is in lateral recumbency. •  Posture—caused by damage to the border cells or their ascending processes, which are interneurons located in the lumbar spinal cord (mainly L2–4) and normally inhibit the extensor motor neurons of the cervical intumescence. SIGNALMENT Any dog suffering from thoracolumbar spinal cord injury. SIGNS

•  Thoracic limbs—rigidly extended; normal

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gait and postural reactions (because the lesion is caudal to the cervical intumescence). •  Pelvic limbs—depends on the severity and location of the lesion; usually upper motor neuron in type, but may be lower motor neuron. •  In severe, acute thoracolumbar myelopathies, spinal shock may be present in addition to the Schiff–Sherrington phenomenon: there is an initial flaccid paralysis caudal to the level of the lesion, with loss of myotatic and flexor reflexes. In dogs and cats, spinal shock is uncommon and usually resolves within an hour, with more typical signs of upper motor neuron disease subsequently developing caudal to the spinal cord lesion. CAUSES & RISK FACTORS •  Trauma secondary to vehicular accident and intervertebral disc disease—most common.

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•  Schiff–Sherrington phenomenon is not a

prognostic indicator; prognosis is determined by the severity of signs caudal to the spinal cord lesion.

 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Decerebrate rigidity—observed with brainstem disease in which all four limbs are rigid and have upper motor neuron dysfunction; opisthotonus present; patient is unconscious. •  Decerebellate rigidity—observed with cerebellar disease in which the forelimbs are rigid but the hind limbs are flexed; consciousness is usually altered. •  Cervical spinal cord injury—may have extensor hypertonia in the thoracic limbs; upper motor neuron and proprioceptive deficits of all four limbs are also seen. •  The key feature in differential diagnosis is that in the Schiff–Sherrington phenomenon, function and postural reactions in the forelimbs are normal despite their extensor rigidity, while they are abnormal in the pelvic limbs.

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 MEDICATIONS

DRUG(S) OF CHOICE As indicated for underlying spinal cord disease.

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 FOLLOW-UP

•  Posture may persist for days to weeks; not

an indication of a hopeless prognosis.

•  With rapid and aggressive treatment, the

patient may recover, especially if there is pain perception caudal to the lesion.

CBC/BIOCHEMISTRY/URINALYSIS N/A

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IMAGING Radiology (radiography, myelography, CT, MRI)—demonstrate the thoracolumbar spinal lesion.

Dewey CW. Functional and dysfunctional neuroanatomy: the key to lesion localization. In: Dewey CW, ed., A Practical Guide to Canine and Feline Neurology, 2nd ed. Ames, IA: Wiley-Blackwell, 2008, p. 41. Author Stephanie Kube

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 TREATMENT

•  Directed toward the underlying

thoracolumbar spinal cord lesion.

•  No specific treatment available. •  Condition resolves if adequate spinal cord

function is restored.

 MISCELLANEOUS

­Suggested Reading



1223

Canine and Feline, Seventh Edition

Schwannoma

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 BASICS

OVERVIEW Schwannomas are tumors of nerve sheath origin, arising from Schwann cells. The term peripheral nerve sheath tumor encompasses schwannomas, neurofibromas, and neuro­ fibrosarcomas, as these tumors arise from the same cell. Importantly, schwannomas are grouped with several other soft tissue sarcomas (e.g., hemangiopericytoma and fibrosarcoma) for therapeutic and prognostic purposes, as the biologic behaviors of this group of tumors are similar. SIGNALMENT •  Dogs—median of 10 years, no sex predis­position, no known breed predilection. •  Cats rarely affected. SIGNS Vary depending on tumor location, which can be peripheral (e.g., skin or tongue) or more central (e.g., axillary region). CAUSES & RISK FACTORS None identified.

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OTHER LABORATORY TESTS None

•  Gabapentin for neuropathic pain

IMAGING

CONTRAINDICATIONS/POSSIBLE INTERACTIONS N/A

•  Myelography may be helpful in cases with

dorsal or ventral nerve root involvement.

•  Contrast CT or, ideally, MRI provides the

most information regarding extent and location of disease.

DIAGNOSTIC PROCEDURES Electromyography consistently reveals abnormal, spontaneous electrical activity in muscles of the affected limb.

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 TREATMENT

•  Surgical excision is the treatment of choice. •  Radiotherapy following incomplete surgical

resection is likely to result in excellent longterm outcome. •  Excision of a distal mass may still result in a functional limb; amputation is required in most cases. •  Radiotherapy as a single treatment modality shows promise for small lesions. •  Laminectomy is necessary in cases of nerve root involvement; local recurrence is common if the primary extends into the spinal canal.

 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Other neoplasia that can involve the connective tissues. •  Orthopedic disease. •  Other neurologic disease (e.g., interverte­ bral disc disease). CBC/BIOCHEMISTRY/URINALYSIS Results usually normal.

alleviation.

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 MEDICATIONS

DRUG(S) OF CHOICE •  Chemotherapy—no successful chemo­ therapeutic management has been described. •  Corticosteroid therapy—may help to reduce peritumoral edema and temporarily relieve clinical signs.

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 FOLLOW-UP

EXPECTED COURSE AND PROGNOSIS •  Recurrence common following incomplete surgical excision (up to 72% of cases). •  The more distal the tumor, the better the possibility of a surgical cure. •  For tumors involving the brachial or lumbosacral plexus, median disease-free interval is 7.5 months. •  For tumors involving dorsal or ventral nerve roots, median disease-free interval is 1 month. •  High-histologic-grade tumors (e.g., grade 3) may metastasize to regional lymph nodes or lung.

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 MISCELLANEOUS

­Suggested Reading

Chase D, Bray J, Ide A, Polton G. Outcome following removal of canine spindle cell tumours in first opinion practice: 104 cases. J Small Anim Pract 2009, 50:568–574. Hansen KS, Zwingenberger AL, Theon AP, et al. Treatment of MRI-Diagnosed Trigeminal Peripheral Nerve Sheath Tumors by Stereotactic Radiotherapy in Dog. J Vet Intern Med 2016;30:1112–1120. Author Ruthanne Chun Consulting Editor Timothy M. Fan

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1224

Blackwell’s Five-Minute Veterinary Consult

Sebaceous Adenitis, Granulomatous •  Destruction of sebaceous glands may be

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 BASICS

OVERVIEW •  A destructive inflammatory disease process directed against cutaneous adnexal structures (sebaceous glands). •  May be genetically inherited, immunemediated, or metabolic. •  Initial defect—a keratinization disorder or an abnormality in lipid metabolism (accumulation of toxic intermediate metabolites). SYSTEMS AFFECTED Skin/exocrine SIGNALMENT •  Young adult to middle-aged dogs; very rare in cats. •  Two forms—long- and short-coated breeds (short-coated form now called “idiopathic pyogranulomatous periadnexal dermatitis”). •  Predisposed—standard poodle, Akita, Samoyed, German shepherd dog, Havanese, Bernese Mountain dog and vizsla. SIGNS Long-Coated Breeds

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•  Symmetrical, partial alopecia. •  Dull, brittle hair. •  Tightly adherent silver-white scale. •  Follicular casts around hair shaft (“keratin-

collaring”). •  Small tufts of matted hair. •  Lesions—often first observed along dorsal midline and dorsum of the head. •  Severe—secondary bacterial folliculitis, pruritus, and malodor. •  Akitas—often relatively severely affected; morbidity associated with deep secondary bacterial infections. •  Standard poodles—affected dogs frequently described as having excellent hair coats prior to developing lesions; secondary bacterial folliculitis rare; most patients do not exhibit systemic illness. Short-Coated Breeds

•  Alopecia—moth-eaten, circular, or diffuse. •  Mild scaling. •  Lesions often plaque-like. •  Affects the trunk, head, and pinnae. •  Secondary bacterial folliculitis rare. •  Lesions can produce significant scarring.

CAUSES & RISK FACTORS

•  Mode of inheritance is being studied; an

autosomal recessive mode of inheritance is documented in the standard poodle and suspected in the Akita. •  Multiple pathophysiologic causes theorized including autoimmunity against sebaceous glands and/or leakage of sebaceous gland contents into surrounding dermis causing an inflammatory reaction and eventual destruction of glands.

secondary—“innocent bystander” from other inflammatory conditions.

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Primary seborrhea—keratinization disorder. •  Bacterial folliculitis. •  Demodicosis. •  Dermatophytosis. •  Pemphigus foliaceus. •  Endocrine skin disease. CBC/BIOCHEMISTRY/URINALYSIS N/A DIAGNOSTIC PROCEDURES

•  Skin scrapings—normal. •  Dermatophyte culture—negative. •  Endocrine function tests—normal. •  Skin biopsy.

PATHOLOGIC FINDINGS

•  Nodular granulomatous to pyogranulo­

matous inflammatory reaction at the level of the sebaceous glands. •  Orthokeratotic hyperkeratosis and follicular cast formation; more prominent in longcoated breeds. •  Advanced—complete loss of sebaceous glands; periadnexal fibrosis. •  Destruction of entire hair follicle and adnexal unit rare.

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 TREATMENT

•  Clinical signs may wax and wane

irrespective of treatment.

•  Controlled studies have not been done to

document efficacy of any therapy.

•  Results extremely variable; response may

depend on severity of disease at the time of diagnosis. •  Akita—breed most refractory to treatment.

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 MEDICATIONS

DRUG(S) OF CHOICE •  Propylene glycol and water—50–75% mixture; spray every 24 hours to affected areas. •  Baby oil—soak affected areas for 1 hour; follow with multiple shampoos to remove oil and scales; used monthly or as needed to reduce severe accumulations of crusts. •  Frequent bathing with keratolytic shampoos (twice weekly). •  EFA supplementation and evening primrose oil (500 mg PO q12h); possible side effects include vomiting, diarrhea, and flatulence.

•  Cyclosporine 5 mg/kg PO q12–24h; side

effects include vomiting, diarrhea, gingival hyperplasia, hirsutism, papillomatous skin lesions, increased incidence of infections, nephrotoxicity, and hepatotoxicity. •  Doxycycline 5 mg/kg PO q12h and niacinamide 250 mg PO q8h, 10 kg with vitamin E. •  Isotretinoin (Accutane) 1 mg/kg PO q12h; reduce to 1 mg/kg q24h after 1 month and to 1 mg/kg q48h after 2 months; continue as needed for maintenance; rarely used. •  Bactericidal antibiotics for secondary bacterial folliculitis. CONTRAINDICATIONS/POSSIBLE INTERACTIONS Isotretinoin (Accutane)—known teratogen; do not use in pregnant dogs; advise owners of risk.

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 FOLLOW-UP

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 MISCELLANEOUS

Affected dogs should be registered so that mode of inheritance can be determined.

­Suggested Reading

Gross TL, Ihrke PJ, Walder EJ. Skin Diseases of the Dog and Cat: Clinical and Histopathologic Diagnosis. Oxford, UK: Blackwell Science, 2005. Helton Rhodes KA, Werner A. Blackwell’s Five-Minute Veterinary Consult: Clinical Companion: Small Animal Dermatology, 3rd ed. Hoboken, NJ: Wiley-Blackwell, 2018. Mecklenburg L, Linek M, Tobin DJ. Hair Loss Disorders in Domestic Animals. Ames, IA: Wiley-Blackwell, 2009. Muller and Kirk’s Small Animal Dermatology, 7th ed. St. Louis, MO: Elsevier, 2013. Author Guillermina Manigot Consulting Editor Alexander H. Werner Resnick Acknowledgment The author and editors acknowledge the prior contribution of Karen Helton Rhodes.



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Canine and Feline, Seventh Edition

Seizures (Convulsions, Status Epilepticus)—Cats

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 BASICS

DEFINITION •  Epilepsy—recurrence of seizures from primary brain origin. •  Genetic epilepsy— syndrome that is only epilepsy, with no demonstrable underlying brain lesion or other neurologic signs; the genetic origin must be proven through family studies, gene isolation, or other specific forms of evidence (International League Against Epilepsy); rare in cats. •  Structural epilepsy—syndrome in which the epileptic seizures are the result of identifiable structural brain lesions; frequent in cats. •  Epilepsy of unknown cause— structural epilepsy suspected but a lesion cannot be demonstrated; frequent in cats. •  Cluster seizures—>1 seizure/24 hours. •  Status epilepticus (SE)—continuous seizure activity, or seizures repeated at brief intervals without complete recovery between seizures. Can be nonconvulsive. •  Convulsive SE— life-threatening medical emergency. PATHOPHYSIOLOGY

•  Paroxysmal disorganization of one or several

brain functions originating from the thalamocortex. Any thalamocortical disturbance or disease process may lead to seizure activity. •  Not all cortical regions have the same propensity to seize; from the most to the least likely to cause seizures—temporal, frontal, parietal, and occipital lobes. •  As more seizures occur, the tendency for neuronal damage and propensity for more seizures or SE increases; this kindling effect does not occur in all cortical regions. •  The clinical appearance of the seizure is directly related to the location of the neuronal hyperactivity. If the electrical abnormality remains regional, the seizure is focal. If there is recruitment of both hemispheres, the seizure is generalized. •  Great majority of seizures and SE in cats are secondary to structural brain lesions. SYSTEMS AFFECTED Nervous INCIDENCE/PREVALENCE Unknown GEOGRAPHIC DISTRIBUTION Worldwide SIGNALMENT Cats of any breed, age, or sex. SIGNS General Comments

•  Nonconvulsive generalized seizures— frequent in cats; movements of facial musculature predominate, such as bilateral twitches of eyelids, whiskers and ears, salivation, lip smacking; may be associated with whole body trembling/shaking, piloerection, dilated pupils. Nonconvulsive SE frequent in cats.

•  Focal seizure—when limited to one hemisphere; frantic running and colliding with objects (aura), unilateral facial twitches or eyelid blinks, unilateral limb motions or head/neck turning to one side. Focal seizures often generalize. •  Generalized convulsive seizures— bilateral symmetrical tonic–clonic contractions of limb muscles and dorsiflexion of the head, often associated with autonomic signs such as salivation, urination, defecation. At time of admission, the gross motor activity may have stopped, but there may still be twitching of the lids and body/limb jerks. •  Mutilation frequent—biting of tongue, nail avulsion.

non-feline infectious peritonitis (FIP), FIP, toxoplasmosis, cryptococcosis. •  Toxicity— organochlorines, pyrethrins, and pyrethroids; seizures usually observed at end stage; chlorambucil in lymphoma treatment. •  Vascular—polycythemia vera secondary to hyperviscosity, feline ischemic encephalopathy secondary to Cuterebra larva. •  Trauma has not been linked to seizures in cats. RISK FACTORS

•  Any forebrain lesion. •  Diabetes mellitus. •  Treatment with chlorambucil. •  Renal

failure.

Historical Findings

•  Confirm that seizure activity has indeed occurred. •  Pattern of seizures (age at seizure

onset, type and frequency of seizures)—most important factor in listing the possible causes. •  Metabolic diseases may cause generalized seizures (GS). •  With most seizurogenic toxins, there is a crescendo of hyperexcitability, shaking, trembling, with ultimately GS and death. •  Asymmetry in the signs (eyelid twitches, limb movements primarily on one side, circling) before, during, or after the seizure suggests focal cortical lesion. •  Overdose of insulin, postrenal transplant, or bilateral thyroidectomy lead to GS shortly after the fact. •  Presence of abnormal behavior in the days/weeks preceding the seizure activity indicates structural brain disease. •  Presence of concomitant gastrointestinal (GI), respiratory, or other systemic signs indicates multisystem disease. Physical Examination Findings

•  If chorioretinitis present, look for infectious diseases. •  Dark red mucous membranes

suggest polycythemia vera.

Neurologic Examination Findings

•  Mental status, menace responses, responses

to nasal septum stimulation, and proprio­ ceptive positioning are neurologic tests that evaluate the cerebral cortex. Asymmetry indicates structural brain lesion on the contralateral side of the deficits. •  In most cases of structural epilepsy, neurologic deficits are present at presentation. CAUSES

Extracranial

Metabolic—hypoglycemia from insulin overdose, hypocalcemia from bilateral thyroidectomy, severe hyperthyroidism, hypertension secondary to renal transplant, hepatic encephalopathy, uremia, polycythemia vera, severe hypertriglyceridemia. Toxins; Intracranial

•  Anatomic—congenital malformation. •  Metabolic—cell storage disease (e.g.,

neuronal ceroid–lipofuscinosis reported in one cat with myoclonus and seizure activity). •  Neoplastic—meningioma, astrocytoma, lymphoma. •  Inflammatory infectious—viral

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Sleep disorders—the cat does not wake up, or has a normal waking behavior following the episode. •  Syncope—the body is limp with a rapid recovery phase, with no abnormal behavior. •  When seizures are preceded by 2–3 weeks of vague transient systemic illness (decreased appetite, GI signs) in an otherwise healthy cat—viral non-FIP encephalitis or epilepsy of unknown cause. •  When seizures are preceded by systemic signs that persist (>3 weeks)—FIP, cryptococcosis. •  Insidious abnormal behavior with/without circling in a cat >10 years old presented for seizure activity suggests meningioma. •  Cats with hepatic encephalopathy drool excessively. •  Cats with polycythemia vera have GI signs and dark mucous membranes. CBC/BIOCHEMISTRY/URINALYSIS

•  Extracranial metabolic causes are diagnosed

on history, physical examination, and blood test results. •  High packed cell volume (>60%) in polycythemia vera. •  Low blood glucose in insulin overdose. •  Low calcium in bilateral post thyroidectomy. •  High BUN and creatinine with low specific gravity in acute renal failure. •  Creatine kinase—mild to markedly elevated in cats with SE, even nonconvulsive; with or without myoglobulinuria; indicates muscle necrosis. OTHER LABORATORY TESTS

•  Serologic testing—feline immunodeficiency

virus, feline leukemia virus titers often noncontributory to diagnosis; FIP and Toxoplasma gondii titers nonreliable by themselves. •  Bile acid testing—in cats with suspected hepatic encephalopathy. IMAGING

•  Thoracic radiographs and abdominal

ultrasound—if infectious disease suspected; to evaluate lung pathology if SE; to look for neoplasia if tumor suspected. •  MRI— best to define location, extent, and nature of lesion.

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1226

Blackwell’s Five-Minute Veterinary Consult

Seizures (Convulsions, Status Epilepticus)—Cats DIAGNOSTIC PROCEDURES CSF—sensitive to detect structural disease; unspecific in itself to reach diagnosis except when organism is seen (e.g., cryptococcosis). PATHOLOGIC FINDINGS •  Findings reflect etiology. •  It is unknown if hippocampal necrosis is a cause or the consequence of seizures. •  Small lesions may be easily missed in cats diagnosed with epilepsy of unknown cause.

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 TREATMENT

APPROPRIATE HEALTH CARE •  Outpatient—isolated recurrent seizures in an otherwise healthy cat. •  Inpatient—cluster seizures and SE. Isolated recurrent seizures in an ill cat. NURSING CARE

•  Constant supervision. •  Install IV line for drug and fluid administration. •  Draw blood

for rapid measurement of blood gases, glucose, calcium, and antiepileptic drug levels if pertinent. •  Cool if hyperthermia.

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CLIENT EDUCATION Antiepileptic treatment in structural epilepsy may not help until the primary cause is addressed. Seizures can be difficult to stop in cases of SE, especially with nonconvulsive status. SURGICAL CONSIDERATIONS Craniotomy—tumor excision with meningioma or other accessible mass.

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 MEDICATIONS

DRUG(S) OF CHOICE Seizure type and frequency determine therapeutic approach. Isolated Recurrent Generalized Seizures •  First line—phenobarbital 7.5–15 mg/cat

q12h; optimal therapeutic serum levels 100–130 μmol/L (23–30 μg/L). •  Second line—gabapentin 3–8 mg/cat q8–12h. •  Levetiracetam—20 mg/kg q8h (serum levels humans 10–40 μg/mL). •  Initiate gradually to avoid overt sedation. Convulsive Cluster and Status Epilepticus

•  Treat cluster and generalized SE early—the more seizures in a given time, and the more drugs for seizure control, time for recovery, and cost for treatment. •  No ongoing seizure activity at presentation and patient naïve to the drug— phenobarbital IV bolus 10 mg/kg to a maximum of 60 mg/cat over 15 minutes, continued with phenobarbital maintenance dosage PO 12 hours later. •  Ongoing seizure activity at presentation—diazepam IV bolus

0.5–1 mg/kg, continuing with CRI at 0.25–0.5 mg/cat/h in an inline burette using a fluid pump; IV bolus of diazepam can be repeated 5 minutes after the first bolus if gross seizure activity persists; in this case, add phenobarbital to CRI at 4 mg/cat/h. •  Start oral phenobarbital at maintenance dose as soon as patient can swallow. •  After 6 hours seizures-free, wean CRI gradually over 4–6 hours. Persistent Seizures

Subanesthetic doses of IV propofol 1–3.5 mg/ kg bolus and 0.01–0.25 mg/kg/minute CRI titrated to effect. Non-Antiepileptic Drug Treatment

•  Dexamethasone 0.25 mg/kg IV q24h for

1–3 days, to improve edema secondary to SE and treat the primary cause if systemic infectious disease is not suspected; dexamethasone alters CSF results. •  Thiamine—5–50 mg/cat in any cat presented with acute neurologic signs, including seizures.

(continued)

repeat every 6–12 months. •  If structural epileptic patient has recovered from primary disease and remains seizure-free for 6 months—seizures may recur when drug is weaned off. POSSIBLE COMPLICATIONS

•  SE—seizure control may not be reached despite polypharmacy. •  Rare hypersensitivity

to phenobarbital—thrombocytopenia, neutropenia, pruritus, swollen feet; do CBC 4–6 weeks after onset of phenobarbital. •  Diazepam rarely may cause acute hepatic necrosis and death. •  Cardiovascular and respiratory collapse from overdose during SE treatment.

EXPECTED COURSE AND PROGNOSIS

•  Depends on the underlying cause and response to treatment. •  Cats with epilepsy of

unknown cause have good long-term prognosis.

•  Cats can recover despite episode of severe

cluster-seizures and generalized SE.

CONTRAINDICATIONS

•  Do not use KBr in cats; side effects include life-threatening respiratory disease. •  Avoid

giving aminophylline, theophylline, ketamine, and fentanyl to epileptic cats. PRECAUTIONS

•  Prolonged use of propofol (>24 hours) may cause Heinz body anemia in cats. •  Cats on

CRI of antiepileptic drug(s) are often overtly sedated; cardiovascular and respiratory depression may occur; close monitoring necessary; lubricate eyes, express bladder manually, correct hypothermia. •  Close monitoring necessary to observe if mild ongoing seizure activity persists. POSSIBLE INTERACTIONS N/A

ALTERNATIVE DRUG(S) •  Zonisamide—5–10 mg/kg PO q24h (serum levels humans 15–45 μg/mL). •  Diazepam—0.5–2.0 mg/kg/day PO divided q12h.

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 FOLLOW-UP

PATIENT MONITORING •  CBC, biochemistry, urinalysis prior to initiating antiepileptic drug. •  Phenobarbitalinduced hepatotoxicity is not a problem in the cat. •  Creatine kinase to evaluate muscular necrosis and indirectly subtle ongoing seizure activity in cats presented in SE. •  Measure phenobarbital serum level 2 weeks after initiation; correct dosage accordingly; it is difficult to titrate phenobarbital in cats, i.e., a mild increase in dosage often leads to a major increment of the serum levels. •  CBC and biochemistry—

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 MISCELLANEOUS

AGE-RELATED FACTORS Cats with seizure onset prior to 1 year of age and diagnosed with epilepsy of unknown cause have guarded prognosis for seizure control. SEE ALSO •  Feline Ischemic Encephalopathy. •  Meningioma—Cats and Dogs. ABBREVIATIONS

•  FIP = feline infectious peritonitis. •  GI = gastrointestinal. •  GS = generalized seizures. •  SE = status epilepticus.

­Suggested Reading

Barnes HL, Chrisman CL, Mariani CL, et al. Clinical signs, underlying cause, and outcome in cats with seizures: 17 cases (1997–2002). J Am Vet Med Assoc 2004, 225:1723–1726. Pakozdy A, Gruber A, Kneissl K, et al. Complex partial cluster seizures in cats with orofacial involvement. J Feline Med Surg 2011, 13:687–693. Parent J. Seizures and status epilepticus in cats. In: Veterinary Emergency and Critical Care Manual, 2nd ed. Guelph, Ontario: Lifelearn, 2006, pp. 456–459. Wahle AM, Brühschwein A, Matiasek K, et al. Clinical characterization of epilepsy of unknown cause in cats. J Vet Intern Med 2014, 28:182–188. Author Joane M. Parent Client Education Handout available online



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Seizures (Convulsions, Status Epilepticus)—Dogs •  GS—may be mild, the animal remaining

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 BASICS

DEFINITION •  Epilepsy—recurrence of seizures from primary brain origin. •  Genetic epilepsy—epilepsy with no observable underlying brain lesion or other neurologic signs or symptoms. •  Structural epilepsy—seizures are the result of identifiable structural brain lesions. •  Epilepsy of unknown cause—structural epilepsy is suspected but a lesion cannot be demonstrated. •  Cluster seizures—>1 seizure/24 hours. •  Status epilepticus (SE)—continuous seizure activity or seizures repeated at brief intervals without complete recovery between seizures. •  SE can be convulsive or nonconvulsive. •  Seizures are classified as focal (limited to one hemisphere), generalized (involve both hemispheres), and focal with secondary generalization. PATHOPHYSIOLOGY

•  Any thalamocortical disturbance may lead

to seizure activity.

•  Not all cortical regions have equal

propensity to seize; from the most to the least likely to cause seizures—temporal, frontal, parietal, and occipital lobes. •  As more seizures occur, the tendency for neuronal damage and propensity for more seizures or SE increases; this kindling effect does not occur in all cortical regions. •  The clinical appearance of a seizure is related to the location of the neuronal hyperactivity. SIGNALMENT

•  Dogs of any breed, age, or sex. •  SE—overrepresentation of German

shepherd dog, English foxhound, pug, teacup poodle, Boston terrier, Lakeland terrier.

Mean Age and Range

SE—4.2–5 years (0.15–15 years). SIGNS General Comments

•  Prodrome—hours to days prior to the

seizure; no electroencephalogram (EEG) changes. •  Aura—short period (seconds) prior to generalization of a seizure where the dog seeks help, looks lost, frightened or has a glazed look. Focal seizure. If it precedes the tonic–clonic generalized seizure, the seizure has a focal onset. •  Ictus—may start with an aura and progress to generalized seizure (GS); lateral recumbency with bilateral symmetrical tonic–clonic contractions of limb muscles; often with autonomic signs, e.g., salivation, urination, defecation.

sternal or even standing during the event; may be long-lasting, 20 minutes or more. Convulsive or nonconvulsive. •  Post-ictal phase—disorientation, confusion, aimless pacing, blindness, polydipsia, polyphagia. •  A seizure lasts 2 GS within first week of onset, acute onset of focal seizures with gradual progression to GS, or presence of interictal neurologic deficits including behavioral changes. •  Genetic epilepsy—differentiated on age, breed, and seizure pattern; progressive onset of GS with/without aura. •  Cervical pain/spasms—may be mistaken for focal seizures. •  Head bobbing or idiopathic head tremor— dog remains active; can eat, drink, walk. CBC/BIOCHEMISTRY/URINALYSIS

•  Infectious CNS diseases—may reflect

multisystem involvement.

•  Hypoglycemia—small/toy breeds during

SE; insulinoma.

•  Hepatic and renal dysfunction—advanced SE. •  Urinalysis—rule out myoglobinuria.

OTHER LABORATORY TESTS

•  Blood gases—metabolic acidosis frequent

with SE. Respiratory acidosis needs immediate treatment. •  Coagulation profile—disseminated intravascular coagulation (DIC) in advanced SE. •  Bile acids—suspected hepatic encephalopathy. •  Fasting blood glucose and amended insulin: glucose ratio—dogs >5 years with occasional seizures during exercise. •  Serology (infectious diseases)—as suggested by systemic signs and laboratory abnormalities. •  Toxicity screen—cholinesterase levels. IMAGING

•  Thoracic radiographs and abdominal

ultrasound—to identify metastatic or systemic illness, or lung pathology from SE. •  MRI—best to define location, extent, and nature of lesion.

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Seizures (Convulsions, Status Epilepticus)—Dogs DIAGNOSTIC PROCEDURES Electrocardiogram (ECG)—arrhythmias can occur in SE due to myocardial damage. CSF—if intracranial structural cause is suspected; CSF and serum titers and PCR for diagnosing infectious diseases. EEG—to document ongoing seizure activity once physical manifestations have ceased.

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 TREATMENT

APPROPRIATE HEALTH CARE •  Outpatient—isolated seizures in an otherwise healthy dog. •  Inpatient—cluster seizures and SE. NURSING CARE

•  SE and cluster-seizures—constant

supervision.

•  Ensure airway patency. May need to be

suctioned due to excessive salivation.

•  Administer 100% oxygen via non-

rebreathing mask.

•  Cool down if hyperthermia. •  Install IV line for drug and fluid

administration.

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•  Draw blood for rapid measurement of

blood gases, glucose, calcium, renal and hepatic function, and antiepileptic drug (AED) levels if pertinent. •  Monitor urine output with indwelling urinary catheter. CLIENT EDUCATION

•  Treat cluster of GS and generalized status

epilepticus (GSE) early—the more seizures in a given time, and the more drugs for seizure control, time for recovery, and cost for treatment. •  Antiepileptic treatment in structural epilepsy may not help until the primary cause is addressed. •  Client to keep a seizure calendar noting date, time, severity, and length of seizures to objectively evaluate response to treatment. •  Outline an in-home treatment emergency plan for cluster-seizures.

Convulsive Cluster Seizures or Status Epilepticus

Diazepam

•  Administer 0.5–1 mg/kg IV bolus; repeat 5

minutes later if gross motor activity has not subsided; follow with CRI of 0.5–1 mg/kg/h added to hourly maintenance fluids in an inline burette or through syringe pump. •  Rectal—only where IV access cannot be obtained; may diminish or stop gross motor seizure activity to allow IV catheter placement. •  Refractoriness may rapidly develop, necessitating the addition of phenobarbital CRI.

Phenobarbital

•  Add if seizures persist after second

diazepam bolus or during diazepam CRI; administer CRI phenobarbital (2–6 mg/ dog/h added to diazepam infusion) if patient already treated with phenobarbital, or loading dose if patient naïve to phenobarbital. •  Loading dose—12–24 mg/kg given as boluses of 4 mg/kg IV, 20 minutes apart until desired effect is reached, to a maximum of 24 mg/kg. Optimal therapeutic range—100–120 μmol/L (23–28 mg/L). •  If patient already on phenobarbital, obtain serum level prior to initiating phenobarbital CRI. IV bolus 2–6 mg/kg can be administered once while awaiting results if serum levels believed inadequate. •  Once seizures have been controlled for 4–6 hours, gradually wean the patient off CRI over as many hours. •  Start/resume oral maintenance AED using phenobarbital and/or other GS AED as soon as patient can swallow.

Other

 MEDICATIONS

•  Electrolytes imbalance—treat immediately

with fluid therapy. •  Low glucose—50% dextrose diluted to 25% (500 mg/kg IV) over 15 minutes or treat with oral glucose syrup. DRUG(S) OF CHOICE Seizure type and frequency determine the therapeutic approach. Important to seek and treat primary cause.

CONTRAINDICATIONS

•  Potassium bromide—do not use to treat

SE; too long half-life; loading dose not recommended. •  Aminophylline, theophylline—CNS excitement; may cause seizure. •  Steroids—alter CSF parameters; avoid if considering CSF analysis. PRECAUTIONS

•  Phenobarbital—liver disease, lower dose;

monitor levels closely; for SE, add cautiously to diazepam because the drugs potentiate each other, cardiac/respiratory depression may ensue. •  Steroids—contraindicated in infectious diseases, but one dose of dexamethasone 0.2 mg/kg IV may decrease brain edema when impending brain herniation or lifethreatening edema is suspected. POSSIBLE INTERACTIONS

•  Cimetidine, ranitidine, and

chloramphenicol—interfere with phenobarbital metabolism; may lead to phenobarbital toxic level. •  Phenobarbital decreases zonisamide serum levels. Dosage recommended when drugs are used simultaneously—10 mg/kg q12h. •  If levetiracetam used concomitantly with phenobarbital—measure serum levels (humans 10–40 μg/mL). ALTERNATIVE DRUG(S) Levetiracetam—20–60 mg/kg IV; use upper end dosage if patient already on oral phenobarbital. Good alternative in liver disease or portosystemic shunts, as the drug is not metabolized in the liver. Use with caution in patients with renal disease.

•  If seizures continue, propofol at 1–2 mg/kg

IV slowly over 60 seconds, followed by CRI at 0.1–0.6 mg/kg/min to effect; monitor anesthetized patient with EEG to evaluate treatment response. •  Ketamine is also used occasionally at 5 mg/ kg IV bolus followed by CRI at 5 mg/kg/h. •  Dexamethasone—0.2 mg/kg q24h for 1–3 days; reduce cerebral edema. •  Dexamethasone—for acute treatment of cerebral edema secondary to severe inflamm­ atory CNS disease, even if infectious. Acute Focal Status Epilepticus

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(continued)

•  Often harbors brain lesion. •  Diazepam and phenobarbital CRI—

effective for focal and GS.

•  Frequently difficult to reach seizure control. •  Instances of chronic nonconvulsive

generalized or focal SE—owner unaware it is occurring (e.g., senile encephalopathy); if seizures remain focal and patient’s quality of life not significantly altered, no treatment necessary. Long-term antiepileptic treatment if necessary—phenobarbital 3–5 mg/kg q12h PO, levetiracetam 20 mg/kg q8h PO, or zonisamide 5 mg/kg q12h PO.

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 FOLLOW-UP

PATIENT MONITORING •  Inpatients—constant supervision for seizure monitoring. •  Eyelid or lip twitching in a heavily sedated patient is sign of ongoing seizure activity. •  Monitor heart rate, respiratory rate, oxygenation/ventilation, body temperature, blood pressure, urine production, neurologic examination. •  EEG monitoring for ongoing seizure activity. •  Patient may need 7–10 days before returning to normal after SE. POSSIBLE COMPLICATIONS

•  Phenobarbital—hepatotoxicity after

long-term treatment with serum levels >140 μmol/L (>33 μg/L); acute neutropenia (rare) in the first few weeks of use requires permanent withdrawal. •  Paradoxical hyperexcitability. •  Permanent neurologic deficits (e.g., blindness, abnormal behavior, cerebellar signs) may follow severe SE.



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Seizures (Convulsions, Status Epilepticus)—Dogs

•  GSE may lead to hyperthermia, acid–base

and electrolyte imbalances, pulmonary edema, cardiovascular collapse, and death.

after 6 months seizure-free; if seizures recur, reinstate AED.

EXPECTED COURSE AND PROGNOSIS

•  Genetic epilepsy or epilepsy of unknown

cause represents a large proportion of dogs with GSE or cluster-seizures. In-home emergency measure using diazepam rectal/ nasal should be provided. •  Dogs with encephalitis and GSE—poor outcome. •  Structural epileptic dogs recovered from primary disease (e.g., Ehrlichia canis)— slowly (over months) wean patient off AEDs

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 MISCELLANEOUS

AGE-RELATED FACTORS •  The immature brain has a higher propensity to seize. •  Genetic epilepsy—6 months–5 years; often epilepsy refractory when onset at 90

mmHg, heart rate 80–140 bpm (dogs) and 160–225 bpm (cats), capillary refill time 1.5 seconds, urine output >1–2 mL/kg/h, blood lactate 50% of dogs will have hyperestrogenism. Most common clinical signs include: bilateral symmetric alopecia and hyperpigmentation, pendulous prepuce, gynecomastia, galactorrhea, atrophy of the penis, squamous metaplasia of the prostate. •  Clinical signs associated with severe pancytopenia include weakness, hemorrhage, and febrile episodes. •  Abdominal mass—if patient is cryptorchid. CAUSES & RISK FACTORS

•  Cryptorchid testicles 12.7 per 1000

mass.

•  Immunohistochemistry may be necessary to

identify cell of origin.

•  Serum anti-müllerian hormone may

differentiate testicular tumors.

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 TREATMENT

•  Bilateral orchiectomy is the treatment of

choice.

•  Exploratory laparotomy for retained

testicles.

•  Supportive care for dogs with bone marrow

hypoplasia.

­

 MEDICATIONS

DRUG(S) OF CHOICE N/A

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 FOLLOW-UP

PATIENT MONITORING •  Recurrence of feminization may be associated with metastasis. •  Serum hormone levels may be correlated with resolution of clinical signs.

•  Cryptorchid and ≥6 years of age, 68.1 per

POSSIBLE COMPLICATIONS Irreversible bone marrow ablation resulting in life-threatening hemorrhage and recurrent infection.

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•  Good in most patients. •  Guarded if cytopenias exist at diagnosis. •  Poor prognosis if aplastic anemia present. •  Clinical signs of hyperestrogenism expected

dog-years (vs. 0 for scrotally located testicles). 1000 dog-years.

EXPECTED COURSE AND PROGNOSIS

 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Interstitial cell tumor. •  Seminoma. •  Hyperadrenocorticism. •  Hypothyroidism. •  More likely to have an abdominal location than other testicular tumors; high testicular temperature in the abdominal location may destroy spermatogenic cells and leave Sertoli cells unregulated. CBC/BIOCHEMISTRY/URINALYSIS Transient neutrophilia followed by progressive neutropenia, thrombocytopenia, and non-regenerative anemia. OTHER LABORATORY TESTS Low testosterone-to-estradiol ratio. IMAGING Testicular and abdominal sonography to aid in differential diagnosis and identify retained testicles and comorbidities.

dogs. J Comp Pathol 2008, 138(2–3):86–89. Lawrence JA, Saba C. Tumors of the male reproductive system. In: Withrow SJ, ed., Small Animal Clinical Oncology. St Louis, MO: Elsevier Saunders, 2013, pp. 557–571. Morrison WB. Cancers of the reproductive tract. In: Morrison WB, ed., Cancer in Dogs and Cats: Medical and Surgical Management. Jackson, WY: Teton NewMedia, 2002, pp. 555–564. Author Shawna L. Klahn Consulting Editor Timothy M. Fan

to resolve within 1–3 months following castration; however, bone marrow hypoplasia might be irreversible.

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 MISCELLANEOUS

ASSOCIATED CONDITIONS •  50% of dogs with Sertoli cell tumor associated with hyperestrogenism and feminization. •  Hyperestrogenism can cause hematopoietic failure. SEE ALSO Hyperestrogenism (Estrogen Toxicity).

­Suggested Reading

Grieco V, Riccardi E, Greppi GF, et al. Canine testicular tumours: a study on 232

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Sexual Development Disorders

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 BASICS

DEFINITION •  Errors in the establishment of chromosomal, gonadal, or phenotypic sex causing abnormal sexual differentiation. •  Varies from ambiguous genitalia to apparently normal genitalia with sterility.

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PATHOPHYSIOLOGY •  Sexual differentiation is a sequential process—chromosomal sex established at fertilization (dog: 78,XX or 78,XY; cat: 38,XX or 38,XY), development of gonadal sex, and finally development of phenotypic sex. •  Testis differentiation normally determined by sex chromosome constitution; SRY (on the Y chromosome) and SOX9 (autosomal gene), expressed by Sertoli cells, are critical for testis differentiation. •  Ovarian differentiation—an active process involving WNT4/RSPO1 and β-catenin. •  Phenotypic sex differentiation (tubular reproductive tract and external genitalia) depends on gonadal sex—basic embryonic plan is female; male phenotype results if testes are capable of secreting anti-Müllerian hormone and testosterone at the correct time during embryogenesis, and functional androgen receptors (X-linked gene) are present on genital tissues. •  Consensus terminology for categorizing disorders of sexual development (DSD) recently revised. Previous nomenclature also noted. Sex Chromosome DSD

•  Defects in number or structure of sex

chromosomes—chromosomal nondisjunction during meiosis causes trisomy, monosomy; mitotic non-disjunction of a single zygote causes mosaicism; fusion of zygotes leads to chimerism. •  XXY (Klinefelter) syndrome—79,XXY (dog); 39,XXY (cat): hypoplastic testes; phenotypic male (normal to hypoplastic genitalia); sterile; some tortoiseshell male cats. •  XO (Turner) syndrome—77,XO (dog); 37,XO (cat): dysgenetic ovaries; phenotypic female; infantile genitalia; sterile. •  XXX syndrome— 79,XXX (dog): hypoplastic ovaries; anestrus to irregular estrous cycles; female phenotype. •  True hermaphrodite chimera—XX/XY or XX/XXY (dogs and cats): ovarian and testicular tissue; phenotypic sex depends on amount of testicular tissue. •  XX/XY chimera with testes and XY/XY chimera with testes (dogs and cats)—vary from phenotypic female with abnormal genitalia to male with possible fertility; some tortoiseshell males. XY DSD

Disorders of Testicular Development

•  Complete or partial testicular dysgenesis—

SRY-positive 78,XY dog: genitalia

incompletely masculinized (enlarged clitoris); testes undescended or perivulvar; Müllerian and Wolffian duct derivatives variably present. •  Ovotesticular DSD—XY sex reversal, true hermaphrodite.

Disorders in Androgen Synthesis or Action •  Complete androgen insensitivity

syndrome—38,XY cat: testes at caudal pole of kidneys; no Wolffian or Müllerian duct derivatives; blind-ended vagina; vulva. •  Partial androgen insensitivity syndrome— 78,XY dog: vulva; perivulvar scrotal-like swellings at 6 months of age; blind vaginal pouch; hypoplastic testes; epididymides, partially developed vasa deferentia; vulvar fibroblasts unable to bind dihydro­ testosterone. •  Persistent Müllerian duct syndrome (male pseudohermaphrodite)— XY (dogs and cats): testes (50% are unilateral or bilateral cryptorchid); epididymides, vasa deferentia, prostate, oviducts, uterus, cervix, cranial vagina; penis, prepuce, and scrotum usually normal. •  Isolated hypospadias—incomplete masculinization of urogenital sinus during urethral development causing abnormal location of urinary orifice from glans penis (mild) to perineum (severe); external genitalia unambiguous; testes (cryptorchid or scrotal) or bifid scrotum (cats) with spermatogenesis. XX DSD

Ovoteseticular DSD and Testicular DSD •  Canine XX DSD (sex reversal)—SRY-

negative 78,XX reported in 28 dog breeds, not in cats: autosomal gene causing testis induction presently unknown; two phenotypes: ◦  Ovotesticular DSD, XX true hermaphrodite (90% of cases)—ovotestis (at least one); masculinized female phenotype; varies from normal to abnormal vulva, normal or enlarged clitoris (os clitoris possible), uterus, oviducts, epididymides, and vasa deferentia; rarely fertile. ◦  Testicular DSD, XX males (10% of cases)—testes (usually cryptorchid); epididymides, vasa deferentia, prostate; bicornuate uterus, no oviducts; hypoplastic penis and prepuce; hypospadias common.

SYSTEMS AFFECTED •  Reproductive—anomalies of the gonads, tubular tract, and external genitalia. •  Renal/ urologic—occasionally affected (e.g., agenesis, incontinence, hematuria, cystitis). •  Skin/ exocrine—perivulvar dermatitis (hypoplastic vulva); perineal or peri-preputial dermatitis (hypospadias); hyperpigmentation (Sertoli cell tumor). GENETICS

•  Chromosomal sex abnormalities—usually

caused by random events during gamete formation or early embryonic development. •  XX DSD—autosomal recessive trait in American cocker spaniels and likely in beagles, German shorthaired pointers; familial in English cocker spaniels, pugs, Kerry blue terriers, Norwegian elkhounds, Weimaraners; other reported breeds include soft-coated wheaten terriers, vizslas, Walker hounds, Doberman pinschers, basset hounds, American pit bull terriers, border collies, Afghan hounds. •  Persistent Müllerian duct syndrome (PMDS)—autosomal recessive trait in miniature schnauzers in the United States, bassett hounds in the Netherlands, and possibly Persian cats; expression limited to XY individuals. •  Hypospadias familial in Boston terriers. •  Failure of androgen-dependent masculinization (predominantly cats) probably X-linked. INCIDENCE/PREVALENCE

•  Generally rare. •  In affected breeds—may

be common within families or within the breed as a whole. SIGNALMENT Species

Dog and cat. Breed Predilections

See Genetics.

Mean Age and Range

All are congenital disorders, but individuals with normal external genitalia may not be identified until breeding age or at routine gonadectomy. Predominant Sex

Phenotypic females and males.

Androgen Excess

SIGNS

adrenal hyperplasia in a phenotypic male cat (38,XX, ovaries, oviducts, epididymides, vasa deferentia, bicornuate uterus) due to 11 β-hydroxylase deficiency. •  Maternal origin (female pseudohermaphrodite)— XX; ovaries; masculinized genitalia (mild clitoral enlargement to nearly normal male genitalia); oviducts, uterus, cranial vagina; prostate variable; caused by exogenous sex steroid administration (progestegen oversupplementation) during pregnancy.

•  Depends on type of disorder. •  Listed are

•  Fetal origin—single report of congenital

General Comments

possible findings for any of the conditions; not all occur with each specific disorder.

Historical Findings

•  Failure to cycle. •  Infertility and sterility. •  Vulva, clitoris, prepuce, or penis— abnormal size, shape, or location. •  Urine stream—abnormal location. •  Affected

phenotypic males attractive to other males.

•  Urinary incontinence. •  Vulvar discharge. •  Polyuria/polydipsia.



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Sexual Development Disorders

(continued)

Physical Examination Findings

•  Vulva normal or hypoplastic. •  Clitoris normal or enlarged; os clitoris. •  Perivulvar dermatitis and vulvar discharge. •  Testes

scrotal, unilateral or bilateral cryptorchid; bifid scrotum. •  Penis and prepuce normal or hypoplastic. •  Urethral meatus normal or abnormal location. •  Dermatologic signs of hyperestrogenism in males. •  Abdominal mass. CAUSES

•  Congenital—heritable or nonheritable. •  Exogenous steroid hormone administration

during gestation.

RISK FACTORS Androgen or progestagen administration during pregnancy (female pseudohermaphrodite).

IMAGING

•  Routine radiography and

ultrasonography—may be of diagnostic value for suspected abdominal mass (e.g., testicular neoplasia with PMDS, testicular feminization, or XX DSD); males with signs referable to pyometra (female pseudohermaphrodite or PMDS). •  Contrast studies (lower urogenital tract)—may be useful in diagnosing female pseudohermaphrodites. PATHOLOGIC FINDINGS

Gross

Precisely describe the genitalia—size and location of the vulva or prepuce; presence and appearance of the clitoris, penis, scrotum, prostate, caudal vagina, or os clitoris; position of the urinary orifice (identifies the phallic structure as penis or clitoris).

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 MEDICATIONS

CONTRAINDICATIONS Avoid androgen or progestagen use during pregnancy.

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 FOLLOW-UP

PREVENTION/AVOIDANCE Sterilize individuals with heritable disorders. POSSIBLE COMPLICATIONS •  Infertility. •  Sterility. •  Urinary tract problems—incontinence; cystitis. •  Testicular neoplasia.•  Pyometra.

Histopathologic

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS Individuals with Unambiguous Genitalia •  Female infertility—male infertility,

mistimed breeding, subclinical cystic endometrial hyperplasia/endometritis, hypothyroidism. •  Failure to cycle (female)— silent heat, hypothyroidism, hypercorticism, previous gonadectomy. •  Male infertility— female infertility, mistimed breeding, exogenous drug use affecting fertility, orchitis or epididymitis, testicular degeneration or hypoplasia, prostatitis. CBC/BIOCHEMISTRY/URINALYSIS

•  Usually normal. •  Neutrophilia, normo­

chromic, normocytic anemia; hyperglo­ bulinemia, hyperproteinemia, azotemia are possible. •  Urinalysis—may reveal cystitis with anatomic abnormalities that affect the location of the urethral meatus. OTHER LABORATORY TESTS •  Serum concentrations of sex steroid hormones (progesterone, testosterone, and estradiol)—generally below the normal range; may be normal if disorder mild and patient not sterile. •  Detect testicular tissue— gonadotropin-releasing hormone (GnRH) or human chorionic gonadotropin (hCG) simulation test; resting serum anti-Müllerian hormone (AMH; see Cryptorchidism). •  Karyotyping—to define chromosomal sex (Molecular Cytogenetics Laboratory, Texas A&M University).

•  Examination of all tissues removed—to define the type of disorder. •  Gonads—vary

from nearly normal architecture to dysgenic or a combination of ovary and testis (ovotestis). •  Essential to describe the components of the Müllerian and/or Wolffian duct system, if found.

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 TREATMENT

APPROPRIATE HEALTH CARE •  Usually outpatient. •  Inpatient—if exploratory laparotomy. NURSING CARE Phenotypic females with a hypoplastic vulva and perivulvar dermatitis and males with hypospadias—local therapy to improve dermatologic sequelae (see Dermatoses, Erosive or Ulcerative). SURGICAL CONSIDERATIONS •  Most patients with no identified chromosomal abnormalities—exploratory laparotomy to determine the location and morphology of the gonads and internal genitalia. •  Gonadectomy and hysterectomy (if a uterus is found)— recommended. •  Amputation of an enlarged clitoris—recommended if the mucosal surface is repeatedly traumatized. •  Reconstructive surgery of the prepuce and malformed penis—dogs; may be necessary with testicular DSD, XX males, or hypospadias.

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 MISCELLANEOUS

AGE-RELATED FACTORS Patients not diagnosed at an early age— pyometra (e.g., PMDS; female pseudohermaphrodite); testicular neoplasia (e.g., PMDS; any DSD with cryptorchidism). SYNONYMS •  Hermaphrodites. •  Intersexes. •  Klinefelter syndrome. •  Pseudohermaphrodites. •  Sex reversal. •  Turner syndrome. SEE ALSO

•  Breeding, Timing. •  Cryptorchidism. •  Infertility, Female—Dogs. •  Infertility, Male—Dogs.

ABBREVIATIONS

•  AMH = anti-Müllerian hormone. •  DSD = disorders of sexual development. •  GnRH = gonadotropin-releasing

hormone.

•  hCG = human chorionic gonadotropin. •  PMDS = persistent Müllerian duct

syndrome.

­Suggested Reading

Christensen BW. Disorders of sexual development in dogs and cats. Vet Clin Small Anim 2012, 42:515–526. Author Erin E. Runcan Consulting Editor Erin E. Runcan Acknowledgment The author/editor acknowledges the prior contribution of Sara K. Lyle.

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Shaker/Tremor Syndrome, Corticosteroid Responsive ­Suggested Reading

­

 BASICS

OVERVIEW Fine, rapid, whole-body tremor.

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 TREATMENT

­

 MEDICATIONS

Inpatient or outpatient, depending on severity of clinical signs.

SYSTEMS AFFECTED Nervous SIGNALMENT •  Primarily dogs, but similar syndrome recently reported in 2 cats. •  Small to medium-size breed (50% increase in heart rate with abolishment of pauses; dogs with SSS generally have no response or an incomplete response to atropine. •  Electrophysiologic testing of sinus node recovery time and sinoatrial conduction time. •  24-hour ambulatory ECG (Holter) or event recording to correlate clinical signs with arrhythmia.

SURGICAL CONSIDERATIONS

•  Permanent artificial pacemaker necessary

for dogs failing to respond to medical treatment and those exhibiting unacceptable medication side effects. •  Permanent artificial pacemaker usually required for dogs with bradycardia–tachycardia syndrome. •  Transvenous placement of a pacing lead in the right atrium or auricle may successfully abolish the sinus pauses.

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 MEDICATIONS

DRUG(S) OF CHOICE •  Do not treat asymptomatic animals. •  Symptomatic dogs are grouped into those showing primarily bradycardia, sinus arrest, and/or sinoatrial exit block and those with supraventricular tachycardia followed by sinus arrest. •  Atropine-responsive symptomatic dogs with bradycardia or sinus arrest—anticholinergic agents (propantheline: small dogs, 3.75–7.5 mg PO q8–12h; medium dogs, 15 mg PO q8h; large dogs, 30 mg PO q8h; hyoscyamine: 3–6 μg/kg q8h). •  Dogs with bradycardia and sinus arrest—may try theophylline (Theo-Dur) 20 mg/kg PO q12h, terbutaline 0.2 mg/kg PO q8–12h, or hydralazine 1–2 mg/kg PO q8–12h if anticholinergic drugs are ineffective (avoid hydralazine if patient is hypotensive). •  Dogs with bradycardia–tachycardia whose clinical signs are due to tachycardia or tachycardiainduced sinus arrest—can give digoxin 5 μg/kg PO q12h or atenolol 0.5–1 mg/kg PO q12–24h in attempt to suppress the SVT (monitor closely for exacerbation of bradycardia). •  Therapy for tachycardias should only be considered, once pacing is established to avoid worsening of bradyarrhythmias.

PATHOLOGIC FINDINGS Vary with cause.

CONTRAINDICATIONS Avoid drugs that may worsen sinus node dysfunction (e.g., β-adrenergic antagonists, calcium channel blocking agents, phenothiazines, class I and III antiarrhythmic agents, opioids, cimetidine, α2-adrenergic agonists).

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•  Attempts to manage bradycardia–tachycardia

PRECAUTIONS

 TREATMENT

APPROPRIATE HEALTH CARE •  Hospitalization rarely necessary except for electrophysiologic testing or pacemaker implantation. •  Do not treat asymptomatic animals. ACTIVITY Avoid vigorous exercise and stressful situations.

syndrome medically without prior pacemaker implantation carry significant risk because drugs used to control SVT may worsen the bradyarrhythmias, and vice versa. •  Adverse effects of anticholinergic medication (constipation, difficulty voiding, keratoconjunctivitis sicca, emesis, anxiety) occur commonly.

DIET Modifications unnecessary.

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CLIENT EDUCATION Owner should be aware that medical management is often ineffective.

PATIENT MONITORING •  ECG in asymptomatic patients—to detect progression of disease. •  ECG in patients

 FOLLOW-UP

treated medically or with pacemaker implantation. POSSIBLE COMPLICATIONS

•  Rarely, reduced cerebral or renal perfusion

results in chronic renal dysfunction or CNS damage. •  Presence of significant valvular disease has implications for type of permanent pacing mode selected.

EXPECTED COURSE AND PROGNOSIS •  Good, following pacemaker implantation in animals without congestive heart failure. •  Medical management—often ineffective; initial beneficial effects often not sustained.

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 MISCELLANEOUS

SYNONYMS •  Bradycardia–tachycardia syndrome. •  Sinus node dysfunction. •  Tachycardia–bradycardia syndrome. SEE ALSO

•  Sinus Arrest and Sinoatrial Block. •  Sinus Bradycardia. •  Supraventricular Tachycardia.

ABBREVIATIONS

•  AV = atrioventricular. •  ECG = ­electrocardiogram. •  SSS = sick sinus syndrome. •  SVT = supraventricular tachycardia.

­Suggested Reading

Kraus MS, Gelzer ARM. Treatment of cardia arrhythmias and conduction disturbances. In: Smith FWK, Tilley LP, Oyama M, Sleeper M. Manual of Canine and Feline Cardiology, 5th ed. St. Louis, MO: Saunders Elsevier, 2016, pp. 313–329. Santilli R, Moïse NS, Pariaut R, Perego M. Electrocardiography of the Dog and Cat. Diagnosis of Arrhythmias, 2nd ed. Milan, Italy: Edra S.P.A., 2018. Tilley LP. Essentials of Canine and Feline Electrocardiography, Interpretation and Treatment, 3rd ed. Baltimore, MD: Williams and Wilkins, 1992. Willis, R., Oliveira, P., Mavropoulou, A. Guide to Canine and Feline Electrocardiography. Ames, IA: WileyBlackwell, 2018. Authors Larry P. Tilley and Francis W.K. Smith, Jr. Consulting Editor Michael Aherne  Client Education Handout available online

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Sinus Arrest and Sinoatrial Block PATHOPHYSIOLOGY

•  Sympathetic and parasympathetic influences

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 BASICS

DEFINITION •  Sinus arrest—a disorder of impulse formation caused by slowing or cessation of spontaneous sinus nodal automaticity; failure of the sinoatrial (SA) node to initiate an impulse at the expected time. P-P interval does not equal a multiple of basic P-P interval. •  Sinoatrial block—a disorder of impulse conduction; an impulse formed within the sinus node fails to depolarize the atria or does so with delay; most commonly the basic rhythmicity of the sinus node is not disturbed and the duration of the pause is a multiple of the basic P-P interval. Classified into first-, second-, and third-degree SA block (similar to degrees of atrioventricular [AV] block). Difficult to diagnose first- and thirddegree SA block from electrocardiogram (ECG). Second-degree SA block most common: Mobitz type I (Wenckebach) SA block— P-P interval progressively shortens prior to a pause; duration of pause is less than two P-P cycles; Mobitz type II SA block—duration of pause occurring after a sinus beat is exact multiple (two, three, or four times normal) of basic P-P interval. ECG Features

•  A normal P wave exists for each QRS

complex with a pause equal to or greater than twice the normal P-P interval; rhythm is regularly irregular or irregular with pauses (Figure 1). •  Junctional or ventricular escape beats—occur if pauses significantly prolonged. Subsidiary pacemaker takes over rhythm with escape beats normally from AV junctional tissue or Purkinje fibers; intermittent absence of P waves noted or P waves may be negative and precede, be superimposed on or follow the QRS complexes. •  Surface ECG cannot differentiate sinus arrest from block in the dog because of normal R-R interval variation (sinus arrhythmia).

can alter spontaneous sinus node depolari­ zation; vagal stimulation of acetylcholine, which binds to SA nodal receptor sites, can slow automaticity of the sinus node by reducing the slope of phase 4 depolarization; sympathetic stimulation releases norepinephrine that binds to β1 receptors on the SA node, enhancing spontaneous SA nodal discharge rate. •  An overdrive inhibition phenomenon occurs when sinus arrest follows a run of ectopic beats. The sinus node requires a warming-up period until the usual rate of automaticity is reestablished. •  Intrinsic disease of the sinus node may affect the balance between the parasympathetic and sympathetic efferent traffic to the SA node and its spontaneous discharge rate. •  Duration of sinus arrest may be long and possibly irreversible when the sinus node is suppressed by an ectopic tachycardia, particularly with severe underlying heart disease. Persistent sinus arrest that is not drug induced often indicates sick sinus syndrome (SSS). SYSTEMS AFFECTED Cardiovascular—clinical signs of weakness or syncope may appear if sinus arrest or block causes sufficiently long periods (generally 5 seconds or longer) of ventricular asystole with no escape beats initiated by latent pacemakers. GENETICS

•  Seen in purebred pugs with hereditary stenosis of the bundle of His. •  Seen in

female miniature schnauzers predisposed to SSS. Is the most common arrhythmia in miniature schnauzers with SSS. •  Congenitally deaf Dalmatian coach hounds often have abnormal SA node and multiple atrial arteries. May be a genetic component to the cause of SSS in those breeds predisposed (see Breed Predilections). INCIDENCE/PREVALENCE

•  Normal incidental finding in

brachycephalic breeds of dogs in which

inspiration causes a reflex increase in vagal tone. •  Common in dog breeds predisposed to SSS. •  Uncommon in cats. GEOGRAPHIC DISTRIBUTION N/A SIGNALMENT Species

Dog and cat. Breed Predilections

•  Brachycephalic breeds. •  Breeds predisposed to SSS (e.g., miniature schnauzers, dachshunds, cocker spaniels, pugs, boxers and West Highland white terriers).

Mean Age and Range

If associated with SSS, generally middle-aged to older animals. Predominant Sex

If associated with SSS, older females. SIGNS General Comments

Generally no clinical significance by itself if terminated by sinus node depolarization, or latent pacemakers promptly escape to prevent ventricular asystole. Historical Findings

•  Usually none. •  Signs of low cardiac output (e.g., weakness and syncope) may occur with failure of the SA node to fire on time if no lower pacemaker focus takes over the rhythm. •  Sudden death is possible should prolonged periods of ventricular asystole occur.

Physical Examination Findings

•  May be normal. •  Heart sounds following a pause may be louder because the ventricles have longer filling time and therefore eject a larger amount of blood. •  Extremely slow heart rate if arrest or block is prolonged or frequent. •  With significant pathologic cardiac disease—may be findings consistent with poor cardiac output (e.g., prolonged perfusion time, pale mucous membranes, weak femoral pulses).

Figure 1. Intermittent sinus arrest in a brachycephalic breed with an upper respiratory disorder. The pauses (1 and 1.44 seconds) are greater than twice the normal P-P interval (0.46). (Source: From Tilley LP. Essentials of Canine and Feline Electrocardiography, Interpretation and Treatment, 3rd ed. Baltimore, MD: Williams and Wilkins, 1992, Reprinted with permission of Wolters Kluwer.)





Sinus Arrest and Sinoatrial Block

(continued)

CAUSES Physiologic

•  Vagal stimulation secondary to coughing, pharyngeal irritation. •  Ocular or carotid sinus pressure. •  Surgical manipulation.

Pathologic

•  Degenerative heart disease (fibrosis). •  Dilatory heart disease. •  Acute myocarditis. •  Neoplastic heart disease. •  SSS. •  Irritation

of vagus nerve secondary to thoracic or cervical neoplasia. •  Electrolyte imbalance. •  Drug toxicity (e.g., digoxin). RISK FACTORS

•  Certain drugs, including digitalis, quinidine,

propranolol, xylazine, acepromazine, hydromorphone. •  Respiratory tract disease. •  Vagal maneuvers.

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Marked sinus arrhythmia and sinus bradycardia. •  Not always possible to differentiate sinus arrest from SA block without direct recordings of sinus node discharge; pauses that are precise multiples of the dominant beat interval suggest sinus block. CBC/BIOCHEMISTRY/URINALYSIS Serum electrolyte abnormalities, especially hyperkalemia (serum K+ >5.7 mEq/L). OTHER LABORATORY TESTS N/A IMAGING •  Thoracic radiographs if neoplastic or cardiac disease suspected. •  Cardiac ultra­ sound if structural or neoplastic heart disease suspected. DIAGNOSTIC PROCEDURES

•  Provocative atropine response test to assess

sinus node function. Administer 0.04 mg/kg atropine IM; evaluate ECG lead II rhythm strip 30 minutes later for response or administer 0.04 mg/kg atropine IV followed by ECG in 10 minutes. Resolution of the arrhythmia suggests high vagal tone as the underlying cause. •  Ambulatory monitoring may reveal prolonged periods of failure of impulses from the SA node if signs of weakness or syncope. •  In humans, a period of sinus arrest following right carotid massage that lasts longer than 3 seconds suggests inappropriate sinus responsiveness. •  Electrophysiologic studies of sinus node. •  Serum digoxin concentration, if applicable; trough level recommended (just before next dose or at least 8 hours post pill); therapeutic serum concentrations are typically 0.5–1.5 ng/mL.

PATHOLOGIC FINDINGS Histologic study of the SA node may reveal necrosis, fibrosis, and/or degenerative changes.

ALTERNATIVE DRUG(S) If medical therapy does not resolve signs, consider pacemaker implantation.

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 TREATMENT

APPROPRIATE HEALTH CARE Asymptomatic sinus arrest or block does not require therapy. If clinical signs, therapeutic approach depends on cause, underlying cardiac status, and severity of symptoms. Any indicated treatment may be outpatient unless pacemaker implantation is necessary, which necessitates hospital management. NURSING CARE Correct any electrolyte abnormalities.

 FOLLOW-UP

PATIENT MONITORING When indicated, periodic serial ECG evaluation to assess therapeutic efficacy and possible progression to a more serious dysrhythmia. POSSIBLE COMPLICATIONS If associated with primary cardiac disease, CHF may develop and necessitate appropriate therapies.

ACTIVITY Unrestricted unless signs of weakness, syncope, or congestive heart failure (CHF) develop.

EXPECTED COURSE AND PROGNOSIS If cause is SSS, symptomatic patient may respond well to medical intervention; if poorly responsive, permanent pacemaker implantation would improve prognosis.

CLIENT EDUCATION An artificial pacemaker may be necessary when patient is symptomatic and nonresponsive to medical management.

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 MISCELLANEOUS

SURGICAL CONSIDERATIONS Implantation of an artificial demand pacemaker in animals with clinical signs nonresponsive to therapy.

ASSOCIATED CONDITIONS •  Sick sinus syndrome. •  Sinus arrhythmia. •  Sinus bradycardia.

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SEE ALSO •  Sick Sinus Syndrome. •  Sinus Arrhythmia. •  Sinus Bradycardia.

 MEDICATIONS

DRUG(S) OF CHOICE •  Only if patient is symptomatic, consider atropine 0.04 mg/kg IV, IM, glycopyrrolate 5–10 μg/kg IV, IM, or isoproterenol 10 μg/kg IM, SC q6h or dilute 1 mg in 500 mL of 5% dextrose or Ringer’s solution, and infuse IV at 0.04–0.08 μg/kg/min. •  If responsive to injectable anticholinergic drugs (e.g., atropine)— can prescribe parasympatholytic drug such as oral propantheline bromide 0.25–0.5 mg/kg q8–12h or hyoscyamine 3–6 μg/kg q8h for at-home management. Sympathomimetic agents including methylxanthine theophylline 10 mg/kg extended release formulation q12h or terbutaline 0.2 mg/kg q8–12h PO (dogs) and 0.1–0.2 mg/kg q12h (cats) could be considered for oral therapy. CONTRAINDICATIONS If patient is symptomatic secondary to prolonged pauses, discontinue any drugs that may be causative (e.g., digitalis, beta-blockers, calcium channel blockers). PRECAUTIONS Avoid drugs that depress SA node function. POSSIBLE INTERACTIONS N/A

SYNONYMS •  Sinus block. •  Sinus pause.

ABBREVIATIONS

•  AV = atrioventricular. •  CHF = congestive heart failure. •  ECG = electrocardiogram. •  SA = sinoatrial. •  SSS = sick sinus syndrome.

­Suggested Reading

Boyett MR, Honjo H, Kodama I. The sinoatrial node: a heterogeneous pacemaker structure. Cardiovasc Res 2000, 47(4):658–687. Issa ZF, Miller JM, Zipes DP. Sinus node dysfunction. In: Clinical Arrhythmology and Electrophysiology: A Companion to Braunwald’s Heart Disease. Philadelphia, PA: Saunders, 2008, pp. 118–126. Joung B, Ogawa M, Lin S-F, Chen P-S. The calcium and voltage clocks in sinoatrial node automaticity. Korean Circ J 2009, 39(6):217–222. Kittleson MD, Kienle RD. Small Animal Cardiovascular Medicine. St. Louis, MO: Mosby, 2005. Author Deborah J. Hadlock Consulting Editor Michael Aherne

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Sinus Arrhythmia

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 BASICS

DEFINITION •  Normal sinus impulse formation characterized by a phasic variation in sinus cycle length. An irregular R-R interval is present that has more than 10% variation in sinus cycle length (or variability of 0.12 seconds [dog], 0.10 seconds [cat], or more exists between successive P waves) (Figure 1). •  Two basic forms exist—respiratory sinus arrhythmia (RSA): P-P interval cyclically shortens during inspiration due primarily to reflex inhibition of vagal tone and lengthens during expiration; nonrespiratory sinus arrhythmia: phasic variation in P-P interval unrelated to the respiratory cycle. ECG Features

•  Other than the irregular rhythm, all other

criteria for sinus rhythm are present.

•  Normal heart rate. •  Positive P wave in leads, I, II, III, and aVF,

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unless a wandering pacemaker is present, where the P waves may be positive, diphasic, or negative temporarily. •  A P wave is present for every QRS complex. •  A QRS complex is present for every P wave. •  PR interval is relatively constant. PATHOPHYSIOLOGY •  Sinus node discharge rate depends on the two opposing influences of the autonomic nervous system. Vagal stimulation decreases spontaneous sinus nodal discharge rate and predominates over sympathetic stimulation. Negative intrathoracic pressure occurring with inspiration causes decreased pressure on the vagus nerves. Feedback from the cardioregulatory and vasomotor centers in the medulla produces cardiac acceleration by decreasing vagal restraint on the sinus node; the opposite occurs during exhalation. The genesis of sinus arrhythmia also depends on reflexes involving pulmonary stretch receptors (Hering–Breuer

reflex), pressure–volume sensory receptors in the heart (Bainbridge reflex whereby atrial stretch stimulates receptors in the atrial wall, causing vagal inhibition and increase in heart rate; baroreceptors in the carotid sinus and aortic arch elicit inverse changes in heart rate with acute changes in arterial blood pressure), blood vessels, and chemical factors of the blood. •  RSA is measured as a high-frequency component of heart rate variability (HRV) and is used as an index of cardiac vagal control. HRV measures beat to beat changes in heart rate and R-R variability from the ECG. HRV is a widely accepted clinical and research tool for evaluation of cardiac autonomic changes. SYSTEMS AFFECTED Cardiovascular—generally no hemodynamic consequence, but marked sinus arrhythmia may produce a long enough sinus pause to produce syncope if not accompanied by an escape rhythm. GENETICS N/A INCIDENCE/PREVALENCE Most frequent form of arrhythmia in dogs. SIGNALMENT Species

•  RSA frequent normal finding in dogs. •  While common in cats asleep and in home

environment, in a clinical setting sympathetic dominance occurs and RSA is rare without underlying pathology.

Breed Predilections

•  Brachycephalic breeds predisposed. •  Dogs—bulldog, Lhasa apso, Pekingese,

SIGNS General Comments

•  Uncommon, but weakness may develop

if pauses between beats are excessively long; syncope can occur when a marked sinus arrhythmia and sinus bradycardia develop. •  In general, symptoms more common in nonrespiratory than in respiratory form. Historical Findings

•  RSA—none. •  Nonrespiratory sinus arrhythmia—may be

findings related to underlying disease.

Physical Examination Findings

•  May be normal. •  Irregular rhythm on auscultation. •  May be findings related to specific disease

accentuating vagal tone (e.g., stertor and stridor in a patient with brachycephalic airway syndrome). CAUSES

•  Normal cyclic change in vagal tone

associated with respiration in the dog; heart rate increases with inspiration and decreases with expiration. •  Underlying conditions that increase vagal tone—high intracranial pressure, gastrointestinal disease, respiratory disease, cerebral disorders, digitalis toxicity, organophosphates. •  Carotid sinus massage or ocular pressure (vagal maneuver) may accentuate. RISK FACTORS

•  Brachycephalic conformation. •  Digoxin therapy. •  Any disease that increases vagal tone.

pug, shar-pei, shih tzu, boxer.

•  Cats—Persian, Himalayan.

Mean Age and Range

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Predominant Sex

DIFFERENTIAL DIAGNOSIS •  Auscultation of sinus arrhythmia is often confusing; ECG helps differentiate normal

N/A N/A

 DIAGNOSIS

Figure 1. Respiratory sinus arrhythmia with an average rate of 120 bpm (6 complexes between 1 set of time lines or 3 seconds × 20) (paper speed, 25 mm/s; 10 mm/mV). The rate increases during inspiration (INSP) and decreases during expiration (EXP). The fluctuation of the baseline correlates with the movement of the electrodes by the thoracic cavity. (Source: From Tilley LP. Essentials of Canine and Feline Electrocardiography, 3rd ed. Baltimore: Williams & Wilkins, 1992. Reprinted with permission of Wolters Kluwer.)



Canine and Feline, Seventh Edition

Sinus Arrhythmia

(continued)

sinus arrhythmia from true pathologic arrhythmia. •  Wandering sinus pacemaker frequently associated and a variant of sinus arrhythmia. Site of impulse formation shifts within the sinoatrial node or to an atrial focus or atrioventricular (AV) node, changing the configuration of the P wave. •  Important to differentiate normal sinus arrhythmia from pathologic arrhythmias including atrial premature complexes, sick sinus syndrome, slow atrial fibrillation, and AV dissociation. CBC/BIOCHEMISTRY/URINALYSIS N/A OTHER LABORATORY TESTS Cats with chronic respiratory disease may be positive for feline leukemia virus or feline immunodeficiency virus. IMAGING Radiographs, CT, or MRI of head and neck to assess for abnormal anatomic conformation that might predispose to airway problems. DIAGNOSTIC PROCEDURES •  Pharyngoscopy/laryngoscopy if upper airway disease suspected. •  Atropine challenge test (administer atropine 0.04 mg/kg IM followed by ECG in 30 minutes or 0.04 mg/kg atropine IV followed by ECG in 10 minutes) if associated with sinus bradycardia and primary dysfunction of sinus node is suspected. Subsequent heart rate should be greater than 150 bpm. PATHOLOGIC FINDINGS See specific disease.

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 TREATMENT

APPROPRIATE HEALTH CARE Generally, specific treatment required only when associated with symptomatic sinus bradycardia; if not related to respiration, underlying cause is treated. If patient is suffering respiratory distress, appropriate inpatient management indicated until patient is stable. NURSING CARE None unless associated with underlying disease. ACTIVITY Not restricted unless associated with specific disease (e.g., brachycephalic animals may need to limit exercise, especially in high ambient temperatures).

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DIET Caloric restriction for obese animals with airway compromise. CLIENT EDUCATION None unless associated with specific disease. SURGICAL CONSIDERATIONS None unless associated with specific disease.

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 MEDICATIONS

DRUG(S) OF CHOICE •  Generally no therapy indicated; this is a normal rhythm. •  Infectious respiratory diseases require appropriate antibiotic therapy. •  If associated with symptomatic sinus bradycardia or sinus arrest or block, ­anticholinergics may be indicated—atropine 0.02–0.04 mg/kg IV, IM, SC or glycopyrrolate 5–10 μg/kg IV, IM, SC. CONTRAINDICATIONS Discontinue digoxin if toxicity is a problem.

AGE-RELATED FACTORS Generally more pronounced in young adult. ZOONOTIC POTENTIAL N/A PREGNANCY/FERTILITY/BREEDING Increased incidence of arrhythmias. SYNONYMS •  Nonrespiratory sinus arrhythmia = nonphasic sinus arrhythmia; sinus irregularity. •  Respiratory sinus arrhythmia = phasic sinus arrhythmia. •  Ventriculophasic sinus arrhythmia—form of nonphasic sinus arrhythmia in which atrial cycles containing ventricular complexes are shorter than those in which they are absent. That is, the P-P interval that includes the QRS complex is shorter than the P-P interval without a QRS complex. This can be seen with second-degree AV block, complete AV block or in the presence of ventricular premature complexes with a full compensatory pause. SEE ALSO

PRECAUTIONS Avoid atropine in patients with respiratory disease; an adverse effect is drying of secretions.

•  Brachycephalic Airway Syndrome. •  Sick Sinus Syndrome. •  Sinus Arrest and Sinoatrial Block.

POSSIBLE INTERACTIONS N/A

•  AV = atrioventricular. •  HRV = heart rate variability. •  RSA = respiratory sinus arrhythmia.

ALTERNATIVE DRUG(S) N/A

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 FOLLOW-UP

PATIENT MONITORING Only if associated with specific disease. PREVENTION/AVOIDANCE N/A POSSIBLE COMPLICATIONS N/A EXPECTED COURSE AND PROGNOSIS N/A

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 MISCELLANEOUS

ASSOCIATED CONDITIONS •  Sick sinus syndrome. •  Brachycephalic airway syndrome. •  Asthma. •  Chronic obstructive pulmonary disease.

ABBREVIATIONS

­Suggested Reading

Billman GE. Heart rate variability—a historical perspective. Front Physiol 2011, 2:86. Bonow R, Mann D, Zipes D, Libby P. Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine, 9th ed. Ames, IA: Elsevier, 2012. Côté E, MacDonald K, Meurs KM, Sleeper MM. Feline Cardiology. Ames, IA: Wiley-Blackwell, 2011. Lewis K, Scansen BA, Aarnes TK. Respiratory sinus arrhythmia in an anesthetized cat. ECG of the month. J Am Vet Med Assoc 2013, 242:623–625. Tilley LP. Essentials of Canine and Feline Electrocardiography, Interpretation and Treatment, 3rd ed. Baltimore, MD: Williams and Wilkins, 1992. Yasuma F, Hayano J. Respiratory sinus arrhythmia: why does the heartbeat synchronize with respiratory rhythm? Chest 2004, 125:683. Author Deborah J. Hadlock Consulting Editor Michael Aherne

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Sinus Bradycardia Breed Predilections

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 BASICS

DEFINITION Sinus rhythm in which impulses arise from the sinoatrial (SA) node at slower than normal rate for an animal’s signalment and activity (Figure 1). ECG Features

•  Dogs—sinus rate 180 bpm; (kittens HR >240 bpm). •  ECG shows a rapid regular rhythm with possible slight variation in R-R interval. •  P wave of sinus origin for each QRS complex with constant P-R interval. •  P waves may be partially or completely fused with preceding T waves. •  Generally has a gradual onset and termination.

Dog and cat.

PATHOPHYSIOLOGY

Historical Findings

•  Accelerated phase 4 diastolic depolarization

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•  Most common benign arrhythmia in the dog and cat. •  Most common rhythm

of sinus nodal cells (as a result of voltage- and calcium-dependent mechanisms) generally responsible for sinus tachycardia (ST). •  Enhanced adrenergic effect or cholinergic inhibition results in high rate of sinus impulse formation; changes in heart rate usually involve a reciprocal action of the parasympathetic and sympathetic divisions of the autonomic nervous system. SYSTEMS AFFECTED Cardiovascular—cardiac output = heart rate × stroke volume. Changes in heart rate affect preload, afterload, and contractility, which determine stroke volume; severe tachycardia can compromise cardiac output. Rapid rates shorten diastolic filling time, and particularly in diseased hearts, the increased heart rate can fail to compensate for decreased stroke volume, resulting in decreased cardiac output and coronary blood flow. Chronic tachycardias can cause cardiac dilation (tachycardiomyopathy) which often resolves with control of the tachycardia. However, ST is most often present due to elevated sympathetic tone and is physiologic (because of hypovolemia, fear, pain, etc.). GENETICS N/A

Breed Predilections

None

SIGNS

Pharmacologic

•  Atropine. •  Epinephrine. •  Ketamine. •  Tiletamine (Telazol®). •  Quinidine. •  Xanthine bronchodilators. •  β-Adrenergic

agonists.

RISK FACTORS

•  Thyroid medications. •  Primary cardiac diseases. •  Inflammation. •  Pregnancy. •  Anesthesia. •  Certain toxins (Amanita

muscaria, scorpion venom, black widow spider venom), plants (Jimson weed, mandrake), and drugs (antihistamines, tricyclic antidepressants).

General Comments

Often no clinical signs because ST is almost always a consequence of a variety of physiologic or pathophysiologic stresses. •  In general, ST itself does not produce any symptoms. •  If associated with primary

cardiac disease, weakness, exercise intolerance, or syncope may be reported. •  If associated with other medical conditions, signs may be seen specific to the disease present.

Physical Examination Findings

•  High HR. •  May otherwise be normal if not associated with a pathologic condition. •  Pale mucous membranes if associated with anemia or congestive heart failure (CHF). •  Fever may be present. •  Signs of CHF (e.g., dyspnea, cough, cyanosis, ascites) if associated with primary cardiac disease.

CAUSES

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS Must differentiate from supraventricular tachycardia (SVT), including atrial tachycardia, atrial flutter with 2:1 AV block, and AV junctional tachycardia; as sinus rate increases, the P wave appears closer to the T wave of the previous beat. At very rapid rates, it becomes difficult to distinguish this condition from other pathologic SVT. Gradual slowing of the rate is suggestive of ST. CBC/BIOCHEMISTRY/URINALYSIS •  Low packed cell volume if patient is anemic. •  Leukocytosis with left shift if inflammation or infection is causative. OTHER LABORATORY TESTS

•  High serum thyroxine (T4) or free T4

Physiologic

•  Exercise. •  Pain. •  Restraint. •  Excitement. •  Any hyperadrenergic state.

Pathologic

•  Fever. •  CHF. •  Chronic lung disease. •  Shock. •  Pericardial effusion. •  Anemia. •  Pain. •  Infection. •  Hypoxia. •  Pulmonary thromboembolism. •  Hypotension. •  Hypovolemia. •  Functional pheochromo­ cytoma. •  Hyperthyroidism. •  Pericarditis. •  Pneumothorax. •  Hypoglycemia. •  Vestibulosympathetic hypovolemia.

concentration (cats) if secondary to hyperthyroidism. •  Triiodothyronine (T3) suppression test and thyrotropin-releasing hormone (TRH) response test if T4 values are normal and hyperthyroidism is suspected. •  Functional testing for pheochromocytoma: ◦ Metanephrines (breakdown metabolites of epinephrine and norepinephrine); measured in plasma or urine. ◦  Serum inhibin, a hormone involved in reproductive physiology; undetectable levels supportive of pheochromocytoma. •  24-hour Holter monitoring. •  Cardiac

Figure 1. Sinus tachycardia at a rate of 272 bpm in a dog in shock. The rhythm is sinus because the P waves are normal, the P-R relationship is normal, and the rhythm is regular. (Source: From Tilley LP. Essentials of Canine and Feline Electrocardiography, 3rd ed. Baltimore: Williams & Wilkins, 1992. Reprinted with permission of Wolters Kluwer.)



Sinus Tachycardia

(continued)

electrophysiologic studies. •  Plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) assay may be helpful if evaluating for cardiac disease. IMAGING •  Thoracic radiographs and echocardiography to evaluate for evidence of primary cardiac disease. •  Thyroid scintigraphy to evaluate for hyperthyroidism. •  Abdominal ultrasound and angiography to evaluate for adrenal mass. •  CT and MRI as well as functional imaging modalities very sensitive for detecting adrenal masses. DIAGNOSTIC PROCEDURES •  A nonpharmacologic vagal maneuver can differentiate ST from other SVTs; carotid sinus or ocular pressure may terminate ectopic SVT. With effective vagal maneuvers, the HR in ST gradually slows. Less commonly, varying degrees of AV block (usually first-degree or Wenckebach) may occur transiently. ECG monitoring is recommended during these vagal maneuvers. •  Pharmacologic agents can be used if no response to the vagal maneuver. Similarly, an abrupt reduction in HR suggests SVT whereas gradual slowing suggests ST: ◦  IV diltiazem 0.25 mg/kg administered over 2 minutes. If no response, can be repeated in 15 minutes. ◦  IV esmolol 50–100 μg/kg bolus q5min up to 500 μg/kg; 25–200 μg/kg/min CRI. •  A precordial thump may be used to differentiate ST from other SVT. ST usually not affected, whereas the SVT may stop for at least 1 or 2 beats. •  Serial arterial BP measurement may document hypertension in patients with hyperthyroidism, pheochromocytoma, or renal disease. PATHOLOGIC FINDINGS •  None if associated with physiologic or pharmacologic cause. •  Pathologic findings depend on the primary disease process.

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 TREATMENT

APPROPRIATE HEALTH CARE •  Identify and correct underlying disorders whenever possible. •  Whether inpatient or outpatient depends on clinical status of patient and primary disease, if any (e.g., if CHF, treat as outpatient unless animal is dyspneic or severely hypotensive). •  If associated with pericardial effusion, avoid drug therapy and perform pericardiocentesis. •  If associated with a certain drug (e.g., hydralazine, bronchodilators), discontinue the medication or adjust the dose. •  If associated with hypovolemia, replace fluid volume. NURSING CARE Depends on whether associated with a specific disease.

ACTIVITY Exercise restriction recommended if symptomatic cardiac disease. DIET Sodium restriction generally advised with hypertension and CHF. CLIENT EDUCATION Discuss importance of managing any primary disease appropriately, with medical or surgical intervention. SURGICAL CONSIDERATIONS •  Thyroidectomy—treatment option for hyperthyroidism (cats). •  Tumor removal is the definitive treatment for patients with pheochromocytoma.

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 FOLLOW-UP

PATIENT MONITORING Depends on specific disease—for CHF, serial ECG, thoracic radiographs, BUN, creatinine, and serum electrolytes; for hyperthyroidism, serial serum T4, complete blood count, and biochemistry. PREVENTION/AVOIDANCE Minimize stress, exercise, and dietary sodium, if heart disease. POSSIBLE COMPLICATIONS

•  Weakness or syncope if associated with low cardiac output. •  Development of CHF if

persistent ST associated with heart disease.

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 MEDICATIONS

DRUG(S) OF CHOICE •  Establish underlying cause and treat appropriately; specific antiarrhythmic therapy is generally limited to patients in CHF or those with secondary cardiac disease due to hyperthyroidism or hypertension. •  Dogs—if CHF is the cause, administer pimobendan along with appropriate diuretic therapy and angiotensinconverting enzyme inhibitor. Digoxin may be indicated in some cases such as CHF with atrial fibrillation. If ST persists despite above management, consider adding a calcium channel blocker (e.g., diltiazem 0.5–2.5 mg/kg PO q8h) or a beta-blocker (e.g., atenolol 0.25–1 mg/kg q12h, sotalol 1–2 mg/kg q12h PO) only after congestion is controlled. •  Cats—if ST is associated with hyperthyroidism without CHF, a beta-blocker (e.g., atenolol 0.25–1 mg/kg PO q12–24h) may lower the HR. Consider digoxin (0.01875–0.03125 mg per average-size cat, equal to 1/8–1/4 of a 0.125 mg tablet—tablet preferred) if CHF present with atrial fibrillation and rapid ventricular response rate. Although still controversial, pimobendan (0.1–0.3 mg/kg PO q12h) has become more commonly accepted as treatment for CHF. If ST associated with hypertrophic cardiomyopathy, administer atenolol 6.25–12.5 mg/cat PO q12h or diltiazem 1.75–2.4 mg/kg PO q8h. CONTRAINDICATIONS Avoid drugs such as atropine or catecholamines (epinephrine) that may further increase the HR. PRECAUTIONS •  Beta-blockers can potentially worsen signs of congestion and lower cardiac output in patients with systolic dysfunction. •  Suppression of ST may be catastrophic if occurring as natural compensatory response to maintain cardiac output in a systemically ill patient. POSSIBLE INTERACTIONS See manufacturer’s insert for specific drugs. ALTERNATIVE DRUG(S) N/A

EXPECTED COURSE AND PROGNOSIS •  ST usually resolves with correction of the underlying cause. •  Poor despite treatment if ST is associated with CHF. •  Favorable for remission of ST when hyperthyroidism is controlled medically, surgically, or by radioactive iodine.

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 MISCELLANEOUS

ASSOCIATED CONDITIONS See list of pathologic and physiologic causes. PREGNANCY/FERTILITY/BREEDING Increase in cardiac output in late pregnancy (third trimester) largely due to an accelerated HR. SYNONYMS •  Inappropriate sinus tachycardia. •  Postural tachycardia syndrome. SEE ALSO

•  Atrial Fibrillation and Atrial Flutter. •  Congestive Heart Failure—Left-Sided. •  Congestive Heart Failure—Right-Sided. •  Hyperthyroidism. •  Pheochromocytoma. •  Supraventricular Tachycardia.

ABBREVIATIONS

•  AV = atrioventricular. •  CHF = congestive heart failure. •  ECG = electrocardiogram. •  HR = heart rate. •  NT-proBNP = N-terminal pro-brain natriuretic peptide. •  ST = sinus tachycardia. •  SVT = supraventricular tachycardia. •  T3 = triiodothyronine. •  T4 = thyroxine. •  TRH = thyrotropin-releasing hormone.

­Suggested Reading

Côté E, MacDonald K, Meurs K, Sleeper M. Feline Cardiology. Chichester, UK: WileyBlackwell, 2011. Kittleson MD, Kienle RD. Small Animal Cardiovascular Medicine. St. Louis, MO: Mosby, 2005. Olshansky, B., Sullivan, R. Inappropriate sinus tachycardia. J Am Coll Cardiol 2013, 61(8):793–801. Author Deborah J. Hadlock Consulting Editor Michael Aherne

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Sjögren-Like Syndrome •  Positive rheumatoid factor test. •  Positive indirect fluorescent antibody test

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 BASICS

OVERVIEW •  A systemic autoimmune disease characterized by keratoconjunctivitis sicca, xerostomia, and lymphoplasmacytic adenitis. •  Underlying mechanism unknown; however, autoantibodies directed against glandular tissues have been identified. •  Associated with other autoimmune or immune-mediated diseases, such as rheumatoid arthritis and pemphigus.

for autoantibodies. IMAGING N/A

DIAGNOSTIC PROCEDURES Schirmer tear test (0–5 mm/min; reference interval is 15–20 mm/min). PATHOLOGIC FINDINGS

•  Histologic changes in salivary glands—

lymphoplasmacytic adenitis.

•  Conjunctival biopsy—conjunctivitis.

SIGNALMENT

•  Higher incidence in several canine

breeds—English bulldogs, West Highland white terriers, and miniature schnauzers. •  Chronic disease of adult dogs. •  Cats unaffected.

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 TREATMENT

•  Directed at controlling keratoconjunctivitis

sicca.

•  Any concurrent disease must be medically

managed.

SIGNS Historical Findings

•  Adult onset. •  Conjunctivitis and keratitis. •  Keratitis sicca most prominent clinical

feature.

•  May include administration of anti-

inflammatory or immunosuppressive drugs.

•  Surgical management of

keratoconjunctivitis sicca indicated in animals that fail to respond to medical treatment.

Physical Examination Findings

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•  Blepharospasm. •  Conjunctival hyperemia. •  Corneal lesions (opacity to ulceration). •  Gingivitis. •  Stomatitis.

CAUSES & RISK FACTORS

•  Possible genetic predisposition in breeds

with high incidence.

•  Develops concurrently with other immune-

mediated and autoimmune diseases.

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Other causes of keratoconjunctivitis sicca—canine distemper, trauma, and drug toxicities. •  Keratoconjunctivitis sicca associated with other immune-mediated diseases—atopy, lymphocytic thyroiditis, polymyositis, systemic lupus erythematosus, rheumatoid arthritis, and pemphigoid diseases. CBC/BIOCHEMISTRY/URINALYSIS Normal OTHER LABORATORY TESTS

•  Hypergammaglobulinemia revealed by

serum protein electrophoresis.

•  Positive antinuclear antibody test. •  Positive lupus erythematosus cell test.

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 MEDICATIONS

DRUG(S) OF CHOICE •  Topical tear preparations. •  Appropriate topical antibiotics for secondary bacterial infection, if present. •  Immunosuppressive or anti-inflammatory drugs. •  For more aggressive medical treatment and surgical intervention, see Keratoconjunctivitis Sicca. CONTRAINDICATIONS/POSSIBLE INTERACTIONS Use of topical steroids in patients with acute keratoconjunctivitis sicca may cause corneal ulceration and is not recommended.

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 FOLLOW-UP

•  Reexamine patients weekly until

keratoconjunctivitis sicca controlled.

•  Additional monitoring may be indicated to

manage underlying or concurrent disease.

•  Immunosuppressive drugs—monitor

patients every other week for possible side effects. •  Prognosis variable and depends on existence of concurrent disease.

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 MISCELLANEOUS

SEE ALSO Keratoconjunctivitis Sicca.

­Suggested Reading

Quimby FW, Schwartz RS, Poskitt T, et al. A disorder of dogs resembling Sjogren’s syndrome. Clin Immunol Immunopathol 1979, 12:471–476. Author Paul W. Snyder Consulting Editor Melinda S. Camus



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Skin Fragility Syndrome, Feline CBC/BIOCHEMISTRY/URINALYSIS

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 BASICS

OVERVIEW •  A disorder of multifactorial causes characterized by extremely fragile skin. •  Tends to occur in old cats that may have concurrent hyperadrenocorticism, diabetes mellitus, excessive use of megestrol acetate or other progesterone compounds, or as a para­neoplastic syndrome. •  A small number of cats have no biochemical alterations. SYSTEMS AFFECTED

•  Skin/exocrine. •  Endocrine/metabolic.

SIGNALMENT

•  Naturally occurring disease tends to be

recognized in old cats.

•  Iatrogenic cases have no age predilection. •  No breed or sex predilection.

SIGNS Historical Findings

•  Gradual onset of clinical signs. •  Progressive alopecia (not always present). •  Often associated with weight loss, lusterless

coat, poor appetite, and lack of energy.

Physical Examination Findings

•  Skin becomes markedly thin and tears with

normal handling.

•  Skin rarely bleeds upon tearing. •  Multiple lacerations (both old and new)

may be noted on close examination.

•  Partial to complete alopecia of the truncal

region may be noted. •  Sometimes associated with “rat tail,” pinnal folding, pot-belly appearance. •  Differentiated from cutaneous asthenia by lack of hyperextensibility.

•  Little diagnostic significance in most cases. •  Approximately 80% of cats with hyper-

adrenocorticism have concurrent diabetes mellitus (hyperglycemia, glucosuria). OTHER LABORATORY TESTS

•  Adrenocorticotropic hormone (ACTH)-

stimulation test—70% of cats with hyperadrenocorticism have an exaggerated response. •  Low-dose dexamethasone-suppression test—15–20% of normal cats may fail to decrease cortisol levels; typically unsuppressed with hyperadrenocorticism and nonadrenal illness. •  High-dose dexamethasone-suppression test—normal cats show decreases in cortisol concentrations; typically decreased with nonadrenal illnesses; considered by many clinicians to be the best screening test for hyperadrenocorticism; unreliable for discriminating between adrenal tumors and pituitary-dependent causes of hyperadrenocorticism, because both conditions fail to show suppression. •  Endogenous ACTH levels—normal range for most labs is 20–100 pg/mL. IMAGING

•  Abdominal ultrasonography—adrenal

masses are often small until end-stage disease; cholangiocarcinoma and hepatic lipidosis have been reported. •  CT and MRI—small pituitary tumors may be difficult to visualize; MRI may be more successful. PATHOLOGIC FINDINGS Histopathology—suggestive, not diagnostic; epidermis and dermis are thin; attenuated collagen fibers are evident.

CAUSES & RISK FACTORS

•  Hyperadrenocorticism—pituitary- or

adrenal-dependent. •  Iatrogenic—secondary to excessive corticosteroid or progesterone drug administration. •  Diabetes mellitus—rare, unless associated with hyperadrenocorticism. •  Possibly idiopathic or paraneoplastic syndrome.

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Cutaneous asthenia. •  Feline paraneoplastic syndrome—pancreatic neoplasia, hepatic lipidosis, cholangiocarcinoma.

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 TREATMENT

•  Underlying metabolic disease should be

ruled out.

•  Many patients are debilitated and require

supportive care.

•  Surgical correction of the lacerations—dif-

ficult because the tissue cannot withstand pressure from sutures. •  Protect skin—clothing; reduce activities that can traumatize the skin; remove sharp edges from the environment; prevent damage from interaction with other animals. •  Discontinue exogenous corticosteroids if administered. •  Hyperadrenocorticism—adrenalectomy is the preferred treatment. •  Cobalt-60 radiation therapy—variable success in the treatment of pituitary tumors.

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 MEDICATIONS

DRUG(S) OF CHOICE •  Medical management—may be useful for preparing patient for surgery and for minimizing postoperative complications (e.g., infections and poor wound healing). •  No known effective medical therapy for feline hyperadrenocorticism. •  Mitotane (1,1-(o,p′-dichlorodiphenyl)-2,2dichloroethane [o,p′-DDD]) 12.5–50 mg/kg PO q12h; response has been equivocal; side effects include anorexia, vomiting, and diarrhea. •  Metyrapone 65 mg/kg PO q12h; clinical improvement noted more often with this drug than the others. CONTRAINDICATIONS/POSSIBLE INTERACTIONS Hyperadrenocorticism—closely monitor diabetic cats; adjust insulin to prevent hypoglycemia when the cortisol levels fall.

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 FOLLOW-UP

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 MISCELLANEOUS

Patients are often quite debilitated, making any form of treatment risky; close monitoring is required in all cases.

ABBREVIATIONS •  ACTH = adrenocorticotropic hormone.

­Suggested Reading

Gross TL, Ihrke PJ, Walder EJ. Veterinary Dermatopathology. Philadelphia, PA: Mosby, 1992. Little SE. August’s Consultations in Feline Internal Medicine, Volume 7. Philadelphia, PA: Saunders, 2016. Vogelnest LJ. Skin as a marker of general feline health: cutaneous manifestations of systemic disease. J Feline Med Surg 2017, 19(9): 948–960. Author Guillermina Manigot Consulting Editor Alexander H. Werner Resnick Acknowledgment The author and editors acknowledge the prior contribution of Karen Helton Rhodes.

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Small Intestinal Dysbiosis

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 BASICS

DEFINITION •  Small intestinal dysbiosis (SID) is a clinical syndrome caused by an alteration of the small intestinal microbiota. •  Previously, a variety of different terms have been used to describe SID: ◦  Small intestinal bacterial overgrowth (SIBO)—defined as >104 anaerobic and/or >105 total bacterial cfu/mL in duodenal juice from dogs. However, these criteria are now controversial. ◦  Antibiotic-responsive diarrhea (ARD)—used by several authors to describe patients that have diarrhea that responds to antibiotic therapy. Neither the type of bacteria nor the type of antibiotic that is effective has been defined for ARD. ◦  Tylosin-responsive diarrhea (TRD)—used by a group of clinicians in Finland to describe several dogs with chronic diarrhea that failed to respond to a variety of antibiotics or corticosteroids, but did respond to treatment with tylosin. •  Currently, there is no consensus on the quantitative makeup of the gastrointestinal microbiota in healthy dogs or cats. •  Note that SID differs from colonization of the alimentary tract by known pathogenic bacteria (e.g., Salmonella spp., Campylobacter jejuni, enterotoxigenic Clostridium perfringens, enterotoxic Escherichia coli, or others). PATHOPHYSIOLOGY •  Bacteria are constantly ingested with food and/or saliva. •  Host-protective mechanisms prevent overgrowth of pathogenic or potentially pathogenic bacteria through gastric acid secretion, intestinal motility (peristalsis), secretion of antimicrobial substances in bile and pancreatic juice, and local enteric IgA production. •  The ileocolic valve is a physiologic barrier between the large bowel, which is populated by large numbers of bacteria, and the less populated small bowel. •  When these natural defense mechanisms fail and excessive numbers of certain bacterial species persist in the upper small intestine, they may cause pathology, even though they are not considered obligate pathogens. •  Anaerobic bacteria (e.g., Bacteroides spp. and Clostridium spp.) have been considered more likely to cause pathology than many aerobic bacteria. SYSTEMS AFFECTED

•  Gastrointestinal—normal absorptive

function is disrupted, resulting in loose stool and weight loss. •  Hepatobiliary—portal vein carries bacterial toxins and other substances to the liver, which may lead to hepatic changes. GENETICS

•  No genetic basis for SID has been

identified. However, recent studies would suggest that histiocytic ulcerative colitis should be considered a type of dysbiosis of the large intestine. Since the majority of cases have been described in the boxer,

genetic factors that predispose dogs of this breed to this type of dysbiosis are likely. •  Certain canine breeds (e.g., German shepherd dog, Chinese Shar-Pei, and beagle) appear to be at an increased risk for SID.

RISK FACTORS Intestinal diseases that affect local defense mechanisms (e.g., inflammatory bowel disease [IBD], adverse food reactions, parasite infestation, others).

INCIDENCE/PREVALENCE Unknown GEOGRAPHIC DISTRIBUTION N/A SIGNALMENT Species

Dog and cat. Breed Predilections

Subjectively, German shepherd dog, Chinese Shar-Pei, and beagle appear to have an increased incidence. Mean Age and Range

•  Unknown. •  Can be diagnosed in dogs and cats of any age (age range: 8 years).

Predominant Sex

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Secondary gastrointestinal disease (e.g., hepatic failure, renal failure, EPI, chronic pancreatitis, hypothyroidism, hypoadrenocorticism). •  Primary gastrointestinal disease (i.e., infectious, inflammatory, neoplastic, mechanical, toxic, or other). CBC/BIOCHEMISTRY/URINALYSIS

•  Usually unremarkable. •  Hypoalbuminemia—uncommon finding;

when present, it suggests particularly severe intestinal disease and warrants an aggressive diagnostic and therapeutic approach.

No predilection.

OTHER LABORATORY TESTS

SIGNS

Serum Cobalamin and Folate Concentrations

General Comments

Alterations in the gut microbiota can cause clinical signs of small intestinal disease, such as loose stool or diarrhea, weight loss, and/or others. Historical Findings

•  Chronic loose stools or diarrhea (small

bowel or large bowel type diarrhea)— common. •  Weight loss, despite a reasonable appetite—common. •  Borborygmus and flatulence—common. •  Vomiting— occasional/variable. •  Clinical signs of the underlying disease process may be seen in cases of secondary SID. •  Clinical signs may wax and wane or be continuous.

Physical Examination Findings

Unremarkable or evidence of weight loss and decreased body condition. CAUSES •  Primary SID is probably uncommon, but a definitive cause of SID often remains undiagnosed and thus many dogs are diagnosed with idiopathic SID. •  Secondary SID (more common): ◦  Altered small intestinal anatomy—inherited or acquired (e.g., congenital blind loop, partial obstructions, neoplasia, foreign body, intussusception, stricture, adhesion, or diverticulum). ◦  Altered intestinal motility— hypothyroidism, autonomic neuropathies. ◦  Exocrine pancreatic insufficiency (EPI)— approximately 70% of dogs with EPI have concurrent SID. ◦  Hypochlorhydria or achlorhydria—spontaneous or iatrogenic (e.g., proton pump inhibitor treatment). ◦  Altered immune system—immuno­ deficiency, decreased mucosal defense, and preexisting intestinal disease.

•  Serum folate concentration may be

increased, as many bacterial species synthesize folate and an increased abundance of folateproducing bacterial species will lead to an overabundance of folic acid in the small intestine. •  Serum cobalamin concentration may be decreased, as many bacterial species compete with the host for dietary cobalamin. •  The finding of an increased serum folate concentration and a decreased serum cobalamin concentration is suggestive, but not specific for SID in dogs. In addition, not all patients with SID show this pattern. Qualitative and Quantitative Bacterial Culture of Small Intestinal Juice

•  Aerobic and anaerobic quantitative culture of duodenal fluid has long been considered the “gold standard” for the diagnosis of SIBO in human patients. •  Invasive—requires endoscopy or laparoscopy. Not practical and not routinely available. •  Recent work would suggest the species of bacteria that comprise the small intestinal microbiota may be more important than bacterial numbers. •  No standardized protocols have been established for sampling, handling, and culturing of duodenal juice, leading to high variability in bacterial counts.

Dysbiosis index (DI)

•  The fecal DI is a PCR-based assay that quantifies the abundances of eight bacterial groups in fecal samples of dogs and summarizes them in one single number. •  A DI below 0 indicates a normal fecal microbiota; a DI above 0 indicates dysbiosis. Approximately 15% of clinically healthy dogs have an increased DI, with most of them falling into the equivocal range between 0 and 2. •  Many dogs with chronic enteropathy or EPI have an abnormal



Small Intestinal Dysbiosis

(continued)

fecal DI. •  Due to anatomical and physiological differences along the intestine, evaluation of the fecal DI may not accurately reflect microbiota changes in the small intestine. •  Concurrent evaluation of serum concentration of cobalamin/ folate with assessment of the fecal DI may help in the diagnosis of SID. IMAGING Not useful for the diagnosis of primary SID. However, may reveal findings indicative of an underlying cause. DIAGNOSTIC PROCEDURES Therapeutic Trial

•  Treatment of patients with suspected SID

with an antibiotic, a prebiotic, or a probiotic.

•  Interpreting the results of a therapeutic trial

may be difficult as more than one disease (e.g., IBD plus SID, dietary intolerance plus SID) may be present, and lack of a clinical response might lead to the incorrect conclusion that SID is absent; incorrect selection of the treatment that is trialed might also cause failure of a clinical response. PATHOLOGIC FINDINGS

•  No macroscopic findings upon exploratory laparotomy or endoscopy. •  Histopathology

of small intestinal mucosal biopsies is typically unremarkable unless SID is caused by underlying intestinal disease.

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 TREATMENT

APPROPRIATE HEALTH CARE •  Outpatient medical management. •  SID can be managed with antibiotics, prebiotics, probiotics, or a combination thereof: ◦  Antibiotics—see Medications. ◦  Prebiotics—see Diet. ◦  Probiotics—there has been a lot of interest in probiotic use for dogs and cats with chronic diarrhea, although little is known about the efficacy. Currently, because of quality issues with many products, only probiotics from major manufacturers can be recommended. •  Improvement may take a few days to several weeks. NURSING CARE

•  Usually none. •  Supportive care for

alimentary tract neoplasia, partial obstruction) must also be treated. •  Continuous or repeated treatment is often required. SURGICAL CONSIDERATIONS Only indicated for some underlying causes of SID (i.e., partial obstruction, diverticulum, or intestinal mass).

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 MEDICATIONS

DRUG(S) OF CHOICE •  Broad-spectrum, orally administered antibiotics effective against both aerobic and anaerobic bacteria are preferred. •  Tylosin (10–20 mg/kg PO q12h for 6 weeks) is the primary choice. Tylosin is usually used in a powder formulation that is marketed for use in poultry and pigs. It is administered in the food because of its bitter taste. It can be used long-term and is very safe and inexpensive. For small dogs and cats the drug should be reformulated into capsules. For larger dogs the dose can be approximated by using a teaspoon and administering the drug in food. •  Metronidazole (10–15 mg/kg PO q12h for 6 weeks) is used commonly in routine practice because of its activity against anaerobic bacteria. Metronidazole may also have immunomodulatory effects. However, metronidazole can have significant side effects. •  Dogs with SID may be cobalamin deficient, and parenteral or oral supplementation of vitamin B12 is indicated. See Cobalamin Deficiency for dosing information.

DIET •  Highly digestible diet. •  A diet containing fructooligosaccharides has been shown to be beneficial in dogs with SID. CLIENT EDUCATION •  Some patients show clinical improvement within days. •  Some patients require weeks of therapy before demonstrating improvement— treat for 2–3 weeks before concluding that therapy is ineffective. •  Any concurrent or predisposing diseases (e.g., IBD, EPI, dietary intolerance/allergy,

EXPECTED COURSE AND PROGNOSIS Primary SID without complicating factors (e.g., IBD, lymphoma) usually has a good prognosis, although relapses can be seen following cessation of antibiotic therapy.

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 MISCELLANEOUS

ASSOCIATED CONDITIONS •  SID has been suspected as a cause of IBD in some patients. •  EPI. AGE-RELATED FACTORS N/A ZOONOTIC POTENTIAL None PREGNANCY/FERTILITY/BREEDING Avoid oxytetracycline or metronidazole, especially during early pregnancy. SYNONYMS SIBO, ARD, or TRD may be used synonymously by some authors. SEE ALSO

•  Cobalamin Deficiency. •  Diarrhea, Chronic—Cats. •  Diarrhea, Chronic—Dogs. •  Exocrine Pancreatic Insufficiency. •  Inflammatory Bowel Disease. •  Lymphoma—Cats. •  Lymphoma—Dogs.

PRECAUTIONS Metronidazole can be associated with gastro­intestinal side effects and in rare cases with neurologic side effects.

ABBREVIATIONS •  ARD = antibiotic responsive diarrhea. •  DI = dysbiosis index. •  EPI = exocrine pancreatic insufficiency. •  IBD = inflammatory bowel disease. •  SIBO = small intestinal bacterial overgrowth. •  SID = small intestinal dysbiosis. •  TRD = tylosin-responsive diarrhea.

POSSIBLE INTERACTIONS None

INTERNET RESOURCES www.vetmed.tamu.edu/gilab

CONTRAINDICATIONS None

ALTERNATIVE DRUG(S) In dogs with EPI and SID, concurrent therapy for SID is only indicated if enzyme replacement alone does not resolve the diarrhea and/or lead to weight gain.

emaciated or hypoalbuminemic patients. ACTIVITY Unrestricted

POSSIBLE COMPLICATIONS N/A

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 FOLLOW-UP

PATIENT MONITORING •  Body weight and, in hypoproteinemic patients, serum albumin concentrations are the most important parameters; improvement suggests effective therapy. •  Diarrhea should resolve. •  If diarrhea persists despite improved body weight and/or increased serum albumin concentration, investigation for concurrent intestinal disease is indicated. PREVENTION/AVOIDANCE N/A

­Suggested Reading

German AJ, Day MJ, Ruaux CG, et al. Comparison of direct and indirect tests for small intestinal bacterial overgrowth and antibiotic-responsive diarrhea in dogs. J Vet Intern Med 2003, 17(1):33–43. Kilpinen S, Spillmann T, Westermarck E. Efficacy of two low-dose oral tylosin regimens in controlling the relapse of diarrhea in dogs with tylosin-responsive diarrhea: a prospective, single-blinded, two-arm parallel, clinical field trial. Acta Vet Scand 2014, 66:43. Suchodolski JS. Diagnosis and interpretation of intestinal dysbiosis in dogs and cats. Vet J 2016, 215:30–37. Authors Jan S. Suchodolski and Jörg M. Steiner Consulting Editor Mark P. Rondeau  Client Education Handout available online

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Smoke Inhalation

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 BASICS

OVERVIEW •  Injury secondary to direct heat damage to upper airway and nasal mucosa. Inhalation of toxins directly irritates the airway, and particulate matter adheres to the airways and alveoli. •  Carbon monoxide decreases tissue oxygen delivery by preferentially binding to hemoglobin. •  Cyanide interferes with oxygen usage in oxidative phosphorylation. •  Extent of damage depends on the degree and duration of exposure and the material that was burning. •  Serious lung injury possible with little external evidence of burning. •  Lung reaction—initially bronchoconstriction, airway edema, mucus production and airway occlusion; then an inflammatory response, necrotizing tracheobronchitis, and pulmonary fluid accumulation due to increased capillary permeability. •  Lung dysfunction typically progresses during initial 2–3 days. •  Secondary bacterial infections—common cause of morbidity late in the disease.

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SIGNALMENT Dog and cat. SIGNS •  Historical findings consistent with exposure. •  Smoky odor. •  Tachypnea and increased respiratory effort. •  Inspiratory effort suggests upper airway obstruction by edema. •  Postural adaptations to hypoxemia. •  Mucous membranes can be cherry red (from carboxyhemoglobin), pale, or cyanotic. •  Auscultation of wheezes, harsh broncho­ vesicular sounds, or crackles. •  Cough. •  Burns, shriveled whiskers, conjunctival edema, corneal ulcers. •  Neurologic signs indicate carbon monoxide or cyanide toxicity. •  Cardiac arrhythmias and hypotension can be seen secondary to hypoxemia, smoke and carbon monoxide inhalation, and burn injuries. CAUSES & RISK FACTORS Exposure to smoke, usually from being trapped in a burning building.

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 DIAGNOSIS

CBC/BIOCHEMISTRY/URINALYSIS •  Neutropenia—poor prognostic sign; suggests neutrophil sequestration in the lungs. •  Thrombocytopenia—suggests platelet sequestration or consumption. •  Biochemistry profile—evidence of hypoxic damage to other organ systems can be present.

IMAGING Thoracic radiographs—establish a baseline; findings vary from normal to a broncho­ interstitial or alveolar pattern. DIAGNOSTIC PROCEDURES

•  Bronchoalveolar lavage/endotracheal wash

if suspected secondary bacterial infection: culture; cytology—acute suppurative reaction with excessive mucus, neutrophils, and alveolar macrophages; intracellular bacteria indicate concurrent infection. •  Arterial blood gas to confirm hypoxemia. Pulse oximetry difficult to interpret as carboxy­ hemoglobin falsely increases values. Co-oximetry showing carboxyhemoglobin levels >15% indicates toxicity. •  Bronchoscopy demonstrates severity of airway damage, and is used to remove foreign particles and accumulated secretions.

CONTRAINDICATIONS/POSSIBLE INTERACTIONS •  Diuretics—decrease IV volume without a major beneficial effect. •  Corticosteroids— use only once and if absolutely necessary; can predispose the patient to bacterial infection.

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 FOLLOW-UP

PATIENT MONITORING •  Respiratory rate and effort, mucous membrane color, heart rate, pulse quality, lung auscultations, and packed cell volume/total solids for 24–72 hours. •  Repeat radiographs in 72 hours—ensure condition is resolving; monitor for bacterial pneumonia. •  Pulse oximetry and arterial blood gas analysis—to monitor hypoxemia and response to therapy. POSSIBLE COMPLICATIONS

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 TREATMENT

•  Initial management—stabilize respiratory

function; establish patent airway; severe upper airway edema or obstruction can require intubation or temporary tracheostomy. •  Oxygen—administer immediately to displace carbon monoxide from hemoglobin; use the highest available concentration for 2–4 hours (or longer); after elimination of carboxyhemoglobin, supplement as needed. •  Fluid therapy—crystalloid fluid resuscitation as needed to maintain perfusion with care to avoid fluid overload and progressive pulmonary edema. Associated burns can result in significant fluid and protein losses which may also require concurrent colloidal support (synthetic, albumin, plasma). •  Nebulization of saline— moistens airway secretions to facilitate clearance. •  Mechanical ventilation needed in severe cases. •  Nutritional support—maintain body condition and immune status.

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 MEDICATIONS

DRUG(S) OF CHOICE •  Suspected bacterial infection—broadspectrum antibiotics, ideally after bacterial culture has been obtained. •  Bronchodilators— improve respiratory function if severe bronchoconstriction, especially cats (e.g., terbutaline 0.01 mg/kg IV, IM, SC). Inhaled beta-agonists can also be beneficial. •  Corticosteroids—controversial, single early, anti-inflammatory dose or aerosolized corticosteroids may decrease airway edema. •  Analgesia—as required for associated discomfort. Avoid oversedation due to decreased respiratory drive.

•  Bacterial tracheobronchitis or pneumonia. •  Profound pulmonary inflammatory

response or severe systemic inflammatory response syndrome may result in acute respiratory response syndrome. Bronchiectasis can develop secondary to airway injury and impaired mucociliary clearance. •  Carbon monoxide toxicity may lead to acute and delayed neurologic signs including seizures, cerebral edema, ataxia, paresis, and changes in mental status. EXPECTED COURSE AND PROGNOSIS

•  Good if responding to treatment—likely to

worsen prior to improving. Prognosis declines if complications occur. •  Severe burns or organ injury—poor prognosis.

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 MISCELLANEOUS

­Suggested Reading

Berent AC, Todd J, Sergeeff J, Powell LL. Carbon monoxide toxicity: a case series. J Vet Emerg Crit Care 2005, 15(2):128–135. Fitzgerald KT, Flood AA. Smoke inhalation. Clin Tech Small Anim Pract 2006, 21(4):205–214. Mariani CL. Full recovery following delayed neurologic signs after smoke inhalation in a dog. J Vet Emerg Crit Care 2003, 13(4):235–239. Vaughn L, Beckel N, Walters P. Severe burn injury, burn shock, and smoke inhalation injury in small animals. Part 2: diagnosis, therapy, complications, and prognosis. J Vet Emerg Crit Care 2012, 22(2):187–200. Author Cassandra O. Janson Consulting Editor Elizabeth Rozanski Acknowledgment The author and editors acknowledge the prior contribution of Lesley G. King.



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Snake Venom Toxicosis—Coral Snakes •  Hemoglobinuria—dogs only.

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 BASICS

OVERVIEW •  Two clinically important species in North America—Micrurus fulvius, eastern coral snake (North Carolina to the north; southern Florida to the south; west of the Mississippi River) and Micrurus tenere, Texas coral snake (west of Mississippi; in Arkansas, Louisiana, and Texas). •  Family Elapidae—fixed front fangs. •  Color pattern—bands fully encircling the body; red, yellow, and black; distinguished from the harmless tricolored king snake (Lampropeltis elapsoides) by the arrangement of the bands: if yellow (caution) and red (danger) color bands touch, then stay clear; relatively small head; black snout; round pupils. Bites

•  Relatively uncommon due to snake’s

reclusive behavior and nocturnal habits.

•  Often occur on the lip. Snakes remain

attached due to chewing action.

•  Distinct fang marks may not be obvious. •  Primary cause of death—respiratory

collapse.

SIGNALMENT Dogs and cats. SIGNS

•  Onset of clinical signs may be delayed

several hours (up to 18 hours).

•  Localized signs generally absent. •  Generalized weakness and ataxia. •  Bulbar paralysis—affecting cranial motor

nerves, respiratory tract, and skeletal muscles; acute flaccid quadriplegia. •  Salivation—caused by dysphagia. •  Dyspnea. •  Dysphonia. •  Hyporeflexive spinal reflexes. •  Seizures. •  Urinary incontinence. CAUSES & RISK FACTORS

•  Size of the snake. •  Size and duration of bite.

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Myasthenia gravis. •  Botulism. •  Polyradiculoneuritis. •  Tick bite paralysis. •  Black widow spider bite (Latrodectus spp.). CBC/BIOCHEMISTRY/URINALYSIS

•  Hemolysis—dogs only. •  Red blood cell burring. •  May note high creatine kinase.

OTHER LABORATORY TESTS N/A

•  Observe precautions outlined for pit viper

antivenin administration (see Snake Venom Toxicosis—Pit Vipers).

DIAGNOSTIC PROCEDURES N/A

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 TREATMENT

•  First aid—generally avoid; most effective

measure is rapid transport to a veterinary facility for antivenom administration; Australian technique for elapid bites is a pressure wrap of the bitten limb with ace-type bandage to decrease blood flow and venom uptake. •  Caution: do not wait for onset of clinical signs to initiate treatment. •  Inpatient—hospitalize for a minimum of 48 hours. •  Monitor CNS and respiratory function closely for 24 hours. •  Specific antivenin is extremely limited for M. fulvius envenomations in the United States and typically not accessible for veterinary use. However, protective crossreactivity occurs with the following antivenins: Coralmyn (Fab2 equine origin) (Instituto Bioclon, Mexico), Costa Rican coral snake antivenin (Instituto Clodomiro Picado, Costa Rica), and Australian tiger snake Notechis scutatus (CSL Limited, Parkville, Victoria, Australia). Expense may be a consideration. Local zoos may have antivenom available. Application for an INR permit from the US Department of Agriculture may allow a veterinary hospital to acquire these antivenoms. •  If antivenin unavailable—provide ventilatory support for several days in a critical care facility.

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 MEDICATIONS

DRUG(S) OF CHOICE •  M. fulvius reactive antivenin (see Treatment)—indicated if the history includes recent coral snake interaction; evidence of puncture wounds; clinical signs consistent with coral snake envenomation; administer 1–2 vials; additional vials may be necessary (technique same as for pit viper antivenin). •  Broad-spectrum antibiotics are not routinely recommended and should only be used if there is indication of infection. •  Neostigmine – may be useful to reverse neuromuscular blockade if antivenin not available. Has been used successfully to treat M. frontalis envenomation in Brazil. CONTRAINDICATIONS/POSSIBLE INTERACTIONS •  Corticosteroids—not indicated.

 FOLLOW-UP

•  Marked clinical signs may last 1–1.5 weeks. •  Full recovery may take months as receptors

regenerate.

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 MISCELLANEOUS

SEE ALSO Snake Venom Toxicosis—Pit Vipers.

­Suggested Reading

Pérez ML, Fox K, Schaer M. A retrospective evaluation of coral snake envenomation in dogs and cats: 20 cases (1996–2011). J Vet Emerg Crit Care 2012, 22(6):682–689. Pérez ML, Fox KJ, Schaer MA. Retrospective review of coral snake envenomation in the dog and cat: 20 cases 1996 to 2011. Toxicon 2013, 60(2):247–248. Peterson ME. Snake bite: Coral snakes. In: Peterson ME, Talcott PA, eds., Small Animal Toxicology, 3rd ed. St. Louis, MO: Saunders, 2013, pp. 799–805. Author Michael E. Peterson Consulting Editor Lynn R. Hovda

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Snake Venom Toxicosis—Pit Vipers •  Local tissue swelling and pain surrounding

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 BASICS

OVERVIEW •  Pit vipers—Crotalus spp. (rattlesnakes), Sistrurus spp. (pigmy rattlesnakes and massasauga), and Agkistrodon spp. (copperheads and cottonmouth water moccasins); retractable fangs; heat-sensing pit between the nostril and eye; triangle-shaped head. •  Range—throughout the United States (not found in Alaska, Hawaii, Maine). •  Toxicity—considered hemotoxic; several species have subpopulations with lethal neurotoxic components (e.g., Mohave rattlesnake); general ranking of severity: (1) rattlesnakes, (2) moccasins, (3) copperheads. Pathophysiology

•  Venom—enzymes: hyaluronidase and

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phospholipase A (cause local tissue injury) and others that interfere with the coagulation cascade (cause major coagulation defects); non-enzymatic polypeptides: affect the cardiovascular and respiratory systems. •  Bite—80% of victims have altered laboratory values and clinically important swelling; severe hypotension from pooling of blood within the splanchnic (dogs) or pulmonary (cats) vessels; fluid loss from the vascular compartment secondary to severe peripheral edema. •  Approximately 20% crotalid bites considered “dry bites” with little if any venom deposited and no associated toxicity. Systems Affected

•  Behavioral—usually related to pain. •  Cardiovascular—lower blood pressure,

direct cardiotoxins (Eastern and Western Diamondback rattlesnake venom). •  Gastrointestinal—nausea, diarrhea. •  Hematologic—coagulopathies (hypercoagulation or consumptive), thrombocytopenia. •  Musculoskeletal—rhabdomyolysis. •  Nervous—multiple crotalid species have individuals with venom containing Mojave toxin, a potent neurotoxin. •  Skin—puncture wounds possible local tissue necrosis. SIGNALMENT Dogs and cats. SIGNS General Comments

May be delayed for 8 hours after envenomation. Historical Findings

•  Outdoors, rural setting, indigenous snake. •  Owner saw bite or heard snake.

Physical Examination Findings

•  Puncture wounds on head and forelimbs in

most animals.

PATHOLOGIC FINDINGS

bite site. •  Bruising, with possible necrosis and sloughing of bite site tissue. •  Ecchymosis and petechiation of tissues and mucous membranes. •  Hypotension and shock. •  Tachycardia. •  Shallow respiration. •  Depression, lethargy, and muscle weakness. •  Nausea and excessive salivation.

•  Puncture wounds. •  Tissue necrosis. •  Hemorrhage, petechiation, ecchymosis. •  Pulmonary hemorrhage, edema.

CAUSES & RISK FACTORS Outdoor activity.

•  Bite location—may affect uptake of venom;

Snake-Associated

•  Toxic peptide fraction: enzyme fraction

ratio—higher in spring and lower in fall (not well documented); high in very young snakes. •  Amount of venom production since last bite. •  Size, fang length, aggressiveness, and motivation of snake. Victim-Associated

•  Bite site—bites to tongue and torso are of

major concern.

•  Size of victim. •  Elapsed time between bite and initiation of

treatment.

•  Activity level of victim after the bite—activ-

ity increases absorption of venom.

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Angioedema secondary to insect envenomation (spider, scorpion, large centipede). •  Blunt trauma. •  Penetrating wound. •  Animal bite. •  Penetration of foreign body. •  Draining abscess. CBC/BIOCHEMISTRY/URINALYSIS

•  Hemoconcentration. •  Frequent burring of red blood cells within

first 24 hours (echinocytes). •  Thrombocytopenia. •  Hypokalemia. •  Elevated creatine kinase. •  Hematuria or myoglobinuria.

OTHER LABORATORY TESTS Clotting tests—reduced platelets and fibrinogen, monitor for prolonged activated clotting time, prothrombin time, and partial thromboplastin time; may note elevated fibrin degradation products. DIAGNOSTIC PROCEDURES

•  Clinical evaluation of bite for edema,

ecchymosis, fang punctures, pain.

•  Electrocardiogram—may detect ventricular

arrhythmia, especially in severely depressed patients.

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 TREATMENT

•  Tissue reaction around the bite site—not a

reliable indicator of systemic toxicity.

bites to tongue and torso are of major concern. Distal limb bites may result in significant tissue damage and compromise limb function. •  First aid measures—minimize activity, calm patient, provide analgesia if indicated; transport quickly to a veterinary facility. •  Swelling can be objectively monitored with circumferential measurements using a cloth or flexible tape measure. •  Antivenom is only proven specific treatment (see Medications). Expense may be an important factor. •  IV fluids—correct hypotension. •  Analgesics to reduce pain and stress. •  Antibiotics—infection is rare and antibiotics are not recommended unless there is evidence of infection. •  Repeat coagulation profile after administration of antivenom for comparison to earlier labs (typically the author performs on entry, 6 hours and 12 hours unless patient is obviously worsening). Recurrence of clinical signs or coagulation abnormalities can occur with any antivenin. This usually happens when initial coagulopathy is more severe. If initial coagulopathy resolved with antivenin administration, recurrence can occur within the next few days, although rarely as severe as initial. There are no documented cases of clinical bleeding with subsequent coagulopathy; however, the clinician should be aware of the possibility. Activity

Initially restrict exercise as this can increase uptake of venom, once envenomation syndrome under control—activity as the patient will tolerate. Client Education

•  Monitor patient for ecchymosis or

petechiation.

•  Monitor for evidence of serum sickness.

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 MEDICATIONS

DRUG(S) OF CHOICE Antivenom

•  Always flush antivenom vial after initial

removal of antivenom, second flush can increase antibody collection by 30%.



Canine and Feline, Seventh Edition



Snake Venom Toxicosis—Pit Vipers

(continued)

•  Allergic reaction—stop antivenom; give

diphenhydramine; after 5 minutes, restart antivenom infusion at a slower rate. •  Mix each vial of antivenom with 100–150 mL of a crystalloid fluid and administer IV slowly while taking into consideration the patient’s weight and overall fluid load. Infuse over 30 minutes–1 hour. •  Carefully monitor the inner pinna for onset of hyperemia (indicator of possible allergic reaction). •  With the exception of Crofabtm all anti­venoms have approximately 20% of their protein content as actual antibodies against snake venom. •  Frequent administration of antivenom controls the animal’s pain. •  Other analgesics as needed to control pain. Veterinary Licensed

•  VenomVetTM (Crotalidae polyvalent, equine

origin, Fab2). Injectable solution, no need to reconstitute. Two South American immunizing snake species. •  AntiveninTM (Crotalidae polyvalent, equine origin, whole IgG—Boehringer-Ingelheim), reactions more common due to extraneous proteins. Lyophilized. Two North American snake species and two South American species immunizing snake species. •  Rattler AntiveninTM (polyvalent, equine origin, whole IgG—Mg Biologics) equine plasma product, frozen. Four North American immunizing snakes.

clinical trials in dogs. Purified antibody particles much less possibility for reactions. CONTRAINDICATIONS/POSSIBLE INTERACTIONS •  Caution: in animals receiving beta-blockers, the onset of anaphylaxis may be masked; therefore, the condition may be more advanced once recognized and more difficult to treat effectively. •  Corticosteroids—of no value. •  Dimethyl sulfoxide (DMSO)—enhances uptake and spread of venom. •  Heparin—do not use; not effective against thrombin-like enzymes and worsens coagulopathies. Alternative Drug(s)

Rattlesnake vaccine for dogs is currently marketed. Its efficacy is unknown, but several published papers have shown mixed results; only anecdotal evidence at this time. Not recommended until peer-reviewed efficacy data available.

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 FOLLOW-UP

•  Repeated laboratory analysis—6 hours after

admission to hospital.

•  Clinical signs—may last 1–1.5 weeks. •  Once released, owner should monitor for

recurrence of coagulopathies or delayed serum sickness.

FDA Licensed but Published Studies in Dogs

•  Crofab® (polyvalent, ovine Fab1—BTG

International) first prospective clinical trial of antivenom in dogs. Purified antibody fragments provide much less possibility for reactions. 99% protein is Fab1 antibodies against snake venom. •  Antivipmyn® (polyvalent, equine Fab2—Rare Disease Therapeutics) has completed safety and

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 MISCELLANEOUS

AGE-RELATED FACTORS •  None unless underlying pathology (e.g. renal disease). •  Patients receiving other medications (e.g. nonsteroidal anti-inflammatory drugs).

PREGNANCY/FERTILITY/BREEDING

•  Antivenom has been given to pregnant

animals and humans with no adverse events.

•  Pregnancy is at risk from venom effects

upon placenta and fetal tissue. INTERNET RESOURCES App: Snakebite911 ER

­Suggested Reading

Hoose JA, Carr A. Retrospective analysis of clinical findings and outcome of cats with suspected rattlesnake envenomation in Southern California: 18 cases (2007–2010). J Vet Emerg Crit Care 2013, 23(3):314–320. Julius TM, Kaelble MK, Leech EB, et al. Retrospective evaluation of neurotoxic rattlesnake envenomation in dogs and cats: 34 cases (2005–2010). J Vet Emerg Crit Care 2012, 22(4):460–469. Peterson ME, Matz M, Seibold K, et al. A randomized multicenter trial of Crotalidae polyvalent immune Fab antivenom for the treatment of rattlesnake envenomation in dogs. J Vet Emerg Crit Care 2011, 21(4);335–345. Pritchard JC, Birkenheuer AJ, Hanel RM, et al. Copperhead (Agkistrodon contortrix) envenomation of dogs: 52 cases (2004– 2011). J Am Anim Hosp Assoc 2014, online 6131, doi 10.5326. Witsil AJ, Wells R, Woods C, Rao S. 272 cases of rattlesnake envenomation in dogs: demographics and treatment including safety of F(ab′)2 antivenom use in 236 patients. Toxicon 2015, 105:19–26. Woods C, Young D. Clinical safety evaluation of F(ab′)₂ antivenom (Crotalus durissus-Bothrops asper) administration in dogs. J Vet Emerg Crit Care 2011, 21(5):565–569. Author Michael E. Peterson Consulting Editor Lynn R. Hovda

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Sneezing, Reverse Sneezing, Gagging •  Acute sneezing in dogs is most often caused

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 BASICS

DEFINITION •  Sneezing—a normal, protective, expiratory reflex that serves to expel air and material from the lungs through the nasal cavity and mouth. •  Reverse sneezing—a normal protective, repetitive inspiratory reflex that serves to remove irritants from the nasopharynx (also termed the aspiration reflex). •  Gagging—a normal protective reflex to clear secretions from the larynx, trachea, pharynx, or esophagus. Prevents irritating/ toxic material from entering these structures; often misinterpreted as vomiting by owners.

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PATHOPHYSIOLOGY •  Irritation of submucosal irritant receptors; various stimuli (infectious, parasitic, irritant, mechanical—especially accumulated secretions) will elicit these reflexes depending on where the irritation is applied. •  Sneezing—nasal mucosal irritation; improves with chronicity. •  Reverse sneezing—caudodorsal nasopharyngeal mucosal irritation triggers pharyngeal muscle spasms, subsequent laryngeal obstruction and movement of material into the oropharynx. •  Gagging—intraoral stimulation (tracheal, laryngeal, oropharyngeal, potentially esophageal mucosal irritation) detected by afferent limb of gag reflex. Efferent limb gives rise to uncoordinated muscle movement characteristic of gagging. SYSTEMS AFFECTED

•  Respiratory—frequently associated with

infectious or inflammatory conditions involving the upper respiratory tract. •  Gastrointestinal—gagging may also be caused by swallowing, esophageal, or gastric disorders. GENETICS N/A INCIDENCE/PREVALENCE These are common, normal reflexes in both dogs and cats in response to mucosal irritation. GEOGRAPHIC DISTRIBUTION Worldwide SIGNALMENT •  Any dog or cat may be affected. •  These reflexes associated with the conditions that cause them; examples include: ◦  Young animals—infection, congenital defects (cleft palate0, primary ciliary dyskinesia. ◦  Older animals—nasal tumors, dental disease.

by a nasal foreign body, while in cats it is most often associated with acute viral rhinitis.

SIGNS •  Head and mouth position may help owners determine which of these reflexes are present. •  Sneezing typically results in sudden, explosive expiratory effort(s) with the mouth closed and head thrown downward; may result in the animal’s nose hitting the ground. •  Reverse sneezing is a sudden, often paroxysmal, noisy, inspiratory effort with the head pulled back, mouth closed, and lips sucked in. •  Gagging is an expiratory effort; typically, with the head and neck extended and mouth held open; usually ends with the animal swallowing (with little to nothing expelled). •  Nasal discharge commonly seen with sneezing and reverse sneezing. Retching, coughing and vomiting may accompany gagging. CAUSES

•  Any mucosal irritation or inflammation can

elicit these airway reflexes. The reflex localizes the site of irritation for further evaluation. •  Nasal causes of sneezing and reverse sneezing include excess nasal secretions, rhinitis (idiopathic, secondary bacterial, viral or mycotic infections), foreign body, non-neoplastic masses (nasopharyngeal polyps, inflammatory polyps of the nasal turbinates), neoplasia, and parasites; dogs— Pneumonyssoides; dogs and cats—Cuterebra, Eucoleus (Capillaria), Linguatula. •  Extranasal diseases resulting in reverse sneezing, sneezing and gagging— pneumonia, esophageal strictures, megaesophagus, chronic vomiting, cricopharyngeal disorders, dental disease (oronasal fistulas, tooth root abscess). •  Reverse sneezing may be idiopathic, especially in small-breed dogs with no other associated clinical signs. •  Causes of gagging include: ◦  Secretions being coughed up from the lower airways and into the larynx or cervical trachea. ◦  Pharyngeal/laryngeal dysfunction resulting in airway aspiration due to loss of motor and/or sensory function that normally protects the airway. ◦  Vomiting from esophageal and gastro­ intestinal disease. RISK FACTORS

•  Environmental factors like dusty areas,

smoke inhalation, perfumes, cold air.

•  Productive coughing may produce excess

secretions that can be propelled into the nasopharynx and lead to reverse sneezing. •  Nasal mites may cause both reverse sneezing and sneezing in dogs (but not cats); in the United States, incidence is inversely proportional to heartworm preventive usage. •  Reverse sneezing is often associated with excitement.

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS Similar Signs

•  Differentiate regular sneezing (occurs on

expiration) from reverse sneezing (occurs on inspiration and localizes the site of irritation to the nasopharynx). •  Gagging is often misinterpreted as vomiting. CBC/BIOCHEMISTRY/URINALYSIS Nonspecific for any cause of sneezing, reverse sneezing, or gagging. Identifies comorbidities. OTHER LABORATORY TESTS Virus isolation, culture or PCR for upper respiratory tract infections (FCV, FHV-1, feline and canine influenza); retroviral testing (FeLV, FIV); cryptococcal antigen testing; Aspergillosis testing; bacterial cultures (Mycoplasma spp., Bordetella bronchiseptica); cytology, histopathology and coagulation studies if indicated. IMAGING

•  Sneezing and reverse sneezing—skull

radiographs, CT/MRI.

•  Gagging—thoracic radiographs, fluoroscopy

(dynamic swallow study), CT/ MRI. DIAGNOSTIC PROCEDURES

•  Sneezing and reverse sneezing—antegrade

and retrograde rhinoscopy, nasal biopsy (histopathology), nasal culture (deep nasal flush sample), periodontal probing. •  Gagging—neurologic examination (CN V, IX, X, XII), sedated oropharyngeal exam, transtracheal wash, or bronchoalveolar lavage. PATHOLOGIC FINDINGS Nonspecific inflammation can be found in the nasal cavity or nasopharynx.

•  Brachycephalic and dolichocephalic breeds

may be overrepresented.

•  Incompletely or unvaccinated animals are at

a higher risk of developing infection.

•  Outdoor animals, especially hunting dogs,

perhaps more at risk for nasal foreign bodies and nasal infections. •  Chronic dental disease can cause rhinitis and either sneezing or reverse sneezing.

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 TREATMENT

APPROPRIATE HEALTH CARE Removal of the inciting mucosal irritation, where/when possible, will result in relief from these reflexes.



Sneezing, Reverse Sneezing, Gagging

(continued)

NURSING CARE Outpatient therapy generally indicated, except perhaps following rhinoscopic biopsy. ACTIVITY Exercise and activity should be restricted after rhinoscopic biopsies to prevent excessive bleeding. DIET N/A CLIENT EDUCATION •  Educate clients so they understand these are normal reflexes. Diagnostic testing is required to determine the underlying cause and to allow appropriate treatment. •  Close contact with other animals should be limited until treatment for the underlying cause (if infectious) is completed. •  Episodes of paroxysmal reverse sneezing may be lessened by inducing swallowing (rubbing the throat, giving water) or breath holding (cover nose and mouth). SURGICAL CONSIDERATIONS •  Anesthesia for surgery or endoscopy— abscessed tooth, foreign body, masses or anatomical airway abnormality, treatment of fungal infections. •  Use surgery for laryngeal disease with caution when gagging is prominent due to an increased risk of aspiration pneumonia when concurrent esophageal dysfunction is present.

and azathioprine 1–2 mg/kg/day PO in combination with piroxicam 0.3 mg/kg PO daily may be considered. •  Lower airway diseases with excess secretions are treated with antibiotics if bacterial infection is confirmed; Gram-negative bacteria are most common. •  Anti-inflammatory—prednisolone 1–2 mg/ kg q12–24h or piroxicam 0.3 mg/kg PO q24–48h if no infection, for nonspecific airway inflammation. •  No treatment for gagging secondary to sensory loss in the larynx with recurring aspiration; elevation of food and water bowls is recommended. Altering the consistency of food offered may also be helpful. CONTRAINDICATIONS •  Ivermectin in collies and similar breeds (MDR1 gene mutation). •  Use of piroxicam concurrently with other nonsteroidal anti-inflammatory drugs or corticosteroids, as well as in patients with renal insufficiency. PRECAUTIONS The safety of most recommended drugs has not been established in pregnant animals. POSSIBLE INTERACTIONS N/A ALTERNATIVE DRUG(S)

•  Topical decongestants— 0.125%

phenylephrine or 0.025% oxymetazoline.

•  Antihistamines (diphenhydramine, Zyrtec,

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 MEDICATIONS

DRUG(S) OF CHOICE •  There is no drug that specifically suppresses these reflexes; treatment is directed at the underlying irritant. •  Nasal bacterial infections best treated with antibiotics directed against Gram-positive bacteria (most common). Fungal disease treated with systemic and local infusion of antifungals. •  Nasal mites are treated with ivermectin 200–300 μg/kg PO or SC weekly for 3 weeks, selamectin 6–24 mg/kg applied topically every 2 weeks for 3 doses, or milbemycin (in collies and similar breeds) 0.5–1 mg/kg PO weekly for 3 weeks. All dogs in the household should be treated to prevent reinfection. •  When no underlying nasal condition is found to explain sneezing, nasal mite treatment is recommended. Immunomodulatory antibiotics such as doxycycline 5–10 mg/kg PO q12–24h

Claritin) may reduce secretions and sneezing in some cases with underlying allergic component.

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 FOLLOW-UP

PATIENT MONITORING Expect reduction in sneezing/reverse sneezing with appropriate therapy. PREVENTION/AVOIDANCE Limit access to foreign bodies, provide adequate dental care and appropriate vaccination. POSSIBLE COMPLICATIONS If gagging is secondary to laryngeal sensory loss, serious aspiration pneumonia may develop. EXPECTED COURSE AND PROGNOSIS •  Nasal mites should respond to treatment within 3 weeks.

•  Sneezing and reverse sneezing secondary to

foreign material resolve quickly after removal of the foreign body. •  Neoplasia may carry a poorer prognosis (chemotherapy or radiation therapy may be indicated).

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 MISCELLANEOUS

ASSOCIATED CONDITIONS N/A AGE-RELATED FACTORS N/A ZOONOTIC POTENTIAL Rare; immunocompromised individuals at greater risk with infectious causes. PREGNANCY/FERTILITY/BREEDING N/A SEE ALSO •  Nasal Discharge. •  Rhinitis and Sinusitis.

­Suggested Reading

Demko JL, Cohn LA. Chronic nasal discharge in cats: 75 cases (1993–2004). J Am Vet Med Assoc 2007, 230:1032–1037. Doust R, Sullivan M. Nasal discharge, sneezing and reverse sneezing. In: King LG, ed., Textbook of Respiratory Disease in Dogs and Cats. Philadelphia, PA: Saunders, 2004, pp. 17–29. Kook P. Gagging. In: Ettinger SJ, Feldman EC, eds., Textbook of Veterinary Internal Medicine, 6th ed. St. Louis, MO: Saunders, 2005, pp. 152–155. Lopez J. Sneezing and nasal discharge. In: Ettinger SJ, Feldman EC, eds., Textbook of Veterinary Internal Medicine, 6th ed. St. Louis, MO: Saunders, 2005, pp. 111–115. Plickert HD, Tichy A, Hirt RA. Characteristics of canine nasal discharge related to intranasal diseases: a retrospective study of 105 cases. J Small Anim Pract 2014, 55:145–152. Author Jonjo Reece Consulting Editor Elizabeth Rozanski Acknowledgment The author and editors acknowledge the prior contributions of Dominique Peeters and Brendan C. McKiernan. Client Education Handout available online

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Soft Tissue Sarcoma Mean Age and Range

•  Dogs—middle-aged, range 2–15 years.

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 BASICS

DEFINITION •  A mesenchymal neoplasm arising within or from connective tissues. •  Tumors in this heterogeneous group have different histologic origins yet demonstrate similar pathologic features and clinical behavior, and include fibrosarcoma, leiomyosarcoma, peripheral nerve sheath tumor, and myxosarcoma. Histology reports may commit only to soft tissue arcoma (STS) or spindle cell sarcoma, and may not distinguish among cell of origin without immunohistochemistry. •  Because of divergent pathogenesis and biologic behavior, this group of tumors does not include hemangiosarcoma and other tumors that sometimes share the suffix (for example melanosarcoma, osteosarcoma, or lympho­ sarcoma). Histiocytic sarcoma is also considered separately. PATHOPHYSIOLOGY

•  Tumors can arise in connective tissues in any anatomic location. •  Locally invasive

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behavior is typical with tumor extension beyond gross visible margins. •  Tumors often have low (5  cm more likely to recur) and incomplete surgical margins (recurrence). •  Low-grade STS of the distal extremities in dogs might have a low recurrence rate following surgical excision ( males. •  Dogs—commonly seen in large breeds, especially German shepherd dog; also boxer, Airedale terrier, and cocker spaniel. •  Occurrence increases with age. Present in 50% of dogs by 6 years and 75% by 9 years. May be radiographically evident in young dogs with an inherited predisposition. •  Boxers—positive correlation between spondylosis deformans and hip dysplasia. Both heritable traits are detectable in predisposed animals by radiographic examination at 1 year. •  Cats—present in 68% of asymptomatic cats. SIGNS General Comments

•  Neoplasia—may have irregular, ventral,

Non-NSAID Analgesics

nonbridging bone.

•  Use may enable reduction of dose or

CBC/BIOCHEMISTRY/URINALYSIS Normal

•  Tramadol 2–5 mg/kg PO q8–12h in dogs;

Radiographic Findings

•  Gabapentin 10 mg/kg PO q8–12h in dogs

Spinal radiography initially shows osteophytes as triangular projections several millimeters from the edge of the vertebral body. With progression, osteophytes appear to bridge the intervertebral space. True ankylosis is rare. DIAGNOSTIC PROCEDURES In uncommon presentations, MRI, CT, or CT myelography can be used to demonstrate an atypical dorsal osteophyte compressing the spinal cord or nerve roots or encroaching on critical soft tissue structures.

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 TREATMENT

•  Typically not needed. Inform client that the

condition is usually an asymptomatic, incidental finding, and is likely not respons­ ible for any clinical signs that may be present. •  Treat spondylosis on an outpatient basis with strict rest and analgesia, possibly acupuncture. •  If overconditioned, recommend weightreduction program. •  Acupuncture—dry needle or electro­ acupuncture treatment at weekly or biweekly interval and tapered to as-needed basis can be very effective in relief of pain. Useful in animals who do not tolerate medication or when clients prefer an alternative treatment modality.

•  Patients are typically asymptomatic; lesions

are of minor if any clinical importance.

•  Pain may follow fracture of bony spurs or

bridges.

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Historical Findings

DRUG(S) OF CHOICE Use only when the patient is exhibiting signs.

•  Stiffness. •  Restricted motion. •  Spinal pain.

Physical Examination Findings

Neurologic deficits are uncommon. If present, referable to compression of the spinal cord or nerve root. CAUSES & RISK FACTORS •  Repeated microtrauma. •  Major trauma. •  Inherited predisposition. •  Acromegaly.

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Discospondylitis—differentiated by radiographic evidence of endplate lysis. •  Spinal osteoarthritis—degeneration of articular facet joints.

 MEDICATIONS

Nonsteroidal Anti-inflammatory Drugs (NSAIDs)

•  In dogs, NSAIDs are preferable to steroids

(fewer side effects) unless patient has neurologic deficits or concomitant disease prohibits use. Administer with food. •  Carprofen (Rimadyl) 2.2 mg/kg PO q12h or 4.4 mg/kg PO q24h in dogs. •  Meloxicam (Metacam) 0.2 mg/kg once then 0.1 mg/kg q24h in dogs. •  Deracoxib (Deramaxx) 1–2 mg/kg PO q24h in dogs. •  Firocoxib (Previcox) 5 mg/kg PO q24h in dogs. •  Grapiprant (Galliprant) 2 mg/kg PO q24h in dogs. •  If gastrointestinal sensitivity, use in combination with an antacid (famotidine 0.5–1 mg/kg q24h or omeprazole 0.5–1 mg/ kg q24h) or a gastrointestinal protectant (misoprostol at 3–5 μg/kg PO q6–8h or sucralfate 0.5–1 g q8h) to reduce the possibility of ulceration.

frequency of anti-inflammatory medications. 1–4 mg/kg q12h in cats. or cats.

•  Buprenorphine 0.01–0.03 mg/kg PO q8h

in cats.

•  Acetaminophen 5 mg/kg POq12h in dogs.

Corticosteroids

•  Only use in patients with neurologic

deficits.

•  Prednisone 0.25–0.5 mg/kg PO q12h; or

dexamethasone 0.025–0.05 mg/kg PO q12h.

•  Taper to alternate-day prednisone or

twice-weekly dexamethasone.

CONTRAINDICATIONS/POSSIBLE INTERACTIONS •  Acetaminophen and NSAIDs—do not use in cats. •  Avoid prolonged administration of NSAIDs, simultaneous use of of NSAIDs and acetami­ nophen, simultaneous use of NSAIDs and steroids, use of NSAIDs in patients with gastro­intestinal (GI) or renal disease. Doing so decreases risk of GI ulceration and renal pathology.

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 FOLLOW-UP

PATIENT MONITORING •  If signs are present, restrict activity and gradually return the animal to normal activity after signs have subsided for several weeks. •  Relapse can occur with strenuous activity. •  With prolonged use of analgesic medications, periodic biochemistry testing is warranted. PREVENTION/AVOIDANCE Boxers—given genetic correlation between spondylosis deformans and hip dysplasia and potential for early radiographic detection, dogs should be screened and selectively bred.

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 MISCELLANEOUS

ABBREVIATIONS •  CT= computed tomography. •  GI = gastrointestinal. •  MRI = magnetic resonance imaging. •  NSAID = nonsteroidal anti-inflammatory drug.

­Suggested Reading

Romatowski J. Spondylosis deformans in the dog. Compend Contin Educ Pract Vet 1986, 8:531–536. Authors Richard J. Joseph and Anne E. Buglione

1282

Blackwell’s Five-Minute Veterinary Consult

Sporotrichosis

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 BASICS

OVERVIEW •  Zoonotic fungal disease affecting the integument, lymphatics, or generalized. •  Caused by inoculation of the ubiquitous dimorphic fungus Sporothrix schenckii into subcutaneous tissue. SIGNALMENT Cat and dog (less common).

S

SIGNS •  Dogs (cutaneous form)—numerous nodules that may drain or crust; most lesions located on the head, dorsal muzzle; occasionally on the chest, or disseminated on the body and on the limbs. •  Cats (cutaneous form)—lesions appear initially as wounds or abscesses mimicking wounds associated with fighting. •  Cutaneolymphatic form—usually an extension of the cutaneous form through the lymphatics, resulting in the formation of new nodules and draining tracts or crusts; lympha­ denopathy is common. •  Disseminated form—systemic signs including lameness, respiratory symptoms (nasal discharge, sneezing, stertorous breathing), anorexia and weight loss also reported in dogs. CAUSES & RISK FACTORS

CBC/BIOCHEMISTRY/URINALYSIS None unless associated with generalized disease. OTHER LABORATORY TESTS •  Cultures of affected tissue preferred; swab culture may be adequate •  Caution: This is a zoonotic disease; laboratory personnel must be warned of the potential differential diagnosis. •  Serologic testing and PCR assays are available. DIAGNOSTIC PROCEDURES

•  Cytology of exudates—cigar- to round-

shaped yeast found intracellularly or free in the exudates with pyogranulamatous inflammation. •  Biopsy—organisms usually numerous, especially in cats; fungal stains (periodic acid– Schiff or Gomori’s methamine silver) may aid in the diagnosis; the absence of demonstrable organisms in tissues from dogs does not preclude diagnosis; pyogranulomatous inflammation with few mast cells, eosinophils, and plasma cells. Radiographs—evidence of irregular periostal proliferation. •  Immunohistochemistry might be useful for an early diagnosis of sporothricosis in cats. High sensitivity reported with immuno­histochemistry to diagnose sporothricosis in dogs. •  ELISA— screening tool for the detection of specific S. schenckii antibodies in cats with sporotrichosis.

­

 FOLLOW-UP

PATIENT MONITORING Reevaluation, including assessment of liver enzymes, recommended every 2–4 weeks. PREVENTION/AVOIDANCE N/A EXPECTED COURSE AND PROGNOSIS •  Failure of response to therapy possible. •  Fluconazole and terbinafine remain relatively untested but may show promise for treatment.

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 MISCELLANEOUS

ZOONOTIC POTENTIAL •  Caution: This is a zoonotic disease. •  Client education is of paramount importance. •  Absence of a break in the skin does not protect against the disease. •  Reports of zoonotic transmission from bites and scratches from rodents, parrots, cats, dogs, horses, and armadillos. •  Clinically healthy cats sharing a household with an infected cat may be a source of infection. ABBREVIATIONS

•  Dogs—hunting dogs from puncture

•  ELISA = enzyme-linked immunosorbent

•  Cats—intact male outdoor cats: Healthy

­Suggested Reading

wounds associated with thorns or splinters.

cats may have a minor role in sporotrichosis transmission •  Animals exposed to soil rich in decaying organic debris. •  Exposure to infected animals or clinically healthy cats sharing a household with an affected cat. •  Immunosuppressive disease.

­

 DIAGNOSIS

Caution: This is a zoonotic disease and proper precautions should be taken to prevent exposure; the absence of a break in the skin does not protect against the disease. Cats may act as reservoirs for S. schenckii and can transmit the infection to humans by a bite or scratch. DIFFERENTIAL DIAGNOSIS •  Infectious—bacterial (deep) and fungal infection (e.g., cryptococcosis, blastomycosis, feline leprosy, histoplasmosis). •  Neoplasia. •  Granulomas caused by foreign bodies. •  Parasites—Demodex, Pelodera, Leishmania.

assay.

­

 TREATMENT

­

 MEDICATIONS

Zoonotic; outpatient therapy may be a consideration but increases the potential for human exposure.

DRUG(S) OF CHOICE •  Dogs—ketoconazole 5–15 mg/kg PO q12h, itraconazole 5–10 mg/kg PO q24h, terbinafine 30–40 mg/kg PO q24h given with food, administered until 1 month after clinical resolution; resolution usually occurs within 3 months. Disseminated disease— combination of amphotericin B and itraconazole is recommended; terbinafine may also be effective. •  Cats—itraconazole 5–15 mg/kg PO q24h or divided q12h for a minimum of 1 month beyond clinical cure; compounded formulations of itraconazole are not recommended due to inconsistent absorption.

Silva J, Miranda L, Menezes R, et al. Comparison of the sensitivity of three methods for the early diagnosis of sporotrichosis in cats. J Comp Pathol 2018, 160:72–78. Authors W. Dunbar Gram and Andhika Putra Consulting Editor Alexander H. Werner Resnick Acknowledgment The authors and editors acknowledge the prior contribution of Holly Dutton.



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Canine and Feline, Seventh Edition

Squamous Cell Carcinoma, Digit •  Limb radiography—lysis of the third

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 BASICS

OVERVIEW •  Locally invasive malignant tumor usually arising from subungual epithelium. •  Cats—metastasis to one or multiple digits from primary pulmonary site. •  Dogs—most common digital tumor (~50%); up to 25% metastatic rate, up to 22% multiple digits affected (multicentric disease). •  Forelimb more commonly affected than hind limb. •  Organ systems—skin/endocrine, musculoskeletal.

phalanx of the affected digit in 80% of patients with potential secondary extension proximally to phalanx 2 and 1. •  Abdominal ultrasonography—for hind limb lesions, evaluate intra-abdominal lymph nodes for presence of metastatic disease. DIAGNOSTIC PROCEDURES

•  Cytology—diagnostic utility limited if there

is severe inflammation or secondary infection (common), or the tumor is well differentiated. •  Biopsy of lesion—may be needed to confirm diagnosis. •  Cytology of regional lymph nodes to evaluate for metastasis.

SIGNALMENT

•  Dog and rarely cat. •  Median age—dogs and cats 10 years;

reported in dogs as young as 3 years old.

•  Large breeds (>75%) and black/dark-coated

dogs (>90%) predisposed; breeds include standard poodle, Labrador retriever, giant schnauzer, Rottweiler, dachshund, flat-coated retriever, and possibly Beauceron, Briard, and miniature poodle. SIGNS

•  Swollen digit or digital mass which fails to

heal.

•  Lameness. •  Ulceration. •  Fractured or missing nail. •  Multiple digits affected in up to 22% of

dogs; may present in one digit and develop additional digital tumors later. •  Multiple digits commonly seen in cats (30%); due to lung–digit syndrome. •  Regional lymphadenomegaly of the sentinel draining lymph node (uncommon at time of diagnosis). CAUSES & RISK FACTORS Risk factors (dogs)—hereditary; dark skin/ hair pigmentation.

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Nailbed infection (paronychia). •  Trauma. •  Other tumors (dog)—melanoma; soft tissue sarcomas; mast cell tumor; osteosarcoma. •  Benign lesions—epithelial inclusion cyst, keratoacanthoma. CBC/BIOCHEMISTRY/URINALYSIS Usually normal. IMAGING

•  Thoracic radiography—to evaluate for

metastatic disease (develops in up to 25% of dogs) and rule out a primary pulmonary carcinoma (cats).

­

 TREATMENT

•  Amputation of the affected digit at the level

of the metacarpal or metatarsal phalangeal joint. •  In cats with a primary pulmonary tumor, amputation of a single affected digit may provide local palliative care and confirm diagnosis, however multiple digits on multiple limbs are often affected. •  Palliative radiation can be considered for single digits if metastatic disease present or in the setting of multicentric/multiple digits affected. •  Analgesics for pain control, antibiotics for secondary bacterial infections may be indicated. •  Benefit of chemotherapy has not been established; however in patients with advanced stage of disease chemotherapy useful for squamous cell carcinoma of other sites could be considered.

­

 MEDICATIONS

DRUG(S) OF CHOICE Piroxicam—dogs, 0.3 mg/kg PO q24h for analgesia/antineoplastic effects; cats, 0.3 mg/ kg PO q24–48h has been used for other carcinomas. CONTRAINDICATIONS/POSSIBLE INTERACTIONS None

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 FOLLOW-UP

PATIENT MONITORING Physical exam, thoracic radiographs, lymph node evaluation, ± abdominal ultrasound at 1–2 months, then every 3 months after treatment (complete surgical excision).

EXPECTED COURSE AND PROGNOSIS

•  Complete surgical excision of the primary

lesion and no evidence of metastasis; additional treatment may not be required. •  Survival time following complete surgical excision depends upon location of the tumor on the digit; squamous cell carcinoma (SCC) originating from subungual epithelium: 95% 1-year and 74% 2-year survival; SCC originating in other parts of the digit: 60% 1-year and 44% 2-year survival. •  In one study 1- and 2-year survival was 50% and 18%, respectively, while in two other studies only 20–45% of dogs died of SCC (multicentric or metastatic) and the median survival time was not reached. •  Development of multicentric disease (multiple affected digits) in dogs appears more common than lymph node or pulmonary metastasis. •  Surgery to amputate affected digit, regardless of presence of metastases, provides positive impact on survival in the dog. •  Histologic grading does not appear predictive of development of multicentric or metastatic disease in dogs. •  Prognosis for cats is poor with median survival times of 2–3 months if metastatic from pulmonary carcinoma.

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 MISCELLANEOUS

SEE ALSO •  Melanocytic Tumors, Skin and Digit. •  Squamous Cell Carcinoma, Skin. ABBREVIATIONS

•  SCC = squamous cell carcinoma.

­Suggested Reading

Belluco S, Brisebard E, Watrelot D, et al. Digital squamous cell carcinoma in dogs: epidemiological, histological, and immunohistochemical study. Vet Pathol 2013, 50(6):1078–1082. Author Alycen P. Lundberg Consulting Editor Timothy M. Fan Acknowledgment The author and editors acknowledge the prior contribution of Jackie M. Wypij.

1284

Blackwell’s Five-Minute Veterinary Consult

Squamous Cell Carcinoma, Ear ◦  Other neoplasia (ceruminous gland

adenocarcinoma, other).

­

 BASICS

OVERVIEW •  Malignant tumor of squamous epithelium occurring on the pinna, external ear, and/or middle ear (less common). •  Pinna—most common location in cats; tumors of the pinna in dogs are rarely squamous cell carcinoma. •  Organ system—skin/endocrine. SIGNALMENT •  Cat and dog. •  Tumors of the pinna—common in cats with light pigmentation, average 12 years. •  Ear canal tumors—seen in older dogs and cats. •  Cocker spaniels overrepresented for benign and malignant ear canal tumors in one study.

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SIGNS •  Tumors of the pinna: ◦  Slowly developing lesions of the edge of the pinna. ◦  Precancerous stage—crusty eczematous lesions (actinic dermatitis). ◦  Cancerous phase—proliferation and/or ulceration progresses. ◦  Multiple cutaneous lesions (about 10–15% of cats) occur in haired skin (multicentric squamous cell carcinoma in situ). •  Tumors of the ear canal: ◦  Often unilateral, arise from the external ear canal. ◦  Mass lesion (raised, ulcerated, broadbased). ◦  Malodorous aural discharge. ◦  Pruritis. ◦  Pain. ◦  Vestibular signs/Horner’s syndrome (facial nerve paralysis, head tilt, circling) in ~10% of dogs; more common in cats with ear canal tumors. ◦  Difficulty opening jaw. ◦  Cervical lymphadenomegaly (retro­ pharyngeal, mandibular). CAUSES & RISK FACTORS •  Pinna—UV exposure in cats with white fur, light skin. •  Ear canal—chronic inflammation may be a risk factor.

­

 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS

Dogs

•  Pinna: ◦  Other neoplasia (mast cell tumor,

histiocytoma, sebaceous gland tumor).

◦  Trauma.

•  Ear canal/middle ear: ◦  Chronic otitis. ◦  Other neoplasia (ceruminous gland

adenoma or adenocarcinoma, papilloma).

◦  Nasopharyngeal polyps (rare).

CBC/BIOCHEMISTRY/URINALYSIS Usually normal. IMAGING

(middle ear).

prevent progression of precancerous lesions; may not be commercially available. ◦  Acitretin 1 mg/kg PO q24h can be used in place of etretinate. ◦  Vitamin E 400–600 IU PO q12h; may be beneficial to prevent or delay progression of precancerous lesions. •  Ear canal tumors: ◦  Systemic chemotherapy—benefit not yet established; anecdotal benefit. CONTRAINDICATIONS/POSSIBLE INTERACTIONS Women who are pregnant or planning to become pregnant should not handle acitretin.

•  Thoracic radiography—evaluate for

pulmonary metastasis (rare with pinnal lesions). •  CT—shows extent of disease and provides surgical planning; 57–67% locally invasive into surrounding tissues. DIAGNOSTIC PROCEDURES •  Cytology may confirm diagnosis; however, ulceration, inflammation, and secondary infection may limit diagnostic utility. •  Biopsy of pinna/aural mass to confirm diagnosis via histopathology; video otoscopy may aid in visualization of mass lesion and biopsy. •  Lymph node cytology of draining lymph nodes to assess for metastatic disease.

­

 FOLLOW-UP

PATIENT MONITORING •  Pinna—physical examination at 1 month, then every 3 months after treatment (complete surgical excision). •  Ear canal—physical examination, thoracic radiographs, lymph node evaluation, and possible CT every 3 months after treatment. PREVENTION/AVOIDANCE

•  Limit sun exposure. •  Tattoos on nonpigmented areas may be

helpful.

EXPECTED COURSE AND PROGNOSIS

­

 TREATMENT

•  Pinna: ◦  Appropriate surgical excision may require

pinnectomy and possibly vertical ear canal ablation; must remove lesion with margin of normal tissue. ◦  Alternatives include photodynamic therapy (less predictable; multiple treatments may be required), cryosurgery (for small, superficial lesions), strontium plesiotherapy (superficial radiation therapy), electrochemotherapy with bleomycin, or curettage/diathermy. •  Ear canal/middle ear: ◦  Total ear canal ablation and bulla osteotomy is usually needed to achieve complete excision; lateral ear canal resection rarely achieves adequate control. ◦  Radiation therapy may be used for palliation of nonresectable tumors or postoperatively for microscopic disease.

Cats

•  Pinna: ◦  Trauma. ◦  Vasculitis. ◦  Cryoglobulinemia. •  Ear canal/middle ear: ◦  Inflammatory/nasopharyngeal polyp

◦  Etretinate 0.75–1 mg/kg PO q24h; can

­

 MEDICATIONS

DRUG(S) OF CHOICE •  Pinna (cat): ◦  Imiquimod 5% cream—apply topically q24-48h.

•  Pinna—prognosis good with complete

surgical excision; survival >1.5 years with complete pinnectomy. •  Ear canal tumors locally invasive (57–67%) and can recur locally despite surgery; prognosis is guarded. •  Dogs—median survival 5.3 months with bulla involvement compared to >58 months without. •  Cats—median survival 3.8 months; worse prognosis with bulla involvement; median survival 1.5 months with neurologic signs.

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 MISCELLANEOUS

SEE ALSO •  Ceruminous Gland Adenocarcinoma, Ear. •  Squamous Cell Carcinoma, Skin.

­Suggested Reading

Sula MJ. Tumors and tumorlike lesions of dog and cat ears. Vet Clin North Am Small Anim Pract 2012, 42:1161–1178. Author Alycen P. Lundberg Consulting Editor Timothy M. Fan Acknowledgment The author and editors acknowledge the prior contribution of Jackie M. Wypij.



1285

Canine and Feline, Seventh Edition

Squamous Cell Carcinoma, Gingiva •  Thoracic radiography—evaluate for

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 BASICS

OVERVIEW •  Malignant tumor of squamous epithelium. •  Rapid progression, locally invasive, highly osteo-invasive (77%). •  Most common oral malignancy in cats; one of most common oral malignancies in dogs. •  Approximately 10–20% metastasis in dogs and cats with potential involvement of draining lymph nodes (most common) and lung parenchyma.

pulmonary metastasis (uncommon in dogs, rare in cats). DIAGNOSTIC PROCEDURES

•  Cytology—fine-needle aspirate samples can

be sufficient, though ulceration, inflammation, and secondary infection may limit diagnostic utility. •  Deep tissue biopsy—beneficial to differentiate from other oral malignancies via histopathology. •  Cytology of regional lymph nodes to assess for regionally metastatic disease.

SIGNALMENT

•  Mean age (dogs/cats) 10.5 years. •  More common in medium and large-breed

­

 TREATMENT

dogs.

Dogs

SIGNS

hemi-mandibulectomy); usually well tolerated; margins of at least 2 cm necessary. •  Radiation therapy—effective for long-term control; curative-intent treatment used alone or in combination with surgery or chemotherapy. •  Chemotherapy—alone or in combination with other treatment modalities; toceranib phosphate (Palladia) exerts single-agent activity in a substantial fraction (biologic response) of dogs treated. •  Piroxicam may have some antineoplastic effects. •  Cryosurgery or electrochemotherapy— indicated for small lesions with no bone involvement. •  Photodynamic therapy—adjunct to surgery may be effective for local control of small tumors. •  Analgesics for pain or antibiotics for secondary bacterial infections may be indicated.

•  Radical surgical excision required (e.g.,

Historical Findings

•  Mass effect. •  Ptyalism. •  Dysphagia. •  Halitosis. •  Bloody saliva. •  Weight loss. •  Hyporexia or avoidance of hard foods/toys. •  Poor grooming (cats).

Physical Examination Findings

•  Erythematous, ulcerated, fleshy lesion. •  Loose teeth. •  Facial swelling or deformity. •  Exophthalmos. •  Pain on opening jaw.

CAUSES & RISK FACTORS Potential risk factors in cats include flea collars, canned food (tuna), and tobacco smoke.

­

 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Other oral malignancy—fibrosarcoma in cats; melanoma, fibrosarcoma, osteosarcoma in dogs. •  Epulis (acanthamatous, fibrous, ossifying). •  Tooth root abscess. •  Benign growth or polyp. •  Gingival hyperplasia (breed, e.g., boxer, or drug-induced, e.g., cyclosporine). •  Eosinophilic granuloma complex. IMAGING •  Skull radiography—evaluate potential bone involvement. •  High-detail dental radiography—more sensitive in evaluating local disease than skull radiography; best with mandibular masses. •  CT—ideal to evaluate soft tissue extension, bone invasion, regional lymph nodes, and for surgical planning.

Cats

•  Surgery—most tumors are inoperable;

small rostral lesions may be excised with wide 2–3 cm margins; cats do not tolerate aggressive oral surgery as well as dogs. •  Palliative treatments include coarse-fraction radiation therapy (2 cm diameter, older age, incomplete excision. •  Surgical excision—median survival 15–16 months, 34 months combined with radiation therapy; mandibulectomy better outcome than maxillectomy. •  Combination carboplatin and piroxicam with or without surgery—median survival >18 months (7 dogs). •  Piroxicam—17% response rate with a median progression-free interval of 3.5–6 months. Cats

•  1-year survival rate is 10% for multimodal

therapy.

•  In rare cases where surgery is an option,

median survival 1 year.

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 MISCELLANEOUS

SEE ALSO •  Melanocytic Tumors, Oral. •  Squamous Cell Carcinoma, Tongue. •  Squamous Cell Carcinoma, Tonsil.

­Suggested Reading

Biligic O, Duda L, Sanchez, MD, et al. Feline oral squamous cell carcinoma: clinical manisfestations and literature review. J Vet Dent 2015, 32(1):30–40. Author Alycen P. Lundberg Consulting Editor Timothy M. Fan Acknowledgment The author and editors acknowledge the prior contribution of Jackie M. Wypij.

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1286

Blackwell’s Five-Minute Veterinary Consult

Squamous Cell Carcinoma, Lung

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 BASICS

OVERVIEW •  Primary tumor of bronchial epithelium with squamous metaplasia. •  High metastatic potential to regional lymph nodes, pleural surface (carcinomatosis), pulmonary parenchyma, less commonly distant organs. •  Organ system—respiratory. SIGNALMENT

•  Dog and cat—mean age 11–12 years. •  Persian cats may be overrepresented for

pulmonary carcinomas.

SIGNS •  May be incidental finding on radiographs. •  Harsh, nonproductive cough. •  Dyspnea, tachypnea. •  Lethargy, exercise intolerance. •  Hemoptysis. •  Cachexia, weight loss. •  Vomiting, regurgitation, diarrhea (cats). •  Lameness: ◦  Distal limb swelling, pain (hypertrophic osteopathy). ◦  Digital lesions (cats).

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bronchograms; mild–moderate heterogeneous contrast enhancement. ◦  More sensitive than radiographs in detecting pulmonary and lymph node metastasis. •  Limb radiography: ◦  Digit metastases—bony lysis in the distal phalanx (cats, lung–digit syndrome). ◦  Hypertrophic osteopathy—periosteal proliferation, long bones. DIAGNOSTIC PROCEDURES

•  Cytology: ◦  Transthoracic fine-needle aspiration of

peripheral lesions; ultrasound or CT guidance may be needed. ◦  Pleural effusion or intrathoracic lymph node aspirates if primary lesion is not amenable to aspiration. ◦  Endoscopic bronchial brushing may be useful for centrally located lesions. ◦  Bronchoalveolar lavage and transtracheal wash: rarely diagnostic. •  Biopsy necessary for definitive diagnosis; may be obtained via keyhole biopsy, thoraco­ scopy, or thoracotomy. •  Potential complications of diagnostic procedures—pneumothorax, hemothorax, pleural effusion, infection, and iatrogenic tumor seeding (rare).

CAUSES & RISK FACTORS

•  Urban environment, second-hand smoke

suspected.

•  Laboratory dogs trained to smoke cigarettes

develop lung cancer.

­

 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Other primary lung neoplasia—adeno­ carcinoma, bronchoalveolar carcinoma, histiocytic sarcoma. •  Metastatic pulmonary neoplasia. •  Fungal granuloma. •  Abscess. •  Aspiration pneumonia. CBC/BIOCHEMISTRY/URINALYSIS Often unremarkable. IMAGING

•  Thoracic radiography (3-view): ◦  Most often in caudal lung lobes. ◦  Often a solitary mass, well-circumscribed

margins.

◦  May identify tracheobronchial lymphad-

enomegaly, pulmonary metastatic lesions, pleural effusion. ◦  May displace/compress trachea or mainstem bronchi. •  CT: ◦  Determines surgical resectability. ◦  Solitary, well-circumscribed, bronchocentric mass with internal air

­

 TREATMENT

•  Surgery—wide and complete resection of

affected lung lobe; biopsy lymph nodes even if they appear normal; lymph node extirpation when possible. In select cases, thoracoscopic surgery may be considered. •  Chemotherapy—potentially beneficial in adjuvant or palliative setting, intracavitary (IC) chemotherapy may be useful for carcino­ matosis/pleural effusion. •  Palliative medications—cough suppressants and antibiotic therapy for secondary bacterial infections.

­

 MEDICATION

DRUG(S) OF CHOICE •  Doxorubicin—dogs >10 kg, 30 mg/m2 IV; dogs 8 years. •  Photodynamic therapy (cats, superficial)— 96% response rate; often need multiple treatments; does not appear as effective as other therapies long term. •  Electrochemotherapy with bleomycin—risk of recurrence; many achieve complete remission. •  Curettage and diathermy—excellent response; risk of recurrence. •  Dogs (superficial tumors)—surgery alone may be curative. •  Dogs (invasive tumors)—in one study of 8 dogs, average survival time was 5.4 months; in another study of 17 dogs treated with surgery and/or radiation therapy, 70% of tumors recurred with a median survival time of 3–6 months.

­

­

PATHOLOGIC FINDINGS Lesions may vary in appearance depending on stage of disease in cats; typically ulcerative in cats; more likely proliferative in dogs.

SIGNALMENT

•  Common in cat; rare in dog. •  Mean age—cats, 8.5–12.1 years; dogs,

9–10 years.

•  More likely to develop in animals with a

lightly pigmented nose (cats).

•  No reported sex or breed predilection in cats. •  Dogs—overrepresentation of males and

Labrador retrievers in one study. SIGNS

•  Cats—slowly progressive lesion; may begin as

superficial crusting and scabbing, progress to carcinoma in situ, and develop into superficial and then invasive erosive carcinoma; other cutaneous sites may be affected (cats—multicentric squamous cell carcinoma in situ [MSCCIS]). •  Dogs—sneezing; epistaxis; swelling and ulceration of planum, proliferative lesion.

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CAUSES & RISK FACTORS

•  Exposure to ultraviolet light (UVB). •  Absence of protective pigment (cats).

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Infection/abscess. •  Trauma. •  Dermatitis (allergic, other). •  Eosinophilic granuloma complex (cats). •  Immune-mediated disease. •  Cutaneous lymphoma. •  Mast cell tumor. CBC/BIOCHEMISTRY/URINALYSIS Usually normal. IMAGING

•  Thoracic radiography—to evaluate for

­

 TREATMENT

•  Superficial tumors—surgery, cryosurgery,

 MEDICATIONS

DRUG(S) OF CHOICE •  Etretinate—cats, 0.75–1 mg/kg PO q24h; synthetic retinoid; may be useful for early precancerous lesions; may not be commercially available. •  Acitretin—cats, 1 mg/kg PO q24h can be used in place of etretinate. •  Imiquimod 5% cream for nasal planum lesions associated with MSCCIS—apply topically to affected lesions q24–48h; most cats respond but develop new lesions in other sites; these lesions often subsequently respond to topical therapy. CONTRAINDICATIONS/POSSIBLE INTERACTIONS Women who are pregnant or planning to become pregnant should not handle etretinate, acitretin, or imiquimod.

metastasis (rare).

•  CT scan—evaluate soft tissue extension and

bone invasion prior to surgical planning, essential for canine tumors in which extensive underlying structures are often involved. DIAGNOSTIC PROCEDURES

•  Cytology—fine-needle aspirate of primary

lesion may confirm diagnosis; however, ulceration, inflammation, and secondary infection may limit diagnostic utility. •  Biopsy and histopathology—a deep wedge or punch biopsy is often needed to definitively diagnose squamous cell carcinoma. Multiple samples recommended as lesion may have a spectrum of actinic changes ranging from squamous metaplasia to invasive carcinoma.

•  Survival with radiotherapy alone (cats)—

­

 FOLLOW-UP

PATIENT MONITORING •  Physical examination at 1 month, then every 3 months after treatment. •  Biopsy any new suspicious lesion. PREVENTION/AVOIDANCE

•  Limit sun exposure. •  Tattoos on nonpigmented areas may be

helpful.

EXPECTED COURSE AND PROGNOSIS

•  Prognosis—good for small, noninvasive

tumors; guarded for invasive tumors.

 MISCELLANEOUS

SEE ALSO •  Squamous Cell Carcinoma, Ear. •  Squamous Cell Carcinoma, Skin. ABBREVIATIONS

•  MSCCIS = multicentric squamous cell

carcinoma in situ.

­Suggested Reading

Jarrett RH, Norman EJ, Gibson IR, Jarrett P. Nose and nasal planum neoplasia, reconstruction. Vet Clin North Am Small Anim Pract 2016, 46(4):735–750. Author Alycen P. Lundberg Consulting Editor Timothy M. Fan Acknowledgment The author and editors acknowledge the prior contribution of Jackie M. Wypij.



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Canine and Feline, Seventh Edition

Squamous Cell Carcinoma, Skin IMAGING

•  Thoracic radiography—may detect lung

­

 BASICS

OVERVIEW •  Malignant tumor of squamous epithelium. •  Multicentric squamous cell carcinoma in situ (MSSCIS)- also called Bowen’s-like disease or Bowenoid carcinoma in situ (cats). •  Local disease may progress from carcinoma in situ to invasive carcinoma. •  Metastasis is uncommon—most common sites are regional lymph nodes and lungs. •  Systems affected—skin/exocrine. •  Represents 9–25% of all skin tumors in cats; 4–18% in dogs. •  Solar-induced (actinic) SCC is more prevalent in sunny climates and high altitudes. SIGNALMENT

metastasis (rare).

•  Abdominal ultrasonography—evaluate and

monitor sublumbar lymph nodes if skin disease involves the caudal half of the patient.

DIAGNOSTIC PROCEDURES •  Cytology or histopathology of lesion— ulceration, inflammation, and secondary infection may limit diagnostic utility of cytology. A deep wedge or punch biopsy is often needed to definitively diagnose cutaneous SCC. Multiple samples recommended as actinic form may encompass spectrum from actinic changes to carcinoma. •  Cytology of lymph nodes to identify presence of regional metastasis.

•  Cats, mean age 9–10 years; often have

light/unpigmented skin.

•  Dogs, mean age 8 years; Scottish terrier,

Pekingese, boxer, poodle, Norwegian elkhound, Dalmatian, beagle, whippet, and white English bull terrier may be predisposed. SIGNS

•  Proliferative or erosive skin lesions. •  Solar-induced lesions in cats—nasal

planum, eyelids, lips, and pinna.

•  MSCCIS may occur in any site, unrelated

to sun exposure or skin pigmentation; may note 2–30+ lesions on the head, digits, neck, thorax, shoulders, and ventral abdomen; hair in the lesion epilates easily; crusts cling to the epilated hair shaft. •  Dogs—most commonly affects toes, scrotum, nose, legs, and anus. CAUSES & RISK FACTORS

•  Ultraviolet irradiation (actinic form). •  Papillomaviruses may play a role. •  Light/nonpigmented skin. •  Previous thermal injury. •  Risk factors for MSCCIS in cats are

undetermined but may be associated with immunosuppression.

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 TREATMENT

•  Superficial tumors suspected to be

solar-induced—wide surgical excision may be locally curative; other treatment options include cryosurgery, photodynamic therapy, or strontium-90 plesiotherapy. •  Invasive tumors—require aggressive surgical excision, external-beam radiation therapy has shown effectiveness. •  MSCCIS may be treated with curativeintent surgery for local control; however, most cats develop new lesions in other sites; treatment with immune-modulating drugs (imiquimod) may be most effective. •  Adjunctive chemotherapy—recommended with incomplete surgical excision, nonresectable mass, and metastasis. •  Electrochemotherapy (bleomycin) and curettage with diathermy may be effective. Nursing Care

•  Analgesics as needed. •  Antibiotic therapy if secondary skin

 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Infection/abscess. •  Dermatophytosis. •  Trauma. •  Dermatitis. •  Eosinophilic granuloma complex. •  Immune-mediated disease. •  Cutaneous lymphoma. •  Mast cell tumor. CBC/BIOCHEMISTRY/URINALYSIS Usually normal.

CONTRAINDICATIONS/POSSIBLE INTERACTIONS Cisplatin—never use in cats; nephrotoxic in dogs. Alternative Drug(s)

Topical synthetic retinoids (e.g., tretinoin)may be useful for early solar-induced superficial lesions; may be irritating to skin.

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 FOLLOW-UP

PATIENT MONITORING •  Physical examination 1 month after resolution of tumor, then every 3 months after treatment. •  Thoracic radiography and lymph node evaluation at each 3-month recheck examination; abdominal ultrasound if the lesion is on the caudal portion of the patient. PREVENTION/AVOIDANCE

•  Limit sun exposure. •  Tattoos on nonpigmented areas may be helpful.

EXPECTED COURSE AND PROGNOSIS Prognosis—good with superficial lesions that receive appropriate treatment; guarded with invasive lesions, advanced stage of disease, or recurrent lesions.

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 MISCELLANEOUS

SEE ALSO •  Squamous Cell Carcinoma, Ear. •  Squamous Cell Carcinoma, Nasal Planum. ABBREVIATIONS

infections.

•  MSCCIS = multicentric squamous cell

Client Education

•  SCC = squamous cell carcinoma.

development of the tumor.

­Suggested Reading

•  Discuss UV risk factors associated with the

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•  Carboplatin—dogs, 300 mg/m2 IV q3 weeks; cats, 200–250 mg/m2 IV q3–4 weeks for 4–5 treatments. •  Mitoxantrone—dogs and cats, 5–6 mg/m2 IV q3 weeks for 4–5 treatments.

•  Most cats with MSCCIS will develop new

lesions in other sites.

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 MEDICATIONS

DRUG(S) OF CHOICE •  Imiquimod 5% cream for MSCCIS—topically to affected lesions q24–48h; most cats respond but develop new lesions in other sites. •  Cisplatin—dogs, 60 mg/m2 IV q3 or 4 weeks for 4 treatments.

carcinoma in situ.

Murphy S. Cutaneous squamous cell carcinoma in the cat: current understanding and treatment approaches. J Feline Med Surg 2013, 15(5):401–407. Author Alycen P. Lundberg Consulting Editor Timothy M. Fan Acknowledgment The author and editors acknowledge the prior contribution of Jackie M. Wypij.  Client Education Handout available online

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Blackwell’s Five-Minute Veterinary Consult

Squamous Cell Carcinoma, Tongue •  Thoracic radiography—three-view required

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 BASICS

•  Cytology—fine-needle aspirate or

SIGNALMENT

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large-breed dogs most commonly affected. SIGNS

Historical Findings

•  Ptyalism. •  Halitosis. •  Dysphagia. •  Oral bleeding. •  Decreased appetite. •  Weight loss. •  Poor grooming (cats).

Physical Examination Findings

•  Incidental finding. •  Tongue mass—variable appearance, often

nodular and ulcerated.

•  Intramandibular swelling (cats). •  Cervical lymphadenomegaly—occasionally.

CAUSES & RISK FACTORS Potential increased risk of feline oral squamous cell carcinoma (SCC) associated with flea collars, canned food (particularly tuna), and possibly exposure to tobacco smoke.

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Other lingual malignancy (melanoma, sarcoma, mast cell tumor, plasmacytoma, lymphoma, hemangiosarcoma, granular cell tumor). •  Trauma. •  Ulcerative glossitis. •  Benign lesion (papilloma). •  Infection/abscess. CBC/BIOCHEMISTRY/URINALYSIS Usually normal. IMAGING

•  Advanced imaging with CT or MRI

provides greatest information regarding extent of disease.

CONTRAINDICATIONS/POSSIBLE INTERACTIONS N/A

DIAGNOSTIC PROCEDURES

OVERVIEW •  Malignant tumor of squamous epithelium. •  Rare tumor that occurs more commonly in cats than in dogs. •  Usually grows rapidly. •  Cats—most common lingual neoplasia, often progresses locally prior to clinical evidence of metastasis. •  Dogs—one of most common malignant lingual neoplasias (25–32%); variably metastatic by way of lymphatic vessels to regional lymph nodes and lungs (0–43%). •  Organ system—gastrointestinal. •  Cats—middle-aged or older (>7 years). •  Dogs—average 10–11 years; female

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to evaluate lungs for metastasis; more common in dogs.

impression smear from incisional biopsy (wedge); may yield diagnosis; however, ulceration, inflammation, and secondary infection may limit diagnostic utility. •  Deep wedge tissue biopsy—necessary for definitive diagnosis. •  Cytology and/or lymph node biopsy to evaluate for regional metastasis; more common in dogs.

 TREATMENT

•  Surgical—generally inoperable in cats;

aggressive excision warranted in dogs; function of the tongue after recuperation is usually acceptable in dogs, but will require changes in husbandry practices. •  Postsurgical care (e.g., esophagostomy) by owner often required. •  Partial glossectomy—may be performed on the rostral half (mobile tongue) or longitudinal half of the tongue (40–60% removed); ~35–50% of patients have incomplete surgical margins. •  Subtotal glossectomy may be considered in select cases. •  Other surgical methods (e.g., electrocautery and cryosurgery) do not offer additional advantage to conventional excision. •  Response to radiotherapy—poor (10 kg, 30 mg/m2 IV; dogs 5 years of age. SYNONYMS •  Aseptic meningitis. •  Canine juvenile polyarteritis syndrome. •  Corticosteroid-responsive meningomyelitis. ABBREVIATIONS

•  CRP = C-reactive protein. •  NSAID = nonsteroidal anti-inflammatory

drug.

­Suggested Reading

Biedermann E, Tipold A, Flegel T. Relapses in dogs with steroid-responsive meningitisarteritis. J Small Anim Pract 2016, 57:91–95. Author Andrea Tipold



1295

Canine and Feline, Seventh Edition

Stertor and Stridor Breed Predilections

•  Common in brachycephalic dogs and less

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 BASICS

DEFINITION •  Abnormally loud sounds that result from air passing through a narrowed nasopharynx, pharynx, larynx, or trachea. •  Discontinuous sounds heard without a stethoscope. •  Stertor—low-pitched snoring sound that usually arises from the vibration of flaccid tissue or fluid; usually arises from nasal or pharyngeal airway obstruction. •  Stridor—higher pitched sounds that result when relatively rigid tissues are vibrated by the passage of air; result of partial or complete obstruction of the larynx or cervical trachea. PATHOPHYSIOLOGY •  Airway obstruction causes turbulence as air travels through a narrowed passage; with worsening obstruction or increasing airflow velocity, the amplification of airway sounds occur due to increased turbulence and vibration of tissue, secretions, or foreign bodies. •  Obstruction sufficient to increase the work of breathing augments respiratory muscle effort and exacerbates turbulence; inflammation and edema of tissues in the region of the obstruction may develop, further reducing the airway lumen and further increasing the work of breathing, creating a vicious cycle. •  Complete airway obstruction will result in the lack of sounds. •  Obesity further increases respiratory effort and exacerbates airway obstruction. SYSTEMS AFFECTED Respiratory GENETICS

•  Brachycephalic obstructive airway

syndrome is heritable in many breeds, including English and French bulldogs, pugs, Boston terriers, shih tzus, and other brachycephalic breeds. •  Congenital laryngeal paralysis has been identified in bouvier des Flandres, bull terriers, Siberian huskies, Alaskan Malamutes, and white-coated German shepherd dogs. Dalmatians, Rottweilers, Leonbergers, and Pyrenees mountain dogs. •  Older large breed dogs (e.g., Labrador retrievers) commonly develop laryngeal paralysis as part of a geriatric-onset laryngeal paralysis polyneuropathy complex. INCIDENCE/PREVALENCE Common GEOGRAPHIC DISTRIBUTION Worldwide SIGNALMENT Species

Dog more than cat.

so cats

•  Acquired laryngeal paralysis—overrepre-

sented in certain giant breeds (e.g., Saint Bernard and Newfoundlands) and large breeds (e.g., Irish setters, Labrador retrievers, and golden retrievers). •  Cats of any breed due to nasopharyngeal polyps, inflammatory or neoplastic laryngeal diseases, or laryngeal paralysis (the latter far less common in cats than dogs). Mean Age and Range

•  Affected brachycephalic animals and dogs

or cats with inherited laryngeal paralysis are typically younger than 1 year of age when owners detect a problem. •  Acquired laryngeal paralysis typically occurs in older dogs and cats. Predominant Sex

No sex predilection for any cause, although inherited laryngeal paralysis has a 3:1 male predominance. SIGNS •  Change or loss of voice. •  Partial obstruction—produces an increase in airway sounds before producing an obvious change in respiratory pattern or gas exchange. •  Owners may indicate that the sound has existed for as long as several years. •  Breath sounds audible from a distance without a stethoscope—suspect narrowing of upper airway. •  Nature of the sound—ranges from abnormally loud to obvious fluttering to high-pitched squeaking, depending on the degree of airway narrowing. •  Stress or exercise may amplify the sound or induce respiratory distress. •  May note increased respiratory effort and paradoxical respiratory movements (chest wall collapses inward during inspiration and springs outward during expiration) when the effort is extreme; respiratory motions often accompanied by obvious postural changes (e.g., abducted forelimbs, extended head and neck, and open-mouth breathing). CAUSES

•  Brachycephalic airway syndrome (stenotic

nares, elongated soft palate, everted laryngeal saccules, laryngeal collapse). •  Laryngeal paralysis—inherited or acquired. •  Laryngeal neoplasia—benign or malignant. •  Granulomatous/inflammatory laryngitis. •  Tracheal collapse, stenosis, obstruction, neoplasia, foreign body. •  Nasopharyngeal polyp, stenosis, foreign body. •  Cervical bite wounds. •  Acromegaly. •  Neuromuscular dysfunction. •  Anesthesia or sedation—only if predisposing anatomy exists. •  Cleft palate. •  Aplasia of soft palate. •  Redundant pharyngeal mucosal folds. •  Soft palate mass.

•  Edema or inflammation of the palate, pharynx, and larynx (including everted mucosal lining of the laryngeal ventricles)—secondary to coughing, vomiting or regurgitation, turbulent airflow, upper respiratory infection, and hemorrhage. •  Secretions (e.g., pus, mucus, and blood) in the airway lumen.

RISK FACTORS

•  High ambient temperature or humidity. •  Fever. •  High metabolic rate—as occurs with

hyperthyroidism or sepsis.

•  Exercise. •  Anxiety or excitement. •  Any respiratory or cardiovascular disease

that increases ventilation.

•  Turbulence caused by the increased airflow

can lead to swelling and worsen the airway obstruction. •  Hypothyroidism or polyneuropathy. •  Obesity.

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Systematically auscultate over the nose, pharynx, larynx, and trachea to identify the point of maximal intensity of any abnormal sound and to identify the phase of respiration when it is most obvious. •  Important to identify the anatomic location from which the abnormal sound arises and to seek exacerbating causes (see Risk Factors; e.g., a chronic airway obstruction may become manifest when the patient is exposed to extremely high ambient temperatures). •  Must differentiate sounds of pharyngeal, laryngeal, and tracheal narrowing from sounds arising elsewhere in the respiratory system. •  Nasal and tracheal narrowing and severe or extensive narrowing of the bronchi—can cause increased respiratory sounds. •  If the sound persists when the patient opens its mouth, a nasal cause can virtually be ruled out. •  If the owner describes a change in voice, the larynx is the likely abnormal site. OTHER LABORATORY TESTS Arterial blood gases—help characterize the degree of respiratory compromise (e.g., degree of hypoxemia, hypercapnia, or acid–base disturbances). IMAGING

•  Lateral radiographs of the head and

neck—may help identify abnormal soft tissues of the airway (e.g., elongated soft palate or a nasal polyp); limited use for identifying laryngeal paralysis, although experienced radiographers can identify abnormally dilated or swollen laryngeal saccules; cartilaginous destruction is suggestive of neoplasia or granulomatous laryngitis; may detect external masses compressing the upper airway.

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1296

Blackwell’s Five-Minute Veterinary Consult

Stertor and Stridor •  Radiography and fluoroscopy—important

for assessing the cardiorespiratory system; rule out other or additional causes of respiratory difficulty; such conditions may add to an underlying upper airway obstruction, causing a subclinical condition to become clinical. •  Ultrasound can be used to assess laryngeal structure and function, can also be used to document cervical tracheal collapse but air is a poor acoustic window. •  CT can be used to provide additional anatomic detail. DIAGNOSTIC PROCEDURES Laryngoscopy

•  Definitive diagnostic tests for direct visuali­

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zation of pharyngeal or laryngeal changes. •  Requires sedation that preserves laryngeal function. Recommend propofol 4–8 mg/kg IV to effect. •  The patient’s ability to use muscles to open the airway is compromised by anesthesia; be prepared to correct any lesions found, at a minimum, be prepared to intubate. •  If correctable conditions are not identified and corrected—patient’s recovery from anesthesia can be complicated by severe airway obstruction; must be prepared to perform a tracheotomy if airway is obstructed and a definitive surgical remedy cannot be pursued immediately. •  Assess timing and degree of movement of the arytenoids during light anesthesia—laryngeal paralysis results in lack of abduction of the arytenoids during inspiration. Use doxapram 1–2 mg/kg IV to stimulate respiration if needed. •  Normal palate—thin; just barely overlaps the tips of the epiglottis; easily displaced dorsally using the blade of the laryngoscope. •  Overlong soft palate—thick; usually inflamed; may lie 1 cm or more past the tip of the epiglottis.

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 TREATMENT

APPROPRIATE HEALTH CARE •  Inpatient management required for surgical treatment. •  Closely monitor effects of sedatives; sedatives can relax the upper airway muscles and worsen the obstruction; be prepared with emergency methods for securing the airway if complete obstruction occurs. •  In cases of suspected laryngeal paralysis resulting in respiratory distress and partial obstruction in dogs, sedation with butorphanol 0.2–0.3 mg/kg and acepromazine 0.025–0.05 mg/kg with oxygen supplementation and active cooling measures if hyperthermic may be indicated. •  If available, use of high-flow oxygen nasal cannulation has been successful to treat partial airway obstruction. •  Severe or complete airway obstruction— attempt an emergency intubation; if obstruction prevents intubation, emergency tracheostomy or passage of a tracheal catheter to administer oxygen may be the only

(continued)

available means for sustaining life; a tracheal catheter can briefly sustain oxygenation while a more permanent solution is sought. NURSING CARE

•  Treatment requires removal of obstruction,

PRECAUTIONS Sedatives, analgesics, and anesthetics—avoid excessive suppression of laryngeal movement and respiratory suppression to avoid aspiration in animals with laryngeal disease.

supplemental oxygen is variably helpful.

•  IV fluids may be required, particularly if

hyperthermia develops from increased work of breathing. •  Active cooling measures (ice packs in axilla and groin region, alcohol on foot pads, chilled IV fluids) helpful in alleviating hyperthermia but not indicated for fever. ACTIVITY Keep patient cool, quiet, and calm—anxiety, exertion, and pain lead to increased ventilation, potentially worsening the obstruction. DIET

•  NPO if anesthesia is planned. •  Dietary management to avoid obesity, a

known risk factor for developing airway obstruction and associated stertor or stridor. CLIENT EDUCATION Inform client that the patient can make the transition from being a noisy breather to having an obstructed airway in a few minutes or even seconds. SURGICAL CONSIDERATIONS

•  Laryngoscopy and bronchoscopy for foreign

body retrieval and biopsy of laryngeal region and tracheal lumen. Use of small balloon catheters passed beyond the foreign body prior to expansion may be useful in removing some objects. •  Take particular care when inducing general anesthesia or when using sedatives in any patient with upper airway obstruction. •  Surgery—indicated to obtain a diagnosis through biopsy with histopathology, to manage obstruction while awaiting histopathology results or resolution of inflammation/infection (e.g., tracheotomy), or to resolve disease by excision, correction of obstructive lesion, and removal of foreign bodies.

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 MEDICATIONS

DRUG(S) OF CHOICE •  Medical approaches—appropriate only if the underlying cause is infection, edema, inflammation, or hemorrhage; anatomic or neurologic causes are not amenable to medical treatment. •  Steroids—may be indicated if edema or inflammation is thought to be an important contributor; effect with IV administration of a short-acting glucocorticoid such as dexamethasone sodium phosphate (1 mg/kg prednisone equivalent) should be apparent in the first several hours. Single dose may be sufficient, or a tapering dose might be required. Inflammatory laryngitis often requires higher doses administered over a longer dosing schedule with taper of the dose according to resolution of clinical signs.

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 FOLLOW-UP

PATIENT MONITORING Respiratory rate and effort need to be closely monitored. When owner chooses to take an apparently stable patient home, or if continual observation is not feasible, inform client that complete obstruction could occur. PREVENTION/AVOIDANCE Advise client to avoid exercise, high ambient temperatures, and extreme excitement. POSSIBLE COMPLICATIONS Serious complications may occur without therapy to relieve the obstruction; these include airway edema, pulmonary edema (may progress to life-threatening acute lung injury), and hypoventilation; may require tracheotomy and/or artificial ventilation. EXPECTED COURSE AND PROGNOSIS •  Varies with underlying cause. •  Even with surgical treatment, some degree of obstruction may remain for 7–10 days due to swelling.

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 MISCELLANEOUS

ASSOCIATED CONDITIONS Peripheral neuropathy often associated with laryngeal paralysis. SYNONYMS Snoring SEE ALSO •  Brachycephalic Airway Syndrome. •  Hypothyroidism. •  Laryngeal Diseases. •  Myasthenia Gravis. •  Nasal and Nasopharyngeal Polyps. •  Tracheal Collapse.

­Suggested Reading

MacPhail C. Laryngeal disease in dogs and cats. Vet Clin Small Anim 2014, 44:19–31. Sumner C, Rozanski EA. Management of respiratory emergencies in small animals. Vet Clin Small Anim 2013, 43:799–815. Author Sean B. Majoy Consulting Editor Elizabeth Rozanski Acknowledgment The author and editors acknowledge the prior contribution of James C. Preuter.  Client Education Handout available online



1297

Canine and Feline, Seventh Edition

Stomatitis and Oral Ulceration ◦  Cat—squamous cell carcinoma;

­

 BASICS

DEFINITION •  Stomatitis—an inflammation of the tissues of the oral cavity, more specifically defined below. •  Ulceration—focal or multifocal loss of mucosal integrity of the superficial epithelial layers in specific areas of the oral cavity. •  American Veterinary Dental College Nomenclature—oral and oropharyngeal inflammation is classified by location as: ◦  Stomatitis—inflammation of the mucous lining of any of the structures in the mouth; in clinical use the term should be reserved to describe widespread oral inflammation (beyond gingivitis and periodontitis) that may also extend into submucosal tissues (e.g., marked caudal mucositis extending into submucosal tissues may be termed caudal stomatitis). ◦  Gingivitis—inflammation of gingiva. ◦  Periodontitis—inflammation of nongingival periodontal tissue (i.e., the periodontal ligament and alveolar bone). ◦  Alveolar mucositis—inflammation of alveolar mucosa. ◦  Sublingual mucositis—inflammation of mucosa on the floor of the mouth. ◦  Labial/buccal mucositis—inflammation of the lip/cheek mucosa. ◦  Caudal mucositis—inflammation of mucosa of the caudal oral cavity. ◦  Contact mucositis and contact mucosal ulceration (“contact ulcers” and “kissing ulcers”)—lesions in susceptible individuals that are secondary to mucosal contact with a tooth surface bearing the responsible irritant, allergen or antigen. ◦  Palatitis—inflammation of mucosa covering the hard and/or soft palate. ◦  Glossitis—inflammation of mucosa of the dorsal and/or ventral tongue surface. ◦  Cheilitis—inflammation of the lip (including the mucocutaneous junction area and skin of the lip). ◦  Osteomyelitis—inflammation of the bone and bone marrow. ◦  Tonsilitis—inflammation of the palatine tonsil(s). ◦  Pharyngitis—inflammation of the pharynx. PATHOPHYSIOLOGY •  Metabolic: ◦  Diabetes mellitus. ◦  Hypothyroidism. ◦  Renal disease—uremia. •  Nutritional: ◦  Protein-calorie malnutrition. ◦  Riboflavin deficiency. •  Neoplastic: ◦  Dog—malignant melanoma; squamous cell carcinoma; fibrosarcoma.

fibrosarcoma; malignant melanoma. •  Immune-mediated: ◦  Pemphigus vulgaris—90% have oral involvement. ◦  Bullous pemphigoid—80% have oral involvement. ◦  Systemic lupus erythematosus—50% have oral involvement. ◦  Discoid lupus erythematosus. •  Drug-induced—toxic epidermal necrolysis, erythema multiforme. •  Infectious: ◦  Retrovirus—feline leukemia virus/feline immunodeficiency virus (FeLV/FIV). ◦  Calicivirus—cat. ◦  Herpesvirus—cat. ◦  Leptospirosis—dog. ◦  Periodontal disease—dog and cat. •  Traumatic: ◦  Foreign body—bone or wood fragments. ◦  Electric cord shock. ◦  Malocclusion. ◦  Gum-chewer’s disease—chronic chewing of cheek or sublingual mucosa. •  Chemical/toxic: ◦  Acids—etching gels for dental procedures (37% phosphoric acid). ◦  Bases: hypochlorite, cleaning solutions. ◦  Thallium. •  Idiopathic: ◦  Eosinophilic granuloma—cats, Siberian huskies, Samoyeds. ◦  Feline stomatitis—cats; feline chronic gingivostomatitis (FCGS). ◦  Canine ulcerative stomatitis—dogs; allergic, hypersensitivity reaction to plaque. ◦  Idiopathic osteomyelitis—dogs. SYSTEMS AFFECTED Gastrointestinal (oral). INCIDENCE/PREVALENCE Variable SIGNALMENT Species

Dogs and cats of any age and either sex. Breed Predilections

•  Breed predilection for canine ulcerative

stomatitis (aka chronic ulcerative paradental stomatitis [CUPS])—Maltese, cavalier King Charles spaniels, cocker spaniels, bouvier des Flandres. •  Feline stomatitis—FCGS may have predilection for Somali and Abyssinian cats. •  Idiopathic osteomyelitis—may have predilection for cocker spaniels; complication associated with canine ulcerative stomatitis. Mean Age and Range

Any age.

Predominant Sex

Either gender.

SIGNS Historical Findings

•  History and oral examination—foreign

bodies; malocclusions; chemical, toxic, and electrical burns. •  Idiopathic conditions—clinical signs; history; breed predispositions; response to therapy. •  Anorexia. •  Behavior changes secondary to oral sensitivity. •  Note: In canine ulcerative stomatitis, occasionally these signs will start following a routine dental cleaning on a previously “normal” patient; probably would have occurred eventually, just exacerbated by manipulation in the oral cavity. Physical Examination Findings

•  Halitosis. •  Gingivitis. •  Pharyngitis. •  Buccitis/buccal mucosal ulceration. •  Hypersalivation (thick, ropey saliva). •  Pain. •  Contact mucosal ulceration or contact

mucositis—“kissing ulcers” common in canine ulcerative stomatitis. •  Plaque—with or without calculus. •  Exposed, necrotic bone—with alveolar osteitis and idiopathic osteomyelitis. •  Scar formation on lateral margins of tongue—with canine ulcerative stomatitis.

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS See Causes. CBC/BIOCHEMISTRY/URINALYSIS •  CBC, biochemistry, urinalysis, and thyroxine (T4)—diabetes mellitus, renal disease, hypothyroidism, infections, and for preoperative considerations. •  Chronic conditions may have elevated serum total protein and elevated globulin levels due to chronic antigen stimulation; T4 may be decreased secondarily. OTHER LABORATORY TESTS •  Serology—FeLV/FIV test; titers for specific infections. •  Cultures—usually nonspecific; oral flora contaminants. IMAGING Radiography—helps determine bony involvement, and other conditions such as periodontal disease or tooth resorption, and extent of idiopathic osteomyelitis. DIAGNOSTIC PROCEDURES Biopsy/cytology—neoplasia, immune-mediated disease, and chronic inflammation result in predominant lymphocytes and plasmocytes (in canine ulcerative stomatitis and feline stomatitis). PATHOLOGIC FINDINGS See definitions above.

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1298

Blackwell’s Five-Minute Veterinary Consult

Stomatitis and Oral Ulceration •  Anti-inflammatory/immunosuppressive

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 TREATMENT

APPROPRIATE HEALTH CARE Underlying metabolic or other disease—treat systemic illness appropriately. NURSING CARE Supportive therapy—soft diet; fluids; hospitalization in severe cases. DIET •  Nutritional support—via pharyngostomy or esophagostomy feeding tube. •  May consider hypoallergenic diet. CLIENT EDUCATION •  Canine ulcerative stomatitis—continuous, meticulous home care to prevent plaque accumulation; dental cleaning initially and frequently; periodontal therapy; extraction of diseased teeth. •  Warn client that prognosis is guarded, response to therapy depends on underlying cause, and prolonged treatment and/or further extractions may be necessary. •  In canine ulcerative stomatitis or feline stomatitis, any level of home care that can be provided is encouraged (brushing or topical antimicrobials). SURGICAL CONSIDERATIONS •  Select extractions (partial, caudal, or full mouth)—may be indicated for chronic idiopathic conditions (e.g., canine ulcerative stomatitis and feline stomatitis) to remove the source of reaction (plaque/teeth). •  Removal of entire tooth structure is important. •  Removal of necrotic/avascular bone, gingival flap closure, and broad-spectrum antibiotics—indicated for idiopathic osteomyelitis; monitor for recurrence.

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 MEDICATIONS

DRUG(S) OF CHOICE •  Antimicrobials—treat primary and secondary bacterial infections; may be used intermittently between cleanings for therapeutic assistance, but the owner must be cautioned that chronic use could lead to antibiotic resistance; clindamycin 11 mg/kg PO q12h; amoxicillin– clavulanate 12.5–25 mg/kg PO q12h; tetracycline 10–22 mg/kg PO q8h.

drugs—the comfort of the patient must be weighed against potential long-term side effects of corticosteroid usage; prednisone 0.5–1.0 mg/kg q12–24h PO, taper dosage: ◦  For eosinophilic granuloma—prednisolone 2–4.4 mg/kg PO once a day; for chronic cases use 0.5–1.0 mg/kg PO every other day. ◦  Cyclosporine 5 mg/kg PO q24h. Therapeutic serum levels after 6 weeks if no response to therapy. •  Mucosal protectants—for chemical insults; sucralfate 1 g/25 kg q8h PO; cimetidine 5–10 mg/kg q8–12h PO. •  Analgesics—carprofen 0.5 mg/kg PO q12–24h; hydrocodone 0.22 mg/kg q8–12h; tramadol 2.2–4.4 mg/kg PO q6–12h; gabapentin 5–10 mg/kg PO SID. •  Topical therapy—chlorhexidine solution or gel (antibacterial); zinc gluconate/ascorbic acid; stabilized chlorine dioxide for halitosis. •  Appropriate antimicrobial and pain management therapy when indicated. •  Appropriate patient monitoring and support during anesthetic procedures. CONTRAINDICATIONS Corticosteroids are contraindicated in patients with systemic fungal infections. PRECAUTIONS

•  Some antimicrobials may upset the

gastrointestinal tract.

•  Avoid corticosteroids in patients that may

already be immunocompromised (i.e., those with FeLV or FIV). •  Do not use these medications in patients with known hypersensitivities.

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 FOLLOW-UP

PREVENTION/AVOIDANCE Optimal home care and regular professional cleaning and treatment is essential.

­

 MISCELLANEOUS

ASSOCIATED CONDITIONS Idiopathic osteomyelitis may occur in some canine ulcerative stomatitis patients (see above).

(continued)

ZOONOTIC POTENTIAL N/A, unless immunocompromised individuals. SYNONYMS

•  Chronic ulcerative paradental stomatitis

(CUPS).

•  Ulcerative stomatitis. •  Gingivostomatitis. •  Vincent’s stomatitis. •  Necrotizing stomatitis.

SEE ALSO Feline Stomatitis—Feline Chronic Gingivosomatitis (FCGS). ABBREVIATIONS

•  CUPS = chronic ulcerative paradental

stomatitis.

•  FCGS = Feline chronic gingivostomatitis. •  FeLV = feline leukemia virus. •  FIV = feline immunodeficiency virus. •  T4 = thyroxine.

INTERNET RESOURCES https://avdc.org/avdc-nomenclature/

­Suggested Reading

Harvey CE. Veterinary Dentistry. Philadelphia, PA: Saunders, 1985. Lobprise HB, Wiggs RB. The Veterinarian’s Companion for Common Dental Procedures. Lakewood, CO: AAHA Press, 2000. Manfra Maretta S, Brine E, Smith CW, et al. Idiopathic mandibular and maxillary osteomyelitis and bone sequestra in cocker spaniels. In: Proceedings of the Veterinary Dental Forum, Denver, CO, 1997; sponsored by the American Veterinary Dental College, Academy of Veterinary Dentistry, and the American Veterinary Dental Society. Smith MM. Oral and salivary gland disorders. In: Ettinger SJ, ed., Textbook of Veterinary Internal Medicine, 5th ed. Philadelphia, PA: Saunders, 2000, pp. 1114–1121. Wiggs RB, Lobprise HB. Veterinary Dentistry Principles & Practice. Philadelphia, PA: Lippincott-Raven, 1997. Author R. Michael Peak Consulting Editor Heidi B. Lobprise



1299

Canine and Feline, Seventh Edition

Streptococcal Infections •  Coinfection with canine influenza virus

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 BASICS

OVERVIEW •  Streptococcus—Gram-positive, nonmotile, facultatively anaerobic spherical bacteria (cocci): ⚬  Commensal organisms; normal flora of the upper respiratory tract, oropharynx, lower genital tract, and skin. ⚬  Under appropriate conditions, capable of infecting all areas of body; frequent secondary invader of body tissues. •  Classified by ability to hemolyze red blood cells on blood agar plates: ⚬  α-Hemolytic (green zone of partial hemolysis). ⚬  β-Hemolytic (clear zone of hemolysis); usually more pathogenic than α-hemolytic, which is more pathogenic than nonhemolytic strains. ⚬  γ-Hemolytic (no change; nonhemolytic). •  Hemolytic strains further subdivided by differences in cell walls (Lancefield serogroups A–H and K–T); some groups more likely to be associated with disease: ⚬  Group G is associated with cats and dogs; group A with humans). ⚬  Many group D streptococci reclassified as enterococci. •  Produce exotoxins—streptolysins (hemolysins), streptokinases, deoxyribonucleases, and hyaluronidases. •  Adhesins to bind extracellular matrix proteins. SIGNALMENT

•  Dogs and cats. •  Very young—more prone to infection

because of incomplete immunity; particularly kittens born to primiparous queen. SIGNS

•  Vary with site of infection and host

immunocompetence. Sites of infection can include abscesses, genitourinary tract, ears, septicemia (e.g., toxic shock syndrome), joints, lungs, heart valves, lymph nodes, CNS, wounds (e.g., necrotizing fasciitis), tonsil/pharynx, or skin, and may result in abortion, fading puppies/kittens, or bitch/ queen sterility. •  Weakness. •  Coughing. •  Dyspnea. •  Fever. •  Hematemesis. •  Hematuria. •  Lymphadenopathy. •  Pain. CAUSES & RISK FACTORS

•  Age, exposure, and immune response

determine disease severity. •  Virulence—depends on specific organism. •  Opportunistic—surgical or traumatic wounds, viral infections, atopic dermatitis, immunosuppressive conditions.

increases disease severity. Other predisposing conditions—feline leukemia virus, feline infectious peritonitis, immunodeficiency, respiratory viral infections, feline lower urinary tract disease. •  Maternal antibodies generally protect neonates. •  Carrier state occurs. •  Bacterial superantigens may contribute to toxic shock syndrome and necrotizing fasciitis; enrofloxacin-induced bacteriophages may enhance superantigen expression.

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS Other infectious causes—viruses, bacteria, fungi, Rickettsia, protozoa. CBC/BIOCHEMISTRY/URINALYSIS •  Normal or high leukocytes with neutrophilia and left shift or degenerative left shift. •  Cocci—in circulating neutrophils if overwhelming sepsis. •  Biochemistry—suggests predisposing conditions. •  Urinalysis—pyuria (with or without bacteruria). OTHER LABORATORY TESTS •  Direct microscopy. •  Gram stain—of exudates; Gram-positive cocci in chains or singlets. •  Culture and susceptibility testing —affected tissues, exudate or needle aspirates. •  PCR. IMAGING Radiographs—interstitial or alveolar pulmonary pattern (pneumonia); radiodense uroliths (struvite). PATHOLOGIC FINDINGS

•  Acute inflammation—gross or microscopic

abscesses. •  Septicemia—omphalophlebitis, peritonitis, hepatitis, pneumonia, myocarditis.

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 TREATMENT

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 MEDICATIONS

•  Good nursing care. •  Rehydrate. •  Drain and flush abscess. •  Debride necrotic tissue.

DRUG(S) OF CHOICE •  Ampicillin 22–30 mg/kg IV, IM, SC, PO q8h; combined with aminoglycoside (gentamicin or amikacin) for group B.

•  Amoxicillin 22 mg/kg PO q8–12h. •  Amoxicillin–clavulanate 22 mg/kg PO

q12h.

•  Penicillin—penicillin G 10,000–20,000 U/

kg IM, SC q12–24h or penicillin V 8–30 mg/ kg PO q8h. •  Erythromycin 10–20 mg/kg IV, SC, PO q8h. •  Clindamycin 10–15 mg/kg PO, IV, SC q12h. CONTRAINDICATIONS/POSSIBLE INTERACTIONS •  Avoid immunosuppressive drugs; aminoglycosides contraindicated with renal disease. •  Enrofloxacin—contraindicated for necrotizing fasciitis.

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 FOLLOW-UP

PREVENTION/AVOIDANCE •  Avoid overcrowding, maintain clean feeders and environment, segregate infected animals. •  Newborns—dip navel and umbilical cord in 2% tincture of iodine, consider prophylactic antibiotic treatment of kittens born to primiparous queens.

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 MISCELLANEOUS

ZOONOTIC POTENTIAL •  Animals may show no clinical signs with group A streptococci but may serve as reservoir for human infection. •  Streptococci isolated from people are usually of human, not animal, origin. •  S. canis infections in people reported from dog bites and wounds in contact with dogs.

­Suggested Reading

Lappin MR, Blondeau J, Boothe D, et al. Antimicrobial use guidelines for treatment of respiratory tract disease in dogs and cats. J Vet Intern Med 2017, 31:279–294. Little SE. Emerging aspects of streptococcal infections in cats. In: Little SE, ed., August’s Consultations in Feline Internal Medicine, 7th ed. St. Louis, MO: Elsevier, 2016, pp. 64–72. Sykes JE. Streptococcal and enterococcal infections. In: Sykes JE, ed., Canine and Feline Infectious Diseases. St. Louis, MO: Elsevier, 2014, pp. 334–346. Author J. Paul Woods Consulting Editor Amie Koenig

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Stupor and Coma vestibular nystagmus: brainstem involvement.

•  Respiratory patterns—Cheyne-Stokes

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 BASICS

DEFINITION •  Stupor—unconscious but arousable with noxious stimuli. •  Coma—unconscious, not arousable with noxious stimuli. PATHOPHYSIOLOGY Any severe pathologic change (anatomic or metabolic) of the ascending reticular activating system (network of neurons situated in the core of the brainstem) and/or arousal system for the cerebral cortex can lead to depression, stupor, or coma. SYSTEMS AFFECTED •  Nervous. •  Cardiovascular. •  Neuromuscular. •  Ophthalmic. •  Respiratory. SIGNALMENT •  Dog and cat. •  No breed, age, or sex predilection. SIGNS Historical Findings

•  Possibility of trauma or unsupervised roaming. •  Past medical problems of

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significance—diabetes mellitus, insulin therapy; hypoglycemia; cardiovascular problems; hypoxic episodes; renal failure; liver failure; neoplasia. •  Patient’s environment—possible heatstroke; hypothermia; drowning; exposure to drugs, including owner’s medications, narcotics, toxins (e.g., ethylene glycol, lead, anticoagulants). •  Onset may be acute or slowly progressive, depending on underlying cause. Physical Examination Findings

•  Evidence of external or internal trauma. •  Severe hypo- or hyperthermia. •  Evidence

of hypoxia or cyanosis, ecchymosis or petechiation, cardiac or respiratory insufficiency—warrants investigation for metabolic causes. •  Palpate for evidence of neoplasia. •  Retinal hemorrhages or distended vessels—hypertension. •  Papilledema— cerebral edema. •  Retinal detachment— infectious, neoplastic, or hypertensive causes. •  Chorioretinitis—infectious causes (distemper, feline leukemia virus [FeLV]-related diseases, toxoplasmosis, cryptococcosis, or coronavirus). •  Sustained bradycardia (with normal serum potassium)—midbrain, pontine, or medullary lesion.

respiration: severe, diffuse cerebral or diencephalic lesion; hyperventilation: midbrain lesion; ataxic or apneustic breathing: pons or medulla lesion. •  Cranial nerve (CN)—deficits with lesion of cerebrum– diencephalon: CN I, II; deficits of CN III: midbrain lesion; deficits of CN V–XII: pons and medulla lesions. •  Postural changes— decerebrate rigidity: midbrain lesion.

CBC

CAUSES

Biochemistry

glycemia, hyperosmolar syndromes, hypernatremia, hyponatremia, hepatic encephalopathy, hypoxemia, hypercarbia, hypothermia, hyperthermia, hypotension, coagulopathies, renal failure, lysosomal storage disease, severe hypothyroidism. •  Nutritional—hypoglycemia, thiamine deficiency. •  Neoplastic (primary)— meningioma, astrocytoma, gliomas, choroid plexus papilloma, pituitary adenoma, others. •  Metastatic—hemangiosarcoma, lymphoma, mammary carcinoma, others. •  Inflammatory noninfectious—granulomatous meningo­ encephalomyelitis. •  Infectious—bacterial, viral (distemper, feline coronavirus [FCoV]), parasitic (aberrant larva migrants), protozoal (neosporosis, toxoplasmosis), fungal (cryptococcosis, blastomycosis, histoplasmosis, coccidioidomycosis, actinomycosis), tickborne diseases. •  Idiopathic—epilepsy (post status epilepticus). •  Immune-mediated— brain edema, vasculitis and thrombocytopenia leading to hemorrhage. •  Trauma—most common cause. •  Toxins—ethylene glycol, lead, rodenticides, others. •  Vascular— hemorrhage (bleeding disorders, hypertension), infarction (feline ischemic encephalopathy, hypercoagulable disease, microfilaria, or migrating adult heartworm).

Urinalysis

•  Drugs—narcotics, anesthetics, depressants, ivermectin. •  Anatomic—hydrocephalus. •  Metabolic—severe hypoglycemia, hyper­

RISK FACTORS

•  Diabetes mellitus—insulin therapy. •  Hepatic failure. •  Insulinoma. •  Severe heat

or cold exposure without protection. •  Free-roaming animals—trauma. •  Young and unvaccinated animals. •  Hypertension.

Neurologic Examination Findings

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from brainstem lesion (better vs. worse prognosis). •  Determine level of consciousness and if patient arousable. •  Pupillary light reflexes—small responsive pupils: cerebral or diencephalic lesion; dilated unresponsive pupils (unilateral or bilateral) or fixed in midposition: midbrain or severe medullary lesions. •  Oculocephalic reflex (when cervical manipulation possible)—loss of physiologic

DIFFERENTIAL DIAGNOSIS •  Acute onset—most commonly caused by toxins, drugs, trauma, or vascular accidents. •  Slow progression of neurologic signs without systemic abnormalities—suggests primary neurologic disorders of inflammatory, neoplastic, or anatomic causes. •  Bilateral diffuse cortical signs—metabolic diseases, toxins, systemic infection, drugs, and

•  Differentiate cerebrum–diencephalic lesion

nutritional causes. •  Brainstem signs— trauma, inflammation, neoplasia, vascular accidents, or progression of cerebral disease causing tentorial herniation.

 DIAGNOSIS

CBC/BIOCHEMISTRY/URINALYSIS •  Lead toxicity—may show nucleated red blood cells or basophilic stippling. •  Severe

infection—inflammatory hemogram.

•  Severe anemia—suggests hypoxemia.

May see hypoglycemia, hyperglycemia, hypernatremia, azotemia, hyperosmolarity, and other metabolic derangements. •  Diabetes mellitus—glycosuria. •  Renal

failure—isosthenuria, granular casts.

•  Immune-mediated disease or severe infection—proteinuria. •  Hepatic

encephalopathy—ammonium biurate crystals. •  Ethylene glycol toxicity—calcium oxalate or hippurate crystals. OTHER LABORATORY TESTS

•  Serum ethylene glycol level and osmolar gap—acute onset. •  Serum ammonia

concentration and preprandial and postprandial bile acids—high levels indicate hepatic encephalopathy. •  Serum and CSF titers—suspected infectious disease. •  Arterial blood gases—evidence of hypoxemia; severe pH changes; hypo- and hypercarbia. •  Coagulogram—including prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen, fibrin degradation product, D-dimer, platelet count, anti­ thrombin, buccal bleeding time, thrombo­ elastography; suspected intracranial bleeding or thrombosis. •  Serologic testing—FeLV, feline immunodeficiency virus (FIV), FCoV, protozoal and heartworm disease. •  Serum toxicity levels (e.g., lead, macrolide, other toxins). •  Thyroid panel. IMAGING

•  Survey radiographs (thorax and abdomen)—

evidence of heavy metal, organ enlargement, infiltration, or neoplasia. •  Skull radiographs— fractures in trauma cases, lytic lesions, masses. •  CT—excellent for detecting acute hemorrhage within calvaria; depressed fractures; lytic lesions, penetrating foreign bodies. •  MRI with contrast—demonstrates cerebral edema, hemorrhage, mass, infiltrative diseases, vascular interruption. DIAGNOSTIC PROCEDURES

•  CSF—cytology, protein and

immunoglobulin concentrations, and titers for infectious diseases; perform only when no evidence of trauma, increased intracranial pressure, coagulopathies, or metabolic disease. •  Brainstem auditory-evoked response— determine brainstem function. •  ECG, echocardiogram—determine cardiac



Stupor and Coma

(continued) 

dysfunction; abnormalities may contribute to stupor or coma or may be caused by brain disease. •  EEG—detect nonclinical seizure activity that can prolong stupor and coma. PATHOLOGIC FINDINGS Cerebral edema, hemorrhage, infarct, ischemia, inflammation, neoplasia, herniation, laceration, contusion, hematomas, skull fracture, necrosis, and apoptosis.

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 TREATMENT

APPROPRIATE HEALTH CARE Poor Perfusion

•  Small-volume fluid resuscitation technique; a combination of hydroxyethyl starch with balanced isotonic crystalloids. •  Use peripheral veins, leaving the jugular vein blood flow unobstructed; shifting blood volume into the jugular veins is an important compensatory mechanism during high intracranial pressure (ICP). •  Maintain systolic BP >90 mmHg; avoid hypertension. •  Hydration—maintain with a balanced electrolyte crystalloid solution. •  The head and neck should be leveled with the body or elevated to a 20° angle. •  Oxygen supplementation—avoid a cough or sneeze reflex during intubation or nasal cannula placement; administer lidocaine (dogs, topical and/or 1–2 mg/kg IV) before intubation to blunt the gag and cough reflex. •  Pao2 must be >50 mmHg to maintain cerebral blood flow autoregulation in normal brain tissue.

Ventilation

•  Protect airway with intubation. •  Paco2—

maintain between 35 and 45 mmHg. Reduce Increase In ICP

•  Prevent thrashing, seizures, or any other

form of uncontrolled motor activity that can elevate ICP; diazepam infusion 0.5–1 mg/ kg/h, midazolam 0.2–0.4 mg/kg, or propofol 3–6 mg/kg IV titrated to effect; then 0.1–0.6 mg/kg/min CRI; levetiracetam 20 mg/kg IV/ IM/rectal q8h if seizure activity. •  Ensure systolic BP >90 mmHg. •  7% hypertonic saline (2–4 mL/kg IV); can reduce fluid volume needed to reach resuscitation endpoints; can combine with colloid. •  Furosemide 0.75 mg/kg IV; may decrease CSF production. •  Mannitol 0.5–1 g/kg IV bolus repeated at 2-hour intervals 3 or 4 times in dogs, and 2 or 3 times in cats; repeated doses must be given on time; improves brain blood flow and lowers ICP. •  Hyperventilation (Paco2 32–35 mmHg) for 48 hours using mechanical ventilation; requires intensive monitoring. •  Ventriculostomy for CSF drainage if critical elevation of ICP nonresponsive to medical treatment. •  Consider surgical decompression and exploration—if cerebral dysfunction is

progressing to midbrain signs with a history of trauma or bleeding (tentorial herniation); high ICP not responsive to medical therapy (if monitoring instrumentation available); depressed skull fracture fragments; penetrating foreign body; requires intensive monitoring. NURSING CARE

•  Prevent secondary complications of

recumbency—eye lubrication; aseptic technique with catheters; turning; rehabil­ itation exercises. •  Prevent urine/fecal scalding. •  Careful nasogastric tube feeding for early trickle flow feeding; cisapride 0.5 mg/kg PO q8–12h and metoclopramide 1–2 mg/kg/day may promote gastrointestinal motility.

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 MEDICATIONS

DRUG(S) OF CHOICE Underlying Disease

•  Glucocorticosteroids—inflammatory, immune-mediated and space-occupying intracranial abnormalities. •  Lactulose enemas, flumazenil 0.02 mg/kg IV and fluid support— hepatic encephalopathy. •  Fluid diuresis, dialysis—renal failure. •  Rehydration and insulin—diabetes mellitus with hyperosmolality; lower glucose slowly. •  Glucose supplementation—hypoglycemia. •  Support IV volume; cool—hyperthermia. •  Support IV volume; warm to ≥98°F/36.5°C—hypothermia. •  Gastric lavage and instillation of activated charcoal with a cathartic. •  Dialysis—­ low-molecular-weight toxins. •  Antibiotics— use agents that cross the blood–brain barrier for suspected bacterial infections (e.g., trimethoprim-sulfa, clindamycin, doxycycline, metronidazole). •  Adjust crystalloid fluid selection to correct electrolyte disorders. •  Thiamine (cat, 5–50 mg; dog, 1–20 mg IV)—possible thiamine deficiency.

PRECAUTIONS •  Avoid hypo- and hypertension, hypo- and hyperglycemia. •  Avoid IV volume overload.

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 FOLLOW-UP

PATIENT MONITORING •  Serial neurologic examinations—detect deterioration that warrants aggressive therapeutic intervention. •  BP—keep fluid therapy adequate for perfusion while avoiding hypertension. •  Blood gases—assess need for oxygen supplementation or ventilation; monitor Pco2 when hyperventilating. •  Blood glucose—ensure adequate level to maintain brain functions while avoiding hyperosmolality. •  ECG—detect arrhythmias that may affect

perfusion, oxygenation, and cerebral blood flow. •  ICP—detect marked elevations; track success of therapeutics. •  Electrolytes—detect hypernatremia and hypokalemia. PREVENTION/AVOIDANCE •  Keep pets confined or leashed. •  Prevent exposure to toxins or in-home medications. •  Routine healthcare program to minimize infectious and metabolic disease complications. EXPECTED COURSE AND PROGNOSIS

•  Short-term prognosis poor, other than related to hypoglycemia. •  Pathology of

brainstem worse than pathology of cerebral cortex. •  Modified Glasgow Coma Score can provide prognostic information.

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 MISCELLANEOUS

ABBREVIATIONS •  CN = cranial nerve. •  CSF = cerebrospinal fluid. •  ECG = electrocardiogram. •  EEG = electroencephalogram. •  FCoV = feline coronavirus. •  FeLV = feline leukemia virus. •  FIV = feline immunodeficiency virus. •  ICP = intracranial pressure. •  Paco2 = partial pressure of carbon dioxide in arterial blood. •  Pao2 = partial pressure of arterial oxygen. •  PT = prothrombin time. •  PTT = partial thromboplastin time. SEE ALSO Brain Injury. INTERNET RESOURCES https://bvns.net/wp-content/ uploads/2016/09/Neurotransmitter-2.0MGCS-final.pdf

­Suggested Reading

Chrisman CL, Mariani C, Platt S. Dementia, stupor and coma. In: Neurology for the Small Animal Practitioner. Jackson, WY: Teton NewMedia, 2003, pp. 41–84. Parratt CA, Firth AM, Boag AK, et al. Retrospective characterization of coma and stupor in dogs and cats presenting to a multicenter out-of-hours service (2012– 2015): 386 animals. J Vet Emerg Crit Care 2018, 28:559–565. Author Elke Rudloff Acknowledgment The author and editors acknowledge the prior contribution of Rebecca Kirby.  Client Education Handout available online

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Subarachnoid Cysts (Arachnoid Diverticulum) concurrent vertebral malformations at the site of the diverticula.

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 BASICS

DEFINITION Subarachnoid cysts refer to dilation of the subarachnoid space causing compression of the underlying brain or spinal cord. The use of the term “cyst” is misleading, as most do not have a defined cyst wall with an epithelial lining and the term subarachnoid diverticulum is frequently used when the lesion is spinal in location. This term is also problematic in cases in which arachnoid scarring simply causes dilation of the subarachnoid space. PATHOPHYSIOLOGY •  There are several proposed etiologies of subarachnoid cysts. •  Any disease process that causes arachnoiditis has the potential to cause adhesions that result in the formation of one-way valves through which CSF flows, but cannot return, causing accumulation of CSF. •  Congenital forms of the disease may result from abnormal splitting of the arachnoid membrane during development. SYSTEMS AFFECTED Nervous—spinal cord and brain (quadrigeminal cistern).

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GENETICS Certain breeds appear to be predisposed (e.g., pug, Rottweiler for spinal cord, Pekingese, shih tzu for brain). There are no data confirming heritability or a mode of inheritance at this time. INCIDENCE/PREVALENCE No specific data. SIGNALMENT Species

Dog and cat. Breed Predilections

•  Spinal—pug, Rottweiler, French bulldog. •  Brain—small brachycephalic breeds.

Mean Age and Range

Dogs female. SIGNS

Historical Findings

Spinal

•  Owners report a slowly progressive ataxia

and paresis involving all or just the pelvic limbs. •  Fecal incontinence—common early sign of thoracolumbar diverticula, with urinary incontinence developing shortly after. •  Owners do not usually report that the pet is in pain. In a study of 122 cases, 19% of the dogs had pain. •  There may be prior history of previous spinal cord injury (due to trauma, intervertebral disc disease, or fibrocartila­ genous embolism). •  There may be

Brain

•  Cerebellar signs. •  Seizures.

Physical Examination Findings

Usually normal, although possible secondary consequences of the myelopathy include abrasions of the dorsal aspect of the toes, wearing of the nails, and urinary tract infections. Neurologic Examination Findings

Spinal

•  Neurologic signs reflect lesion

localization—hindlimb involvement for thoracolumbar cysts and all limbs for cervical cysts. •  Ataxia frequently characterized by hypermetria. •  Paresis. •  Proprioceptive placing deficits. •  Fecal and/or urinary incontinence; urine retention (due to defective voiding). •  Spinal reflexes may be reduced if the lesion is at the brachial or lumbosacral intumescence but otherwise are normal or increased. •  Spinal pain is rarely elicited.

Brain

•  Quadrigeminal cysts are frequently an

incidental finding. However, extremely large cysts can produce compression of the cerebellum and brainstem. •  Signs of cerebellar disease—hypermetria, intention tremor, wide-based stance. •  Signs of brainstem compression—tetraparesis, head tilt. •  Seizures (the relationship between the cyst and the presence of seizures is unclear). CAUSES

•  Several proposed etiologies. •  Congenital

malformation of the arachnoid mater (dilated septum posticum; in young dogs). •  Secondary to traumatic injury to the arachnoid, causing adhesions and development of one-way valves for CSF flow. •  Secondary to chronic microtrauma to the arachnoid, causing adhesions and development of one-way valves for CSF flow. This mechanism has been proposed for pugs with caudal thoracic subarachnoid cysts. Affected dogs may have hypoplasia of their articular facets leading to chronic instability. RISK FACTORS

•  Traumatic spinal cord injury that damages the arachnoid mater. •  Hypoplastic articular

facets associated with subarachnoid diverticulae in certain dog breeds (pugs).

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Distinctive features—slowly progressive, nonpainful paresis and ataxia with a hyper­ metric gait, and presence of fecal and/or

urinary incontinence in an animal that is still ambulatory. •  Any cause of focal myelopathy could cause the same neurologic presentation. •  Intervertebral disc herniation. •  Neoplasia. •  Trauma. •  Inflammatory or infectious myelitis. •  Congenital vertebral/spinal malformation. •  Intraspinal vascular malformation. CBC/BIOCHEMISTRY/URINALYSIS Urinalysis may show evidence of urinary tract infection (pyuria, hematuria, proteinuria, and bacteriuria). OTHER LABORATORY TESTS Aerobic urine culture if evidence of urinary tract infection. IMAGING

•  Thoracic radiography—in older patients to rule out metastatic neoplasia. •  Spinal

radiography—should be performed in all patients; typically unremarkable in patients with subarachnoid diverticulae. However, some patients may have evidence of spinal fractures, and occasionally there is evidence of a vertebral malformation (articular facet hypoplasia, spina bifida, hemivertebra, or block vertebra) colocalizing with the neurologic signs. •  Myelography—focal dilation of the subarachnoid space most commonly located dorsally but sometimes located ventrally; the dilation may be multilobed. •  CT myelography—further delineates the dilated subarachnoid space in transverse section; without intrathecal contrast, will not demonstrate the lesion. •  MRI— dilation of the subarachnoid space in sagittal and transverse section on T2-weighted images. T2-HASTE images provide even more definition of the CSF accumulation. The presence of active arachnoiditis can be detected on pre- and-postcontrast T1-weighted images. DIAGNOSTIC PROCEDURES CSF—to rule out a primary inflammatory process; may show mild inflammation as secondary consequence of the subarachnoid cyst. PATHOLOGIC FINDINGS

•  At surgery, adhesions may be evident in the

subarachnoid space. Occasionally a thin cyst wall is apparent (this is unusual). •  Histopathology of excised arachnoid—may show fibrosis or mild inflammation. •  Histopathology of the spinal cord shows chronic compressive injury—loss of gray and white matter, Wallerian degeneration, demyelination.

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 TREATMENT

APPROPRIATE HEALTH CARE •  Patients with mild signs can be managed medically; surgery recommended for young dogs with moderate, progressive signs. •  Nonambulatory patients should be



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Canine and Feline, Seventh Edition (continued)

Subarachnoid Cysts (Arachnoid Diverticulum)

hospitalized for diagnostic workup and possible surgical decompression as soon as possible. NURSING CARE •  Patients that have incomplete micturition should have their bladders manually expressed 3–4 times a day. If this is not possible, their bladders should be catheterized in a sterile fashion once or twice a day. •  Appropriate maintenance fluids should be administered in the immediate postoperative period. •  Postoperative pain should be assessed regularly (q6h) and treated as needed with opiates and nonsteroidal anti-inflammatory drugs. •  Surgical incisions should be ice packed for 5–10 minutes three times a day for 24 hours after surgery and then should be hot packed for a similar period for an additional 2–5 days. •  Rehabilitation is important; a patient-specific rehabilitation program should be developed to include gait training and improvement of strength. ACTIVITY

•  Paretic and ataxic patients need to be

restricted to nonslip, flat surfaces to avoid falling. •  Exercise should be restricted to walking on a leash to avoid falling, but controlled exercise is important in maintaining muscle strength and joint integrity. •  Postoperatively, patients need to be restricted to a small, well-padded space (crate) to ensure that they do not fall while the laminectomy site is healing. Limited controlled exercise should be performed during this period. CLIENT EDUCATION

•  Clients need to be educated on the

implications of a chronic compressive myelopathy; permanent damage to the spinal cord has already occurred and may not be reversible. The primary aim of treatment is to prevent further deterioration, with a hope of also producing a clinical improvement. •  There may be an initial deterioration immediately postoperatively; there is a small chance that this deterioration could be permanent. •  Incontinence, if present, is likely to be permanent. •  The disease may recur in spite of surgical therapy. SURGICAL CONSIDERATIONS •  Surgical decompression of spinal subarachnoid cysts is recommended in young dogs and can be attempted in older animals. •  Marsupialization of the meninges may reduce the chance of a recurrence. •  Surgical treatment of quadrigeminal cysts is only recommended if there are clear signs of compression of adjacent cerebellum and cerebral cortex. Direct surgical exploration and decompression or shunt placement can be attempted.

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 MEDICATIONS

DRUG(S) OF CHOICE •  Anti-inflammatory doses of prednisone (0.5 mg/kg orally once to twice a day) may improve signs and reduce inflammation. If there is no improvement, prednisone should be tapered and discontinued. •  Omeprazole may reduce CSF production rate and improve signs. If there is no improvement it should be discontinued. •  Treatment with antiepileptic drugs should be initiated in dogs with more than 1 seizure a month or cluster seizures. Choice of antiepileptic drug depends on a number of patient and client factors. Phenobarbital (starting at 2 mg/kg q12h), zonisamide (starting at 5–10 mg/kg q12h) and levetiracetam (starting at 20 mg/kg q8h) are all appropriate choices for first-line therapy. PRECAUTIONS Corticosteroids should be used with caution if the patient has urinary tract infection.

disease. •  Age at onset of signs and duration of signs are associated with outcome. Dogs less than 3 years of age and with a short duration of signs (less than 4 months) are more likely to have a good long-term outcome. •  There are limited data on the prognosis with medical management, but anecdotally the author can report a good long-term outcome in old dogs with mild signs when treated with prednisone and rehabilitation alone. Quadrigeminal Cysts

Data on prognosis of quadrigeminal cysts managed medically or surgically are limited but suggests that a positive outcome can be attained with both treatment strategies.

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 MISCELLANEOUS

AGE-RELATED FACTORS Cervical cysts are more common in dogs cervical >

lumbar.

•  Exotropia—ventrolateral strabismus when

gazing to the ipsilateral side.

•  Thoracic limb hypermetria.

SM

•  Scratching action induced by rubbing

dermatome corresponding to spinal cord dorsal horn damage by syrinx. •  Cervicothoracic torticollis (shoulder deviated ipsilateral; head tilt contralateral to spinal cord dorsal horn damage by syrinx). •  Weakness—thoracic limbs > epaxial/ hypaxial muscles > pelvic limbs. •  Proprioceptive deficits—thoracic limbs > pelvic limbs. CAUSES

•  SM develops secondary to CSF channel

obstruction.

•  Degenerative—constrictive myelopathy in

pug and screw tail breeds associated with arachnoid adhesions, facet hypoplasia, vertebral malformation, and secondary ligamentous hypertrophy and intervertebral disc disease (IVDD). •  Anomalous—CM, spinal arachnoid diverticulum/web. •  Neoplastic—mass causing obstruction of CSF channels and/or cerebellar herniation. •  Inflammatory/infectious—meningoencephalomyelitis of unknown origin (MUO), feline infectious peritonitis, •  Traumatic—sequel of spinal cord injury and arachnoid adhesions.



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Canine and Feline, Seventh Edition (continued)

Syringomyelia and Chiari-Like Malformation

RISK FACTORS Brachycephalicism and miniaturization.

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 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS Spinal Pain/Weakness/Ataxia

•  IVDD—acute-onset, persistent localized

pain in dogs >18 months.

•  MUO—pain with rapidly progressive

neurologic signs.

•  Atlantoaxial subluxation—tetraparesis and

pain especially on cervical flexion. •  Discospondylitis—pyrexia and neutrophilia at onset; pain constant. •  Degenerative myelopathy—nonpainful progressive pelvic limb weakness and proprioceptive deficit in dogs >8 years. Scratching

Skin and ear disease—generalized, tail head, abdominal and digital pruritus is not a feature of CM/SM. In CM/SM the scratching is localized to the head/ears (CM-P) and neck/ shoulder/sternum (SM). Abnormal Head Position

•  Rule out vestibular dysfunction due to inner ear, cranial nerve VIII, or intracranial disease. •  Rule out brachycephalic obstructive airway syndrome (BOAS) if sleeping with head elevated (with BOAS often wake coughing).

historical, clinical and MRI findings and eliminating other causes of pain. •  MRI features—effacement/narrowed subarachnoid spaces (reduced definition of the sulci); ventriculomegaly; small, ventral olfactory bulbs; rostral forebrain flattening; dorsocaudal displacement of rostrotentorial neuroparenchyma contributing to hindbrain herniation; cerebellum invaginated under occipital lobes; flattening/ indentation of the cerebellum by the supra­occipital bone/occipitoatlantal ligament. Atlas closer to the skull and craniospinal junction flexed over odontoid peg.

SM

•  MRI features as for CM-P, often with more

pronounced CCJ changes.

•  Image entire spinal cord to determine

extent of syrinx and any spinal cord tethering. with SM width ≥4 mm (CKCS).

•  “Active” syrinx indicated by a cavity which

expands spinal cord, has asymmetrical shape on transverse images, and fluid signal-void sign (indicates turbulent flow). •  “Quiescent” syrinx indicated by a cavity which is elliptical on sagittal images, symmetrical and circular/ovoid on transverse images, and does not alter spinal cord outline. DIAGNOSTIC PROCEDURES CSF—to rule out MUO; however CSF analysis in CM/SM may reveal mild inflammatory changes. PATHOLOGIC FINDINGS

•  Gross—cerebellar herniation,

IMAGING

•  Histopathologic—dogs with clinically

Limited value; can suggest CM (short basicranium, minuscule frontal sinus, flattened supraoccipital bone, close proximity of the atlas to the skull). In severe SM may have widening of cervical spinal canal and remodeling and scalloping of C2. Dynamic cervical images to assess for atlantoaxial subluxation. CT

Useful for defining CCJ abnormalities and should be performed if a vertebral malformation is suspected and to facilitate planning of implanted surgical fixation. MRI

•  Aim to establish cause of SM, i.e., CM or

other causes of CSF obstruction. Specialized imaging (e.g., balanced steady-state free precession sequences) may be required. •  Assess if radiological findings are consistent with neurological localization and severity, e.g., seizures (forebrain) cannot be attributed to SM (spinal cord).

CM-P

•  There is no objective measure of CM-P on

MRI. Diagnosis is suggested by appropriate

most common surgical procedure— establishing a CSF pathway via the removal of majority of supraoccipital bone and dorsal arch of C1; may be combined with a durotomy, with or without patching with a suitable graft material and with or without cranioplasty. •  Successful in reducing pain and improving neurologic deficits in ~80% cases; ~45% cases have satisfactory quality of life 2 years postoperatively. SM persists postoperatively. •  Clinical improvement probably attributable to reduction in CM-P; most cases require additional medical management. •  Atlantoaxial stability should be assessed prior to CCD.

•  Clinically relevant disease is more likely

CBC/BIOCHEMISTRY/URINALYSIS N/A Skull and Cervical Radiographs

SURGICAL CONSIDERATIONS

•  Craniocervical decompression (CCD)

ventriculomegaly, spinal cord cavitation. relevant SM have asymmetrical syrinx with altered dorsal horn structure and altered expression of pain-related neuropeptides, substance P, and calcitonin gene-related peptide.

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 MEDICATIONS

DRUG(S) OF CHOICE CM-P

•  Nonsteroidal anti-inflammatory drugs

(NSAIDs)—at data sheet dosage.

•  First-line adjuvant analgesics—gabapentin

10–20 mg/kg q12h/q8h; or pregabalin 5 mg/ kg q12h/q8h. •  Second-line (add-on) adjuvant analgesics— topiramate 10 mg/kg q8h; or amitriptyline 0.25–2 mg/kg q12–24h (titrate up to effective dose); or memantine 0.3–1 mg/kg twice daily (titrate up to effective dose); or amantadine 3–5 mg/kg q24h. •  “Top up” analgesia—acetaminophen 10 mg/kg PRN up to q8h and/or opioids at data sheet dosage. SM-Associated Phantom Scratching

Gabapentin or pregabalin as above.

SM-Associated Weakness and Postural Deficits •  Drugs that may reduce CSF pressure—

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 TREATMENT

NURSING CARE •  Raise food bowls. •  Avoid neck collars if phantom scratching. •  Complementary therapy, e.g., acupuncture may be useful. ACTIVITY

•  Exercise encouraged to within own limits. •  Grooming may be poorly tolerated. •  Hydrotherapy may improve strength if

SM-associated weakness.

DIET Obesity positively correlated with a reduced quality of life but not greater neuropathic pain. CLIENT EDUCATION Periodic exacerbations of pain common, requiring “top-up” medication.

proton pump inhibitors (omeprazole 0.5–1.5 mg/kg q24h); or H2-receptor antagonists (cimetidine 5–10 mg/kg q8h); or diuretics (furosemide 1–2 mg/kg q12h; acetazolamide 4–8 mg/kg q9–12h). •  Corticosteroids—as last resort and lowest possible dose that controls signs, starting with 0.5 mg/kg prednisolone or methylprednisolone daily; withdraw NSAIDs. CONTRAINDICATIONS Amitriptyline should not be combined with drugs metabolized by cytochrome P450 2D6, e.g., cimetidine. PRECAUTIONS •  Furosemide may activate renin-angiotensin aldosterone system which may be deleterious in dogs predisposed to myxomatous mitral valve disease (MVD).

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Syringomyelia and Chiari-Like Malformation •  Long-term acetazolamide or corticosteroids

not recommended due to potential adverse effects.

POSSIBLE INTERACTIONS CM/SM does not increase risk of anesthesia unless there is syringobulbia (syrinx in brainstem).

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 FOLLOW-UP

PATIENT MONITORING •  Periodic review of pain management and neurologic status. •  Serial MRI may be useful. •  Periodic CBC/biochemistry if receiving medication. PREVENTION/AVOIDANCE Purchase from a breeder that is health screening and can provide appropriate health certificates.

S

EXPECTED COURSE AND  PROGNOSIS •  Approximately three-quarters of CM-P/ SM-affected CKCS deteriorate on medical management. However, many dogs maintain acceptable quality of life. •  15–20% of CM-P/SM-affected CKCS are euthanized. •  25–47% of CM-P/SM-affected dogs having surgical management have recurrence or deterioration of signs within 0.2–3 years of surgery.

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 MISCELLANEOUS

ASSOCIATED CONDITIONS CKCS have high prevalence of unrelated comorbidities, including BOAS, sleep disordered breathing, MVD, pancreatic disorders, biliary tree calcification, epilepsy, myoclonus, fly-catching behavioral disorder, gastroesophageal reflux, otitis media with effusion, deafness, macrothrombocytopenia, keratoconjunctivitis sicca, idiopathic facial nerve paresis, idiopathic vestibular disease. AGE-RELATED FACTORS Older brachycephalic toy breeds are more likely to have comorbidities such as MVD. Head and neck myoclonus is extremely common in older CKCS. PREGNANCY/FERTILITY/BREEDING •  Official health schemes exist in many countries (e.g., the British Veterinary Association CM/SM scheme). •  Breeding recommendations based on SM status and age available. SYNONYMS •  BOCCS. •  Caudal occipital malformation syndrome. •  Syringohydromyelia. ABBREVIATIONS

•  BOAS = brachycephalic obstructive airway

syndrome.

•  BOCCS = brachycephalic obstructive CSF

channel syndrome.

•  CCD = craniocervical decompression.

(continued)

•  CCJ = craniocervical junction. •  CFA = Canis familiaris autosome. •  CKCS = cavalier King Charles spaniel. •  CM = chiari-like malformation. •  CM-P = chiari-like malformation-

associated pain.

•  CSF = cerebrospinal fluid. •  IVDD = intervertebral disc disease. •  QTL= quantitative trait loci. •  MVD = myxomatous mitral valve disease. •  MUO = meningoencephalomyelitis of

unknown origin.

•  NSAID = nonsteroidal anti-inflammatory

drug.

•  SM = syringomyelia.

INTERNET RESOURCES

•  Frequently asked questions: http://

veterinary-neurologist.co.uk/ chiari-like-malformation-and-syringomyelia/ •  Treatment algorithm: http://veterinaryneurologist.co.uk/ cmsm-treatment-algorithm/ •  British Veterinary Association CM/SM scheme: https://www.bva.co.uk/CanineHealth-Schemes/CM-SM-scheme/

­Suggested Reading

Knowler SP, Galea GL, Rusbridge C. Morphogenesis of canine chiari malformation and secondary syringomyelia: disorders of cerebrospinal fluid circulation. Front Vet Sci 2018, 5:171. Rusbridge C, Stringer F, Knowler SP. Clinical application of diagnostic imaging of chiari-like malformation and syringomyelia. Front Vet Sci 2018, 5:280. Author Clare Rusbridge



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Canine and Feline, Seventh Edition

Systolic Anterior Motion SIGNS Historical Findings

­

 BASICS

OVERVIEW Systolic anterior motion (SAM) is paradoxical dynamic movement of the mitral valve apparatus or some of its individual components in an anterior direction toward the left ventricular outflow tract (LVOT) and interventricular septum during systole. When the chordae tendineae are the sole component of the valve apparatus displaced anteriorly, the term chordal anterior motion (CAM) is sometimes used. Pathophysiology

•  When SAM was first recognized it was

believed to be specific to the setting of hypertrophic cardiomyopathy (HCM) however, it has since been identified to occur under any circumstances that alter the dynamic geometry of the left ventricle (LV). •  There are multiple factors that can contribute to the development of SAM which can broadly be broken down into three main groupings: structural abnormalities, altered ventricular kinetics, and altered ventricular geometry (see Causes). •  Clinical manifestations occur on a spectrum of severity ranging from clinically silent changes to severe dynamic LVOT obstruction (LVOTO). •  Significant LVOTO can result in a pressure overload on the LV, resulting in myocardial hypertrophy; if severe enough, myocardial ischemia and ventricular arrhythmias may ensue. •  Cardiac output is also reduced with severe LVOTO and may result in weakness or collapse. Systems Affected

Cardiovascular Genetics

N/A, but certain underlying conditions have a genetic basis in certain breeds (e.g., HCM, subvalvular aortic stenosis [SAS]). Incidence/Prevalence

True prevalence is unknown. One study identified SAM in 5.8% of apparently normal cats, of which 91.1% had HCM. SIGNALMENT Species

Dog and cat. Breed Predilections

N/A, but certain breeds may be predisposed to certain underlying conditions (e.g., SAS in Newfoundlands; HCM in Maine coons). Mean Age and Range

Unknown

•  SAM may occasionally be observed in

completely healthy animals.

•  Most animals are asymptomatic. •  Signs are often attributable to underlying

disease process.

•  Weakness, lethargy, or collapse may be

­

Physical Examination Findings

DIFFERENTIAL DIAGNOSIS •  Must differentiate SAM from other causes of murmurs. •  It can be diagnostically challenging to distinguish if LVOTO due to SAM is the cause or the effect of myocardial hypertrophy.

observed with severe LVOTO. •  Patients with advanced underlying cardiac disease may have signs of left-sided or right-sided congestive heart failure (CHF) (e.g., tachypnea, dyspnea, cough, ascites). •  Systolic murmur which may be static,

intermittent, or labile, i.e., variable in intensity from moment to moment. •  Diastolic gallop sounds may be present in patients with underlying cardiomyopathies. •  Femoral pulse quality may be reduced in patients with severe LVOTO. •  Arrhythmias may be appreciated (may be a direct sequela of severe LVOTO or may be due to the underlying disease process). CAUSES & RISK FACTORS Causes

SAM is a complex and dynamic condition that may arise from interactions of one or more of the following factors: •  Structural abnormalities: ◦◦ Papillary muscle displacement. ◦◦ Anterior and/or posterior mitral leaflet redundancy. ◦◦ Abnormal chordae tendineae. ◦◦ Bulging of the interventricular septum. ◦◦ Small LV. •  Altered ventricular kinetics: ◦◦ Hyperdynamic LV (generalized or regional). •  Altered ventricular geometry: ◦◦ Reduced distance between septum and mitral coaptation point. ◦◦ Mitral apparatus displaced anteriorly. ◦◦ Decreased anterior:posterior length ratio. ◦◦ Decreased mitro-aortic angle. Risk Factors

•  Any condition or intervention that alters

left ventricular geometry or loading conditions. •  HCM. •  SAS. •  Systemic hypertension. •  Hypovolemia. •  Right ventricular systolic hypertension (e.g., pulmonic stenosis, tetralogy of Fallot, pulmonary hypertension). •  Stress/excitement. •  Mitral valve dysplasia. •  Thyrotoxicosis. •  Excess catecholamines. •  Positive inotropic drugs (e.g., dobutamine). •  Surgical mitral valve repair is identified as a risk factor in humans.

 DIAGNOSIS

CBC/BIOCHEMISTRY/URINALYSIS N/A OTHER LABORATORY TESTS N/A IMAGING Echocardiography

•  Paradoxical systolic motion of the anterior

mitral leaflet/mitral apparatus toward the interventricular septum is identified on 2D and m-mode echocardiography, and is often best seen from right-parasternal five-chamber views that highlight the LVOT. •  Color-flow Doppler assessment of the LVOT identifies turbulent blood flow. •  The degree of LVOTO, if present, can be quantified via continuous-wave ± pulsedwave Doppler interrogation. Doppler flow profiles in the setting of SAM are typically characterized by late systolic acceleration through the LVOT resulting in a “scimitarshaped” profile. •  Mitral regurgitation is often identified; this is usually mild, with an eccentric jet that is posteriorly directed. •  Myocardial hypertrophy may be present (can be both a cause and an effect of SAM with significant LVOTO). •  Subvalvular ridge may be present in the LVOT of patients with SAS. •  Underfilling of the LV may be appreciated in some patients with SAM. •  Other echocardiographic findings, depending on the type and severity of underlying conditions. Radiography

•  May be normal. •  Radiographic changes, if present, usually

reflect the underlying cause.

•  Evidence of left- or right-sided cardiomegaly ±

CHF may be present on thoracic radiographs. DIAGNOSTIC PROCEDURES ECG

•  May be normal. •  Atrial or ventricular arrhythmias may be

present, depending on underlying pathology.

•  Evidence of left- or right-sided cardiomegaly

may be present, depending on underlying cause and severity.

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Blackwell’s Five-Minute Veterinary Consult

Systolic Anterior Motion SEE ALSO

•  May see evidence of myocardial ischemia

(e.g., S-T segment elevation/depression) with severe LVOTO. PATHOLOGIC FINDINGS Gross or histopathologic findings reflect any underlying conditions, if present.

­

 FOLLOW-UP

PATIENT MONITORING Type and frequency depends on any underlying disease processes. PREVENTION/AVOIDANCE N/A

­

 TREATMENT

POSSIBLE COMPLICATIONS N/A

 MEDICATIONS

EXPECTED COURSE AND PROGNOSIS •  Depends on the nature and severity of underlying cause. •  In a study of cats with HCM, cats with SAM had longer survival times than those without. It is speculated that this may be due to SAM allowing earlier identification of the disease due to the presence of a murmur.

Treat or remove underlying cause(s)

­

DRUG(S) OF CHOICE •  Only as needed to manage an underlying condition or CHF, if present. •  Therapy with beta-blocker drugs (e.g., atenolol) is controversial. Beta-blockers are empirically used by some clinicians to reduce the severity and/or the effects of SAM/LVOTO, however evidence of efficacy or any survival benefit is lacking.

S

CONTRAINDICATIONS/POSSIBLE INTERACTIONS •  The use of positive inotropic drugs (e.g., dobutamine, pimobendan) in the setting of SAM with significant LVOTO is theoretically concerning and thus warrants prudence. Hypotension has been reported in a cat with SAM that received pimobendan for the treatment of heart failure, however a recent study of pimobendan administration in cats with HCM showed no difference in the incidence of LVOTO between treatment and placebo groups. •  Beta-blockers may reduce systolic function and should be used cautiously in patients with known systolic dysfunction.

(continued)

­

 MISCELLANEOUS

ASSOCIATED CONDITIONS N/A AGE-RELATED FACTORS N/A PREGNANCY/FERTILITY/BREEDING Certain underlying causes (e.g., HCM, SAS) may be heritable. SYNONYMS •  Chordal anterior motion. •  CAM. •  Dynamic LVOTO. •  When LVOTO due to SAM is present concurrently with a HCM phenotype, the term hypertrophic obstructive cardio­ myopathy is used.

•  Aortic Stenosis. •  Cardiomyopathy, Hypertrophic—Cats.

ABBREVIATIONS

•  CAM = chordal anterior motion. •  CHF = congestive heart failure. •  HCM = hypertrophic cardiomyopathy. •  LV = left ventricle. •  LVOT = left ventricular outflow tract. •  LVOTO = left ventricular outflow tract

obstruction.

•  SAM = systolic anterior motion. •  SAS = subvalvular aortic stenosis.

­Suggested Reading

Fox P, Keene B, Lamb K, et al. International collaborative study to assess cardiovascular risk and evaluate long-term health in cats with preclinical hypertrophic cardiomyopathy and apparently cats: The REVEAL study. J Vet Intern Med 2018, 32(3):930–943. Ibrahim M, Rao C, Ashrafian H, et al. Modern management of systolic anterior motion of the mitral valve. Eur J CardioThorac Surg 2012, 41(6):1260–1270. Levine R, Vlahakes G, Lefebvre X, et al. Papillary muscle displacement causes systolic anterior motion of the mitral valve. Experimental validation and insights into the mechanism of subaortic obstruction. Circulation 1995, 91(4):1189–1895. Payne JR, Borgeat K, Connolly DJ, et al. Prognostic indicators in cats with hypertrophic cardiomyopathy. J Vet Intern Med 2013, 27(6):1427–1436. Author Michael Aherne Consulting Editor Michael Aherne



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Canine and Feline, Seventh Edition

Tapeworms (Cestodiasis) DIAGNOSTIC PROCEDURES

•  Fecal flotation to detect eggs; false negatives

­

 BASICS

OVERVIEW •  Infection of small intestine with adult tapeworms of Taenia (especially T. pisiformis of dogs and T. taeniaeformis of cats), Dipylidium caninum, Echinococcus spp., Mesocestoides, Diphyllobothrium, or Spirometra. •  Infection by ingestion of intermediate host containing tapeworm larvae. •  Most cause no apparent harm to host other than perianal pruritus; Spirometra may cause diarrhea, weight loss, vomiting. •  Peritoneal larval cestodiasis (PLC)—potentially fatal peritoneal infection in dogs (accidental intermediate hosts) caused by Mesocestoides larvae. SIGNALMENT Dog and cat. SIGNS

if eggs not released from proglottids; crush minced segments between two glass slides to release eggs, add drop of water, examine microscopically. •  Dipylidium—press adhesive cellophane tape to perianal skin, then apply tape to microscope slide; packets contain multiple pale yellow eggs ~50 μm in diameter with hexacanth embryo with three pairs of hooks. •  Taenia, Echinococcus—individual spherical brown eggs ~30–35 μm in diameter with hexacanth embryo. •  Mesocestoides—individual oval thin-shelled eggs with hexacanth embryo. •  PLC—detect larvae in peritoneal fluid by microscopy or PCR-restriction fragment length polymorphism. •  Diphyllobothrium/Spirometra—individual eggs with operculum; contain fully developed coracidium.

•  Motile or dried, white to cream-colored,

single proglottids or chains of square or rectangular proglottids of Taenia and barrelshaped proglottids of Dipylidium visible on perineum or in feces; Mesocestoides proglottids are club-shaped, smaller, more numerous; Echinococcus proglottids too small to see. •  Dragging or rubbing anus on ground (pruritus). •  Diarrhea, weight loss—possible with Spirometra. •  PLC—abdominal distension (ascites), anorexia, lethargy. CAUSES & RISK FACTORS

•  Taenia, Echinococcus, Mesocestoides—eating

viscera of intermediate hosts (birds, reptiles, rabbits, rodents, sheep). •  Dipylidium infections—eating fleas, lice. •  Spirometra—ingesting copepods; uncooked amphibians, reptiles, birds, mammals. •  Diphyllobothrium—eating uncooked fish.

­

 DIAGNOSIS

DIFFERENTIAL DIAGNOSIS •  Anal sac disease. •  Other causes of diarrhea. •  PLC—causes of ascites. CBC/BIOCHEMISTRY/URINALYSIS PLC—leukocytosis, hypoalbuminemia. OTHER LABORATORY TESTS N/A IMAGING PLC—abdominal ultrasonography, radiography.

­

 TREATMENT

•  Outpatient anthelmintic treatment. •  Flea (or louse) control (Dipylidium). •  PLC—anthelmintic treatment, may require

­

 FOLLOW-UP

PATIENT MONITORING •  Post-treatment examination for tapeworm segments or eggs; incompletely removed adult Mesocestoides can repopulate by asexual multiplication. •  PLC—ultrasonography, abdominocentesis to detect recurrence; larvae difficult to eliminate (repopulate by asexual multiplication). PREVENTION/AVOIDANCE

•  Flea (or louse) control to prevent Dipylidium

infection. •  Prevent hunting, scavenging, eating of intermediate hosts.

EXPECTED COURSE AND PROGNOSIS •  Anthelmintic treatment eliminates adult Taenia, Echinococcus, Dipylidium; reinfection often occurs. •  Incomplete removal of adult Mesocestoides can result in recurrence without reinfection. •  PLC treatment provides clinical remission, often not curative.

peritoneal lavage or surgery to remove larvae.

­ ­

 MEDICATIONS

DRUG(S) OF CHOICE •  Fenbendazole 50 mg/kg PO q24h for 3 days. •  Praziquantel 5 mg/kg PO, SC once: ◦◦ Resistance to praziquantel in Dipylidium is emerging issue. ◦◦ 7.5 mg/kg PO for 2 days for Diphyllobothrium (dogs, extra-label). •  Praziquantel/pyrantel pamoate—label dose (cats). •  Praziquantel/pyrantel pamoate/febantel— label dose (dogs). •  Epsiprantel 5.5 mg/kg PO (dogs), 2.8 mg/ kg PO (cats) for Taenia, Dipylidium; 7.5 mg/ kg PO (dogs) for Echinococcus. •  Emodepside 3 mg/kg/praziquantel 12 mg/ kg, topically for Taenia, Dipylidium (cats). •  Canine PLC—praziquantel 5 mg/kg SC, repeat in 2 weeks; fenbendazole 50–100 mg/ kg PO q24h for 4–8 weeks (extra-label; clinical remission, often not curative). CONTRAINDICATIONS/POSSIBLE INTERACTIONS Do not use praziquantel or epsiprantel in animals 10% corrosive damage to all tissues are expected. Oral exposure causes burns to the mouth, oropharynx, and esophagus. Hypersalivation, panting, agitation, and vomiting progress to tremors, cardiac arrhythmias, shock, and coma. Methemoglobinemia, respiratory alkalosis, and renal and hepatic damage may develop. Dermal and ocular exposure results in a short period of intense pain followed by local anesthesia. Necrotic skin areas are white followed in a few days by a dry, gray black eschar. Ocular exposure results in severe corneal burns and erosions

Pine oils (terpene alcohols) and turpentine (mixture of terpenes derived from pine oil)— concentration of pine oil in disinfectants varies from 0.3% to 60%. Turpentine is used to thin oil-based paints. May also be found in equine hoof dressings

Moderate to severe toxicity risk is concentration dependent. The oral LD50 of pine oil varies from 1 to 2.7 mL/kg BW but much lower doses may result in severe toxicosis. Cats are more susceptible than dogs. Pine oil products are direct irritants to mucous membranes resulting in erythema in contact areas (mouth, oropharynx, skin). Ingestion results in profuse salivation, abdominal pain, and vomiting ± blood. Systemic effects include respiratory depression, CNS depression, weakness, ataxia, and hypotension. Aspiration during ingestion or emesis or chemical pneumonitis secondary to systemic absorption results in pulmonary toxicity. Myoglobinuria and acute renal may develop with massive ingestions. Dermal exposure causes redness and irritation. Ocular signs include photosensitivity, blepharospasm, epiphora, and conjunctival and scleral erythema

Oral dilution is recommended as soon as possible but choice diluent is considered controversial. Dilute with water or milk at home prior to obtaining veterinary care. Some sources recommend mineral oil for dilution. Emesis is contraindicated and anti emetic should be administered promptly. The mouth and oropharynx should be examined carefully for evidence of mucosal damage prior to gastric lavage. If present gastric lavage is contraindicated. If there is no mucosal damage, activated charcoal with a cathartic may be administered. Further care is supportive and includes monitoring of renal and hepatic function, acid-base status, and respiratory effort. Shock and respiratory depression are complicating factors. N-Acetylcysteine (NAC) and SAMe may be used to limit hepatic and renal toxicity. Individuals treating dermal exposures should protect themselves prior to animal treatment. Polyethylene glycol (PEG) or glycerol is recommended for the initial dilution and removal of phenolic compounds followed by washing with a mild soap and water. Oil-based creams and ointments should be avoided as they may increase phenol absorption. Affected eyes should be irrigated for 20–30 minutes with isotonic saline and a slit lamp examination performed. Medications and further therapy depend on exam results All oral exposures should be diluted with water. Induction of emesis is contraindicated, and gastric lavage carries a risk. Activated charcoal is not indicated. Further treatment is symptomatic and includes close monitoring of renal perfusion, electrolytes, and acid base status. Affected skin should be washed well with a mild soap and copious amounts of water. Ocular exposures should be irrigated for at least 15 minutes with isotonic saline and monitored for further signs

(Continued )

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Toxic Home and Garden Hazards for Pets ( continued ) Table VI–C Household cleaners, disinfectants, and solvents—products, clinical signs, and treatment (continued ) Products SOLVENTS AND ALCOHOLS Acetone—found in nail polish remover, glues and rubber cement, paint thinner, varnish.

Isopropanol—found in model engine fuel, deicers, windshield washer fluid, fuel additives, and varnish and stain removers

Methanol (methyl or wood alcohol, “denatured alcohol”)—found in windshield wiper solutions, antifreeze products for door locks Ethanol—found in certain mouthwashes, alcohol for consumption (see individual entry), perfumes, cologne, hand sanitizers

Toxicity and Clinical Signs

Treatment

The oral LD50 in dogs is 8 mL/kg BW but doses as low as 2–3 mL/kg BW may be toxic. The odor of acetone and presence of elevated urinary ketones indicate exposure. Clinical signs associated with a mild exposure include CNS depression, ataxia, and vomiting; stupor and coma occur with larger amounts. Hyperglycemia and ketonemia may be present The toxic dose of 70% isopropanol is 2 mL/kg BW but doses as low as 0.5 mL/kg BW may be toxic. Signs occur rapidly, generally within 30–60 minutes, and include vomiting ± blood, stupor, and ataxia which may progress to CNS and respiratory depression, severe hypotension, and coma. Mild acidosis may occur

Emesis followed by activated charcoal with a cathartic has been suggested but is controversial due to rapid absorption of acetone and poor binding of activated charcoal. It may be useful if performed within 15–30 minutes of ingestion. Further therapy is symptomatic and supportive and may need to be continued for several days due to the long plasma half-life The rapid onset of signs prevents most forms of decontamination. Emesis may be induced in asymptomatic animals if the ingestion occurred with 15–30 minutes. Activated charcoal is not recommended as it does not readily bind alcohols. Further treatment includes IV fluids and monitoring of acid-base and electrolyte status. Hemodialysis may be useful in animals with severe hypotension and coma Treatment is similar to isopropanol toxicosis

The lethal dose of oral methanol in dogs is 4–8 mL/ kg BW. Clinical signs include CNS and respiratory depression, ataxia, hypothermia, vomiting, and coma. Metabolic acidosis is rare. Blindness only occurs in humans and primates The lethal dose of oral methanol in dogs is 5–8 mL/ kg BW. Clinical signs are similar to those associated with methanol exposures. Metabolic acidosis more likely than with a methanol exposure

Treatment is similar to isopropanol toxicosis



Canine and Feline, Seventh Edition

Appendix VII

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Leigh A. Lamont, Kurt A. Grimm, and William J. Tranquilli Pain Management

Table VII-A Recommended parenteral opioid dosages and indications Opioid

Dose/Route/Duration

Indications

Comments

Butorphanol (injectable)

Dog: 0.2–0.4 mg/kg IM, IV, or SC Cat: 0.2–0.4 mg/kg IM, IV, or SC Duration: 1–3 h Dog: 0.005–0.03 mg/kg IM, IV Cat: 0.005–0.03 mg/kg IM, IV or transmucosal Duration: 3–8 h Cat: 0.12–0.24 mg/kg SC once daily for up to 3 days for post-operative pain (SIMBADOL) Duration: 24 h Dog: 0.2–1.0 mg/kg IM or SC; 0.05–0.5 mg/kg IV Cat: 0.05–0.2 mg/kg IM or SC Duration: 3–6 h Dog: 0.25–0.5 mg/kg IV, IM or SC Cat: 0.1–0.25 mg/kg IV, IM or SC Duration 3–4 h Dog: 0.05–0.2 mg/kg IM, IV, or SC Cat: 0.05–0.2 mg/kg IM, IV, or SC Duration: 3–6 h Dog: 0.002–0.01 mg/kg IV Cat: 0.001–0.005 mg/kg IV Duration: 20–30 min

Mild to moderate pain

Mild or no sedation; mild ventilatory depression

Mild to moderate pain

May be difficult to antagonize, onset of effect 15–30 minutes

Moderate to severe pain

Sedation; respiratory depression; bradycardia; nausea; hypothermia; dysphoria in cats without pain or with large dosage; rapid IV injection may cause histamine release

Moderate to severe pain

Sedation; dysphoria, vomiting, and constipation are reportedly less than with morphine

Moderate to severe pain

Similar side effects as those observed with morphine, but less vomiting and minimal histamine release. May be associated with hyperthermia in cats Sedation; respiratory depression; bradycardia; nausea; inadequate duration of analgesia from single IV bolus or IM injection

Buprenorphine (injectable)

Morphine (injectable) Methadone (injectable) Hydromorphone (injectable) Fentanyl (injectable)

Moderate to severe pain; CRI necessary for long-term analgesia

Table VII-B Recommended dispensable opioid dosages and indications Opioid

Dose/Route/Duration

Indications

Comments

Codeine (tablets)

Dog: 1.0–2.0 mg/kg PO Cat: 0.1–1.0 mg/kg PO Duration: 4–8 h Dog: 0.5–1.0 mg/kg PO Cat: 0.5–1.0 mg/kg PO Duration: 2–4 h Dog: 2–10 mg/kg PO q8–12h Cat: 2–5 mg/kg PO q8–12h

Mild to moderate pain Mild to moderate pain

Minimal side effects; when dosed with acetaminophen, avoid in dogs with liver disease or Heinz body anemia; do not use in combination with acetaminophen in cats Mild or no sedation; mild ventilatory depression.

Mild to moderate pain

Sedation, anxiety, urinary retention

Butorphanol (tablets) Tramadol (immediaterelease tablets)

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Pain Management ( continued ) Table VII-C Recommended parenteral local anesthetic dosages and indications Local Anesthetic

Dose/Route/Duration

Indications

Comments

Moderate to CNS and cardiac toxicity with inadvertent IV injection causing Lidocaine (inject able) Dog: 6–10 mg/kg infiltrate/nerve block; severe pain excessive plasma concentrations 4 mg/kg epidural; 1–2mg/kg IV bolus followed by 0.05–0.1 mg/kg/min IV CRI Cat: 3–5 mg/kg infiltrate/ nerve block; 4 mg/kg epidural Duration: 1–1.5 h Bupivacaine Dog: 2 mg/kg infiltrate/nerve block; 1 mg/ Moderate to Cardiac and CNS toxicity with inadvertent IV injection causing severe pain excessive plasma concentrations (injectable) kg epidural Cat: 1–1.5 mg/kg infiltrate/nerve block; 1 mg/kg epidural Duration: 3–10 h Bupivacaine (liposome Dog: 5.3 mg/kg infiltrated into tissue layers Moderate to Cardiac and CNS toxicity with inadvertent IV injection causing severe pain excessive plasma concentrations; incisional inflammation/ injectable during incisional closure of cranial discharge in small number of dogs; hyperthermia in small suspension) cruciate ligament surgery (NOCITA) number of cats Cat: 5.3 mg/kg infiltrated in each forelimb for peripheral nerve block for onychectomy (NOCITA) Duration: 48–72 h

Table VII-D Recommended parenteral NSAID dosages and indications NSAID

Dose/Route/Duration

Indications

Comments

Carprofen (injectable)

Dog: 2–4 mg/kg IV, SC q24h Cat: 1.0 mg/kg SC only once

Mild to moderate pain

Meloxicam (injectable)

Dog: 0.2 mg/kg initially IM, IV, or SC; 0.1 mg/kg thereafter SC Cat: 0.1–0.2 mg/kg initially IM, SC (single dose only per label) Duration: 24 h Dog: 1.0–2.0 mg/kg initially IM, IV, or SC; 0.5–1.0 mg/kg thereafter SC Cat: 1.0–2.0 mg/kg initially IM, IV, or SC; 0.5–1.0 mg/kg thereafter SC Duration: 24 h Dog: 2.0 mg/kg SC q24h for up to 3 days; PO administration as per Table VII-E thereafter Cat: 2.0 mg/kg SC q24h for up to 3 days

Mild to moderate pain

Primarily used perioperatively before switching to oral formulation; GI irritation and altered renal function Can be mixed with food; GI irritation and altered renal function

Ketoprofen (injectable)

Robenacoxib (injectable)

Mild to moderate pain; approved in Canada for dogs and cats and in the US for horses Mild to moderate postoperative pain and inflammation

GI irritation and altered renal function. Dosing should not exceed 5 days for dogs and 3 days for cats



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Pain Management ( continued ) Table VII-E Recommended dispensable NSAID dosages and indications NSAID

Dosage/Route/Duration

Indications

Comments

Carprofen (tablets and chewables)

Dog: 4.4 mg/kg PO q24h or divided q12h Cat: 1.0 mg/kg PO (1 dose only) Duration: 12–24 h Dog (post-operative pain): 3.0–4.0 mg/kg PO q24 h as needed for 7 days Dog (osteoarthritis): 1–2 mg/kg PO q24h for long-term treatment over 7 days Cat; not used Duration: 24 h Dog: 5 mg/kg PO q24h Cat: not used Duration: 24 h

Mild to moderate pain; approved for use in dogs with osteoarthritis or perioperative pain

Toxicity associated with chronic use in cats due to variable half-life; may cause GI irritation and altered renal function in some patients

Pain and inflammation associated with osteoarthritis. Post-operative pain and inflammation associated with orthopedic surgery in dogs with osteoarthritis

GI irritation and altered renal function

Pain and inflammation associated with osteoarthritis and perioperative pain

GI irritation and altered renal function

Dog: 2 mg/kg PO q24h; cannot be dosed accurately in dogs weighing less than 3.6 kg Cat: not used Duration: 24 h

Pain and inflammation associated with osteoarthritis

Dog: 10–25 mg/kg PO Cat: 10–15 mg/kg PO Duration: 8–12 h for dogs, 24–72 h for cats Dog: 0.2 mg/kg initially PO; 0.1 mg/kg thereafter PO Cat: 0.1–0.2 mg/kg initially PO; 0.05–0.1 mg/kg thereafter PO (reduce to minimum effective dose) Duration: 24 h Dog: 2.0 mg/kg PO q24h for up to 3 days Cat: 1 mg/kg PO q24h for up to 3 days Duration: 24 h Dog: 1.0–2.0 mg/kg initially PO; 0.5–1.0 mg/kg thereafter PO Cat: 1.0–2.0 mg/kg initially PO; 0.5–1.0 mg/kg thereafter PO Duration: 24 h Dog: 10–15 mg/kg PO Cat: contraindicated Duration (in dogs): 8–12 h

Mild to moderate pain and inflammation

Non-COX inhibiting-NSAID; most common adverse reactions are vomiting, diarrhea, decreased appetite, decreased albumin/serum protein; give on an empty stomach to optimize oral bioavailability GI irritation and altered renal function; more likely at higher doses

Deracoxib (chewable tablets)

Firocoxib (chewable tablets) Etodolac (tablets) Grapiprant (tablets)

Aspirin (tablets)

Meloxicam (oral liquid suspension, tablets)

Robenacoxib (oral tablets)

Ketoprofen (tablets)

Acetaminophen (tablets and oral liquid suspension)

Mild to moderate pain

GI irritation and altered renal function; can be mixed with food. Cats should not be given meloxicam for > 5 days

Mild to moderate postoperative pain and inflammation

GI irritation and altered renal function

Mild to moderate pain; approved in Canada for dogs and cats and in the US for horses

GI irritation and altered renal functions. Limit administration to 5 days for both dogs and cats

Mild to moderate pain; low antiinflammatory action

Toxic to cats; often given in combination with codeine to dogs

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Pain Management ( continued ) Table VII-F Dosages and indications for selected drugs used to treat neuropathic pain Drug

Dosage/Route

Duration (PO) Comments

Ketamine (NMDA antagonist) Amantadine (NMDA antagonist)

Dog: 0.1–1.0 mg/kg IM, SC, or PO Cat: 0.1–1.0 mg/kg IM or SC Dog: 3.0–5.0 mg/kg PO Cat: 3.0–5.0 mg/kg PO

4–6 h 4–6 h 24 h 24 h

Amitriptyline (tricyclic antidepressant) Gabapentin (antiepileptic)

Dog: 1.0 mg/kg PO Cat: 2.5–10.0 mg/cat PO Dog: 2–10 mg/kg PO q8–12h; dose can be titrated up to 20 mg/kg q8–12h if necessary Cat: 1–8 mg/kg PO q8–12h

12–24 h 24 h 24 h 24 h

Low doses potentiate postoperative analgesics. Do not use with intracranial hypertension Used to potentiate or prolong analgesia. Efficacious when combined with an NSAID for management of osteoarthritisassociated pain in dogs Used to potentiate or prolong analgesia. Usually associated with few side effects other than sedation, and, occasional ataxia in cats. Has shown good results in human and animal studies

To select and administer an adjuvant analgesic properly, the veterinarian should be aware of the drug’s clinical pharmacology. The following information about the drug is necessary: (1) approved indication, (2) unapproved indication (e.g., as an analgesic) widely accepted in veterinary medical practice, (3) common side effects and potentially serious adverse effects, (4) pharmacokinetic features, and (5) specific dosing guidelines for pain.



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Appendix VIII

David Dycus, Canny Fung, and Mathieu Glassman Medications and Supplements for Osteoarthritis

This appendix has been provided to act as a quick reference for supplements and medications commonly used to treat animals with joint pain and osteoarthritis (OA). The contraindications, precautions, and interactions include all of the most common concerns for these categories. For a comprehensive list of warnings, we recommend referring to one of the many veterinary drug reference that are available.

The authors have also included a subjective evaluation of the level of evidence-based, peer-reviewed research that is available to support the use of these medications and supplements in clinical practice to support animals with osteoarthritis and inflammation: •  NONE—No evidence to support use in the clinical veterinary patient. •  WEAK—Evidence that shows minimal benefit to the veterinary patient clinically or

in vitro. There may be human literature that could be inferred to the veterinary patient. •  MODERATE—Evidence that shows in vitro and/or in vivo benefit for OA and joint pain. •  STRONG—Compelling evidence that shows benefit for OA and joint pain support in the clinical veterinary patient.

Table VIII-A Anti-inflammatories and pain medications

Category

Dosage

NMDA antagonist (amantadine)

Contraindications

Precautions

Interactions

NONE—for OA Concurrent May reduce seizure management administration with threshold monoamine Sedation at higher oxidase inhibitors, doses anipryl, SSRIs due Anticholingeric to potential of properties serotonin syndrome (constipation and urinary retention) Taper when discontinuing NONE—for OA Concurrent Patients with renal Sedation at higher Dog: 2–10 mg/kg GABA analogue, management administrations doses or hepatic therapeutic action PO q8–12h; with oral antacids Abrupt discontinuation insufficiency on neuropathic pain dose can be can reduce can lead to severe may require less is thought to involve titrated up to absorption from GI rebound pain, frequent dosing voltage-gated 20 mg/kg tract tapering the dose is or lower doses N-type calcium ion recommended channels, complete MOA unknown MODERATE Use caution in patients Concurrent Patients with Dog: 3.0–5.0 mg/ NMDA receptor administrations with seizure hypersensitivity antagonist, kg PO with urinary disorders or patient to it. Reduce complete MOA Cat: 3.0–5.0 mg/ acidifiers may on medications that dose in face of unknown. Best used kg PO increase excretion lower the seizure renal when combined or anticholinergic threshold dysfunction with another drugs and TMS may GI upset analgesic such as an enhance effects/ NSAID decrease excretion

Dog: 1.0 mg/ Amitriptyline kg PO (tricyclic antidepressant Cat: 2.5– 10.0 mg/cat [TCA]) PO

Antiepileptic (gabapentin)

Mechanism of Action

Evidence-Based Support in the Literature

TCAs inhibit serotonin Patients with renal or hepatic or and norepinephrine thyroid or reuptake and cardiac possible actions at disorders opioid receptors and nerve transmission, complete MOA unknown

(Continued )

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Medications and Supplements for Osteoarthritis ( continued ) Table VIII-A Anti-inflammatories and pain medications (continued )

Category

Dosage

Mechanism of Action

Contraindications

Precautions

Interactions

NSAIDs (various)

See Table VIII-C

Inhibit prostaglandin synthesis through cyclooxygenase enzymes. Inhibition of EP4 receptor-specific

NSAIDs must not be given with steroids

Opioids (various)

See Tables VIII-A and VIII-B

Natural opioid prodrug None with suspected metabolism to active metabolites including morphine. Efficacy reflects the agonistic action of mu opioid receptors

Steroids with NSAIDs NSAIDs may cause gastric ulceration or upset COX-2 selective drugs may interfere with liver function when used outside of dosage range When switching NSAIDs wait 3 days for washout before starting new drug When switching from aspirin to NSAID 7 days for washout is required Use caution in patients May decrease the with head trauma effects of diuretics in patients with CHF

Evidence-Based Support in the Literature STRONG

MODERATE

To select and administer an adjuvant analgesic properly, the veterinarian should be aware of the drug’s clinical pharmacology. The following information about the drug is necessary: (1) approved indication, (2) unapproved indication (e.g., as an analgesic) widely accepted in veterinary medical practice, (3) common side effects and potentially serious adverse effects, (4) pharmacokinetic features, and (5) specific dosing guidelines for pain. NMDA = N-methyl-d-aspartate; GI = gastrointestinal; NSAID = nonsteroidal anti-inflammatory drug.

Table VIII-B Recommended parenteral NSAID dosages and indications NSAID

Dose/Route/Duration

Indications

Carprofen (injectable)

Dog: 2–4 mg/kg IV, SC q24h Cat: 1.0 mg/kg SC only once

Mild to moderate pain

Ketoprofen (injectable)

Dog: 1.0–2.0 mg/kg initially IM, IV, or SC; 0.5–1.0 mg/kg thereafter SC Cat: 1.0–2.0 mg/kg initially IM, IV, or SC; 0.5–1.0 mg/kg thereafter SC Duration: 24 h Dog: 0.2 mg/kg initially IM, IV, or SC; 0.1 mg/kg thereafter SC Cat: 0.1–0.2 mg/kg initially IM, SC (single dose only per label) Duration: 24 h

Meloxicam (injectable)

GI = gastrointestinal; NSAID = nonsteroidal anti-inflammatory drug.

Comments

Primarily used perioperatively before switching to oral formulation; GI irritation and altered renal function. GI irritation and altered renal function. Mild to moderate pain; Dosing should not exceed 5 days for dogs approved in Canada for dogs and 3 days for cats. and cats and in the US for horses Mild to moderate pain

Can be mixed with food; GI irritation and altered renal function



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Medications and Supplements for Osteoarthritis ( continued ) Table VIII-C Recommended oral NSAID dosages and indications NSAID

Dosage/Route/Duration

Acetaminophen (tablets and oral Dog: 10–15 mg/kg PO liquid suspension) Cat: contraindicated Duration (in dogs): 8–12 h Aspirin (tablets) Dog: 10–25 mg/kg PO Cat: 10–15 mg/kg PO Duration: 8–12 h for dogs, 24–72 h for cats Carprofen (tablets and Dog: 4.4 mg/kg PO q24h or divided q12h chewables) Cat: 1.0 mg/kg PO (1 dose only) Duration: 12–24 h Deracoxib (chewable tablets)

Dog (postoperative pain): 3.0–4.0 mg/kg PO q24h as needed for 7 days Dog (OA): 1–2 mg/kg PO q24h for long-term treatment over 7 days Duration: 24 h

Etodolac (tablets)

Dog: 10–15 mg/kg PO Cat: not used Duration: 24 h

Firocoxib (chewable tablets)

Dog: 5 mg/kg PO q24h

Gapriprant (tablets)

Dog: 2mg/kg PO q24h Cat: up to 15mg/kg/day for 28 days

Ketoprofen (tablets)

Dog: 1.0–2.0 mg/kg initially PO; 0.5– 1.0 mg/kg thereafter PO Cat: 1.0–2.0 mg/kg initially PO; 0.5– 1.0 mg/kg thereafter PO Duration: 24 h Dog: 0.2 mg/kg initially PO; 0.1 mg/kg thereafter PO Cat: 0.1–0.2 mg/kg initially PO; 0.05– 0.1 mg/kg thereafter PO (reduce to minimum effective dose) Duration: 24 h Dog: 2 mg/kg SC once prior to surgery, 1 mg/kg PO q24h for up to 12 days Cat: 1 mg/kg PO up to 3 days in US Duration: 24 h Dog: Load 20 mg/kg, then 10 mg/kg PO q24h

Meloxicam (oral liquid suspension, tablets)

Robenacoxib (oral tablets and injectable in some countries) Tepoxalin (tablets)

Indications

Comments

Mild to moderate pain; low anti-inflammatory action

Toxic to cats; often given in combination with codeine to dogs

Mild to moderate pain and inflammation

GI irritation and altered renal function; more likely at higher doses. Not commonly used as there are better options available today Toxicity associated with chronic use in cats due to variable half-life; may cause GI irritation and altered renal function in some patients GI irritation and altered renal function

Mild to moderate pain; approved for use in dogs with OA or perioperative pain Pain and inflammation associated with OA. Post-operative pain and inflammation associated with orthopedic surgery in dogs with OA. Postoperative ≥ 1.8 kg Mild to moderate pain Hypoproteinemia; GI irritation and altered renal function. Associated with KCS in a small number of dogs Not commonly used as there are better options available today Pain and inflammation GI irritation and altered renal function associated with OA and perioperative pain Pain and inflammation GI irritation. No safety evaluation in associated with OA dogs younger than 9 months of age or weighing less than 3.6 kg. FDA approved in dogs GI irritation and altered renal Mild to moderate pain; functions. Limit administration to 5 approved in Canada for days for both dogs and cats. dogs and cats and in the US Not commonly used as there are for horses better options available today Mild to moderate pain GI irritation and altered renal function; can be mixed with food. Cats should not be given meloxicam for >5 days Mild to moderate pain; not approved for dogs in US

GI irritation and altered renal function. Only FDA-approved NSAID for cats

Pain and inflammation associated with OA

GI irritation. Give with food. Caution in patients with hepatic, cardiac and renal dysfunction No safety evaluation in dogs younger than 6 months of age or weighing less than 3 kg

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Avocado Soybean unsaponifiables (ASU)

Mechanism of Action

Large variation in products Large variation in products

None

Use cautiously in patients prone to pancreatitis, high dosages of omega-3 fatty acids without incorporation of diet and daily exercise will lead to weight gain Use caution in patients with underlying clotting or platelet pathology

None

None None

None

None

None

GAGs = glycosaminoglycans; MMP = matrix metalloproteinsases; IL-1 = interleukin-1; TIMP = tissue inhibitors of metalloproteinase.

None

None

None

None

None

WEAK

STRONG

STRONG

None

None

STRONG

WEAK

WEAK

STRONG

Evidence-Based Support in the Literature

None

None

None

Interactions

Contraindications Precautions

Disease-Modifying Drugs (DMOADs)

Stimulates aggrecan production and restored aggrecan production after IL-1β treatment and decreased MMP-3 production and stimulated TIMP-1 production Chondroitin 800 mg/day Stimulates synthesis of GAGs and inhibit degradative enzymes Glucosamine 1000 mg/day Used in the synthesis of disaccharide units of GAGs and proteoglycans. May have anti-inflammatory properties and may stimulate GAGs , proteogylcan and collagen synthesis, may scavenge oxygen-derived free radicals, stimulate hyaluronic acid synthesis May have chondroprotective and Green-lipped mussel 20–49 mg/kg/day; 4 (dogs 40 kg BW) capsules/ day for 10 days then continuing with half of the loading dose Competes with omega-6 fatty Omega-3 fatty acid Eicosapentaenoic acid (EPA), acids in particular arachadonic Dochosahexaenoic acid (DHA) acid to minimize the (150–175 mg/kg of DHA and/or EPA inflammatory cascade, in daily; canine addition can cause the inhibition of release of cyclooxygenase and lipoxygenase Polysulfated (2 mg/lb IM twice weekly for 4 weeks; Not completely known suspected to inhibit serine proteinases, glycosaminoglycans Canine) (Adequan) Off label usage for SC route, for felines, prostaglandin E2 synthesis, and metalloproteases. May stimulate and for monthly maintenance synthesis of protein, collagen, proteoglycan, and hyaluronic acid Unknown; homeopathic T-Relief Dogs: 1–3 tablets PO q8h ingredients including arnica Newborn puppies: ½ tablet PO q24h Montana and belladonna to Weaned puppies: 1 tablet PO q8h help with minor injuries Cats: 1 tablet PO q8h

Dosage

Category

Table VIII-D

Medications and Supplements for Osteoarthritis



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Appendix IX

Christopher L. Mariani Glossary of Terminology for Seizures and Epileptic Disorders

­GLOSSARY OF TERMINOLOGY FOR SEIZURES AND EPILEPTIC DISORDERS There is no formally approved classification system for seizures or epilepsy in veterinary medicine and authors proposing such systems in the past have largely adapted human classification schemes (1–5). This proposed glossary is no different and is based mainly on publications sanctioned by the International League Against Epilepsy (ILAE) (6–11). Terms have been added, changed or eliminated to better reflect the seizure types seen in veterinary patients and the challenges inherent with the interpretation of such events in animals. This glossary is adapted from a more detailed proposal of terminology for veterinary patients (12), and interested readers are referred to this work for more details on seizure description and semiology, background on ILAE classification and adaptations for animals, and rationale for the currently proposed terms. ­ ENERAL TERMS AND DEFINITIONS G Seizure: a discrete episode suspected to be epileptic in origin. Synonym: ictus. Epileptic seizure: manifestation(s) of excessive and/or hypersynchronous activity of neurons in the brain; usually self-limiting. Epilepsy: a chronic neurologic condition characterized by recurrent seizures; has an intracranial origin. Focal seizure: a seizure whose initial signs indicate, or are consistent with, initial activation of only part of one cerebral hemisphere. Synonym: partial. Generalized seizure: a seizure whose initial signs indicate, or are consistent with, more than minimal involvement of both cerebral hemispheres. ­CLASSIFICATION OF EPILEPTIC SEIZURES 1. Motor Seizures: involving somatic musculature in any form. May consist of an increase (positive) or decrease (negative) in muscle contraction to produce a movement. 1A. Elementary Motor: a single type of contraction of a muscle or group of muscles that is usually stereotyped. •  Tonic: a sustained increase in muscle contraction lasting a few seconds to minutes. •  Myoclonic: sudden, brief (< 100 ms), involuntary single or multiple contractions of muscles or muscle groups of variable topography (axial, proximal limb, distal limb, facial). ◦  Clonic: myoclonus that is regularly repetitive, involves the same muscle groups, at a frequency of approximately 2–3 per second, and is prolonged.

•  Tonic-clonic: a sequence consisting of a

tonic followed by a clonic phase. ◦  Generalized tonic-clonic seizure: bilateral symmetric tonic contraction and then bilateral clonic contractions of somatic muscles, usually associated with autonomic phenomena and loss of consciousness. Synonyms: grand mal seizure, bilateral tonic-clonic seizure, major motor seizure. •  Atonic: sudden loss or diminution of muscle tone without an apparent preceding myoclonic or tonic event lasting greater than 1–2 seconds and involving the head, trunk, jaw or limb musculature. •  Astatic: loss of erect posture that results from an atonic, myoclonic or tonic mechanism. Synonym: drop attack. 1B. Automatism: a more or less coordinated, repetitive, motor activity usually occurring when cognition is impaired. Often resembles a voluntary movement. Examples might include chewing, licking, aimless running, or vocal utterances (e.g., barking, meowing, whining or growling). 2. Non-motor Seizures Aura: an ictal phenomenon that may precede an observable seizure or if occurring alone, constitutes a sensory seizure. Sensory seizure: a perceptual experience not caused by appropriate stimuli in the external world. Note: Although sensory seizures almost certainly occur in animals, documenting their existence is obviously very difficult without the ability of the patient to describe sensory phenomena. Therefore, we are left to observe the behavior that the suspected sensory seizure produces. Some potential sensory phenomena include visual events (e.g., flashing or flickering lights, or other objects or patterns; the animal may bite or snap in response [“fly biting”]), somatosensory events (tingling, numbness or electric-shock sensations; the animal may bite or lick itself or run frantically during episode), auditory, olfactory, gustatory and affective events (e.g., fear, depression, joy or anger; the animal may become aggressive towards people or other animals). Dyscognitive seizure: events in which disturbance of cognition is the predominant or most apparent feature. Note: In the ILAE glossary, cognition is composed of perception, attention, emotion, memory and executive function (which includes decision making and initiation of motor activity) (8). In animals, without a description from the patient it may again be difficult to prove that certain dyscognitive seizure types exist or differentiate them from sensory seizures. However, certain examples (e.g., events where animals

suddenly stop what they are doing and stare into space, often with a lack of appropriate responsiveness to external stimuli [“behavioral arrest”]) might be best classified here. 3. Autonomic Seizures: an objectively documented and distinct alteration of autonomic nervous system function involving cardiovascular, pupillary, gastrointestinal, sudomotor, vasomotor, and thermoregulatory functions. ­MODIFIERS AND DESCRIPTORS OF SEIZURE TIMING Duration: time between the beginning of initial seizure manifestations and the cessation of observed seizure activity. Does not include prodrome or postictal states but might include aura. Cluster seizures: two or more seizures within a 24-hour period. Synonyms: acute repetitive seizures, serial seizures Status epilepticus: 1) a seizure that persists for greater than 5 minutes or 2) recurrent seizures without interictal resumption of baseline central nervous system function. Prodrome: a pre-ictal phenomenon. A subjective or objective clinical alteration (e.g., agitation, attention-seeking) that heralds the onset of an epileptic seizure but does not form part of it. Note: It may be quite challenging or impossible to differentiate a prodrome (pre-ictal period) from an aura (start of ictus) in many veterinary patients although videotaping of the episodes, close observation and/or ictal electroencephalography may be helpful in this regard. Postictal phenomenon: a transient clinical abnormality of central nervous system function that appears or becomes accentuated when clinical signs of the ictus have ended. May manifest as impaired mentation, altered behavior or motor or sensory deficits. Provocative factor: transient and sporadic endogenous or exogenous element capable of augmenting seizure incidence in animals with chronic epilepsy or evoking seizures in susceptible individuals without epilepsy. •  Reactive: occurring in association with transient systemic perturbation or illness such as some metabolic conditions (e.g., hypoglycemia, electrolyte disorders) or intoxications. •  Reflex: objectively and consistently demonstrated to be evoked by a specific afferent stimulus or by activity of the patient. Examples include stimuli such as light flashes, certain noises or startling and activities such as specific motor movements or more complex behaviors. ­CLASSIFICATION OF EPILEPSY Epilepsy is defined here as a chronic neurologic disorder that causes recurrent seizure activity, and that has an intracranial (Continued )

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etiology. As stated by the ILAE Classification Core Group in 2006, “the diagnosis of epilepsy implies a persistent epileptogenic abnormality of the brain that is able to spontaneously generate paroxysmal activity. This is in contrast to a brain that has an acute seizure as a natural response to a transient insult or loss of homeostasis” (10). Thus, seizures caused by extracranial disorders such as metabolic conditions (e.g., hypoglycemia, electrolyte abnormalities) or toxins are not considered to be epilepsy, even when repetitive seizures occur over time (e.g., with hypoglycemia secondary to an insulinoma). These seizures are termed reactive seizures (see definition under “provocative factor” above). Note however that such a disorder might secondarily cause structural damage to a previously normal brain (e.g., through necrosis or excitotoxicity) and result in true epilepsy. An explanation of the term “idiopathic epilepsy” is also warranted here, as veterinarians use the word “idiopathic” in various ways. Some use this term to imply epilepsy of genetic or heritable origin (as it was originally intended for use in humans), while others use “idiopathic” to mean “cause unknown.” The following classification is proposed to replace those previously used in veterinary medicine and has been adapted from a 2010 ILAE report (11). Genetic epilepsy: Epilepsy as a direct result of a known or strongly suspected genetic defect or defects in which seizures are the core sign of the disorder. Generally, genetic epilepsies have no identifiable structural brain lesion or other neurologic signs, and have an age-dependent onset. Synonyms: Primary, inherited, idiopathic (for some).

Structural epilepsy: Epilepsy as a result of one or more identifiable structural lesions of the brain. Synonyms: Symptomatic, secondary. Structural epilepsies include disorders such as brain tumors, encephalitis, and cerebrovascular accidents. Note that some disorders that may have a genetic cause or that are strongly heritable may still be best classified here; these include anomalous disorders such as hydrocephalus, lissencephaly, degenerative disorders such as ceroid lipofuscinosis, and others. Unknown epilepsy: The underlying cause of the epilepsy is unknown. This may be the result of a subtle structural lesion that is undetectable with currently available diagnostic technologies or an as yet unrecognized genetic disorder. Synonyms: Cryptogenic, probably symptomatic, idiopathic (for some).

­References

1 Berendt M, Gram L. Epilepsy and seizure classification in 63 dogs: A reappraisal of veterinary epilepsy terminology. J Vet Intern Med 1999;13:14–20. 2 March PA. Seizures: Classification, etiologies, and pathophysiology. Clin Tech Small Anim Pract 1998;13:119–131. 3 Podell M. Seizures in dogs. Vet Clin North Am Small Anim Pract 1996;26:779–809. 4 Podell M. Seizures. In: Platt SR, Olby NJ, editors. BSAVA manual of canine and feline neurology. Gloucester: British Small Animal Veterinary Association; 2013, pp. 117–135. 5 Podell M, Fenner WR, Powers JD. Seizure classification in dogs from a nonreferralbased population. J Am Vet Med Assoc 1995;206:1721–1728.

  6 Proposal for revised classification of epilepsies and epileptic syndromes. Commission on Classification and Terminology of the International League Against Epilepsy. Epilepsia 1989;30: 389–399.   7 Blume WT, Luders HO, Mizrahi E, Tassinari C, van Emde Boas W, Engel J, Jr. Glossary of descriptive terminology for ictal semiology: Report of the ILAE Task Force on Classification and Terminology. Epilepsia 2001;42:1212–1218.   8 Engel J, Jr. A proposed diagnostic scheme for people with epileptic seizures and with epilepsy: Report of the ILAE Task Force on Classification and Terminology. Epilepsia 2001;42:796–803.   9 Fisher RS, van Emde Boas W, Blume W, Elger C, Genton P, Lee P, et al. Epileptic seizures and epilepsy: Definitions proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE). Epilepsia 2005;46:470–472. 10 Engel J, Jr. Report of the ILAE classification core group. Epilepsia 2006;47:1558–1568. 11 Berg AT, Berkovic SF, Brodie MJ, Buchhalter J, Cross JH, van Emde Boas W, et al. Revised terminology and concepts for organization of seizures and epilepsies: Report of the ILAE Commission on Classification and Terminology, 2005–2009. Epilepsia 2010;51:676–685. 12 Mariani CL. Terminology and classification of seizures and epilepsy in veterinary patients. Top Companion Anim Med 2013;28:34–41.



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Appendix X Common Procedures and Testing Protocols

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Abdominocentesis and Fluid Analysis

­

 BASICS

TYPE OF PROCEDURE Diagnostic sample collection. PROCEDURE EXPLANATION AND RELATED PHYSIOLOGY •  Abdominocentesis is the percutaneous removal of peritoneal fluid for diagnostic and/ or therapeutic purposes. •  Characterization of abdominal fluid may help determine primary disease process or pathophysiologic mechanism responsible for fluid accumulation. •  Blind abdominocentesis is easily performed when a large amount of fluid is present; ultrasound-guided abdominocentesis is useful when fluid volume is limited or localized. •  Diagnostic peritoneal lavage (DPL) is most often considered if abdominocentesis has failed to yield any fluid and undiagnosed intra-abdominal disease is suspected. •  Therapeutic abdominocentesis may improve quality of life in conjunction with medical management of chronic ascites.

bladder) and iatrogenic peritonitis. •  Spread of infection, especially from a localized lesion (e.g., abscess, pyometra). •  Tearing of a fenestrated over-the-needle catheter in the abdomen during removal. •  Large-volume abdominocentesis may cause rapid fluid shifts and electrolyte changes: ◦  Avoid removing large volumes from animals that have serum albumin of ≤2 g/dL. •  In addition to the above, DPL may result in subcutaneous hematoma or leakage of lavage fluid.

examination (abdominal distention, fluid wave) or diagnostic imaging. •  Blunt or penetrating abdominal trauma (e.g., dog bite, gunshot wound, motor vehicular accident). •  Suspicion of ruptured bowel, peritonitis, or postoperative GI dehiscence. •  Acute abdominal pain. •  Shock without apparent cause. •  DPL—with suspicion of undiagnosed intra-abdominal disease in face of negative abdominocentesis. •  Therapeutic abdominocentesis—when increased intra-abdominal pressure causes respiratory distress, decreased blood flow to visceral organs, or discomfort. CONTRAINDICATIONS

•  Abdominocentesis should be performed with

For Abdominocentesis

•  Hypodermic needle: 18- through 22-gauge,

diagnostic procedure that is generally easy to perform and associated with minimal risk and discomfort. •  Abdominocentesis is usually performed in awake patients, but sedation and/or analgesia may be necessary.

1- to 1½-inch or over-the-needle IV catheter of similar size. Butterfly catheters may be used in small or thin patients. •  Consider addition of fenestrations in large gauge (14–18 gauge) over-the-needle catheters using a sterile scalpel blade. Fenestrations should be small and smooth and should not be directly opposite each other, as this may lead to catheter weakening and possible kinking or tearing within abdomen. •  Optional: extension set. •  For therapeutic abdominocentesis, a three-way stopcock, 20- to 60-mL syringe, and collection vessel.

BODY SYSTEMS ASSESSED

For DPL

CLIENT EDUCATION

•  Abdominocentesis is a minimally invasive

•  Hepatobiliary. •  Urinary. •  Gastrointestinal. •  Vascular (as with hemoabdomen).

INDICATIONS

•  Peritoneal fluid suspected based on physical

•  2% Lidocaine (injectable). •  Glass slides. •  EDTA and serum tubes and culturettes.

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 PROCEDURE

PATIENT PREPARATION Pre-Procedure Medication or Preparation

Consider emptying a distended urinary bladder prior to abdominocentesis or DPL. Anesthesia or Sedation

Patients should be restrained either manually or with sedation/analgesia to prevent unwanted motion that could result in complications. Prior to drug administration, consider patient’s general and cardio­vascular condition (e.g., shock) and procedure being performed (sedation and local analgesia almost always indicated for DPL). Patient Positioning

caution or is contraindicated in presence of: ◦  Dilated hollow abdominal viscus (stomach and intestines), generalized ileus. ◦  Organomegaly. ◦  An enlarged uterus because of pregnancy or pyometra. ◦  Coagulopathy, thrombocytopenia. •  An uncharacterized large intra-abdominal mass is contraindication for blind abdominocentesis. •  Avoid DPL if diaphragmatic hernia suspected.

Patient in left lateral recumbency (to prevent splenic puncture) or can remain standing to improve gravity-dependent fluid retrieval. Patient positioning may be altered based on visualization of fluid using ultrasound guidance.

POTENTIAL COMPLICATIONS •  Hemorrhage from a punctured vessel or lacerated abdominal organ. •  Perforation of a hollow viscus (bowel,

•  Clippers. •  Surgical scrub. •  Sterile gloves. •  Syringes of various sizes (3, 5, or 10 mL).

Patient Monitoring

Blood pressure, pulse oximetry, and heart rate/ECG should be monitored as indicated by patient’s clinical status. Patients should be monitored for signs of pain or discomfort. Equipment or Supplies

•  A commercially available peritoneal dialysis

catheter or alternatively a 20- to 14-gauge, over-the-needle, 1–2 inch IV catheter, fenestrated as described previously. •  A bag of warmed sterile isotonic saline solution with an administration set. •  3- to 12-mL syringes. •  A three-way stopcock attached to an extension set (optional). TECHNIQUE Closed or Open Needle Abdominocentesis

•  Abdominocentesis site is just caudal to

umbilicus, on ventral midline or slightly lateral to the right (2–3 cm in mid-sized dogs). In a standing patient, site is at most dependent part of abdomen. •  A 10 × 10 cm area should be clipped, and skin prepared aseptically. •  Lidocaine 2% local anesthetic may be infused at the abdominocentesis site. •  Needle is inserted through skin and abdominal wall; if using an over-the-needle catheter, catheter is fed off stylet once in the abdomen (typically fluid visible in hub): ◦  If needle or catheter is not attached to a syringe, collect the fluid into a sterile tube as it drips from the hub (this technique may introduce air into abdomen). ◦  If needle or catheter is attached to syringe or extension set and syringe, apply gentle suction; vigorous suction may result in false-negative result. •  Collect fluid aseptically, perform cytologic analysis, bacteriologic culture, other diagnostics as indicated. •  For therapeutic abdominocentesis, extension set and 3-way stopcock are mounted on needle or catheter and attached to a syringe.



Canine and Feline, Seventh Edition



Abdominocentesis and Fluid Analysis

(continued)

•  When using an over-the-needle catheter

with added fenestrations, take care to remove it completely by gently rotating it or dissecting it from subcutaneous tissue.

Four-Quadrant Abdominocentesis

•  Divide ventral surface of abdomen into 4

quadrants by an imaginary line that bisects linea alba and through the umbilicus. •  Wide surgical prep centered at umbilicus. •  Insert needles, one at a time, in each quadrant until fluid is retrieved. •  Fluid should flow through needle into sampling tubes. •  False-negative results more likely if suction applied. Ultrasound-Guided Abdominocentesis •  Locate small volume or localized effusion

with ultrasonography.

•  Clip hair on a 10 × 10 cm area and prepare

aseptically.

•  Mount needle on syringe or extension set

attached to syringe, insert under ultrasound guidance into pocket of fluid and gently aspirate.

Diagnostic Peritoneal Lavage (Closed Technique)

•  Consider imaging (abdominal radiographs,

CT, or ultrasound) prior to DPL as this procedure will alter results. •  DPL site is 1–3 cm caudal to umbilicus, on midline or just right from midline. •  Wide surgical prep centered at umbilicus. •  Infiltrate skin and abdominal wall with local anesthetic at puncture site. •  Make a stab incision through skin with a number 11 scalpel blade at site of local anesthetic infusion. •  Introduce catheter with stylet into abdomen through stab incision. •  Slide catheter off stylet dorsocaudally into abdomen. •  Once catheter is in abdomen, attach syringe and aspirate gently. If fluid is retrieved, there is no need to proceed with lavage. •  In the absence of fluid, infuse 20–22 mL/ kg of warm sterile 0.9% saline solution through catheter using an IV infusion set with rapid gravity flow. •  After completing infusion, have patient walk around (if able) or roll patient gently from side to side to disperse fluid, taking care not to dislodge catheter. •  Aspirate catheter gently with a syringe to remove fluid sample. Most often, only a small portion of instilled fluid is retrieved; remaining fluid will be reabsorbed by peritoneum. •  Collect lavage fluid aseptically and analyze.

◦  EDTA tube for cytologic evaluation,

including red blood cell and nucleated cell counts and differential (not for culture). ◦  A serum tube for biochemical analysis as indicated (may need concurrent analysis on peripheral blood; see below). ◦  A culturette or an additive-free glass tube, for aerobic and anaerobic bacterial culture, depending on laboratory preference. •  Determine specific gravity and total solids (TS) by refractometry. •  Direct microscopic cytologic evaluation: smear small drop of fluid across a slide, air-dry, and apply Romanovsky-type stain (Diff-Quik, Hema III, Giemsa, or Wright stain). For hypocellular fluids (2,000–50,000 cells/μL), a drop from the resuspended pellet of a centrifuged sample can be evaluated. Cytospin preparation may be necessary for very hypocellular (100 mg/dL. •  FIP—abdominal fluid albumin/globulin ratio 5% in DPL fluid is indicative of hemorrhage. •  Uroabdomen—abdominal fluid creatinine concentration higher than serum creatinine concentration (>2:1), potassium concentration in effusion greater than serum potassium (>1.4:1). BUN is not reliable for diagnosis of uroabdomen (rapidly equilibrates across peritoneum). •  Bile peritonitis—fluid bilirubin concentra­ tion higher than that of serum, extra- or intracellular bile pigment usually found on cytologic examination. •  Pancreatitis—higher fluid amylase and lipase concentrations than serum suggest pancreatitis. Peritoneal fluid canine-specific pancreatic lipase (cPL) concentration is very sensitive in dogs as an aid in diagnosis of acute pancreatitis. •  Peritonitis—>1,000 WBCs/μL in lavage fluid. •  Septic peritonitis—intracellular bacteria (± extracellular bacteria), presence of degenerate neutrophils are diagnostic for septic effusion. Additionally, the fluid lactate concentration is higher in septic vs. nonseptic effusions. In dogs, a fluid lactate concentration >2.5–4 mmol/L and a blood-to-fluid lactate difference of >2 mmol/L has good sensitivity and specificity for diagnosing septic effusion. This may be less reliable in cats. A blood-tofluid glucose difference of >37 mg/dL is sensitive and specific for septic peritoneal effusion in dogs and cats. •  Eosinophilic effusion—>10% eosinophils in fluid. •  Aberrant cestodiasis—the presence of Mesocestoides spp.

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Abdominocentesis and Fluid Analysis CRITICAL VALUES •  After adequate cardiovascular resuscitation, the following conditions need immediate attention and might require exploratory celiotomy: ◦  Septic peritonitis. ◦  Uroabdomen. ◦  Bile peritonitis. ◦  Hemoabdomen. INTERFERING FACTORS Drugs That May Alter Results of the Procedure

Avoid sedative agents that induce spleno­megaly. Conditions That May Interfere with Performing the Procedure •  If there is abdominal distention,

differentiate between organomegaly, intra-abdominal fat, and fluid accumulation before abdominocentesis. •  Adhesions from previous surgeries may interfere with DPL. •  Insufficient fluid quantity for technique used. •  Flocculent or fibrinous fluid. •  Fluid localized in a difficult to access space (e.g., cranial to liver). •  Negative abdominocentesis is possible in a patient with an acute disease process. Repeat imaging and/or abdominocentesis can be considered if indicated based on clinical signs and increased suspicion of intra-abdominal disease. •  A negative abdominocentesis is possible in a patient with severe dehydration or hypo­ volemia; repeat imaging and abdominocentesis following IV fluid resuscitation. Procedure Techniques or Handling That May Alter Results •  Vigorous suction can result in needle or

catheter blockage by omentum or viscera.

•  In the absence of coagulopathy, blood from

traumatic sampling will usually clot when exposed to an artificial surface, whereas peritoneal effusion will not. •  Degenerate neutrophils and intracellular bacteria are signs of septic peritonitis; while bacteria and debris may be present if a loop of

(continued)

bowel is aspirated, typically degenerate neutrophils are absent.

SEE ALSO Ascites.

Influence of Signalment on Performing and Interpreting the Procedure

ABBREVIATIONS •  DPL = diagnostic peritoneal lavage. •  PCV = packed cell volume. •  TS = total solids.

Species None

­Suggested Reading

Breed None

Age

None

Gender None

Pregnancy

Relative contraindication because of an enlarged uterus.

Clinical Perspective

•  Many different diseases may manifest with

peritoneal effusion; cytologic and fluid analysis are indicated for every effusion. •  Use of a fenestrated catheter vs. a needle may increase likelihood of fluid retrieval. •  DPL may provide superior diagnostic accuracy but is much more time intensive to perform, and samples are diluted.

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 MISCELLANEOUS

ANCILLARY TESTS •  CBC, serum biochemistry, and urinalysis. •  Abdominal ultrasonography: assess parenchymal integrity, identify small fluid volume. •  Any additional testing to determine primary etiology of abdominal effusion (nonexhaustive list; see Ascites): ◦  Thoracic radiography, echocardiogram, and ECG (right-sided heart failure, pericardial effusion, metastatic neoplasia). ◦  Excretory urography or contrast cystourethrogram if uroabdomen is suspected. ◦  Serum bile acids if hepatic failure/portal hypertension is suspected. SYNONYMS

•  Abdominal tap.

Bonczynski JJ, Ludwig LL, Barton LJ, et al. Comparison of peritoneal fluid and peripheral blood pH, bicarbonate, glucose, and lactate concentration as a diagnostic tool for septic peritonitis in dogs and cats. Vet Surg 2003; 32:161–166. Chartier MA, Hill SL, Sunico S, et al. Pancreas-specific lipase concentrations and amylase and lipase activities in the peritoneal fluid of dogs with suspected peritonitis. Vet J 2014, 201: 385–389. Connally HE. Cytology and fluid analysis of the acute abdomen. Clin Tech Small Anim Pract 2003, 18:39–44. Jandry KE. Abdominocentesis and diagnostic peritoneal lavage. In: Silverstein D, Hopper K, eds., Small Animal Critical Care Medicine, 2nd ed. St. Louis, MO: Elsevier, 2015, pp1036–1039. Koenig A, Verlander LL. Usefulness of whole blood, plasma, peritoneal fluid, and peritoneal fluid supernatant glucose concentrations obtained by a veterinary POC glucometer to identify septic peritonitis in dogs with peritoneal effusion. J Am Vet Med Assoc 2015, 247:1027–1032. Levin GM, Bonczynski JJ, Ludwig LL, et al. Lactate as a diagnostic test for septic peritoneal effusions in dogs and cats. J Am Anim Hosp Assoc 2004; 40:364371. Martiny P, Goggs R. Biomarker guided diagnosis of septic peritonitis in dogs. Front Vet Sci 2019, 6:208. Schmiedt C, Tobias, KM, Otto CM. Evaluation of abdominal fluid: peripheral blood creatinine and potassium ratios for diagnosis of uroperitoneum in dogs. J Vet Emerg Crit Care 2001, 11:275–280. Author Kim Slensky Consulting Editor Benjamin M. Brainard Acknowledgment The author and editors acknowledge the prior contribution of Karine Savary Bataille.



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Arthrocentesis With Synovial Fluid Analysis •  Dexmedetomidine 3–10 μg/kg IM or IV to

effect.

­

 BASICS

TYPE OF PROCEDURE Diagnostic sample collection. PROCEDURE EXPLANATION AND RELATED PHYSIOLOGY Synovial fluid is normally a clear, viscous fluid essential in the mechanical function of joints. Synovial fluid analysis is integral in the diagnosis and characterization of joint disease in canine and feline patients. Joint disease can involve one or more joints and can be due to infectious, inflammatory or noninflammatory etiologies. Synovial fluid analysis can differ­ entiate inflammatory vs. noninflammatory arthropathies and can aid in determination of the underlying cause. Arthrocentesis is a safe, quick, and relatively easy procedure to perform in most clinical settings and involves fine-needle aspiration of joint fluid. The equipment needed is minimal and inexpensive, and the techniques are not difficult to learn, requiring only basic knowledge of joint anatomy. INDICATIONS •  Joint pain or effusion. •  Lameness/stiffness or gait abnormality. •  Fever of unknown origin. •  Undefined lethargy or nonspecific pain. CONTRAINDICATIONS

•  No absolute contraindications. •  Caution with coagulopathy. •  Caution with severe thrombocytopenia

(24 mmol/L) and respiratory if associated with a decreased Pco2 (95% of domestic shorthairs); 1–2/LPF associated with degeneration/ necrosis of tubules (e.g., ischemia, toxins, infarct)

Fatty

Common in cats with renal tubular degeneration

Waxy

Associated with chronic degeneration/necrosis of tubules (e.g., ischemia, toxins, infarct)

Yeast Fungi (hyphae or budding) Nematode ova Microfilariae Algae

Lipids Mucus Contaminants

Pollen grains Sperm Glove powder Fibers

Infection of the urinary tract, infection of the genital tract (voided sample), in vitro growth with delayed sample analysis, or contamination (voided and some catheterized samples) Often Candida spp. Blastomyces spp., Cryptococcus spp., or Aspergillus spp. (German shepherd dogs can have a disseminated infection) Dioctophyma renale or Capillaria plica Seen with significant hematuria Prototheca spp. (dogs can have disseminated infection) No clinical significance; may be normal; a common finding in cats Genital secretions, suggestive of urethral irritation; mucous strands may form linear structures resembling casts Occasionally found in urine sediment, not significant but may be potentially confused with other constituents

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Urine Sediment (uncommon) have been associated with crystal formation in dogs and cats. Disorders That May Alter Results

•  Casts and cells, especially RBCs, may lyse

in poorly concentrated (USG