High-yield Internal Medicine (High-Yield Series) [3 ed.] 0781781698, 9780781781695

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High-Yield Internal Medicine THIRD EDITION

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High-Yield Internal Medicine THIRD EDITION

R. Nirula, MD, MPH, FACS Assistant Professor of Surgery University of Texas Southwestern Medical Center Parkland Hospital, Division of Trauma/Burns/CC Dallas, TX

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Acquisitions Editor: Donna Balado Managing Editor: Tenille A. Sands Marketing Manager: Jennifer Kuklinski Production Editor: Eve Malakoff-Klein Designer: Holly Reid McLaughlin Compositor: Nesbitt Graphics, Inc. Printer: Data Reproductions Corporation Copyright © 2007 Lippincott Williams & Wilkins 351 West Camden Street Baltimore, MD 21201 530 Walnut St. Philadelphia, PA 19106 All rights reserved. This book is protected by copyright. No part of this book may be reproduced in any form or by any means, including photocopying, or utilized by any information storage and retrieval system without written permission from the copyright owner. The publisher is not responsible (as a matter of product liability, negligence, or otherwise) for any injury resulting from any material contained herein. This publication contains information relating to general principles of medical care that should not be construed as specific instructions for individual patients. Manufacturers’ product information and package inserts should be reviewed for current information, including contraindications, dosages, and precautions. Printed in the United States of America First Edition, 1997 Second Edition, 2003 Library of Congress Cataloging-in-Publication Data Nirula, R. (Raminder) High-yield internal medicine / R. Nirula. -- 3rd ed. p. ; cm. -- (High-yield) Includes bibliographic references and index. ISBN-13: 978-0-7817-8169-5 ISBN-10: 0-7817-8169-8 1. Internal medicine--Outlines, syllabi, etc. I. Title. II. Series: High-yield series. [DNLM: 1. Internal Medicine--Outlines. WB 18.2 N721h 2007] RC59.N55 2007 616--dc22 2006020295 The publishers have made every effort to trace the copyright holders for borrowed material. If they have inadvertently overlooked any, they will be pleased to make the necessary arrangements at the first opportunity. To purchase additional copies of this book, call our customer service department at (800) 6383030 or fax orders to (301) 223-2320. International customers should call (301) 223-2320. Visit Lippincott Williams & Wilkins on the Internet: http://www.LWW.com. Lippincott Williams & Wilkins customer service representatives are available from 8:30 am to 6:00 pm, EST. 06 07 08 09 10 1 2 3 4 5 6 7 8 9 10

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Dedication To my family . . . who keep me balanced. Derek and I anxiously awaited the emergence of our housemate from his slumber. The door opened, and a sunken shadow appeared in the doorway. Just one more step . . . that’s it. Then it happened. The silence was finally broken and our hopes were vindicated. The sounds of water hitting the flat surface of a squarish head echoed throughout the house. Then a split second of silence swallowed the walls, only to be smashed by the shrill of obscenities and the boyish laughter of two grown men. I turned to Derek with a devilish look, realizing finally the true gift of gravity and the laws of physics. —FOR SIR ISAAC NEWTON

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Contents Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .xi

1 Cardiovascular Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1 I. II. III. IV. V. VI. VII.

Congestive Heart Failure (CHF) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1 Ischemic Heart Disease (IHD) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .3 Atrial Fibrillation (AF) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .5 Valvular Heart Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .5 Cardiomyopathies and Pericardial Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .9 Deep Venous Thrombosis, Pulmonary Embolus, and Aortic Aneurysms . . . . . . . . . .13 Systemic Hypertension . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .16

2 Pulmonary Diseases I. II. III. IV. V. VI.

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .19

Obstructive Lung Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .19 Diffuse Interstitial Lung Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .24 Adult Respiratory Distress Syndrome (ARDS) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .27 Disorders of the Pleural Space, Mediastinum, and Chest Wall . . . . . . . . . . . . . . . . . .28 Neoplasms of the Lung . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .33 Pulmonary Disease of Unknown Etiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .36

3 Renal, Fluid, and Electrolyte Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .38 I. II. III. IV. V.

Renal Failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .38 Abnormal Urinalysis and Glomerulonephropathy . . . . . . . . . . . . . . . . . . . . . . . . . . .40 Renal Calculi . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .42 Renovascular Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .43 Assessment and Diagnosis of Volume and Electrolyte Disorders . . . . . . . . . . . . . . . .44

4 Gastrointestinal Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .53 I. II. III. IV. V. VI. VII.

Diseases of the Esophagus and Stomach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .53 Diseases of the Small Intestine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .59 Diseases of the Colon, Rectum, and Anus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .65 Pancreatic Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .71 Biliary Tract Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .73 Liver Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .75 Gastrointestinal Bleeding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .80

vii

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viii

CONTENTS

5 Infectious Diseases I. II. III. IV. V. VI. VII. VIII.

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .82

Central Nervous System (CNS) Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .82 Head and Neck Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .84 Respiratory Tract Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .84 Gastrointestinal Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .88 Genital and Sexually Transmitted Infectious Diseases . . . . . . . . . . . . . . . . . . . . . . . .88 Urinary Tract Infections (UTIs) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .90 Osteomyelitis and Joint Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .91 Other Infectious Syndromes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .92

6 Endocrinologic and Metabolic Disorders I. II. III. IV. V. VI. VII. VIII.

Disorders of the Pituitary Gland . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .97 Disorders of the Thyroid Gland . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .101 Disorders of the Parathyroid Gland . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .106 Glucose Homeostasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .108 Adrenal Gland Dysfunction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .111 Female Reproductive Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .116 Male Reproductive Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .119 Disorders of Bone Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .120

7 Rheumatic Diseases I. II. III. IV. V. VI. VII. VIII.

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .123

Osteoarthritis and Rheumatoid Arthritis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .123 Crystal-Related Joint Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .126 Spondyloarthropathies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .129 Systemic Lupus Erythematosus (SLE) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .132 Systemic Sclerosis (Scleroderma) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .134 Polymyositis and Dermatomyositis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .135 Sjögren Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .136 Vasculitic Syndromes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .136

8 Oncologic Diseases I. II. III. IV. V. VI. VII. VIII. IX. X. XI. XII.

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .97

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .141

Head and Neck Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .141 Renal and Bladder Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .142 Prostatic Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .142 Testicular Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .143 Ovarian Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .144 Gastric Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .144 Pancreatic Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .145 Colorectal Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .146 Lung Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .149 Multiple Myeloma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .150 The Lymphomas . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .151 The Leukemias . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .153

9 Hematologic Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .157 I. Anemias . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .157 II. Hematocrit Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .166

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III. Leukocyte Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .167 IV. Hemostasis and Coagulation Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .170

10 Neurologic Diseases I. II. III. IV. V. VI. VII. VIII. IX. X. XI.

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .175

Cerebrovascular Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .175 Disorders of Higher Cognitive Function . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .179 Dementia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .180 Seizure Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .181 Headaches . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .183 Movement Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 185 Spinal Cord Syndromes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .188 Neurocutaneous Syndromes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .192 Peripheral Neural Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .193 Neuromuscular Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .196 Multiple Sclerosis (MS) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .198

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .200

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Preface Upon completing my clerkship in Internal Medicine, I must admit that I believed I had reached a new level in my training. My senior residents had congratulated me and patted me on the back, telling me how my knowledge base was “phenomenal” and my diagnostic skills “superb.” Having my ego boosted was a wonderful sensation, and so I looked forward to the following week with vigorous delight, when I would have the opportunity to review my evaluation. The evaluation was completed by the Chief-of-Staff of Internal Medicine—a somewhat rust-colored individual with a tired look that seemed to say, “Only two more years until retirement!” Needless to say, I had never worked with him and was content with this fact. Still, I was confident that the praise that I had received from my upper colleagues had traversed the compounded cerumen of his external ear. As I flipped through my evaluations, I triumphantly reached the Internal Medicine section. With the excitement of a child on Christmas morning, I read, “. . . Dr. Nirula’s performance has been fully satisfactory . . . .” “What?!” I checked the sheet to ensure that this was, in fact, the appropriately filed evaluation. Fully satisfactory? What does that mean? Is that somehow better than simply satisfactory, and can someone be partially satisfactory, or barely satisfactory? Either you are satisfactory or you are not. Who was this guy trying to kid? Reeling from my less than gratifying review, I rationalized my meager evaluation as being the writings of an eccentric and fully psychotic individual. This rationalization allowed me to cope with the remainder of my training with minimal emotional trauma. While the experience left me jaded, I still firmly believe that clinicians should attempt to learn as much as possible during their training. Time constraints are incredible during this phase, and so reading should be devoted to sources that are concise, informative, and pertinent to one’s education. High-Yield Internal Medicine, 3rd edition, is such a book. It covers only the material you really need to know in order to pass the Step 2 board exams and survive the medicine clerkship. It employs the outline format as a user-friendly format, which is particularly effective for review. It gives useful information about common medical illnesses, presented in such a way that a young clinician can develop a rational approach to clinical medicine. In my humble opinion, it is more than a fully satisfactory resource. R. Nirula, MD

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Chapter

1

Cardiovascular Diseases I

Congestive Heart Failure (CHF) A. GENERAL CHARACTERISTICS 1. CHF is a sign of heart disease. 2. CHF is usually secondary to myocardial infarction (MI) due to coronary atherosclerotic disease. 3. Other causes include myocarditis, cardiomyopathies, valvular insufficiency or stenosis, hypertension, constrictive pericarditis, and arrhythmias. B. CLINICAL FEATURES 1. Left-sided CHF: Low cardiac output (if measured by Swan), hypotension and tachycardia (if severe), elevated pulmonary venous pressure and dyspnea. 2. Right-sided CHF: Edema in the lower extremities, hepatic congestion (possibly ascites), distended neck veins indicative of increased jugular venous pressure (JVP). 3. Left-sided failure is most frequently the cause of right-sided failure. 4. Orthopnea (dyspnea in recumbent position) is often gauged by the number of pillows the patient requires to decrease dyspneic symptoms. 5. Tachycardia occurs as a compensatory measure for decreased stroke volume. 6. Crackles on inspiration are caused by transudation of fluid into the alveoli. 7. The most reliable sign of left heart failure is the S3 heart sound occurring early in diastole due to rapid filling of the left ventricle. 8. 9. 10. 11.

S4 may also occur. Nocturia occurs due to increased renal blood flow during recumbency.

Acute CHF may present secondary to acute MI (see II.B.2). An irregular pulse may be detected that may be the cause of the CHF.

C. LABORATORY FINDINGS 1. Laboratory results vary, depending on the etiology of CHF. Elevated creatinine may indicate hypoperfusion and may indicate that all inhibitors should be avoided initially. Measurement of B-type natriuretic peptide (BNP) is specific to CHF and helps to distinguish CHF from pulmonary pathology as the etiology of dyspnea. 2. Chest radiographic study reveals an enlarged heart with increased pulmonary congestion (Figure 1-1). 3. Electrocardiogram (ECG) is useful in determining rhythm, rate, and condition abnormalities as possible causes for CHF. 4. Echocardiogram is useful in determining the degree of dysfunction as well as revealing possible etiologies such as myocardial infarction, valvular dysfunction, or pericardial effusion. 5. Cardiac catheterization is used when the etiology of the CHF must be found to treat the underlying disease effectively. 1

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2

CHAPTER 1

● Figure 1-1. Radiographic chest film showing acute congestive heart failure and pulmonary edema. Note the central symmetric butterfly pattern and the vascular redistribution, with increased pulmonary vascular markings at the apices of the lungs. (Reprinted with permission from Freundlich IM, Bragg DG: A Radiologic Approach to Diseases of the Chest, 2nd ed. Baltimore, Williams & Wilkins, 1996, p 21.)

D. TREATMENT 1. The underlying cause must be treated, if possible. Hypertension control reduces the incidence of CHF and should be undertaken before CHF develops as well as when patients present in acute CHF. 2. Treatment of pulmonary edema secondary to CHF involves: a. Oxygen by face mask b. Diuretics (furosemide) in low initial doses, if the patient is not presently taking them c. Morphine, if the patient is extremely anxious or is experiencing pain that increases demands on the heart d. Sublingual nitroglycerin, if the patient is experiencing angina; this drug is a useful adjunct to diuretic drugs in producing vasodilation, thereby reducing cardiac load e. Digoxin, which increases cardiac contractility and also is useful in controlling heart rate in patients in atrial fibrillation. It has a limited role in patients with sinus rhythm. f. Angiotensin-converting enzyme (ACE) inhibitors are effective in reducing symptoms, Na retention, and afterload. They have been shown to improve survival in patients with mild, moderate, and severe CHF. Caution should be used in renal insufficiency, and hypotension should be avoided. Angiotension-receptor blockers (ARB) have also been shown to reduce CHF-related mortality and are useful in patients in whom side effects develop to ARB inhibitors (e.g., cough). ARBs may be added to ACE inhibitors for added benefit. Renal function and hyperkalemia must be monitored.

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CARDIOVASCULAR DISEASES

3

β-Blockers have also been shown to reduce mortality and readmission rates. Their use must be started gradually because failure may be worsened if started too rapidly. h. In severe CHF, aldosterone blockage (e.g., spironolactone) is beneficial when added to β-blockage and ACE inhibitors. Their efficacy in mild to moderate CHF is unproven. If oxygenation fails to improve the patient’s deteriorating condition (e.g., persistent cyanosis, obtundation), intubation is indicated with positive pressure ventilation. Invasive hemodynamic monitoring is reserved for those cases of pulmonary edema that do not resolve. Implantable cardioverter defibrillators (ICDs) have been shown to reduce the risk of death; about half of patients with CHF die of sudden ventricular arrhythmias. g.

3. 4. 5.

II

Ischemic Heart Disease (IHD) A. GENERAL CHARACTERISTICS 1. The most common cause of IHD is atherosclerotic disease. 2. Risk factors include increasing age, male gender, elevated serum cholesterol level, smoking, hypertension, diabetes mellitus, and family history of coronary artery disease. B. CLINICAL FEATURES 1.

Angina pectoris is caused by myocardial ischemia.

a.

2.

Angina pectoris is initially precipitated by exertion and relieved by rest, but may occur at rest as IHD progresses. b. Patients experience pressure or a burning sensation in the chest, with gradual onset over 2 to 3 minutes that lasts up to 20 minutes; if pain lasts longer than 30 minutes, MI is likely. c. Pain may radiate to the arm, jaw, or neck. d. Patient is uncomfortable and anxious and has tachycardia and hypertension. e. Holosystolic murmur may be present, which indicates papillary muscle dysfunction secondary to ischemia. MI is indicated by severe chest pain or pressure that lasts longer than 30 minutes. a. Nausea and vomiting may be present. b. Patient is diaphoretic and short of breath. c. Onset is usually at rest, with pain radiation similar to that of angina. d. Patient often appears ill and has tachycardia and hypertension (hypotension may occur if infarction is substantial). e. Signs and symptoms of CHF may also be present.

C. COMPLICATIONS 1.

MI may be silent and without consequence, depending on the size of the infarct. Silent MI is more common in diabetic patients.

2. 3. 4.

Patients may develop CHF and pulmonary congestion. Hypotension and cardiogenic shock may occur in significant infarction. Acute onset of CHF in conjunction with holosystolic murmur after MI usually

5.

indicates papillary muscle rupture with mitral valve insufficiency or ventricular septal rupture. Life-threatening ventricular arrhythmias are common in the first 24 hours after MI.

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CHAPTER 1

6.

Inferior wall MIs often produce sinus bradycardia and/or atrioventricular nodal

block. 7. 8. 9.

Bundle-branch blocks are more likely with anterior MIs. Left ventricular arrhythmias may lead to systemic emboli. Pulmonary embolus (PE) and deep venous thrombosis (DVT) may also occur.

D. LABORATORY FINDINGS 1.

ECG reveals evidence of MI in 85% of patients.

a.

2.

3.

Initially, ST segment elevation occurs (current of injury or infarction) in leads associated with the infarcted area. b. ST segments then begin to fall, and Q waves appear along with inversion of T waves. c. ST segment depression occurs during angina, but often the ECG shows no significant changes. Analysis of cardiac enzymes reveals elevated creatine kinase levels (occurs 6–12 hours after onset of infarction), followed by elevated lactate dehydrogenase (LDH) levels (occurs >24 hours after onset of infarction). Elevation of troponin levels within 12 hours of the infarction is extremely sensitive and specific and has replaced most other enzymatic laboratory tests. Echocardiography confirms the diagnosis and can be used to quantitate the severity of the infarction.

E. TREATMENT. Intravenous (IV) access oxygen and monitors should be in place in any individual with signs and symptoms of acute MI or angina. 1. Unstable angina a. Acetylsalicylic acid (ASA) decreases the risk of death and MI. b. Glycoprotein IIb/IIIa inhibitors may reduce the risk of death/MI. c. β-Blockers are useful in relieving tachycardia and hypertension but may not decrease mortality. d. Clopidogrel/ticlopidine reduce mortality and MI but may be associated with bleeding. e. Sublingual nitroglycerin reduces pain and myocardial oxygen demands. 2. Acute MI a. β-Blockers are useful in relieving tachycardia and hypertension, thereby reducing oxygen demands, and reduce mortality. b. Morphine for pain relief. c. ASA reduces mortality and reinfarction. d. ACE inhibitors reduce mortality but should be avoided in hypotensive patients or patients with renal dysfunction. e. Thrombolysis should be performed with tissue plasminogen activator (t-PA) within 3 hours. f. Glycoprotein IIb/IIIa inhibitors in addition to thrombolysis have not been shown to decrease mortality and should be used carefully with thrombolysis because of bleeding risks. g. Primary percutaneous transluminal angioplasty may be superior to thrombolysis alone for acute MI. h. Symptomatic bradycardia may require atropine until a transvenous pacemaker can be placed. i. Mitral regurgitation requires afterload reduction. j. In patients who develop ventricular aneurysms, PE or DVT therapeutic anticoagulation with heparin or low-molecular-weight heparin followed by longterm oral anticoagulation is needed.

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CARDIOVASCULAR DISEASES

III

5

Atrial Fibrillation (AF) A. GENERAL CHARACTERISTICS 1. The most common chronic arrhythmia 2. May be secondary to myocardial infarction, rheumatic heart disease, dilated or hypertrophic cardiomyopathy, atrial septal disease, trauma, hypothyroid surgery, hypertension, ethanol intoxication, or mitral valve prolapse, or it may be idiopathic. B. CLINICAL FEATURES 1. Irregularly irregular rhythm with a rate 140/90 mm Hg. 2. At least 15% of Caucasians and 25% of African Americans are hypertensive. 3. Hypertension may be essential (primary) or secondary. 4. Diagnosis is made when the patient has at least two consistently elevated blood pressure readings on separate occasions, with the patient at rest for at least 15 minutes before measurement. B. ESSENTIAL (PRIMARY) HYPERTENSION 1.

General characteristics

a. b. c. d. e. f.

2.

Essential hypertension is defined as hypertension that occurs without any identifiable cause. Ninety to ninety-five percent of hypertensive patients fall into this category. Essential hypertension is usually detected during middle age. If the condition is not treated, the mortality rate increases dramatically due to stroke, coronary artery disease, and/or congestive heart failure. Retinal hemorrhages indicate more severe disease. Malignant hypertension is a rapidly progressive form of essential hypertension with diastolic readings >120 mm Hg and widespread end-organ dysfunction.

Clinical features

a. b.

Patients are often asymptomatic until they are seen with complications as described previously. Patients who have malignant hypertension may report blurred vision, headache, and dyspnea. i. Papilledema, fundal hemorrhages, and infarctions (cotton wool spots) are additional signs. ii. Encephalopathy may develop. iii. Renal damage with microangiopathic hemolytic anemia is common with longstanding hypertension.

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CARDIOVASCULAR DISEASES

3.

Laboratory findings

a. b.

4.

17

Patients who have hypertension should have baseline studies to give an indication of end-organ function. Studies should include ECG, complete blood count, urinalysis, and serum studies, including electrolytes, creatinine, urea, glucose (to check for possible coexisting diabetes), triglycerides, cholesterol, and uric acid.

Treatment

a. b.

Treatment should be aimed at reducing diastolic pressures to 20 mmol/L,

e.g., diuretics

● Figure 3-2. Diagnostic approach to hypernatremia.

Non-renal loss

e.g., insensible losses

Urine osmolality > Plasma osmolality,

Urine osmolality < Plasma osmolality, e.g., diabetes insipidus

Non-renal loss

Renal loss

Usually iatrogenic

Excess total body [Na] and water, but more Na than water

Normal total body [Na], depleted in water

Depleted in total body [Na] and water, but more water loss

Renal loss

Hypervolemia

Euvolemia

Hypovolemia

Hypernatremia

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RENAL, FLUID, AND ELECTROLYTE DISORDERS 47

Check for ketones, lactate, salicylate, alcohols, or renal failure

Anion-gap acidosis

Low, i.e., 50 mmol/L Excessive mineralocorticoids or diuretics

e.g., increased sympathetic drive, insulin overdose

Transcellular shifts,

Normal

48

Check Acid-Base Status

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49

D. ACID–BASE DISORDERS 1.

General considerations

a. b.

c.

d.

e.

f. g.

Acid–base disorders can be either metabolic (changes in serum [bicarbonate] level) or respiratory (changes in PaCO2 level). An increase or decrease in hydrogen ion concentration may occur in either metabolic or respiratory causes; these changes lead to four possible disease processes: metabolic acidosis (decreased serum [bicarbonate] level), metabolic alkalosis (increased serum [bicarbonate] level), respiratory acidosis (increased PaCO2 level), and respiratory alkalosis (decreased PaCO2 level). Each of these disturbances can lead to a compensatory response by the body in an attempt to maintain a normal pH. i. For example, a patient who has metabolic acidosis will begin to hyperventilate to increase the serum pH toward its normal value (a response that occurs in a matter of hours). ii. A patient who has a primary respiratory condition such as respiratory acidosis (increased PaCO2 level) will develop a metabolic alkalosis (increased serum [bicarbonate] level; this response, mediated by the kidneys, may require 2 to 3 days). Determining whether a patient has one primary metabolic derangement with an appropriate physiologic response as opposed to two or three primary derangements must be accomplished to institute appropriate therapy. The following rules should be committed to memory: i. Metabolic acidosis: for every 1 mol/L decrease in [bicarbonate] level, the appropriate physiologic response is a decrease of 1.2 mm Hg in PaCO2 level. ii. Metabolic alkalosis: for every 1 mmol/L increase in [bicarbonate] level, the appropriate physiologic response is an increase of 0.6 mm Hg in PaCO2 level. iii. Respiratory acidosis: for every 1 mm Hg increase in PaCO2 level, the appropriate physiologic response is an increase of 0.4 mmol/L in [bicarbonate] level. iv. Respiratory alkalosis: for every 1 mm Hg decrease in PaCO2 level, the appropriate physiologic response is a decrease of 0.4 mmol/L in [bicarbonate] level. When calculating the appropriate physiologic response of a patient with an acid–base disturbance, allow /2 units. Causes of metabolic acidosis and alkalosis disorders are shown in Figures 3-4 and 3-5.

CLINICAL EXAMPLE 3–1 A patient’s [HCO3] (bicarbonate level)  12, and his PaCO2 level  26 mm Hg. Does this patient have a metabolic acidosis with an appropriate physiologic response of respiratory alkalosis, or does the patient have a respiratory alkalosis with an appropriate physiologic response of metabolic acidosis? If the patient has a primary metabolic acidosis, the bicarbonate level has decreased 12 mmol/L (24  12  12). The appropriate drop in PaCO2 level is 12  1.2  14.4 mm Hg; therefore, the expected PaCO2 level for this patient is 40  14.4  25.6 mm Hg, which is within the accepted range of his actual PaCO2 level. Therefore, the patient has a primary metabolic acidosis with an appropriate physiologic response of respiratory alkalosis. If we were to assume that the patient’s primary disturbance was a respiratory alkalosis, then the patient’s physiologic response should be to decrease his bicarbonate level by (40  26)  (0.4)  5.6. The patient’s bicarbonate level should be 24  5.6  18.4, which it is not. Therefore, our assumption that this patient’s primary acid–base disturbance was a respiratory alkalosis is incorrect. (continued)

Type IV hyperkalemic distal RTA secondary to decreased aldosterone or renal aldosterone resistance

Type II proximal RTA associated with hypokalemia

Type I distal RTA associated with hypokalemia

RTA (renal tubular acidosis)

● Figure 3-4. Diagnostic considerations in a patient who has metabolic acidosis. GI, gastrointestinal.

Phosphates (advanced renal disease)

Lactate (often seen in those with necrotic bowel)

Ureterosigmoidostomy

Fistula

Beta-hydroxybutyrate also seen in DKA

Salicylates and other toxins

Diarrhea

Ketones [i.e., diabetic ketoacidosis (DKA)]

GI losses

Non–anion-gap acidosis (hyperchloremic)

50

Anion-gap acidosis

Metabolic acidosis

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51

Metabolic alkalosis

Chloride responsive*

Chloride resistant

Low urine chloride (usually 20 mmol/L)

Vomiting (loss of HCl)

Primary hyperaldosteronism (also hypokalemic)

Nasogastric suction

Cushing syndrome (excess mineralocorticoids)

Diuretic use in a patient with NaCl restriction

Bartter syndrome

* Note: Patients who are chloride responsive are typically volume contracted and are avidly hanging on to sodium. The lack of chloride results in reabsorption of sodium, with the extrusion of hydrogen ions and the generation of more bicarbonate. This cycle perpetuates the alkalosis. If the patient is rehydrated with NaCl, then the patient will decrease reabsorption of bicarbonate, and the cycle is broken. Treatment of the alkalosis rarely necessitates acid administration. The underlying disorder should be treated.

● Figure 3-5. Diagnostic considerations in a patient who has metabolic alkalosis.

CLINICAL EXAMPLE 3–1

(CONTINUED)

It is important to recognize which acid–base disorder is the primary disorder and which is the appropriate physiologic response. If the patient has a primary metabolic acidosis, the cause should be ascertained and treated appropriately, after which time the patient’s PaCO2 level will return to normal. If the primary disorder is respiratory alkalosis, the patient is hyperventilating. The hyperventilation is chronic, because it takes 2 to 3 days for the bicarbonate level to increase in response. In the latter instance, one might imagine a patient on a ventilator with a setting that is too high, which results in overventilation. In this instance, the treatment is to simply readjust the ventilator settings. If a metabolic acidosis is discovered, it must be further characterized as an anion-gap or a non–aniongap acidosis as follows: Anion gap  serum [Na]  serum [Cl]  serum [HCO3] • A normal anion gap is usually between 8 and 12 mEq/L. • An anion gap >12 mEq/L in the presence of a metabolic acidosis indicates an anion-gap metabolic acidosis. • In the presence of an anion-gap acidosis, it is important to determine the bicarbonate level before the anion-gap acidosis ensues to detect an underlying acid–base disturbance.

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CLINICAL EXAMPLE 3–2 A patient’s blood workup reveals the following laboratory results: [Na]  136 mEq/L; [Cl]  81 mEq/L; [HCO3]  32 mEq/L; PaCO2  35 mm Hg This patient has an elevated bicarbonate level; therefore, he or she may have a metabolic alkalosis. The PaCO2 level should therefore be elevated for an appropriate physiologic response, but it is actually low. If we assume that the primary disorder is a respiratory alkalosis, then the bicarbonate level should be low, but it is elevated. Therefore, the patient has both a respiratory alkalosis and a metabolic alkalosis. Is that all? Check the anion gap. It is 23 mEq/L (11 more than it should be). Therefore, the patient also has an anion-gap metabolic acidosis. The increase in the anion gap by 11 mEq/L means that the bicarbonate level must have initially been 32  11  43 mEq/L before the anion-gap acidosis ensued. Therefore, this patient has a severe metabolic alkalosis that is masked by the presence of his anion-gap acidosis.

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Chapter

4

Gastrointestinal Disorders I

Diseases of the Esophagus and Stomach A. GENERAL CHARACTERISTICS 1. These diseases cause inflammation and irritation. 2. Diseases of the esophagus and stomach include reflux esophagitis, gastritis, neoplasms of the esophagus and stomach, esophageal dysmotility and gastric emptying disorders, and peptic ulcer disease. B. REFLUX ESOPHAGITIS/GASTROESOPHAGEAL REFLUX DISEASE (GERD) 1.

General characteristics

a. b.

2.

Clinical features

a. b. c. d. 3.

Heartburn is brought on by bending over or lying down and is associated with a bitter taste in the mouth. This may or may not progress to esophagitis. The disease may lead to the formation of strictures, which may cause dysphagia for solid foods. Blood from esophageal erosions may be present in regurgitated material. Signs and symptoms of anemia may be present if bleeding is chronic or severe.

Laboratory findings

a.

b. c. 4.

Reflux esophagitis may be associated with a primary defect in lower esophageal sphincter (LES) tone. Secondary causes include pregnancy, drugs (anticholinergics, β2-agonists, calcium channel blockers), surgical vagotomy, smoking, and alcohol and caffeine ingestion.

Barium swallow and upper gastrointestinal (GI) series test results are positive only in patients who have severe disease; therefore, these tests are not very sensitive. They are useful in ruling out other esophageal disorders such as achalasia. Esophageal manometry allows assessment of LES pressures at rest and during swallowing. Endoscopy with biopsy is used to rule out associated peptic ulcer disease and Barrett esophagus (premalignant epithelial changes associated with chronic reflux).

Treatment

a. b. c.

d.

Mild disease responds to simple measures such as elevating the head of the bed and not eating before bedtime. Patients can try liquid antacids after meals and before bed. H2-receptor blockers (cimetidine, ranitidine) are also effective; however, proton pump inhibitors (e.g., omeprazole) are now considered the treatment of choice. As several randomized trials show, they are superior to H2 blockers. Antireflux surgery (Nissen fundoplication) should be performed if the patient’s disease resists medical therapy and anoscopy reverse esophagitis and other esophageal contractility disorders have been ruled out. 53

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C. GASTRITIS 1.

Acute gastritis

a.

b.

c. d.

2.

General characteristics i. Acute gastritis is defined as a self-limited inflammation of the gastric mucosa. ii. Acute gastritis is commonly associated with the use of acetylsalicylic acid and other nonsteroidal anti-inflammatory drugs (NSAIDs), ethanol ingestion, ingestion of caustic substances, and stress. Clinical features i. Common signs and symptoms include dyspepsia, nausea and vomiting, and epigastric pain. ii. GI bleeding may occur and cause hematemesis and shock, if severe. Laboratory findings from endoscopic examination are best for diagnosis. Treatment i. The patient should refrain from ingestion of the offending agents. ii. Antacids, sucralfate (a surface-acting agent), and H2-receptor blockers lead to rapid healing within days. iii. Patients who have severe hemorrhage respond best to fluid and blood replacement and usually do not require surgery.

Chronic gastritis

a. b. c.

d. e.

Chronic gastritis is associated with the use of NSAIDs, ethanol ingestion, radiation injury, and immunologic factors (pernicious anemia). This disease lacks definite clinical manifestations other than anemia associated with atrophic gastritis. Patients who have pernicious anemia lack gastric production of intrinsic factor (IF); the Schilling test will therefore be positive (i.e., vitamin B 12 administration alone will not increase urinary vitamin B 12 excretion, but vitamin B 12 with IF will increase urinary vitamin B 12 excretion, which indicates the lack of IF in patients who have pernicious anemia). Patients with chronic gastritis have an increased incidence of gastric ulcer and gastric carcinoma. No specific therapy is indicated except when pernicious anemia is present, which requires systemic administration of vitamin B12.

D. NEOPLASMS OF THE ESOPHAGUS AND STOMACH 1.

Esophageal neoplasms

a.

b.

c.

General characteristics i. Incidence of esophageal neoplasms is low in the United States. ii. Esophageal neoplasms occur most often in men. iii. Associated risks include smoking, ethanol ingestion, geographic location (China), lye ingestion, achalasia, and Barrett esophagus. Clinical features i. Patients experience a progressive dysphagia for solids. ii. Signs and symptoms of advanced disease include pain, weight loss, dysphagia for liquids, cough, and hoarseness. Laboratory findings i. Barium swallow with a barium-coated bolus is effective in detecting obstruction. ii. Endoscopy is the best test because it allows for biopsy as well as direct visualization of the mass.

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55

iii. Computed tomography (CT) scan is useful in assessing spread to adjacent structures. d. Treatment i. Radiotherapy is indicated for proximal tumors. ii. Surgery is indicated for middle and distal tumors, provided metastasis has not occurred. iii. Stent therapy to relieve obstruction may be necessary in those who are poor surgical candidates and/or have metastatic disease. iv. Survival rates are low. 2. Gastric neoplasms a. General characteristics i. Incidence of gastric neoplasms is low in the United States but is considerably higher in Japan. ii. Gastric neoplasms occur most frequently in elderly men. iii. Risk factors include family history, pernicious anemia, Helicobacter pylori infection, smoking, previous gastrectomy, and gastric polyps. iv. These neoplasms are typically adenocarcinomas but occasionally may be due to a gastric lymphoma resulting from non-Hodgkin lymphoma. b. Clinical features i. Signs and symptoms include weight loss, anorexia, fatigue, epigastric pain, early satiety, and vomiting. ii. The left supraclavicular node (Virchow node) may be palpable. c. Laboratory findings i. Upper Gl series is often effective at revealing a mass. ii. Endoscopy is most effective diagnostically and allows for biopsy to establish the diagnosis. iii. Elevated serum carcinoembryonic antigen (CEA) level is a useful biologic marker. d. Treatment i. Surgical resection of the affected area is indicated. ii. Adjuvant chemotherapy has minimal, if any, survival benefit. iii. Surgery and radiotherapy are indicated for confined gastric lymphoma, with the addition of chemotherapy for systemic lymphoma. E. ESOPHAGEAL DYSMOTILITY AND GASTRIC EMPTYING DISORDERS 1.

Esophageal dysmotility

a.

b.

c.

General characteristics i. Esophageal dysmotility may be the result of achalasia or diffuse esophageal spasm (DES). ii. Achalasia results from absent peristalsis combined with increased LES tone (Figure 4-1). iii. This disorder may also be seen in patients who have scleroderma (see Chapter 7, Rheumatic Diseases). Clinical features i. Signs and symptoms include dysphagia for solids and liquids, chest pain, odynophagia (particularly in diffuse esophageal spasm), and weight loss. ii. Achalasia may be associated with nocturnal cough due to overflow aspiration or with recurrent aspiration pneumonia. Laboratory findings i. On a cine-esophagram, a dilated fluid-filled esophagus (bird-beak) indicates achalasia; simultaneous, noncoordinated contractions indicate DES.

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● Figure 4-1. Esophagram of a patient who has achalasia. Note the marked esophageal dilatation and narrowing at the gastroesophageal junction due to failure of lower esophageal sphincter relaxation.

d.

2.

ii. A high LES resting pressure that fails to relax during swallowing (detected with esophageal manometry) is associated with achalasia; the presence of low-amplitude, coordinated contractions or even the complete absence of peristalsis distinguishes achalasia from DES. Treatment i. For achalasia, pneumatic dilatation is often more effective than medical therapy, but this procedure carries a mortality rate of 0.2% and a perforation rate of 2%–3%. ii. Surgical therapy (Heller myotomy) for achalasia is also effective but has a 3%–4% complication rate as well as a high risk for the development of postoperative reflux. iii. For DES, medical therapy is generally used first and consists of anticholinergics, nitrates, or calcium channel blockers. iv. Longitudinal myotomy is reserved for DES patients who are incapacitated by the disease.

Gastric emptying disorders

a.

General characteristics i. Gastric emptying disorders are due to pyloric stenosis, gastric volvulus, gastric bezoars, or gastroparesis.

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b.

c.

d.

F.

57

ii. Pyloric stenosis may be acquired, as in scarring from peptic ulcer disease, or congenital. iii. Gastric volvulus is often secondary to a paraesophageal hernia. iv. Gastric bezoars occur in individuals who have had previous gastric surgery or in mentally ill patients who consume indigestible substances such as hair (trichobezoars). v. Gastroparesis is most commonly associated with longstanding diabetes. Clinical features i. Signs and symptoms of gastric outlet obstruction predominate, including abdominal pain with minimal distention, nausea, vomiting (which may be projectile), hematemesis, early satiety, and abdominal tenderness and rigidity. Fever may be present, particularly when the volvulus is strangulated. Laboratory findings i. Laboratory findings vary with the etiology. ii. Abdominal radiographic study reveals air in the stomach but little air distal to the obstruction (in gastroparesis, air distal to the stomach is observed); two separate left upper quadrant fluid levels may be present in gastric volvulus. iii. Endoscopy may be necessary to rule out malignancy, especially when bezoars are present. iv. Gastric manometry reveals the presence of gastroparesis. Treatment i. Myotomy is indicated for pyloric stenosis. ii. Bezoars can be broken down with enzymes or surgically removed. iii. Recurrent nasogastric suction for volvulus with surgical correction is necessary if vascular compromise is present. iv. Metoclopramide is indicated for patients who have gastroparesis. If they fail to respond to medical therapy, gastrectomy may be warranted.

PEPTIC ULCER DISEASE 1.

General characteristics

a. b. c. d. e. 2.

Clinical features

a. b. c. d. 3.

Peptic ulcers occur in the stomach or proximal duodenum. Peptic ulcer disease occurs most commonly in middle-aged men. Associated risk factors include smoking, NSAID use, corticosteroid use, ethanol ingestion, family history, and chronic anxiety. Duodenal ulcers are benign, but gastric ulcers may be malignant. Approximately 75% of duodenal ulcers are associated with H. pylori infection. The main symptom is an epigastric burning sensation. If the ulcer is gastric, the pain is exacerbated by eating; if duodenal, pain diminishes with eating but occurs 2–3 hours after a meal. Patients may initially be seen with upper GI hemorrhage, that is, hematemesis, melena, and abdominal pain. Signs and symptoms of anemia may be present if chronic and/or significant upper GI hemorrhage has occurred.

Laboratory findings

a.

Upper GI series is more effective in detecting ulcer if performed with air contrast. i. If no ulcer is found and the clinical suspicion is high, endoscopy is still indicated.

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● Figure 4-2. Upper gastrointestinal series in a patient who has a benign gastric ulcer. Note the deformity in the greater curvature of the antrum. Mucosal folds radiate into the base of the ulcer (an indicator of benignity).

ii. Features that suggest a benign gastric ulcer include gastric folds radiating into the base of the ulcer, thick radiolucent edematous collar (Hampton line), smooth crater, and pliable gastric wall in the area of the ulcer (Figure 4-2). b. Endoscopy with biopsy is indicated if initial therapy does not alleviate signs and symptoms or if the clinical situation is highly suggestive of malignant disease. H. pylori gastric biopsy should also be performed in this setting. c. In patients who are diagnosed with ulcer disease without endoscopy, serologic testing for H. pylori should be performed. d. Serum gastrin measurements are rarely indicated unless suspicion of Zollinger-Ellison syndrome (pancreatic gastrinoma leading to recurrent ulcers in distal portions of the duodenum or jejunum) exists. 4. Treatment a. Antacids and H2 blockers are equally effective in promoting healing within approximately 4 weeks. b. H2 blockers are more convenient than antacids, but cause side effects (cimetidine especially) including confusion, tremor, and gynecomastia; ranitidine is more widely tolerated. c. Sucralfate is as effective as ranitidine and causes fewer side effects, making this drug particularly efficacious. d. Proton pump inhibitors show superior healing rates and reduced rebleeding rates and are now the agents of choice for therapy. e. H. pylori treatment must be given if patients with peptic ulcer disease are infected due to the high ulcer recurrence rate if inadequately treated. A combination of two antibiotics, bismuth, and a proton pump inhibitor is necessary

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f.

II

59

for 10-14 days. Commonly effective antibiotics include amoxicillin, metronidazole, and clarithromycin. Surgery for intractable cases or complicated (perforated, bleeding, obstructed) peptic ulcer disease is indicated.

Diseases of the Small Intestine A. DIARRHEA 1.

General characteristics

a. b.

c. d. 2.

Diarrhea is defined as increased volume and liquidity of stool. Types of diarrhea include: i. Secretory (caused by Escherichia coli toxin, Salmonella spp., and Clostridium perfringens enterotoxin). ii. Osmotic (caused by ingestion of nonabsorbable, osmotically active substances such as laxative and lactose in individuals who have lactase deficiency). Abnormal intestinal motility (from rapid or slow peristalsis) causes diarrhea and is most often associated with longstanding diabetes. Longstanding diarrhea may be associated with irritable bowel syndrome.

Clinical features

a. b. c.

Persistent diarrhea in the absence of food intake suggests a secretory diarrhea. Absence of diarrhea after a 2- to 3-day fast suggests osmotic diarrhea. Abnormal intestinal motility producing diarrhea may be seen in patients who have hyperthyroidism or diabetes; this is largely a diagnosis of exclusion. d. Alternating diarrhea and constipation with postprandial discomfort and no evidence of nausea, vomiting, weight loss, fever, or GI bleeding suggest irritable bowel syndrome. 3. LABORATORY FINDINGS a. Stool culture and sensitivity test may reveal the presence of a pathogenic bacterial strain. Campylobacter, Salmonella, and E. coli are most common. b. Microscopic examination of stool may reveal ova or parasites that can cause diarrhea (Table 4-1); often, three samples are sent in order to increase sample yield. c. Ion gap calculations can be useful in differentiating secretory from osmotic diarrhea. i. Absence of ion gap between measured stool osmolarity and 2([Na
]
[K
]) present in the stool suggests secretory diarrhea. ii. The presence of such an ion gap with an elevated stool osmolarity suggests osmotic diarrhea. d. Guaiac test is used to detect occult blood in the stool. i. Blood in the stool may occur in invasive infectious diarrhea. ii. Blood in the stool may suggest another pathologic process, such as inflammatory bowel disease. e. Wright or methylene blue staining of stool detects the presence of white blood cells, which indicates an invasive infectious cause of diarrhea (see Table 4-1). f. Figure 4-3 shows the standard diagnosis algorithm for diarrhea. B. BACTERIAL FOOD POISONING SYNDROMES are summarized in Table 4-2. C. SMALL BOWEL OBSTRUCTION 1.

General characteristics

a.

Small bowel obstruction may be due to a mechanical obstruction such as adhesions from prior surgery or hernia.

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CHAPTER 4 TABLE 4-1

COMMON CAUSES OF INFECTIOUS DIARRHEA

Organism

Spread

Comments

Treatment

Escherichia coli

Fecal contamination of food/water Secretory diarrhea

Most common cause of traveler’s diarrhea

TMP-SMX if severe Pepto-Bismol for symptomatic relief

Self-limited Campylobacter

Salmonella spp.

Contaminated water or milk

Contamination of eggs or milk

One of the most common causes of bacterial diarrhea in United States Self-limited, short duration Acute, self-limited

Crampy, abdominal pain with fever Shigella spp.

Fecal-oral

Most common in day care centers and urban poor Seen in “gay bowel syndrome” Crampy, abdominal pain progressing to bloody diarrhea if untreated

Usually not required

Ciprofloxacin if prolonged Usually no treatment because can lead to prolonged carrier state Severe disease treated with ampicillin or TMP-SMX Ampicillin or TMP-SMX Amoxicillin cannot be substituted because ineffective

Giardia lamblia

Fecal contamination of water

Most common cause of water-borne infectious diarrhea in United States Causes mild or severe symptoms

Metronidazole

Norwalk agent/ rotavirus

Person to person

Common cause of self-limited diarrhea

Not necessary

TMP-SMX, trimethoprim-sulfamethoxazole.

b. 2.

Clinical features

a.

b.

c. d. 3.

Small bowel obstruction can also be secondary to an adynamic (paralytic) ileus that can occur with trauma, abdominal surgery, hypokalemia, and peritonitis. Predominant symptom is crampy, intermittent abdominal pain. i. The pain is not severe if obstruction is secondary to an adynamic ileus. ii. If obstruction is distal, abdominal distention is present. In a mechanical obstruction, high-pitched bowel sounds with peristaltic rushes and tinkles can be heard; in adynamic ileus, few bowel sounds can be heard. Additional symptoms include vomiting and constipation. Obstruction may lead to intestinal ischemia and gangrene.

Laboratory findings

a.

b.

Abdominal radiographic study usually establishes the diagnosis. i. In mechanical obstruction, characteristic air-fluid levels in distended loops of bowel are evident; air is absent in the rectum. ii. In adynamic ileus, intestinal gas is diffuse, and air may be present in the rectum. If strangulation and ischemia occur, leukocytosis may occur.

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61

Blood or leukocytes in stool

YES

NO

Systemic signs and symptoms

Nausea and vomiting

Mild

NO

Moderate/Severe

YES

(>5 days illness, fever, >8 stools/day)

SIGNS OF BOWEL OBSTRUCTION OBSERVE

Stool culture and exam for parasites

VIRAL, FOOD POISONING, HISTORY OF LAXATIVES NO

ORGANISM IDENTIFIED

DRUGINDUCED?

YES

FECAL IMPACTION OR PARTIAL OBSTRUCTION

NO YES

NO Stool culture and exam for parasites

SPECIFIC THERAPY FOR ORGANISM

NEGATIVE

Radiographs and biopsy to rule out inflammatory bowel disease and ischemia

POSITIVE

SPECIFIC THERAPY FOR ORGANISM

● Figure 4-3. Workup for acute diarrhea.

4.

Treatment

a. b.

Therapy for adynamic ileus includes continuous decompression via nasogastric tube and treatment of the primary cause. Therapy for mechanical obstruction includes operative correction if the obstruction is complete and strangulation is in progress; intravenous (IV)

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CHAPTER 4 TABLE 4-2

BACTERIAL FOOD POISONING SYNDROMES

Organism

Incubation Period

Source of Infection

Comment

Staphylococcus aureus

2–6 h

Meat and dairy handlers

Sudden onset of vomiting, abdominal pain, and diarrhea Therapy usually not required

Brucella cereus

2–8 h

Reheated fried rice

Vomiting followed by diarrhea Often resolves in 24 h

Clostridium perfringens

8–14 h

Reheated meats, poultry, and legumes

Profuse diarrhea with severe abdominal cramping Rarely lasts 24 h No therapy required

Salmonella spp.

24–48 h

Foods (e.g., eggs)

Diarrhea with low-grade fever Antimicrobial therapy may produce carrier state; therefore, not usually treated

Pathogenic Escherichia coli

1–3 d

Food and water

Causes traveler’s diarrhea Prophylaxis with TMP-SMX

Vibrio cholerae

1–3 d

Fecally contaminated water

Common in southeast Asia Produces life-threatening diarrhea Treated with intravenous and oral rehydration

Shigella spp.

1–3 d

Fecal-oral spread

Diarrhea, fever, bloody stools Treated with ampicillin or TMP-SMX

Clostridium botulinum

1–2 d

Canned foods

Neurologic manifestations Ventilatory support required Requires immediate administration of antitoxin

Clostridium difficile

During or within 4 weeks of discontinuing antibiotic therapy

Antibiotic-associated

Produces pseudomembranous colitis Treated with vancomycin or metronidazole

hydration, small bowel decompression, correction of electrolyte imbalances, and broad-spectrum antibiotics should be administered before surgery if time permits. D. MALABSORPTION 1.

General characteristics

a. b.

c. d.

Malabsorption may be secondary to a large number of clinical entities. The most common of these entities include lactase deficiency, inflammatory bowel disease (e.g., Crohn disease), small bowel infections, chronic pancreatitis (often secondary to alcoholism), obstructive liver disease leading to bile salt deficiency (e.g., cholangiocarcinoma), celiac disease, and longstanding diabetes mellitus. Calcium, folic acid, and iron are absorbed from the proximal small bowel; bile acids and vitamin B12 are absorbed from the ileum. Absorption of the fat-soluble vitamins A, D, E, and K is impaired when fat absorption is impaired, as can occur in bacterial overgrowth syndrome or pancreatic lipase insufficiency.

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2.

Clinical features

a. b.

c. d. e. 3.

Features vary with the etiology of the malabsorptive process. Signs and symptoms of malabsorption may include steatorrhea (greasy, foul-smelling stools that may float in the toilet bowl), weight loss, hypoalbuminemia leading to edema and ascites, and anemia. Fractures secondary to poor vitamin D absorption may occur. Paresthesias and tetany may result from hypocalcemia. Coagulation disorder may occur due to decreased vitamin K absorption.

Laboratory findings

a.

b. c. d. e. f. 4.

63

Seventy-two-hour fecal fat analysis is useful in diagnosing malabsorption. i. Fecal fat more than 6 g /day indicates fat malabsorption. ii. Fecal fat more than 20-30 g/day on a fat diet of 100 g/day is often associated with pancreatic disease. Decreased absorption seen in the xylose absorption test indicates injury to intestinal mucosa. 14C-xylose conversion to 14CO is increased in patients who have bacterial 2 overgrowth that can be measured during a breath test. Abdominal radiographic study may reveal a fistula, blind loop, or areas of stasis, which indicate bacterial overgrowth syndrome. Decreased stool pH suggests unabsorbed carbohydrates; this sign is usually seen in patients who have lactase deficiency or celiac disease. Schilling test (see I C 2 c)

Treatment

a. b. c. d.

Treatment is based on the underlying cause of the malabsorption. Pancreatic enzyme replacement is indicated in patients who have chronic pancreatitis. Ampicillin or tetracycline may be useful in patients who have bacterial overgrowth syndrome. Gluten-free diet should be prescribed for patients who have celiac disease.

E. CROHN DISEASE 1.

General characteristics

a. b. c.

2.

Crohn disease is a chronic granulomatous disease that most often affects the ileum. The disease is often seen in persons who are in early adulthood or over age 50. Features of Crohn disease include thickened intestinal wall with inflammation, mesenteric lymphadenopathy, ulcerative lesions that may progress to fistula formation, alternating areas of normal and involved bowel wall, and stricture formation secondary to scarring.

Clinical features

a. b. c. d. e.

Signs and symptoms include fever, weight loss, anorexia, colicky pain, and diarrhea. A right lower quadrant abdominal mass may be palpable if the ileum is extensively involved; this sign mimics appendicitis. Fecal occult blood is present. Colon and rectum involvement produce significant diarrhea, perirectal fissures, fistulas, and abscesses. Peripheral arthritis may occur in 10% of patients (see Chapter 7, Rheumatic Diseases).

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● Figure 4-4. Radiographic appearance of Crohn disease. Swollen folds of mucosa, which are coarse and nodular at the distal jejunum.

3.

Laboratory findings

a. b. c. 4.

Abdominal radiographic study reveals deep ulcerations and long, strictured segments alternating with uninvolved areas (Figure 4-4). Endoscopy may reveal inflammatory changes; inflammation can be confirmed with biopsy of affected areas. Anemia, leukocytosis, and protein loss may be present; however, these findings are nonspecific.

Treatment

a. b.

c. d.

e. f. g.

In severe disease, bowel rest with intravenous fluid/total parenteral nutrition (TPN) and broad-spectrum antibiotics are indicated. In acute disease, sulfasalazine (or other 5-aminosalicylate [5-ASA] agents) therapy with or without corticosteroids is indicated (corticosteroids for severe disease). Surgery is often required for fistula formation, abscesses, or obstruction. Surgical removal of the affected areas is useless because new diseased regions tend to occur proximal to the removed segments; in addition, a significant risk of adhesion and obstruction exists postoperatively. Vitamin B12 may be required if the ileum is significantly involved. Metronidazole is useful in fistulous perianal disease. Infliximab, an antitumor necrosis factor antibody, has been effective in disease refractory to 5-ASA and steroids.

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III

65

Diseases of the Colon, Rectum, and Anus A. GENERAL CHARACTERISTICS 1. 2.

The main disorders of the colon include constipation, appendicitis, diverticular disease, ulcerative colitis, and colonic tumors. Disorders of the rectum and anus are largely surgical.

B. CONSTIPATION 1. Constipation is defined as fewer than three bowel movements per week. 2. Constipation may be due to a low-fiber diet or a disease process. 3. Associated diseases include ulcerative proctitis, rectal abscess, hypothyroidism, and longstanding diabetes. 4. Simple constipation can be treated with increased dietary fruits, vegetables, and bulking agents, whereas disease-associated constipation requires treatment of the underlying cause. C. APPENDICITIS 1.

General characteristics

a. b.

c.

2.

Maximum incidence occurs in the second and third decades of life, but appendicitis may occur at any time. The disease begins with obstruction of the appendiceal lumen by a fecalith, followed by distention of the appendix with mucous secretions from the mucosa. Bacterial invasion of the appendiceal wall concomitant with venous engorgement and arterial insufficiency occur as a result of the increasing intraluminal pressure.

Clinical features

a.

Initially, the patient complains of periumbilical or epigastric abdominal pain that may be crampy in nature; pain eventually localizes to the right lower quadrant. b. Nausea and vomiting then develop in 50%–60% of individuals. d. Anorexia is extremely common. e. Tenderness to percussion and palpation in the right lower quadrant is often present. f. Rovsing sign may be present. g. If generalized tenderness to palpation and percussion are present, peritonitis from a ruptured appendix should be considered. h. Positive psoas or obturator signs tend to occur late in the disease process. i. Low-grade temperature is common, but temperature greater than 38.3°C suggests perforation.

3.

Laboratory findings

a. b.

4.

Leukocytosis is common. Abdominal radiographs are of little value unless fecalith is shown in the right lower quadrant. c. Ultrasound can often confirm the diagnosis when the appendix can be visualized; however, if the appendix cannot be seen by ultrasound, the diagnosis cannot be ruled out. d. When uncertain, CT scan is very sensitive in identifying appendicitis. Differential diagnosis includes mittelschmerz (rupture of graafian follicle), mesenteric lymphadenitis, ectopic pregnancy, pelvic inflammatory disease, and Crohn disease.

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5.

Treatment

a. b. c.

Appendicitis is a mechanical disease, and therefore appendectomy is the treatment of choice. Intravenous fluids should be administered because these patients often have had little fluid intake during the onset of the disease. Antibiotics effective against enteric organisms such as E. coli and Bacteroides fragilis should be given (e.g., ampicillin/sulbactam) at the time of diagnosis and should be continued postoperatively, depending on the presence of perforation.

D. DIVERTICULAR DISEASE 1.

General characteristics

a. b. c. 2.

Clinical features

a.

b. c.

3.

Patients who have this disease are usually asymptomatic but may occasionally have alternating diarrhea and constipation or crampy abdominal pain that is relieved by a bowel movement. Occasionally, significant painless bleeding from a diverticulum occurs. Diverticulitis is a frequent complication. i. Signs and symptoms of diverticulitis include left lower quadrant abdominal pain that worsens with defecation, abdominal tenderness, and fever. ii. Inflammatory mass may be palpated in the left lower quadrant. iii. Bleeding is usually microscopic.

Laboratory findings

a. b. c. d. e. 4.

Diverticular disease is common in persons older than age 60. The disease is most often found in the sigmoid colon. Diverticular disease may be associated with a low-fiber diet.

Plain film abdominal radiographs may suggest the presence of diverticula. Barium enema is often diagnostic but should not be performed during the acute phase of diverticulitis due to risk of perforation (Figure 4-5). Sigmoidoscopy/colonoscopy is diagnostic but should be performed cautiously in the acute phase. Leukocytosis is often present in diverticulitis. CT scan is now the diagnostic modality that shows thickening of the sigmoid colon and may show an abscess as free air if perforation is present.

Treatment

a.

b. c. d.

Increased fiber consumption can relieve some of the uncomfortable symptoms of diverticular disease but should be done after resolution of acute inflammation. Diverticulitis requires bowel rest and broad-spectrum antibiotics. More than two bouts or an episode of diverticulitis with abscess, fistula, or free perforation are indications for sigmoidectomy. Surgery may be required if bleeding does not respond to medical management.

E. ULCERATIVE COLITIS 1.

General characteristics

a.

b. c. 2.

Ulcerative colitis is characterized by diffuse inflammation of the rectum and colon; unlike Crohn disease, inflamed areas do not alternate with uninflamed areas. Ulcerative colitis is more common in women than in men. Microabscesses are produced.

Clinical features

a. b.

The disease may be limited to the rectum, which leads to ulcerative proctitis. Nocturnal passage of small amounts of blood and mucus may occur.

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67

● Figure 4-5. Barium enema in a patient who has diverticular disease of the sigmoid colon. Note the “thumblike” imprints along the wall of the bowel.

c. d. e. 3.

Laboratory findings

a. b. c. d.

e. f. 4.

Severe disease may involve diarrhea, fever, weight loss, abdominal pain, and rectal bleeding. Severe disease may progress to toxic megacolon (Figure 4-6), colonic perforation, hypokalemia, and shock. Individuals who have ulcerative colitis are at increased risk of colonic malignancy. Bacterial and parasitic infection must be ruled out with appropriate stool cultures. Malignancy must be ruled out with colonoscopy and biopsy. Analysis of stool sample reveals presence of blood, mucus, and white blood cells without parasites or bacterial pathogens. Barium enema should not be performed on severely ill patients. i. Barium enema may reveal ulcerations and pseudopolyps. ii. This test is an important diagnostic tool that can delineate the extent of bowel involvement. Proctoscopy reveals friable, edematous, hyperemic mucosa with ulcerations. Yearly colonoscopic evaluations are required to rule out neoplastic changes.

Treatment

a.

Acute flare-ups can be treated with bowel rest, IV solutions, and TPN, if necessary.

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● Figure 4-6. Toxic megacolon. Marked dilatation of the transverse and descending colon is evident in this patient.

b. c. d. e.

F.

Corticosteroids, sulfasalazine, and 5-ASA have been shown to reduce symptoms and induce remission in the acute phase of the disease. Sulfasalazine should be used on a regular basis to prevent recurrence. Total colectomy is required for recurrent, severe disease, or if the patient shows evidence of neoplastic disease. Toxic megacolon requires immediate hospitalization with broad-spectrum antibiotics, replacement of blood and electrolytes, and prompt surgical consultation.

COLONIC NEOPLASTIC DISEASE 1.

General characteristics

a. b. 2.

Colonic neoplastic disease includes benign tumors and adenocarcinoma. Also included are the familial polyposis syndromes; because these syndromes are relatively uncommon, they are not discussed here.

Benign tumors

a.

General characteristics i. Polyps may be benign but premalignant. ii. Benign polyps are commonly found in persons over age 40.

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b.

c.

d.

69

iii. Increased risk of polyp malignancy is associated with a polyp that is 2 cm in size, villous rather than tubular, and sessile rather than pedunculated. Clinical features i. Patients who have benign tumors may be asymptomatic or may have rectal bleeding that can be significant. ii. Patients who have large polyps may have signs and symptoms of incomplete obstruction. Laboratory findings i. Abdominal radiographic study is usually not diagnostic unless the polyp is large and causes obstruction; however, radiographic study can be useful in excluding other diagnoses of GI bleeding. ii. Air-contrast barium enema is a useful diagnostic tool (Figure 4-7). iii. Endoscopy with barium enema is the diagnostic procedure of choice. Treatment i. If pedunculated or small, the polyp may be removed during endoscopy. ii. Other types of polyps require surgical consultation because a segmental resection may be required.

● Figure 4-7. Barium enema in a patient who has carcinoma of the descending colon. Numerous loops of distended bowel (small and large) are evident. An annular constricting lesion in the distal portion of the descending colon permits the passage of only a small amount of contrast material to the proximal bowel.

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3.

Adenocarcinoma

a.

b.

c.

d.

General characteristics i. Adenocarcinoma is one of the most common life-threatening malignancies. ii. Adenocarcinoma is associated with high red meat and animal fat ingestion. Clinical features i. Symptoms include a change in bowel habits or a decrease in stool size. ii. Patients who have left-sided tumors often have obstruction and/or hematochezia. iii. Patients who have right-sided tumors often have iron deficiency anemia. Laboratory findings i. Air-contrast barium enema can delineate the lesion, but endoscopy with biopsy is required for diagnosis. ii. Stool analysis for occult blood is not sufficiently sensitive to identify patients with malignancy. iii. Analysis of CEA levels is not a useful screening tool but can be used for follow-up in patients who have been treated for the disease; elevated titers indicate a recurrence or metastasis. Treatment involves surgical consultation for removal and appropriate postoperative management. Postoperative chemotherapy has been shown to improve survival in patients with metastatic nodal disease (e.g., fluorouracil and leukovorin).

G. INFECTIOUS PROCTITIS 1.

General characteristics

a. b. 2.

Clinical features

a. b. c. 3.

Tenesmus, constipation, anorectal pain, hematochezia, and mucopurulent discharge may be present. The nonspecific signs of fever and leukocytosis may be present. Anoscopy reveals mucosal exudate and friable mucosa.

Laboratory findings

a. b. 4.

Infectious proctitis is common in men who have sex with men. The disease is caused by syphilis, gonorrhea, chlamydia, and herpes simplex.

Culture of sample taken from the anus is often diagnostic. Microscopy of anal sample is also often diagnostic.

Treatment

a. b.

Appropriate antibiotic therapy is required, for example, ceftriaxone for gonorrhea and doxycycline for chlamydia. Acyclovir is indicated for prolonged, frequently recurrent herpes.

H. PSEUDOMEMBRANOUS COLITIS (ALSO KNOWN AS CLOSTRIDIUM DIFFICILE COLITIS) 1.

General characteristics

a. b. c. d. e. 2.

Associated with antibiotic use leading to C. difficile overgrowth. Symptoms usually begin during or shortly after antibiotic therapy. Ampicillin, clindamycin, and third-generation cephalosporins are most often the causative agent, but virtually all antibiotics have been implicated. May progress to toxic megacolon in severe cases. Most common cause of diarrhea among hospitalized patients.

Clinical features

a. b.

Foul-smelling, watery diarrhea, occasionally bloody (more than three watery stools per day for more than 2 days) Lower abdominal cramping

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c. d. 3.

b.

c.

Stool is positive for toxin A or B on enzyme-linked immunosorbent assay testing. This test has a 10%-30% false-negative rate, and testing should be redone if suspicion is high and the initial result is negative. This test is most often used because it is faster than stool cultures for C. difficile. Flexible sigmoidoscopy shows yellow adherent plaques (pseudomembranes), which should undergo biopsy to show their characteristic fibrin and neutrophil exudate. Patients with severe disease may show dilated (
9 cm) colon on plain film or CT if toxic megacolon is present.

Treatment

a. b. c. d.

IV

Fever, mental status changes, dehydration, and hypotension may be present in more severe cases. Abdominal tenderness, often left-sided or generalized, with mild to moderate distension and guaiac positive stools

Laboratory findings

a.

4.

71

Discontinue offending antibiotic. Do not use antiperistaltic/antidiarrheal agents because these worsen the disease. Metronidazole is the first-line therapy. Oral administration is best but can be given IV. Vancomycin (given orally) is used for patients who cannot tolerate metronidazole or who do not improve. In severe cases unresponsive to medical treatment, total abdominal colectomy may be necessary.

Pancreatic Disorders A. ACUTE PANCREATITIS 1.

General characteristics

a. b. 2.

Acute pancreatitis is defined as acute inflammation of the pancreas, which begins with edema but may progress to autodigestion, necrosis, and hemorrhage. Gallstones and alcohol are most commonly associated with pancreatitis.

Clinical features

a. b. c. d. e. f. 3. 4.

Patients experience steady, severe epigastric pain that may radiate to the back. Nausea and vomiting usually are not present unless disease is severe. In severe disease, abdominal distention may result from ileus. Severe disease may lead to fever, tachycardia, and shock. Epigastric mass may be palpable if pseudocyst develops. Hemorrhagic pancreatitis may cause Grey-Turner sign (discoloration of the flanks) or Cullen sign (periumbilical discoloration). Differential diagnoses include biliary colic, perforated viscus (especially if patient has had gastroduodenal ulcers), and acute cholecystitis. Laboratory findings

a. b. c. d. e.

CT is diagnostic showing an edematous, inflamed pancreas and may reveal areas of necrosis and/or peripancreatic fluid. Diagnosis is confirmed when a positive CT scan occurs with a significantly elevated serum amylase level (often more than three times normal). Hemoconcentration, increased blood urea nitrogen/creatinine, and acidosis are present when severe disease produces hypovolemia and hypoperfusion. Hypoxia, hyperglycemia, and hypocalcemia are signs of severe disease. In patients with alcohol ingestion, right upper quadrant (RUQ) ultrasound should be obtained to assess for gallstones as the cause.

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5.

Treatment

a. b. c. d. e.

IV fluid replacement is required. Pain relief can be achieved with narcotics. Nasogastric suction should be performed in patients with significant nausea/vomiting, but it des not change the course of the pancreatitis. Associated findings should be treated; for example, hypocalcemia requires calcium, and hyperglycemia requires insulin. Prophylactic antibiotics (carbepenums) should be administered in cases in which evidence of pancreatic necrosis is present on CT.

B. CHRONIC PANCREATITIS 1.

General characteristics

a. b. 2.

Clinical features

a. b. c. d. e. 3.

Abdominal malignancy must be considered, especially carcinoma of the pancreas. Patients who have peptic ulcer disease may have similar presenting symptoms. Biliary tract disease should also be considered.

Laboratory findings

a. b. c. d. e. 5.

Patients experience severe, intractable abdominal pain. Eventually, diabetes and malabsorption with steatorrhea may occur, which lead to weight loss. Obstructive jaundice can occur if fibrous tissue envelops the common bile duct (CBD). Gastritis is commonly seen secondary to excessive alcohol intake. Fifteen percent of patients with idiopathic chronic pancreatitis have a genetic basis for the disease.

Differential diagnosis

a. b. c. 4.

Chronic pancreatitis is the progressive destruction and distortion of the pancreas and its ducts. The disease is associated with alcoholism in adults and cystic fibrosis in children.

Analysis of the serum amylase level is usually not helpful because the amylase level is elevated only in acute pancreatitis, not in chronic disease. Abdominal radiographic study may reveal pancreatic calcification, a cardinal sign of chronic pancreatitis. CT scan may help determine the presence of pancreatic calcification and may also reveal the presence of pseudocysts. Endoscopic retrograde cholangiopancreatography (ERCP) is useful in diagnosing the distorted ductal anatomy. Pancreatic stimulation tests are usually unnecessary but reveal decreased secretion of virtually all pancreatic substances.

Treatment

a. b. c. d.

Patients must reduce alcohol consumption if alcohol is a factor. Pancreatic digestive enzyme supplements can be used to reduce the effects of malabsorption. Insulin is indicated for diabetes mellitus. Nonaddictive analgesics should be used for relief of pain when possible.

C. PANCREATIC CARCINOMA 1.

General characteristics

a.

Smokers and individuals with hereditary forms of pancreatitis have an increased risk of pancreatic carcinoma.

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GASTROINTESTINAL DISORDERS

b. c. 2.

Pancreatic carcinoma has a high mortality rate. The tumor is usually an adenocarcinoma (90%); islet cell tumors constitute the remaining 10% of pancreatic cancers.

Clinical features

a. b. c. d. e. f. g. 3.

73

Epigastric pain and weight loss are the cardinal symptoms. Pain is often noncolicky, dull, and persistent. Additional signs and symptoms include anorexia, nausea, vomiting, and diarrhea/steatorrhea. Obstructive jaundice is common when carcinoma affects the head of the pancreas and may lead to a palpable gallbladder. Paraneoplastic syndromes such as Cushing syndrome or hypercalcemia can occur. Invasion of the tumor into the GI tract may cause upper GI bleeding. The diagnosis should be considered in older patients who have unexplained weight loss, abdominal pain, or recent onset of diabetes without obesity.

Laboratory findings

a.

4.

V

Presence of tumor markers (CEA, cancer antigen 19-9) suggests the diagnosis but is only about 80% sensitive; therefore, if normal, cancer cannot be excluded. b. CT scan detects the lesion 80% of the time. c. ERCP often is used in conjunction with endoscopic ultrasound when the diagnosis is uncertain. Negative brushings from ERCP can occur in 10%–30% of cancer cases; a negative result is not 100% specific. d. Biopsy with guided aspiration cytology is required to confirm the diagnosis. Treatment is mostly palliative due to the poor response to therapy.

Biliary Tract Disease A. ACUTE CHOLECYSTITIS 1.

General characteristics

a. b. 2.

Acute cholecystitis is defined as an inflammation of the gallbladder. It is most commonly due to obstruction of the cystic duct by an impacted gallstone.

Clinical features

a.

3. 4.

Patients experience crampy epigastric or RUQ pain; pain is often postprandial and subsides in several hours. b. Fever, nausea, vomiting, and ileus may occur. c. RUQ tenderness on inspiration (Murphy sign) is common. d. Jaundice may be present if the stone impacts the CBD. e. Perforation of the gallbladder may occur, which leads to abscess formation and/or peritonitis. Differential diagnoses include choledocholithiasis, choledochal cysts, and gallbladder or bile duct carcinoma in elderly individuals. Laboratory findings

a. b. c.

Because most gallstones are composed of cholesterol and hence are radiolucent, abdominal radiographic study is often of little value. Abdominal ultrasound is useful in detecting gallstones within the gallbladder, and may reveal pericholecystic fluid and gallbladder wall thickening. Radionuclide biliary scan reveals absence of filling of the gallbladder due to the obstruction; it is not usually necessary unless ultrasound is inconclusive.

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d. 5.

Serum analysis reveals leukocytosis. Bilirubin level may be mildly elevated but usually 3.

Treatment

a. b. c.

Patients should receive IV fluids, be given nothing by mouth, and receive IV antibiotics (ampicillin/sulbactam or piperacillin/tazobactam). Surgical removal of the gallbladder during the acute phase (within 2–3 days of onset) offers the best chance for laparoscopic removal. IV fluids, antibiotics, and a cholecystostomy tube are indicated for patients who are poor surgical candidates.

B. CHOLEDOCHOLITHIASIS 1.

General characteristics

a. b. 2.

Clinical features

a. b. 3.

Jaundice and RUQ pain are the most common signs and symptoms. Sepsis with cholangitis and shock may occur in severe disease.

Laboratory findings

a. b. c. d.

4.

Choledocholithiasis is defined as the presence of gallstones in the CBD. This condition is most often caused by stones that have formed in the gallbladder.

Serum analysis reveals elevated alkaline phosphatase (AP) and transaminase levels. Total serum bilirubin is 85 mol/L. Cholangiography reveals the obstructed CBD. Ultrasound of the gallbladder often reveals the presence of stones and may show a dilated CBD (1.0 cm). It usually cannot, however, visualize the CBD stone because of the duodenum obstructing an adequate view of the distal duct.

Treatment

a. b.

Patients should receive antibiotics (e.g., piperacillin/tazobactam) until the obstruction has been alleviated. Stones can be removed surgically or via endoscopic extraction.

C. ASCENDING CHOLANGITIS 1.

General characteristics

a. b. c. d. 2.

Clinical features

a. b. c. d. e. 3.

Most often secondary to biliary obstruction due to gallstones (choledocholithiasis) that migrate from the gallbladder. Carcinoma of the head of the pancreas, ampulla of Vater, or CBD should be considered in the differential diagnosis, particularly in the absence of gallstones. Extrinsic compression of the CBD from metastatic cancer may also occur. If untreated, may result in sepsis, biliary cirrhosis, and hepatic failure. Often a previous history of biliary colic—sharp intermittent RUQ pain. Jaundice develops with prolonged obstruction, typically 1–2 days. Charcot’s triad is the classic presentation of cholangitis and includes fever, RUQ pain, and jaundice. Altered mental status and septic shock with hypotension indicates acute suppurative cholangitis, which is an emergency. A history of clay stools and tea urine may be present.

Laboratory findings

a. b. c.

Hyperbilirubinemia (predominantly conjugated) (85/L) Elevated alkaline phosphatase is highly suggestive of biliary obstruction. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels may be transiently increased.

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d. e. f.

4.

75

Prothrombin time (PT) is often mildly elevated. Leukocytosis develops as the infection progresses. Ultrasound should be the first diagnostic test. It often shows coexistent cholelithiasis and a dilated CBD (
1 cm), and occasionally a CBD stone may be seen.

Treatment

a.

b. c. d.

ERCP should be performed emergently in patients with shock and urgently in those with less severe symptoms. Stone extraction and papillotomy via ERCP is effective in most cases. Surgical decompression may be necessary if ERCP fails. Patients with coexistent cholelithiasis should have cholecystectomy after ERCP. Vitamin K should be administered prior to procedures if PT is elevated. Antibiotics should be administered until the obstruction is resolved (e.g., piperacillin/tazobactam).

D. TUMORS OF THE BILIARY SYSTEM 1.

General characteristics

a. b. 2.

Clinical features

a.

b. 3.

Adenocarcinoma of the gallbladder is most common in older women and is associated with a history of gallstones. Adenocarcinoma of the bile duct (cholangiocarcinoma) is most common in older men and is associated with a history of ulcerative colitis. Signs and symptoms of adenocarcinoma of the gallbladder mimic those of acute cholecystitis (e.g., RUQ pain); jaundice may be seen if the tumor involves the CBD. Weight loss is common. The gallbladder may be palpable. Signs and symptoms of adenocarcinoma of the bile duct include jaundice with or without pain and weight loss.

Laboratory findings

a.

4.

VI

Adenocarcinoma of the gallbladder is generally diagnosed by the presence of a calcified gallbladder as revealed by abdominal radiographic study. i. Histologic examination from ultrasound or CT-guided biopsy confirms the diagnosis. ii. Serum bilirubin levels do not increase unless the tumor involves the bile ducts and/or liver. b. Adenocarcinoma of the bile duct is diagnosed by elevated serum AP and bilirubin levels and only mild elevations in liver enzyme levels; diagnosis is confirmed via ERCP with biopsy. Treatment is palliative because the prognosis is poor for patients who have either tumor. If significant metastatic disease is not present at the time of diagnosis, then surgical resection is warranted.

Liver Disease A. VIRAL HEPATITIS 1.

General characteristics

a. b. c. 2.

Viral hepatitis is defined as a viral inflammatory disease of the liver. Viral hepatitis may be associated with hepatitis A, B, C (non-A, non-B), or the delta agent (Table 4-3). Less commonly seen in the United States is hepatitis E. All except hepatitis B are RNA viruses; hepatitis B is a DNA virus.

Clinical features (Figure 4-8)

a.

Signs and symptoms include malaise, anorexia, fatigue, arthritis, urticaria, and jaundice.

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CHAPTER 4 TABLE 4-3

COMPARISON OF VIRAL HEPATITIS AGENTS

Agent

Mechanism of Spread

Incidence With Blood Transfusion

Hepatitis A

Fecal-oral

Rare

Hepatitis B

Parenteral (e.g., 10%–20% intravenous drug abusers); sexual contact

Hepatitis C

Parenteral

Delta agent Parenteral

b. c. d. e. 3.

Prevention

Complications

Immune serum globulin; Fulminant hepatitis give to close contacts (very rare) Hepatitis B immune globulin; hepatitis B vaccine; may attain symptoms if given 7 days after exposure

Chronic active hepatitis, occasionally causes fulminant hepatitis; increased risk of hepatocellular carcinoma if chronic hepatitis

60%–70%

Immune serum globulin

Same as hepatitis B

Unknown

Unknown

Often present with hepatitis B in cases of fulminant or chronic active hepatitis

Influenza-like syndrome may be present with nausea, vomiting, myalgias, and headache. Dark urine/light-colored stools are caused by impaired bilirubin conjugation. The liver is enlarged and tender. Splenomegaly may occur.

Laboratory findings

a. b. c. d.

Serum AST and ALT levels are elevated as much as 20-fold. AP level is usually not significantly elevated (in contrast to biliary disease). Serum and urine bilirubin levels are increased. Serum antibodies and antigens are useful diagnostically. i. Presence of anti-hepatitis A immunoglobulin M (IgM) antibody indicates a current or recent infection with hepatitis A within the last 2–3 months. ii. Presence of anti-hepatitis A immunoglobulin G (IgG) antibody indicates prior hepatitis A infection and confers immunity. iii. Presence of hepatitis B surface antigen (HBsAg) indicates acute or chronic hepatitis B infection. iv. Anti-HBsAg antibody is present in late convalescence in acute hepatitis B infection (confers immunity) and is absent in chronic hepatitis. Individuals vaccinated with hepatitis B will be positive. v. Presence of anti-hepatitis B core antigen (anti-HBcAg) of the IgM type indicates current infection with hepatitis B. vi. Presence of hepatitis B e antigen (HBeAg) without anti-HBeAg antibody indicates high viral infectivity. vii. Presence of anti-HBeAg antibody indicates low infectivity. viii. Presence of anti-hepatitis D antibody (IgG or IgM) indicates hepatitis D infection. e. HBV DNA, HDV RNA, and HCV RNA tests are now available. 4.

Treatment

a.

b.

Most patients with acute hepatitis B infections will recover with conservative therapy and not require antiviral medication. Chronic hepatitis B should be treated with lamivudine. Patients should maintain good hydration and dietary intake.

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77

A Symptomatic Phase IgM

Titer

IgG

Fecal HAV

0

4

8 Wks After Exposure

Exposure

16

12

20

B Symptomatic Phase

HBeAg

Anti-HBe

Titer

IgG Anti-HBc HBsAg

0

4

Anti-HBs

8

12

16

20

Exposure

24 28 Wks After Exposure

32

36

40

52

C Symptoms

Anti-HCV

HCV RNA

0

1

2

3

4 Months

5

6

1

2

3 Years

Exposure ● Figure 4-8. A. Course of acute hepatitis A virus (HAV) infection. B. Course of acute hepatitis B virus (HBV) infection. C. Course of acute and chronic hepatitis C virus (HCV) infection. Ag, antigen; Ig, immunoglobulin.

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CHAPTER 4

c. d. e. f.

Vitamin K administration may be necessary if coagulation parameters are abnormal. Hospitalization is indicated for patients who have severe nausea/vomiting, prolonged prothrombin time, or severe liver dysfunction. Incidence of chronic hepatitis C infection may be reduced if interferon and ribavirin is given in acute hepatitis C infection. There is no treatment for hepatitis A; hepatitis D may be treated with interferon.

B. ALCOHOLIC LIVER DISEASE 1.

General characteristics

a. b. 2.

Alcoholic fatty liver disease and alcoholic hepatitis

a.

b.

c.

3.

Alcoholic liver disease is seen in the acute stage as alcoholic fatty liver disease or alcoholic hepatitis. Chronic injury results in alcoholic cirrhosis. Clinical features i. Patients who have alcoholic fatty liver disease usually are asymptomatic, with hepatomegaly as the only sign. ii. Fever, jaundice, hepatomegaly, and liver tenderness occur in alcoholic hepatitis. iii. Variceal bleeding, encephalopathy, and ascites can be present in more severe disease. Laboratory findings i. Serum γ-glutamyltransferase, AST, ALT, and AP levels are elevated in fatty liver disease. ii. Biopsy reveals large-droplet fatty change in the liver. iii. Elevated liver enzymes and bilirubin levels with decreased serum albumin level often indicate alcoholic hepatitis. iv. Alcohol-induced thrombocytopenia may be present. v. Liver biopsy confirms the diagnosis of alcoholic hepatitis. Treatment i. Patients must maintain adequate caloric intake. ii. Thiamine and folate supplements are required because these patients are often deficient in these vitamins.

Alcoholic cirrhosis

a.

b.

Clinical features i. Fibrosis with nodular formation and destruction of normal liver architecture leads to portal hypertension. ii. Initially the liver may be enlarged, but it eventually becomes small and hard; a nodular liver may be palpable. iii. Signs of portal hypertension include ascites, splenomegaly, caput medusae, and variceal bleeding. iv. Liver dysfunction causes jaundice, spider angiomata, palmar erythema, Dupuytren contracture, gynecomastia, testicular atrophy, bruising, and fetor hepaticus. v. Hepatic encephalopathy occurs with confusion, mood changes, drowsiness, disorientation, and coma. vi. Patients who have hepatorenal syndrome demonstrate oliguria and progressive renal failure. Laboratory findings i. Ultrasound or CT scan effectively demonstrates the characteristic appearance of the cirrhotic liver.

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c.

79

ii. Serum liver enzyme levels may initially be elevated as dying hepatocytes liberate their enzymes into the blood; as cell death occurs, levels may in fact normalize; serum albumin level is often profoundly decreased. iii. Azotemia and electrolyte disturbances are common. iv. In hepatorenal syndrome, elevated blood urea nitrogen and creatinine levels indicate decreased renal function. v. Prothrombin time is prolonged. Treatment i. Acute deterioration requires hospitalization and management of complications. ii. Patients should consume a low-protein diet. iii. Electrolyte levels must be stabilized. iv. Lactulose decreases nitrogen absorption from the gut. v. If necessary, ascitic fluid should be removed in small amounts due to the risk of hepatorenal syndrome associated with removal of large amounts of fluid. vi. If severe bleeding is present, clotting factors should be administered. vii. Variceal bleeding or other types of GI bleeding should be managed.

C. HEPATIC ABSCESS 1.

General characteristics

a. b.

2.

Clinical features

a. b. 3.

Signs and symptoms include fever, chills, night sweats, anorexia, liver tenderness, and RUQ pain. Pleuritic pain may also occur.

Laboratory findings

a. b. c. d.

4.

Hepatic abscess may be due to Entamoeba histolytica (which is seen frequently in homosexual men). Hepatic abscess is also associated with infection by the following anaerobes: E. coli, Klebsiella spp., Staphylococcus spp., and Streptococcus spp. in conjunction with cholecystitis and cholangitis.

Blood cultures may be positive for bacteria, which indicates bacteremia. Serum liver enzyme levels are elevated. Serum analysis reveals leukocytosis. Ultrasound and/or CT scan are useful in detecting abscesses 2 cm in size and can also be used to guide needle aspiration for culture and microscopy to confirm the diagnosis.

Treatment

a. b.

E. histolytica is treated with amebicides (e.g., metronidazole) with aspiration of the abscess. Broad-spectrum antibiotics (e.g., ampicillin and gentamicin) are often used to treat bacterial abscesses, which are commonly polymicrobial; aspiration of sizable abscesses is also indicated.

D. HEPATIC TUMORS 1.

General characteristics

a. b. c. d.

Hepatic tumors consist of both benign and malignant lesions. Benign tumors are usually of little clinical relevance (unless complicated by hemorrhage). The liver is one of the most common organ sites for metastatic disease. The most common primary malignant tumor is hepatocellular carcinoma (hepatoma).

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2.

Hepatoma

a.

b.

c.

d.

VII

General characteristics i. Hepatoma is most common in middle-aged men. ii. Common associated risks include cirrhosis and prior hepatitis B infection. Clinical features i. Signs and symptoms include malaise, weight loss, abdominal pain, and hepatomegaly. ii. Hepatic bruit may be audible. iii. Ascites (may be hemorrhagic) may occur. iv. Sudden increase in AP level and acute deterioration in a stable cirrhotic patient are hallmarks of hepatoma. Laboratory findings i. Serum AP level is elevated, with a less significant increase in liver transaminase levels. ii.
-Fetoprotein level is often elevated. iii. CT reveals hypervascular liver mass. iv. Liver biopsy must be performed cautiously because of the vascular nature of the tumor. Treatment i. Prognosis is poor. ii. Surgical resection/cryoablation may be curative if tumors are localized. iii. Chemoembolization is used for palliation. iv. Liver transplant has been successful in those patients with solitary tumors (5 cm) or fewer than three tumors each 3 cm in size associated with cirrhosis.

Gastrointestinal Bleeding 1.

General characteristics

a. b.

c.

2.

May be upper (site proximal to ligament of Treitz) or lower (distal to ligament of Treitz) Common causes of upper GI bleeds include peptic ulcer disease (50%), esophageal varices (10%–20%), Mallory-Weiss tear (5%–10%), and vascular anomalies (10%). Common causes of lower GI bleeds include diverticulosis (50%), arteriovenous malformation (AVM) (5%–10%), malignancy (10%), ischemia, infectious colitis, inflammatory bowel disease (IBD), or anorectal disease.

Clinical features

a.

b.

Upper GI bleed i. Hematemesis: bright red or coffee grounds ii. Melena—black stool iii. Hematochezia is less common and indicates massive upper GI hemorrhage. Its presence is more often seen in lower GI bleeds. iv. Hemodynamic instability occurs with significant (1.0 L) blood loss. v. Stigmata of liver disease may be present in those with variceal bleed or Mallory-Weiss tear associated with retching after significant alcohol consumption. vi. History of NSAIDs or steroids suggests peptic ulcer disease. vii. Nasogastric tube placement helps confirm upper GI source. Lower GI bleed i. Brown stool mixed with or streaked with blood suggests the rectosigmoid or anus as the site of hemorrhage.

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ii. iii. iv. v. 3.

Maroon stools suggest a right colon or small intestine source. Hematochezia suggests a colonic source. Painless bleeding is typical of diverticular or AVM bleeding. Bloody diarrhea suggests IBD or infectious or ischemic colitis.

Laboratory findings

a. b. c. d.

e.

f.

g. 4.

81

Decreased hematocrit depending on severity of hemorrhage. Leukocytes may be present in infectious or ischemic etiologies. Liver function test results may be abnormal in those with coexistent liver disease, suggesting esophageal variceal hemorrhage as the etiology. Upper endoscopy should be performed if an upper GI source is suspected; if bleeding is significant, this should be done urgently. This will identify the source, determine the risk of rebleeding, and be therapeutic. Colonoscopy localizes the lower GI bleeding site in up to 85% of lower GI bleeds. Occasionally visualization is impaired due to blood and angiography or nuclear medicine scans are necessary. Angiography requires about 1 mL/min of blood loss to identify the bleeding site but is necessary to guide surgical treatment, or may be used to embolize the bleeding vessel. Nuclear medicine scan detects 0.5 mL/min of bleeding but is less sensitive in localization of the bleeding site than angiography.

Treatment

a.

b.

Upper GI bleeds i. Endoscopy to cauterize peptic ulcer bleeds plus proton pump inhibitors to reduce rebleeding ii. Endoscopy for variceal bleeding may be augmented by octreotide as well as a transvenous intrahepatic portosystemic shunt to reduce esophageal variceal pressure. Long-term -blockers for varices reduces recurrence. iii. Surgical therapy is indicated if there is
6 units of blood loss despite endoscopic therapy. Lower GI bleed with cautery i. Colonoscopy with cautery is very effective in diverticular and AVM-associated bleeds, with low recurrence. ii. Vasopressin intra-arterially produces splanchnic vasospasm and arrests bleeding but is associated with high recurrence. iii. Embolization is useful in poor operative candidates. There is a 15% incidence of subsequent infarction. iv. Surgery is indicated for
6 units of blood loss or for recurrent diverticular hemorrhage.

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24 Chapter 5

Cervical Neoplasia Infectious Diseasesand Cancer I

Central Nervous System (CNS) Infections A. MENINGITIS 1.

General characteristics

a.

2.

3.

4.

Meningitis may be bacterial (Table 5-1) or aseptic (viral). Streptococcus pneumoniae is the most common cause in adults. b. Most cases occur in children or young adults. Clinical features a. Signs and symptoms include fever, headache, stiff neck, lethargy, and irritability. b. Palpable purpura suggests Neisseria meningitidis. c. Focal neurologic findings and seizures may occur in bacterial meningitis but are less common in viral infections of the meninges. Laboratory findings a. Gram stain of cerebrospinal fluid (CSF) is often positive in bacterial infection. b. Lumbar puncture should not be performed if suspicion of an intracranial space-occupying lesion exists. c. CSF, blood, and purpuric fluid culture studies should be performed (Table 5-2). Treatment a. Treatment for bacterial meningitis includes intravenous ampicillin for pneumococcal or meningococcal disease. b. Cefotaxime or ceftriaxone is indicated for patients who have Haemophilus influenzae infection. c. Broad-spectrum antibiotics such as ampicillin and a third-generation cephalosporin should be administered until the organism is identified. S. pneumoniae resistance to penicillins and cephalosporins is emerging, and vancomycin should be used empirically until sensitivities are obtained. d. Prophylaxis with rifampin should be administered to household contacts (younger than age 4) of patients who have H. influenzae infection. e. Rifampin should be administered to all household contacts of patients who have meningococcemia. f. Viral meningitis is usually self-limited and requires no treatment.

B. Encephalitis 1. General characteristics a. Encephalitis is usually caused by a virus. b. Common viral causes include: herpes simplex virus (HSV), varicella zoster virus (VZV), and equine encephalitis viruses.

82

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TABLE 5-1

BACTERIAL CAUSES OF MENINGITIS ACCORDING TO AGE

Organism

Group Affected

Haemophilus influenzae Neisseria meningitidis Streptococcus pneumoniae Listeria monocytogenes

Infants Adolescents and young adults Adults
20 years old Immunosuppressed and elderly

2.

Clinical features

a. b. c. 3.

Signs and symptoms include fever, headache, behavioral changes, altered levels of consciousness, delirium, and speech difficulty. Seizures (focal or generalized) may occur. A prodrome of upper respiratory tract signs and symptoms may occur.

Laboratory findings

a.

b. c. d. 4.

83

CSF analysis reveals a moderately elevated protein level, normal glucose level, and lymphocytic pleocytosis. CSF polymerase chain reaction (PCR) is now used to detect virus with excellent sensitivity. Electroencephalogram shows a characteristic pattern in HSV infection. Serum analysis that measures antibody titers to various encephalitic viruses can be helpful. Computed tomography (CT) scan and magnetic resonance imaging can reveal focal abnormalities after a few days of infection.

Treatment

a. b. c. d.

Acyclovir is commonly used to treat HSV and VZV encephalitis. Other viral causes are treated supportively. Avoid hypotonic intravenous (IV) fluid to decrease cerebral edema. Anticonvulsants for seizures.

C. INTRACRANIAL ABSCESS 1.

General characteristics

a. b.

2.

Intracranial abscesses usually arise from infection of a contiguous site (e.g., ear or sinus infection). Infection is commonly caused by streptococci and/or anaerobes. Recently, fungi and parasites (Toxoplasma, Aspergillus, Nocardia, mycobacteria) have emerged as a common cause among immunosuppressed patients.

Clinical features

a. b. c.

TABLE 5-2

Cells Percent neutrophils Glucose Protein

Signs and symptoms include fever with worsening headache, decreased level of consciousness, and vomiting. Focal neurologic signs are present. Seizures occur.

CSF FINDINGS IN MENINGITIS Bacterial

Aseptic

1000–10,000/L
50% 40 mg/dL
45 mg/dL

10–2,000/µL
50% Normal 100 mg/dL

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3.

Laboratory findings

a.

4.

II

CT scan is an important diagnostic tool because lumbar puncture is contraindicated in these patients (Figure 5-1) due to the risk of herniation. b. Serum analysis reveals leukocytosis; blood culture may be positive if septicemia has occurred. Treatment includes surgical drainage with appropriate antibiotics. Antibiotics for the community-acquired brain abscess in the immunocompetent patient should include a third-generation cephalosporin (good CNS penetration) and metronidazole. Patients in the hospital and at risk for methicillin-resistant Staphylococcus aureus (MRSA) should have vancomycin included. Duration of antibiotics is at least 6 weeks.

Head and Neck Infections A. OTITIS 1. 2.

3.

4.

Otitis is an infection that may occur in the inner, middle, or outer ear. Patients who have outer ear infections demonstrate minor irritation in the exter-

nal auditory canal usually secondary to pseudomonas or S. aureus, and are treated with a topical antibiotic (gentamicin drops). Middle ear infections typically occur in children; signs and symptoms include ear pain and decreased hearing. a. Otoscopy reveals a hyperemic, bulging tympanic membrane with pus behind it. b. Middle ear infections are often caused by pneumococcus, Streptococcus pyogenes, or H. influenzae; these infections often respond to amoxicillin or trimethoprim-sulfamethoxazole (TMP-SMX). Inner ear infections are usually viral and are thus often untreatable; signs and symptoms include tinnitus and vertigo.

B. SINUSITIS 1.

2.

Sinusitis is usually viral in etiology, but when bacterial in origin it is caused by pneumococcus or H. influenzae (in the community). Nosocomial cases are secondary to S. aureus, Pseudomonas, and other resistant gram-negative organisms. Clinical features

a.

3. 4.

III

Patients often have a prodrome of upper respiratory tract signs and symptoms. b. Signs and symptoms of sinusitis include pain and stuffiness in the affected sinuses and tenderness to palpation over the affected sinuses. Symptoms
7 days duration should raise suspicion of a bacterial etiology. Laboratory findings are usually unnecessary for diagnosis, although sinus radiography may reveal opacification of the affected sinus. Treatment of patients who have symptoms 7 days is decongestants and an appropriate antibiotic (e.g., penicillin). Amoxicillin should be used for patients with
7 days of symptoms.

Respiratory Tract Infections A. UPPER RESPIRATORY TRACT INFECTION (URTI) 1. These infections are also known as the common cold and are usually virally induced.

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● Figure 5-1. Computed tomography scan of a patient who has an intracranial abscess. Note the surrounding edema and mass effect.

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2. 3.

Signs and symptoms include cough, coryza, rhinorrhea with or without a sore throat, and a slight fever. Treatment is symptomatic because infection is self-limited.

B. PHARYNGITIS 1.

General characteristics

a. b.

2.

Clinical features

a. b. c. d.

e. 3.

The main symptom is a sore throat. Exudate may be present in either a bacterial or viral infection. The presence of URTI-like symptoms suggests a viral pharyngitis. Malaise, fever, generalized lymphadenopathy, and splenomegaly associated with hypertrophied tonsils with a white exudate strongly suggest EBV (infectious mononucleosis). EBV infection is more common in the young adult population.

Laboratory findings

a.

b. 4.

Pharyngitis is caused by viruses (e.g., Epstein-Barr virus [EBV]); Mycoplasma; or group A streptococci. Persistence of signs and symptoms for longer than 1 week, respiratory stridor, excess secretions, difficulty swallowing, or the presence of a palpable mass should alert the clinician to a more serious cause, such as malignancy or epiglottitis.

Because clinical distinction of streptococcal pharyngitis from viral pharyngitis is difficult, a throat swab and culture for group A streptococcus is recommended for patients who have pharyngitis. Monospot test results for heterophile antibodies are positive in patients who have EBV infection.

Treatment

a. b. c.

Penicillin therapy for streptococci infections should last for at least 10 days to prevent rheumatic fever. Viral pharyngitis is usually self-limited. Tetracycline or erythromycin is indicated for Mycoplasma.

C. PNEUMONIA 1. Pneumonias can be community acquired or hospital acquired. 2. Community-acquired pneumonias a. General characteristics i. The most common cause of community-acquired pneumonia is Streptococcus pneumoniae (also called pneumococcus). ii. Atypical form is associated with Mycoplasma pneumoniae, which has a different clinical presentation from that of S. pneumoniae. Infection with M. pneumoniae is commonly seen in young adults. iii. H. influenza is another common cause. iv. Aspiration pneumonia is associated with anaerobic infections. b. Clinical features i. Signs and symptoms include fever, chills, and a productive cough with rust-colored sputum. ii. If the pneumonia is caused by M. pneumoniae, the cough is typically dry and hacking. iii. In aspiration pneumonia, the sputum is foul-smelling. iv. Breath sounds are decreased over the infiltrated area. v. Pleural rub may be appreciated.

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● Figure 5-2. Chest radiograph of a patient who has a right upper lobe infiltrate that may be consistent with pneumonia caused by S. pneumoniae. (Reprinted with permission from Freundlich IM, Bragg DG: A Radiologic Approach to Diseases of the Chest, 2nd ed. Baltimore, Williams & Wilkins, 1996, p 246.).

c.

d.

3.

vi. Splinting on inspiration may occur. vii. Signs and symptoms associated with M. pneumoniae tend to be less severe. viii.A history of loss of consciousness (e.g., passing out after an alcohol binge); seizures; or vocal cord paralysis should alert the clinician to the diagnosis of an aspiration pneumonia. Laboratory findings i. Sputum microscopy with Gram stain often provides the diagnosis, revealing large numbers of neutrophils and streptococci. ii. Sputum culture confirms the diagnosis. iii. Mycoplasma sputum analysis is often less diagnostic. iv. Bronchial washings may be required if sputum cultures are not diagnostic and the patient’s condition deteriorates despite empiric antibiotic therapy. v. Chest radiographs may reveal infiltrates that are often arranged in a reticulonodular pattern in S. pneumoniae and Mycoplasma infection (Figure 5-2). vii. Cavitating lesions are common in aspiration pneumonia (Figure 5-3). Treatment i. Streptococcus or Mycoplasma infections are now treated with a macrolide (e.g., azithromycin) orally. ii. Aspiration pneumonia is treated with fluoroquinolones or piperacillin/ tazobactam.

Hospital-acquired pneumonias

a. b. c. d.

These pneumonias often involve gram-negative bacilli (e.g., Klebsiella, Pseudomonas, and Escherichia coli) or MRSA. Clinical features are as previously described. Diagnosis involves chest x-ray and may require bronchoscopy with alveolar lavage to identify the agent. Treatment involves a penicillinase-resistant penicillin or cephalosporin plus an aminoglycoside (e.g., gentamicin).

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● Figure 5-3. Chest radiograph illustrating right upper lobe pneumonia (anterior segment) with multiple areas of necrosis and cavitation associated with an aspiration pneumonia. Note the horizontal fissure in the middle of the right lung field, which defines an upper lobe pneumonia.

IV

Gastrointestinal Infections A. DIARRHEA, FOOD POISONING SYNDROMES, and liver and biliary tract infections are discussed in Chapter 4, Gastrointestinal Disorders. B. APPENDICITIS is also discussed in Chapter 4, Gastrointestinal Disorders.

V

Genital and Sexually Transmitted Infectious Diseases A. URETHRITIS 1.

General characteristics

a. b. c. 2.

This infection occurs in sexually active individuals (usually males). Urethritis is classified as gonococcal (Neisseria gonorrhoeae) or nongonococcal (usually Chlamydia or Mycoplasma). Infections with both organisms may be present in a single patient.

Clinical features

a. b. c.

Dysuria is the main symptom. Purulent discharge is often present in gonococcal disease. Cloudy discharge may be present in nongonococcal disease.

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3.

89

Laboratory findings from microscopy and culture of urethral swab are diagnostic,

showing gram-negative intracellular diplococci if gonococcal infection is present. 4.

Treatment

a. b.

Gonococcal disease is treated with a single dose of ceftriaxone intramuscularly or a fluoroquinolone. If chlamydial infection is suspected, use azithromycin or doxycycline.

B. PELVIC INFLAMMATORY DISEASE (PID) 1.

General characteristics

a. b. c. d. 2.

Clinical features

a. b. c. d. e. 3.

PID occurs with increased frequency during menses because menstrual blood provides a growth medium for bacteria. Patients have lower abdominal pain. Fever may be present. Cervix, uterus, and adnexae are tender, with pain during intercourse. Cervical discharge may be observed during speculum examination of the pelvis.

Laboratory findings

a. b. c. d.

4.

PID is defined as infection of the uterus and other adnexal structures. Infection may be caused by N. gonorrhoeae, Chlamydia, or pelvic anaerobes. Intrauterine device use increases risk of PID. PID may lead to infertility or ectopic pregnancy due to scarring of adnexal structures.

Cervical swab for culture is often diagnostic. Levels of serum
-human chorionic gonadotropin should be measured to rule out ectopic pregnancy. Appendicitis should be ruled out by an abdominal ultrasound. Pelvic ultrasound may be necessary if a mass is palpated during pelvic examination (e.g., abscess) or if discomfort is so severe that it precludes a thorough examination.

Treatment

a. b. c.

For severe disease, the patient should be hospitalized and parenteral antibiotics should be administered. Clindamycin plus gentamicin are often effective when anaerobes are suspected. Doxycycline plus cefoxitin is often the first line of treatment because this drug combination is effective against both chlamydial and gonorrheal infections.

C. GENITAL ULCER AND LYMPHADENOPATHY SYNDROMES 1.

General characteristics

a. b. c. d. 2.

These conditions are more common in males than in females. Genital herpes is the most common cause of genital ulcer disease in the United States, followed by syphilis. Less common causes include lymphogranuloma venereum, chancroid, and granuloma inguinale. Gonorrhea does not cause genital ulcers.

Clinical features

a.

Features of genital herpes: i Onset occurs with soreness and itching, followed by genital erythema. ii. Herpetic vesicles then develop. iii. Sores eventually heal; however, outbreaks continue to occur throughout the patient’s lifetime.

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b.

c.

d.

e.

3.

Laboratory findings

a. b. c. d. e. 4.

For herpes, the Tzanck test and culture are diagnostic. For syphilis, dark-field examination and rapid plasma reagin (RPR) testing are diagnostic. For lymphogranuloma venereum, culture of expressed pus and serologic testing for presence of anti-C. trachomatis antibodies are diagnostic. For chancroid, culture of Haemophilus ducreyi from the ulcer or suppurative nodes is diagnostic. For granuloma inguinale, scrapings of the ulcer edge show Donovan bodies with Giemsa or Wright stain.

Treatment

a. b. c. d. e. VI

Features of syphilis include: i. Patients who have primary syphilis are initially seen with a painless ulcer. ii. The base of the ulcer is often hard. Features of lymphogranuloma venereum include: i. Large inguinal lymph nodes accompany the genital ulcer. ii. This condition is caused by Chlamydia trachomatis. Features of chancroid include: i. Patients have multiple, painful ulcers. ii. The edges of the ulcers are often undermined and rough. iii. Suppurative inguinal nodes may be present. Features of granuloma inguinale include: i. Patient has a painless lesion with a beefy red appearance. ii. The ulcer edges are rolled. iii. Adenopathy is not a predominant finding. iv. Causative organism is Calymmatobacterium granulomatis; this organism causes a slowly advancing infection.

Herpes symptoms are self-limited but recur; acyclovir can reduce the severity of outbreaks but is not curative. Syphilis is treated with penicillin. Lymphogranuloma venereum is treated with tetracycline or erythromycin. Chancroid is treated with azithromycin, ceftriaxone, or ciprofloxacin. Granuloma inguinale is treated with tetracycline or TMP-SMX.

Urinary Tract Infection (UTI) A. GENERAL CHARACTERISTICS 1. UTI may occur as a result of inoculation during instrumentation or sexual intercourse. 2. UTIs are more common in females, especially those who have vaginal or periurethral colonization. 3. Risk factors include obstruction (leading to urinary stasis) and reflux, pregnancy, diabetes mellitus, and immunodeficiency states. 4. If untreated, a UTI may lead to pyelonephritis. B. CLINICAL FEATURES 1. Signs and symptoms include urinary frequency and urgency, dysuria (burning), suprapubic pain, and malodorous and/or cloudy urine. 2. Signs and symptoms of pyelonephritis include flank pain with fever in conjunction with signs and symptoms of UTI. 3. Mental status changes in the elderly may be the only presenting sign of a UTI.

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C. LABORATORY FINDINGS 1. Urinalysis may reveal bacteria on microscopy. a. Leukocyturia may be present. b. Positive test results for leukocyte esterase and/or nitrites suggest the diagnosis. 2. Urine culture gives a definitive diagnosis. a. A clean-catch midstream specimen is required. b. Colonization of
105 colonies/mL is diagnostic. c. If the colony count is 105 colonies/mL, treatment may still be warranted if the patient is symptomatic or is known to have recurrent UTIs. d. If routine cultures are negative and the patient remains symptomatic, cultures for Ureaplasma or Chlamydia should be specifically ordered. 3. Intravenous urography may be necessary in patients who are suspected of having vesicoureteral reflux, obstruction, or renal calculi. D. TREATMENT 1. 2. 3. 4.

VII

Uncomplicated lower UTI often responds to TMP-SMX or quinolone during a treatment course of 5–7 days. Prolonged antibiotic coverage may be required for recurrent or chronic UTIs (e.g., nitrofurantoin). Acute pyelonephritis requires broad-spectrum antibiotic coverage such as ampicillin and gentamicin. Urologist referral is necessary for patients who have anatomic obstructions because chronic reflux can lead to renal failure.

Osteomyelitis and Joint Infections A. OSTEOMYELITIS 1.

General characteristics

a. b. c. d. e. 2.

Clinical features

a. b. c. d. 3.

Infection of the bone may occur from infection at a contiguous site (history of trauma or surgery to the affected area) or from hematogenous spread. Staphylococcus aureus is the most common cause of osteomyelitis. S. aureus and E. coli infections are also common among IV drug abusers. Osteomyelitis commonly affects long bones and vertebral bodies. Individuals with prosthetic joint replacements have an increased incidence of joint infections. Local pain and tenderness may be present. Redness overlying the infection may be present. Fever may or may not be present. Draining sinus tracts result from chronic infections or implants.

Laboratory findings

a. b. c. d. e. f.

Diagnosis is confirmed with isolation of S. aureus from the blood and/or bone in a patient who has symptoms of focal bone involvement. If blood cultures are negative, bone biopsy and culture should be considered to isolate the organism. Bone scan is effective in localizing the site of infection. Radiographs are often normal early in the course of the infection, because radiographic changes often lag behind clinical onset by as much as 1 week. CT scan is more sensitive than plain radiographs and can localize abscesses. MRI is very sensitive and is the procedure of choice for vertebral osteomyelitis.

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4.

Treatment

a. b. c.

Osteomyelitis is treated with nafcillin or oxacillin IV for 2–4 weeks, followed by an oral regimen with an antibiotic such as dicloxacillin. Total antibiotic therapy should continue for 4–6 weeks. Vancomycin can be used for patients who are allergic to penicillin or who have MRSA.

B. JOINT INFECTIONS 1.

General characteristics

a. b. c. d. 2.

Clinical features

a. b. c. d. e. 3.

c.

Joint fluid should be aspirated for Gram stain and culture. Crystal disease can be ruled out with a specimen for polarizing microscopy (see Chapter 7, Rheumatic Diseases). In gonococcal infection, skin lesions and joint cultures may be negative; however, a cervical culture may reveal the diagnosis.

Treatment

a. b. c. VIII

Patients have acute onset of monoarticular pain that commonly involves the knee. Signs and symptoms include joint pain, swelling, redness, and a decreased range of motion. Patients who have a joint prosthesis may experience pain and loosening of the prosthesis. Disseminated gonococcal infection is suggested by additional tenosynovitis and a vesicopustular skin rash. Gout or pseudogout must also be considered in the differential diagnosis.

Laboratory findings

a. b.

4.

Patients who receive intra-articular corticosteroids and patients who have existing joint disease (e.g., rheumatoid arthritis) are at risk for joint infections. The most common causes are N. gonorrhoeae, streptococci, and S. aureus. Pseudomonas is a common cause of joint infection in IV drug abusers. S. epidermidis is a common pathogen in individuals who have prosthetic joints.

Treatment involves repeated aspiration of infected joint material or surgical drainage. Systemic antibiotic therapy is recommended for at least 4–6 weeks if a staphylococcal infection is present (e.g., vancomycin). Gonococcal arthritis responds well to penicillin within 7–10 days.

Other Infectious Syndromes A. INFECTIOUS MONONUCLEOSIS 1.

General characteristics

a. b. c. 2.

Infectious mononucleosis is caused by EBV. This disease tends to occur in adolescence and young adulthood. In immunocompromised patients, EBV may be associated with lymphoproliferative diseases (Burkitt lymphoma, Hodgkin disease).

Clinical features

a. b. c. d.

Patients have a fever and discrete, nonsuppurative, slightly painful enlarged lymph nodes that often involve the posterior cervical chain. Splenomegaly is present in approximately half of the patients. Sore throat, anorexia, and malaise are often present. Ampicillin may induce a petechial rash in these patients.

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e. f. 3.

Exudative pharyngitis may be present on physical examination. Occasionally, patients may develop hepatitis.

Laboratory findings

a. b. c. d. e. 4.

93

Complete blood count shows an initial granulocytopenia followed by a lymphocytic leukocytosis (leukocytes are large in appearance). Positive Monospot test results indicate presence of heterophile antibodies. False-positive Venereal Disease Research Laboratory and RPR test results can occur with this disease. If the CNS is involved, the CSF will show increased levels of lymphocytes and protein. Levels of liver enzymes and bilirubin are often elevated.

Treatment

a. b. c.

No specific treatment is available. Nonsteroidal anti-inflammatory drugs may provide symptomatic relief. Contact sports should be avoided in patients who have splenomegaly to decrease the incidence of splenic rupture.

B. TUBERCULOSIS (TB) 1.

General characteristics

a. b. 2.

Clinical features

a. b. 3.

Pulmonary-related TB signs and symptoms include increased cough, weight loss, hemoptysis, and fatigue. Extrapulmonary signs and symptoms affect kidneys, bones, and meninges.

Laboratory findings

a.

b. c. 4.

Increased incidence is largely caused by human immunodeficiency virus (HIV) infection. TB is common in immigrant and underprivileged groups.

Tuberculin skin test results are positive but indicate only prior exposure: this does not confirm that the patient’s current signs and symptoms are caused by tuberculosis. Pulmonary TB is detected with acid-fast stain and appropriate culture of sputum. Bronchial washings may be necessary to obtain an appropriate specimen.

Treatment

a. b.

Isoniazid and rifampin are first-line therapies and should be administered for at least 6 months. For the first 2 months, pyrazinamide and ethambutol are added. Chemoprophylaxis with isoniazid alone for the following high-risk individuals is necessary: i. Younger than 30 years of age with a positive tuberculin skin test ii. Individuals of any age with a recently converted skin test iii. Individuals with a positive skin test who receive chronic steroid therapy iv. Individuals who are in close contact with an infectious patient

C. EOSINOPHILIA-ASSOCIATED INFECTIONS 1.

General characteristics

a. b. 2.

Eosinophilia is associated with multicellular parasitic infections (e.g., schistosomes, pinworms). Parasitic causes must be differentiated from allergic causes of eosinophilia, which are commonly associated with drug reactions.

Clinical features of pinworm infection

a. b. c.

Pinworms commonly affect young children. Cecum and adjacent bowel are often inhabited by the organism. Eggs are laid at the anus after infection occurs.

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d. e. 3.

Laboratory findings

a. b. c. 4.

Patients have perianal pruritus, irritability, restlessness, and enuresis. Patients have vague abdominal complaints, particularly in the right lower quadrant. The presence of eggs on perianal skin is diagnostic. Stool examination may reveal adult worms. Eosinophilia may be present.

Treatment

a. b.

Oral mebendazole is highly effective and should be used in symptomatic patients. In asymptomatic patients, good hand-washing after defecation and clean bed linens will kill the organism and prevent reinfection.

D. TOXIC SHOCK SYNDROME (TSS) 1.

General characteristics

a. b. c. 2.

Clinical features

a. b. 3.

Signs and symptoms include fever, hypotension, desquamative rash on the hands and feet, vomiting, and diarrhea. Nonpurulent conjunctivitis may occur.

Laboratory findings

a. b. c. 4.

TSS is caused by toxin formed by certain strains of S. aureus. TSS often involves vaginal colonization by the staphylococci, with increased incidence in females using tampons. TSS may occur with infection at other sites as well.

Blood cultures are usually negative because the disease is caused by an immune reaction to the toxin. The toxin-producing organism may be cultured from wound scrapings or the vagina if colonization has occurred. Increased liver function tests (LFTs), azotemia, leukocytosis, and thrombocytopenia are common.

Treatment

a. b. c.

Patients require rapid IV rehydration. If vaginal colonization is present, the tampon should be removed. Antibiotics such as nafcillin or vancomycin are indicated.

E. LYME DISEASE 1.

General characteristics

a. b. 2.

Clinical features

a.

b. c. d. 3.

Lyme disease is characterized by multiorgan involvement. The causative organism is Borrelia burgdorferi, which is transmitted to humans by a biting tick. Patients initially have a skin rash. i. The rash begins at the site of the tick bite and spreads. ii. The rash is a target-like lesion known as erythema chronicum migrans; rash develops on the thighs, buttocks, and trunk. Patient may develop aseptic meningitis weeks to months after the tick bite; signs and symptoms include neck pain and stiffness, headache, and low-grade fever. Arthritis (usually a migratory polyarthritis) may develop months after initial infection as well. Myocarditis may also occur after initial infection.

Laboratory findings

a. b.

Diagnosis is established by detection of antibodies against the organism. Joint fluid aspiration for culture is negative.

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F.

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Treatment involves tetracycline, erythromycin, or penicillin; these drugs can hasten recovery and reduce the severity of late manifestations.

AIDS 1.

General characteristics

a.

b. c. d. 2.

AIDS patients are HIV positive and show a CD4 lymphocyte count
200 cells/L and/or opportunistic infections (e.g., Mycobacterium, coccidioidomycosis, histoplasmosis, Pneumocystis) and/or unusual neoplasms (lymphoma, Kaposi sarcoma). Risk factors include sexual contact with an HIV-positive person, IV drug abuse with needle sharing, and health occupational-related exposure. Risk of transmission from blood transfusion is now about 1:8,000,000. HIV, a retrovirus, predominately infects CD4 cells leading to immunodysfunction.

Clinical features

a. b. c. d.

e. f.

TABLE 5-3

Asymptomatic phase is approximately 10 years after exposure. Infectious complications correlate with CD4 counts (Table 5-3). Constitutional symptoms are common (e.g., fever, night sweats, weight loss). Anorexia, nausea, and vomiting, which may occur in isolation or secondary to intestinal infection Cough i. Infectious causes. Cough may indicate pneumonia secondary to communityacquired bacterial, Mycoplasma, Pseudomonas, cytomegalovirus (CMV), histoplasmosis, coccidioidomycosis, cryptococcal, or pneumocystis organisms. Hypoxia may occur with severe infections. ii. Other (noninfectious) causes of pulmonary symptoms include lymphoid interstitial pneumonitis, lymphoma, and less commonly, Kaposi sarcoma. Chronic sinusitis is common. CNS infections produce encephalopathy, meningitis, or intracerebral spaceoccupying lesions. i. Toxoplasmosis usually causes multiple intracerebral space-occupying lesions causing headache, seizures, altered mental status, or focal deficits. ii. Non-Hodgkin lymphoma commonly causes space-occupying lesions. iii. AIDS dementia complex results in mental status changes (diagnosis of exclusion). iv. Cryptococcal meningitis presents with fever, headache, and sometimes meningismus (20% of cases). v. HIV myelopathy and progressive multifocal leukoencephalopathy appear late in the disease.

OPPORTUNISTIC INFECTIONS CORRELATED WITH CD4 COUNT

CD4  600

CD4  200

CD4  50

Bacterial infection Tuberculosis Herpes simplex/varicella zoster Vaginal candidiasis Hairy leukoplakia Kaposi sarcoma

Pneumocystis Toxoplasmosis Cryptococcus Coccidioidomycosis

Disseminated mycobacterium

CMV, cytomegalovirus.

Histoplasmosis CMV Lymphoma

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g. Large-joint arthritis is common. h. Retinitis may occur due to CMV infection and appears as perivascular hemorrhages and fluffy exudates on funduscopy. i. Oral and esophageal candidiasis and hairy leukoplakia are highly suggestive of HIV infection. j. Diarrhea due to HIV, CMV, Campylobacter, Salmonella, Shigella, Giardia, cryptosporidium, or Entamoeba may occur. k. Skin manifestations include herpes simplex or zoster, folliculitis, and Kaposi sarcoma. 3.

Laboratory findings

a. b. c.

d. e. f. 4.

HIV serology is positive and is confirmed by Western blot analysis indicating HIV infection. CD4 lymphocyte counts should be done every 6 months for those with 350 cells/L, which necessitates prophylaxis. Viral load tests measure the amount of actively replicating HIV and indicate response to retroviral therapy. Counts 30,000 by branched-chain DNA test (
55,000 by PCR) and CD4
350 cells/L require initiation of antiretroviral therapy. Measurements should be done every 3–6 months. Anemia, lymphopenia, and thrombocytopenia are common. Purified protein derivative (PPD), Toxoplasma immunoglobulin G serology, and CMV immunoglobulin G serology should be performed. Radiologic evaluation should be directed toward the presenting symptoms.

Treatment

a.

b.

c.

d.

Antiretroviral therapy i. Therapy should be initiated when viral load 30,000 by branched-chain DNA test (55,000 by PCR) and CD4
350 cells/L. ii. First-line therapy includes two nucleoside analogs (e.g., AZT and 3TC) plus either a protease inhibitor (e.g., Indinavir) or nonnucleoside reverse transcriptase inhibitor (e.g., Nevirapine). iii. If viral load does not decrease or is intolerable, other combinations should be used. iv. Therapy should be offered to those with exposure to HIV-positive blood. Opportunistic infection prophylaxis i. CD4 count
200 cells/L: start P. carinii prophylaxis with TMP-SMX ii. CD4 count
100 cells/L: M. avium prophylaxis with azithromycin may stop prophylaxis if CD4 count
100 for 6 months iii. If positive PPD: M. tuberculosis prophylaxis with rifampin and pyrazinamide iv. Toxoplasma prophylaxis with TMP-SMX if serology is positive v. Prior CMV disease requires prophylaxis. vi. Frequent HSV recurrences: acyclovir vii. Frequent candidal infections: fluconazole Hematopoietic stimulation i. Anemia is treated with erythropoietin. ii. Human granulocyte colony-stimulating factor increases neutrophil counts in neutropenic patients to keep count 1,000 cells/L. Malignancy treatment i. Lymphoma: modified CHOP (cyclophosphamide, doxorubican, vincristine, prednisone) ii. Kaposi sarcoma: interferon alpha

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Chapter

6

Endocrinologic and Metabolic Disorders I

Disorders of the Pituitary Gland A. GENERAL CHARACTERISTICS 1. Diseases may affect the anterior and/or posterior pituitary gland. 2. Anterior pituitary diseases include pituitary tumors, anterior pituitary hypofunction, and pituitary hyperfunction. 3. Posterior pituitary diseases include diabetes insipidus and syndrome of inappropriate antidiuretic hormone secretion (SIADH). B. PITUITARY TUMORS 1.

General characteristics

a. b. c. d. e. 2.

Clinical features

a. b.

c. 3.

Patients who have pituitary tumors may be seen with headache or visual disturbance (bitemporal hemianopia). Patients who have functioning tumors may be seen with endocrinologic manifestations, for example, galactorrhea-amenorrhea (PRL-secreting tumor), acromegaly (GH-secreting tumor), Cushing syndrome (ACTH-secreting tumor). Patients who have nonfunctioning tumors may be seen with signs and symptoms of anterior pituitary hypofunction (see I C).

Laboratory findings

a. b.

c. 4.

Pituitary tumors account for 10% of intracranial tumors. Pituitary tumors may be nonfunctioning. Functioning tumors are usually chromophobic adenomas that produce adrenocorticotropic hormone (ACTH), growth hormone (GH), or prolactin (PRL). Secretion of thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), or luteinizing hormone (LH) is rare. May be associated with multiple endocrine neoplasia syndrome (MEN I), which includes parathyroid adenoma and pancreatic islet cell adenomas.

Computed tomography (CT) scans with contrast medium are useful in diagnosing adenomas
10 mm in diameter (microadenomas). Magnetic resonance imaging (MRI) is the diagnostic procedure of choice, with adenoma density appearing low on T1-weighted and high on T2-weighted images. Growth hormone, prolactin, or ACTH (and cortisol) levels are often elevated even when diagnostic imaging cannot visualize the tumor.

Treatment

a.

Transsphenoidal surgical removal of the tumor is indicated if neurologic symptoms or syndromes of excess hormone production are present. Small 97

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b. c. d.

(
10 mm) asymptomatic microadenomas may be observed and removed when they enlarge or become functional. Radiotherapy alone or as an adjunct to surgery often reduces tumor size, but often results in hypopituitarism. Bromocriptine (dopamine agonist) often sufficiently controls small PRLsecreting adenomas. In nonfunctioning tumors, hormonal replacement is required.

C. ANTERIOR PITUITARY HYPOFUNCTION 1.

General characteristics

a. b. 2.

Clinical features

a. b. c. d.

e. 3.

GH deficiency causes growth failure if disease occurs during childhood, but adults are not affected by GH deficiency. LH/FSH deficiency causes amenorrhea and breast atrophy in women, genital atrophy, and loss of potency and libido in men. TSH deficiency causes signs and symptoms associated with hypothyroidism (see II C). ACTH deficiency causes secondary adrenal insufficiency (which differs clinically from primary adrenal insufficiency). i. Hyperpigmentation does not occur as in primary adrenal insufficiency because ACTH levels are decreased. ii. Decreased serum sodium and increased serum potassium levels are not severe in secondary adrenal insufficiency because aldosterone secretion is largely dependent on the renin-angiotensin system rather than ACTH. iii. Hyponatremia may occur secondary to decreased cortisol levels, which is necessary for free water excretion. PRL deficiency causes no clinical manifestations except in Sheehan syndrome, in which it results in postpartum failure of lactation.

Laboratory findings

a.

b.

c.

4.

Anterior pituitary hypofunction may occur secondary to destruction of the pituitary by a nonfunctioning pituitary tumor. The disease may also occur secondary to infarction resulting from hypotension during childbirth (Sheehan syndrome) or surgical removal of the pituitary gland.

The diagnosis is established by low levels of target organ hormones (cortisol, thyroxine, testosterone, estrogen) and an absence of compensatory increases in corresponding pituitary hormones (ACTH, TSH, FSH/LH). The metyrapone test, which blocks cortisol production, is used to evaluate pituitary ACTH production. Corticotropin-releasing hormone administration does not cause a normal increase in ACTH. Necessary GH secretion may be assessed by the insulin-induced hypoglycemia test; this test stimulates pituitary GH release in response to hypoglycemia induced by an injection of regular insulin.

Treatment

a. b. c. d.

e.

An underlying cause for hypopituitarism (e.g., a tumor) must be ruled out. GH replacement is necessary only in affected children. PRL replacement is generally unnecessary. Thyroxine and cortisol are necessary: cortisol should be given before or with thyroxine to prevent an Addisonian crisis (thyroxine alone causes increased clearance of endogenous glucocorticoids). Testosterone is indicated to restore libido and potency in men, and estrogenprogesterone is indicated to restore menstrual function in women.

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D. PITUITARY HYPERFUNCTION 1.

General characteristics

a. b.

2.

Clinical features

a.

b. c.

d. e. 3.

In women, hyperprolactinemia produces persistent galactorrhea (unprovoked by breast stimulation), infertility, and amenorrhea; in men, it may also produce galactorrhea, but loss of libido and impotence are more common. Before adulthood, gigantism occurs because of increased linear growth of bones before epiphyseal closure. Acromegaly occurs after epiphyseal closure and is associated with thickening of skin, acral enlargement (enlargement of fingers and toes), coarsening and enlargement of facial features, and frontal bossing. Impaired glucose tolerance occurs as a result of the glucose-elevating effect of GH; overt diabetes is uncommon. GH increases renal phosphate reabsorption, which results in hyperphosphatemia.

Laboratory findings

a.

b.

4.

Pituitary hyperfunction primarily presents as hyperprolactinemia (most common hormone produced in pituitary hyperfunction) or acromegaly/gigantism. Because PRL secretion is inhibited by hypothalamic dopamine, damage to the pituitary stalk or inhibition of dopamine will produce hyperprolactinemia (e.g., phenothiazines, which act as dopamine antagonists, will cause hyperprolactinemia).

Hyperprolactinemia is confirmed by elevated PRL levels (normal
20 g/L); these levels suggest PRL-secreting adenoma. i. PRL levels
150 ng/dL suggest nonneoplastic causes (e.g., drugs, stress, pituitary stalk lesion, hypothyroidism). ii. Multiple tests of PRL levels may be necessary because PRL may be secreted intermittently. Gigantism/acromegaly can be confirmed by GH levels 10 ng/mL under basal conditions (before rising from bed in the morning); the diagnosis is more conclusive if GH is not suppressed to
1 g/L) within 2 hours of ingestion of 75 g glucose.

Treatment

a.

b.

Treatment of hyperprolactinemia includes: i. Initial trial of bromocriptine or cabergoline for patients who have smaller PRL-secreting tumors ii. Transsphenoidal microsurgery for larger tumors that produce neurologic symptoms (surgery causes hypopituitarism less frequently than radiotherapy) Treatment for gigantism/acromegaly includes pituitary adenomectomy for small tumors; adenomectomy is less effective in reducing GH levels to normal when tumors are large. i. Radiotherapy reduces GH levels over a period of years and therefore is not as effective as adenomectomy. ii. Somatostatin analogues can shrink large tumors preoperatively. iii. Bromocriptine may be used as an adjunct to radiotherapy.

E. DIABETES INSIPIDUS (DI) 1.

General characteristics

a. b.

Diabetes insipidus is caused by an impaired urinary concentrating mechanism. The disease may occur because renal distal tubules fail to respond to antidiuretic hormone (ADH) (nephrogenic DI) or because ADH is lacking (central DI). c. Fifty percent of cases are idiopathic. d. Head trauma, neurosurgical procedures, and brain tumors account for the remainder of cases.

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TABLE 6-1

RESULTS OF WATER DEPRIVATION TEST FOR DIABETES INSIPIDUS (DI)

Patient Type

Increase in [Urine] With Dehydration

Further Response to ADH

Normal Nephrogenic DI Central DI

Yes None None

None None Yes

ADH, antidiuretic hormone.

2.

Clinical features

a. b. 3.

Laboratory findings

a. b.

c.

4.

Urine is dilute with specific gravity
1.010 and osmolality
300 mOsm/kg. Serum osmolality is high or normal (>280 mOsm/kg) in DI secondary to excess water loss; in psychogenic polydipsia, serum osmolality tends to be
280 mOsm/kg because of excess water intake. Water deprivation test i. Normally, overnight water restriction stimulates ADH release, which leads to a more concentrated urine. ii. Once urine osmolality stabilizes, ADH is injected into the patient, and the urine osmolality is reassessed; Table 6-1 lists results of the water deprivation tests.

Treatment

a. b. c. F.

Polyuria is a prominent symptom (3–15 L/d is not uncommon). Patients report excessive thirst, which is a physiologic response to water loss.

In acute central DI (e.g., head injuries), DDAVP (desmopressin) acts rapidly. For partial ADH deficiency, chlorpropamide (an oral hypoglycemic agent) will potentiate the effects of ADH on the renal tubule. Thiazide diuretics are the only treatment for nephrogenic DI.

SIADH 1.

General characteristics

a.

2. 3.

Excess ADH may be produced by malignant tumors (e.g., oat cell carcinoma of the lung), pulmonary diseases (e.g., pneumonia, tuberculosis), central nervous system (CNS) disorders (e.g., stroke, head injury), or drugs (e.g., chlorpropamide, carbamazepine). b. SIADH causes increased free water retention. i. The body compensates for the increased water retention through natriuresis. ii. This compensation results in only mild volume expansion and hyponatremia. Clinical features of SIADH are those of hyponatremia, such as lethargy, confusion, headache, focal neurologic abnormalities, convulsions, and coma. Laboratory findings

a. b. 4.

Hyponatremia is indicated by a serum Na+ level
135 mmol/L; hyponatremia is critical if serum Na+ level falls acutely below 125 mmol/L. Urinary sodium excretion continues despite hyponatremia (>20 mmol/day) and Uosm (urine osmolality) > Sosm (serum osmolality).

Treatment

a. b. c.

It is necessary to treat the underlying cause of SIADH. Fluid restriction of 500–1,000 mL/day will effectively correct hyponatremia. If serum sodium
120 mmol/L, hypertonic saline (3%–5%) should be used as a temporizing measure. Rapid correction to normal Na levels may lead to

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II

101

central pontine myelinolysis; infuse 3% saline at a rate of
0.05 mL/kg/min and check serum Na frequently. Demeclocycline inhibits the effects of ADH on renal tubules (which is a side effect), thereby minimizing free water reabsorption, and is used to treat chronic SIADH.

Disorders of the Thyroid Gland A. Diseases of the thyroid gland include hyperthyroidism, hypothyroidism, thyroiditis, thyroid cancer, and thyroid nodules. B. HYPERTHYROIDISM 1.

General characteristics

a.

b.

c. d. 2.

Graves disease (diffuse toxic goiter) is the most common form of hyperthyroidism. i. Graves disease is an autoimmune disorder in which TSH receptor antibodies are produced. ii. Production of TSH receptor antibodies leads to diffuse thyroid enlargement and thyroid hormone (TH) production. Plummer disease (nodular toxic goiter) affects older individuals. i. This disease is characterized by discrete areas of autonomously hyperfunctioning thyroid gland. ii. Normal thyroid tissue functions are suppressed because of negative feedback on TSH. Subacute thyroiditis is another type of hyperthyroidism (see thyroiditis, II D). Factitious hyperthyroidism is caused by excessive ingestion of TH by patients.

Clinical features

a.

Metabolic changes include elevated metabolic rate, weight loss, increased appetite, sweating, and heat intolerance. b. Cardiovascular signs and symptoms include widened pulse pressure, sinus tachycardia, atrial fibrillation (producing palpitations), and premature ventricular complexes. c. Gastrointestinal (GI) signs and symptoms include loose stools and diarrhea. d. Skin is warm and moist because of peripheral vasodilation and perspiration; hair becomes thin and fine. e. CNS signs and symptoms include fine tremor, emotional lability and restlessness, and brisk return phase of deep tendon reflexes. f. Musculoskeletal signs and symptoms include muscle weakness and fatigue. g. Ophthalmopathy includes exophthalmos (in Graves disease only), lid lag (on downward gaze), lid retraction, tearing, irritation, pain, and diplopia. h. A thyroid storm is a sudden exacerbation of hyperthyroidism characterized by marked fever, agitation, and tachycardia progressing to coma and hypotension. i. In Graves disease, a uniformly enlarged thyroid gland is palpable, whereas in Plummer disease, one or more nodules may be palpable. 3.

Laboratory findings

a. b.

Elevated serum levels of T3 and T4 (thyroid hormones) with low TSH indicate hyperthyroidism. Radioactive iodine uptake test measures uptake of iodine by the thyroid gland, which indicates functional state; in factitious hyperthyroidism, thyroid uptake is decreased because exogenous TH suppresses the gland’s function.

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c.

4.

In the T3 resin uptake test, the patient’s serum is combined with radiolabeled T3 and a T3-binder. (1) If excess T3 is present, an increased amount of T3 will bind to the binder (normal T3 resin uptake is approximately 30%). (2) Elevated T3 resin uptake indicates hyperthyroidism.

Treatment

a.

b. c.

d.

e.

Thirty percent of patients who have Graves disease will go into spontaneous remission within 2 years; therefore, cautious medical management is preferred to total thyroid ablation (which causes hypothyroidism).
-Blockers can be used initially to stabilize the patient’s cardiovascular function. Methimazole and propylthiouracil (PTU) inhibit TH production, but effects are not seen for weeks to months because large endogenous storage pools of hormone are present. i. PTU also inhibits peripheral conversion of T4 to T3; the drug dose is tapered and discontinued after 1–2 years. ii. PTU is often used in younger patients with mild disease, who have a better chance of remission. iii. Side effects of PTU include skin rash in 3%–5% of patients and agranulocytosis in
0.5% of patients. Subtotal thyroidectomy offers rapid therapy with a high cure rate and eliminates the need for long-term patient compliance with medications. i. Complications include recurrent laryngeal nerve paralysis, hypothyroidism, hypoparathyroidism, or precipitation of thyroid storm preoperatively. ii. Subtotal thyroidectomy is reserved for patients who have large goiters and severe disease or for those who are unlikely to be compliant with medication. Radioactive iodine therapy involves a single dose of iodine 131 and is the most common approach used in North America. i. Single-dose radiotherapy produces euthyroidism in 75% of Graves disease patients (during a 6-week period). ii. Radiotherapy often results in subsequent hypothyroidism; therefore, it is generally used in patients older than 40 years of age.

C. HYPOTHYROIDISM 1.

General characteristics

a. b. c. d. e. f. 2.

Hypothyroidism is most commonly caused by Hashimoto (chronic) thyroiditis (see II D 3). Idiopathic atrophy (often associated with antithyroid antibodies) is also common. Hypothyroidism frequently develops as a result of treatment for Graves hyperthyroidism. Drugs such as lithium, iodide, and amiodarone have been reported to cause hyperthyroidism as well. Hypothyroidism may be secondary to hypothalamic-pituitary dysfunction. Iodine deficiency is an uncommon cause in developed countries, but may be more common in other areas of the world.

Clinical features

a. b. c.

Symptoms include weakness, lethargy, slowness of thought and speech, sleepiness, and fatigue. Signs include puffy appearance, nonpitting edema (myxedema), dry skin, coarse hair, and cold intolerance. Patients report diminished appetite but experience mild weight gain (due to decreased metabolic rate) and constipation.

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d. e. f. g.

3.

Edema of the larynx and middle ear leads to voice changes and hearing loss. Menstrual irregularities may also occur and are associated with anovulatory cycles. Slow return phase of deep tendon reflexes is observed. Myxedema coma i. Is caused by severe hypothyroidism, which is triggered by stress, such as infection, alcohol, or drugs ii. Leads to respiratory insufficiency, hypothermia, hypoglycemia, sluggish cerebral perfusion, and coma iii. Has a significant mortality rate

Laboratory findings

a. b. c. d. 4.

103

Serum levels of T3, T4, and T3-resin uptake are decreased. Radioactive iodine uptake is decreased. In primary hypothyroidism, serum TSH is increased. Thyroid peroxidase antibodies are present in Hashimoto thyroiditis.

Treatment

a. b. c. d.

L-thyroxine is the agent of choice (maintenance dose is 0.1–0.15 mg/day in adults; half dose in the elderly). Treatment must be started slowly because patients who have severe disease have increased sensitivity to TH. Myxedema coma must be treated rapidly despite the risks associated with sudden hormone replacement (0.5-mg intravenous bolus). Therapy adequacy is determined by a return of TSH and serum thyroid hormones to normal levels.

D. THYROIDITIS 1. Thyroiditis is a group of disorders consisting predominantly of subacute thyroiditis (de Quervain thyroiditis), Hashimoto (chronic) thyroiditis, and painless thyroiditis. 2.

Subacute thyroiditis

a. b.

c.

d.

Subacute thyroiditis has a viral etiology (mumps or coxsackievirus). Clinical features i. Patients report a 1- to 2-week prodrome of malaise, upper respiratory tract symptoms, and fever. ii. The thyroid gland becomes enlarged (goiter), firm, and painful. iii. Symptoms of hyperthyroidism occur as a result of leakage of TH from the inflamed gland. iv. Disease lasts for weeks to months and then subsides; gland returns to normal size. Laboratory findings i. T3 and T4 levels are elevated, and radioactive iodine uptake is decreased; these results are due to leakage of TH from the gland rather than hyperfunction of the gland. ii. TSH levels are low because of excess thyroid hormone. Treatment i. Symptomatic treatment is sufficient until disease remits. ii. Nonsteroidal anti-inflammatory drugs (NSAIDs) relieve pain of inflammation, whereas β-blocking agents are used to relieve symptoms of hyperthyroidism. iii. If NSAIDs are inadequate, prednisone is effective. iv. PTU and methimazole are not useful because excess hormone is not produced.

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3.

Hashimoto thyroiditis

a.

b.

c.

d.

4.

General characteristics i. Hashimoto thyroiditis is an autoimmune disease in which antithyroid antibodies are produced. ii. The disease primarily affects women. Clinical features i. Autoimmune damage leads to thyroid fibrosis and enlargement (goiter). ii. Pain and tenderness of the gland sometimes occur. iii. Patients often report symptoms of hypothyroidism. Laboratory findings i. Antithyroid antibodies (thyroid peroxidase antibodies) are present in serum. ii. Serum T3 and T4 levels are decreased, and serum TSH level is increased if hypothyroidism occurs. Treatment i. L-thyroxine is necessary in the hypothyroid patient. ii. L-thyroxine also decreases the size of the goiter, which makes this thyroid hormone useful therapy in the euthyroid patient who has thyroid enlargement.

Painless thyroiditis (lymphocytic thyroiditis)

a.

b.

c.

Clinical features i. Painless thyroiditis is similar to subacute thyroiditis; that is, it is a selflimiting hyperthyroidism secondary to inflammatory damage (lymphocytic infiltration), which produces thyroid enlargement. ii. Hyperthyroidism, goiter, and absence of pain also suggest the diagnosis of Graves disease, which may lead to inappropriate therapy. Laboratory findings i. Radioactive iodine uptake is decreased in painless thyroiditis because the thyroid gland is damaged (as in subacute thyroiditis), but uptake is increased in Graves disease (Table 6-2). ii. T3 and T4 levels are elevated, and the TSH level is increased in serum. Treatment i. Symptomatic therapy is given with
-blockers until remission occurs. ii. Antithyroid drugs are not useful.

E. THYROID CANCER 1.

General characteristics

a. b. c.

Thyroid cancer is associated with previous radiotherapy to the neck. A genetic association has been found to medullary carcinoma of the thyroid. Thyroid cancer often presents as a solitary thyroid nodule rather than multiple nodules.

TABLE 6-2

LABORATORY FINDINGS IN THYROID DYSFUNCTION

Condition

T4

RTU (T3 Uptake)

Free T4 Index

TSH

Primary hypothyroid

↓

↓

↓

↑

Secondary hypothyroid

↓

↓

↓

↓

Primary hyperthyroid

↑

↑

↑

↓

RTU, reverse thyroid uptake; T3, triiodothyronine; T4, thyroxine; TSH, thyroid-stimulating hormone

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2.

Types of thyroid cancer include:

a.

b.

c.

d.

3.

Papillary carcinoma i. Papillary carcinoma accounts for 80% of all thyroid cancers. ii. This cancer usually affects persons younger than 40 years of age. iii. The cancer is slow growing and remains localized for years; the cancer then spreads to regional lymph nodes. iv. Patients have few recurrences after treatment. Follicular carcinoma i. Follicular carcinoma is the second most common type of thyroid cancer. ii. Follicular carcinoma is TSH-dependent and looks and functions like normal thyroid tissue. iii. This cancer metastasizes to bone, brain, and lung. iv. Ten-year survival rate is 50%. Anaplastic carcinoma i. Anaplastic carcinoma accounts for 5% of thyroid cancers. ii. This type of thyroid cancer primarily affects older patients. iii. The tumor is aggressive, with early metastasis and death within months. Medullary carcinoma i. Medullary carcinoma arises from parafollicular cells. ii. The tumor can produce calcitonin. iii. This cancer is associated with MEN type II.

Treatment

a. b. c. d.

F.

105

Prognosis is worse if there is distant metastasis, age 50 years, or tumor size 4 cm. Papillary, follicular, and medullary carcinoma are first surgically removed. Because these tumors are TSH sensitive, L-thyroxine is then administered indefinitely to suppress TSH. Radioactive iodine therapy is used to ablate distant metastases and any remaining thyroid gland tumor after surgery.

THYROID NODULES 1.

General characteristics

a. b. c.

2.

Thyroid nodules are present in up to 5% of the population. Ten to twenty percent of nodules are malignant; the remainder may be cystic, colloid, hemorrhagic, or inflammatory. Nodules are more likely malignant when: i. They occur in young men. ii. Patients report a history of radiotherapy to the head or neck during childhood. iii. The nodule grows rapidly, and growth is not suppressed by L-thyroxine therapy. iv. The nodule appears “cold” on a radioactive iodine scintiscan (i.e., no uptake). Note: warm or hot nodules may be malignant in 10%–20% of cases; therefore, this does not rule out malignancy. v. The nodule appears solid or heterogeneous with irregular borders on ultrasound.

Diagnosis

a. b.

Radioactive iodine scintigraphy determines whether the lesion is more likely to be malignant (i.e., cold), but this procedure is not diagnostic. Fine-needle aspiration is most diagnostic and is easily performed with little risk to the patient.

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Treatment

a.

b.

III

Surgery is indicated if history and physical examination suggest malignancy, cytology is equivocal or malignant, or the nodule continues to grow despite thyroid hormone therapy. Conservative management and observation are indicated if the nodule is “warm,” history and physical examination are not suspicious, and cytology is benign.

Disorders of the Parathyroid Gland A. PRIMARY HYPERPARATHYROIDISM AND HYPERCALCEMIA 1.

General characteristics

a. b. c. d. e.

2.

Clinical features of hypercalcemia

a. b. c. d.

3.

In the renal system, increased serum calcium leads to urinary calculi and nephrocalcinosis, which may progress to renal failure. CNS signs and symptoms include lethargy, stupor, fatigue, proximal myopathy and hypotonia, and coma. GI signs and symptoms include anorexia, nausea, vomiting, constipation, and abdominal pain. Hypercalcemia causes osteitis fibrosa cystica, which is characterized by bone pain, fractures, deformities, bone cysts, generalized osteopenia, and subperiosteal bone resorption in the phalanges.

Laboratory findings

a.

b. c.

4.

Oversecretion of parathyroid hormone (PTH) causes hypercalcemia. Primary hyperparathyroidism affects 1 in 1,000 persons (primarily middleaged and elderly women). Most cases are due to parathyroid adenoma. Primary hyperparathyroidism may be associated with MEN syndromes. Secondary hyperparathyroidism results from ongoing stimulation of the parathyroid glands due to low serum calcium, which is most commonly caused by chronic renal failure (decreased vitamin D hydroxylation).

Serum analysis indicates increased Ca2 with elevated PTH levels, decreased _ PO42 level, elevated alkaline phosphatase level (in patients who have signifi_ cant bone disease), decreased HCO3 level, and elevated Cl level (an effect of excess PTH). Urinalysis may indicate hypercalciuria. Ultrasound and CT may reveal parathyroid adenomas in more than half of cases; subperiosteal bone resorption of the phalanges is highly suggestive of the diagnosis.

Differential diagnosis of hypercalcemia

a. b.

Differential diagnosis of hypercalcemia is based on PTH levels. Disorders in which PTH levels are decreased are secondary causes of hypercalcemia and include: i. Tumors with bone metastases (e.g., breast, myeloma, lymphoma) ii. Tumors without bone metastases in which a PTH-like substance is produced by the malignancy, such as squamous cell carcinoma of the lung or cervix and pancreatic carcinoma iii. Sarcoidosis, which results in vitamin D3 production within the granulomas and leads to hypercalcemia iv. Vitamin D intoxication v. Familial hypocalciuric hypercalcemia

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vi. Hyperthyroidism, which leads to increased bone turnover vii. Rhabdomyolysis a. Initially, calcium and phosphate are deposited in damaged muscle. b. Calcium and phosphate then enter the blood as acute renal failure subsides, producing hypercalcemia (over 2–3 weeks). viii. Medications (e.g., lithium) 5.

Treatment

a.

b. c.

Emergency therapy is required if serum calcium levels rise above 13–15 mg/dL. i. Diuresis with furosemide and intravenous saline (5–10 L/day) increases renal calcium excretion. ii. Bisphosphonates (e.g., zoledronate) inhibit bone resorption to lower calcium. iii. Calcitonin quickly acts to lower bone resorption and raise urinary calcium excretion, but the effects are short-lived. iv. Glucocorticoids lower calcium absorption from the gut, which is effective in sarcoidosis and vitamin D intoxication only. v. Phosphate decreases serum calcium levels, but calcium phosphate deposition in tissues may occur. Surgical removal of parathyroid adenoma is indicated in patients who have elevated serum calcium levels (11.0 mg/dL). Medical therapy is indicated for patients who have mildly elevated serum calcium levels. i. Increased fluid intake increases renal calcium excretion. ii. Oral phosphate can decrease serum calcium levels and usually does not produce calcium phosphate deposition in small doses. iii. Estrogen decreases bone resorption and may be beneficial in postmenopausal patients who have mild hypercalcemia.

B. HYPOPARATHYROIDISM AND HYPOCALCEMIA 1.

General characteristics

a. b. 2.

Clinical features

a.

b. c.

3.

Hypoparathyroidism is most commonly caused by surgical removal of the parathyroid glands during a neck procedure. Idiopathic cases occur less commonly. Latent tetany, which occurs with mild hypocalcemia, may manifest as muscular fatigue and weakness with circumoral paresthesias. i. Patients exhibit positive Chvostek sign (tapping anterior to the ear on the facial nerve elicits facial muscle contraction). ii. Patients exhibit positive Trousseau sign (carpal tunnel spasm is induced by inflated blood pressure cuff on arm). Overt tetany, which occurs with severe hypocalcemia, manifests as muscle twitching and spasm progressing to laryngeal stridor and seizures. Long-term effects of hypocalcemia include brittle, ridged nails; dry skin; and enamel defects of teeth. i. Calcification of basal ganglia may lead to parkinsonian signs and symptoms. ii. Calcification of lens leads to cataract formation.

Differential diagnosis of hypocalcemia

a.

Hypoalbuminemia leads to decreased protein-bound serum calcium. i. Decreased protein-bound serum calcium results in a decreased total serum calcium. ii. However, the ionized fraction of serum calcium is unchanged; therefore, no clinical manifestations of hypocalcemia occur (for every 1 g/L decreasae in serum albumin, serum calcium decreases by 0.8 mg/dL).

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TABLE 6-3

LABORATORY FINDINGS IN CALCIUM METABOLISM ABNORMALITIES Ca++

Condition

Primary hyperparathyroid Secondary hyperparathyroid (from renal failure∗) Primary hypoparathyroid

↑ ↓ ↓

Po

_

↓ ↑ ↑

4

PTH

↑ ↑ ↓

Renal failure causes ↓ Ca++ reabsorption with reduced Po4 clearance, producing the observed laboratory abnormalities and causing an elevation in PTH. Ca++, calcium; Po4, phosphate; PTH, parathyroid hormone.

∗Note:

b. c. d. e. 4.

Laboratory findings

a. b. 5.

Serum analysis indicates low calcium and high phosphate levels, with a concomitantly decreased PTH level (Table 6-3). Radiography indicates no specific changes.

Treatment

a. b.

IV

In renal failure, decreased 1,25-dihydroxyvitamin D3 leads to decreased calcium absorption. Osteoblastic metastasis of lung, prostate, or breast cancers may cause rapid uptake of calcium by bone. Hypomagnesemia leads to decreased production of PTH and inhibits action of PTH and vitamin D on bone. In acute pancreatitis, an association with hypocalcemia has been established, but the cause remains uncertain.

PTH is not available for treatment. Therapy consists of replacement of serum calcium orally or intravenously (if severe) along with vitamin D.

Glucose Homeostasis A. DIABETES MELLITUS 1.

General characteristics

a.

b.

2.

Type 1 affects young, lean individuals. i. Patients are insulin dependent secondary to autoimmune destruction of pancreatic B cells necessary for insulin production. ii. Patients are prone to diabetic ketoacidosis (DKA). iii. Human leukocyte antigen and autoimmune associated. Type 2 affects obese, older individuals. i. Patients produce an insufficient amount of insulin and are insulin-resistant. ii. Patients do not develop DKA. iii. Disease has a genetic association.

Clinical features

a. b. c. d.

Symptoms include polyuria, polydipsia, blurred vision, and weight loss and weakness despite increased food intake. Patients have an increased frequency of skin and urinary tract infections. A complication of diabetes is retinopathy, which is most commonly associated with soft exudates, microaneurysms, and retinal hemorrhages. Other sequelae include: i. Diabetic nephropathy commonly develops in insulin-dependent diabetes mellitus but rarely occurs in non–insulin-dependent diabetes mellitus.

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ii. Cerebral, coronary, and peripheral vascular diseases occur earlier and are more extensive than in the general population. iii. Symmetric distal polyneuropathy and paresthesias occur with loss of sensation in a stocking-glove distribution, which can lead to neuropathic foot ulcers or Charcot joints. iv. Autonomic neuropathies may present as neurogenic bladder, urinary retention and urinary tract infections, gastroparesis, intermittent diarrhea and constipation, and orthostatic hypotension. v. Diabetic retinopathy leads to progressive blindness. 3.

Laboratory findings

a. b.

c.

d. 4.

Persistent fasting blood sugar 126 mg/dL is diagnostic. Glucose tolerance test suggests diabetic tendencies if blood sugar (BS) 140 mg/dL 2 hours after glucose challenge, and the test is diagnostic if BS 200 mg/dL. Glycosylated hemoglobin levels reflect the degree of hyperglycemia during a period of 6–12 weeks and are thus a useful tool in monitoring therapy and compliance. Urine glucose levels are often variable, and therefore are not useful in diagnosis.

Treatment

a.

b.

c. d.

TABLE 6-4

Therapy for type 1 consists of dietary management and insulin. Tight glycemic control is associated with prolonged complication-free life expectancy. i. The recommended diet should consist of 25%–30% lipid, 50%–60% carbohydrate, and 10%–20% protein. ii. Initially, patients take one dose of short-acting insulin (Table 6-4) before morning and evening meal; serial serum glucose levels are measured before each meal and at bedtime. iii. Intermediate-acting insulin should be taken in the morning and early evening. iv. If all serum glucose measurements are uniformly elevated after beginning treatment, the morning dose of insulin is increased. v. If only morning serum glucose levels are high, the prior evening’s intermediate-acting insulin should be increased. vi. If only evening serum glucose levels are high, the intermediate-acting morning insulin should be increased. Therapy for type 2 consists of dietary management and may include oral hypoglycemic agents or insulin. i. Dietary management is of greatest importance and should emphasize weight loss. ii. If dietary management results in insufficient control, oral hypoglycemic agents (e.g., chlorpropamide [may cause SIADH-like symptoms], glyburide, or glipizide) or insulin is indicated. Exercise lowers serum glucose and raises insulin sensitivity. Pancreas transplant is an option for type I diabetes mellitus.

CLASSIFICATION OF INSULIN TYPES

Insulin Type

Classification

Onset of Action (h)

Regular Isophane insulin Zinc (Lente) insulin Ultralente insulin

Short-acting Intermediate-acting Intermediate-acting Long-acting


1 h 2–3 h 2–3 h 4–6 h

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B. DIABETIC KETOACIDOSIS 1.

General characteristics

a.

b.

2.

Clinical features

a. b. c. d. 3.

Patients exhibit a decreased level of consciousness. Deep rapid breathing (Kussmaul respirations) occurs. Acetone breath is detected. Signs of dehydration are apparent, for example, dry mucous membranes and axillae, tachycardia, and postural hypotension.

Laboratory findings

a.

b. c.

4.

Diabetic ketoacidosis occurs in type 1 diabetes mellitus patients because of stress (e.g., infection, injury, alcohol) or worsening glucose control, which produces hyperglycemia → osmotic diuresis → dehydration and hyponatremia. Insufficient insulin → increased lipolysis → increased ketones → anion gap metabolic acidosis (see IV B 3 a) → compensatory respiratory alkalosis (hyperventilation).

Serum analysis indicates hyperglycemia (glucose often 500 mg/dL), elevated ketone levels (acetoacetate, acetone, -hydroxybutyrate), and decreased serum bicarbonate level (HCO3) [anion gap metabolic acidosis]. Urinalysis indicates elevated glucose and ketone levels; this test allows rapid diagnosis of the condition. Serum potassium levels are initially increased because of intracellular shifts secondary to acidosis; later, serum potassium levels decrease as acidosis is corrected.

Treatment

a.

b.

c.

Because a 3- to 5-L fluid deficit usually exists, fluids should be given. i. One liter of normal saline (0.9%) per hour for 2 hours is given, followed by a decreased rate to complete the rehydration process. ii. When serum glucose levels decrease to between 200 and 300 mg/dL, a 5% or 10% solution of glucose is added to the infusion to prevent hypoglycemia. If vascular collapse is evident, insulin should be given intravenously at an initial dose of 0.1 U/kg of regular insulin. i. This dose should be followed by an infusion of 0.1 U/kg/h, with frequent glucose monitoring and titration of the infusion. ii. Treatment with intermediate-acting insulin is resumed after acute hyperglycemia and acidosis are corrected. When levels of potassium decrease toward normal, 20–40 mmol/h should be infused intravenously; HCO3 is given only if pH falls below 7.1.

C. HYPEROSMOLAR NONKETOTIC COMA 1.

General characteristics

a. b.

c. 2.

This condition occurs primarily in elderly patients who have type 2. Hyperglycemia occurs secondary to stress of illness or increased glucose ingestion over days to weeks → osmotic diuresis → dehydration (if patient is unable to maintain adequate oral fluid intake) → progressive decline in mental status. Ketoacidosis does not occur because type 2 patients have sufficient insulin to inhibit ketogenesis.

Clinical features

a.

Signs of dehydration (tachycardia, dry mucous membranes, poor skin turgor, and postural hypotension) are evident.

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b. c. 3.

Patients exhibit cloudy sensorium that may progress to coma. Seizures can occur.

Laboratory findings

a.

b. 4.

111

Serum analysis indicates glucose levels often reaching 1,000 mg/dL, which produce elevated serum osmolality and increased urea:creatinine ratio (indicative of dehydration). Mild metabolic acidosis secondary to decreased renal excretion of organic acids as well as from starvation ketosis may be present.

Treatment

a. b.

Therapy is similar to that for DKA (fluids, insulin, and electrolyte replacement). Because this complication is often secondary to infection, a septic workup is indicated for these patients.

D. HYPOGLYCEMIC COMA 1.

General characteristics

a. b. c. 2.

Clinical features

a. b. c. 3.

b. c.

Fingerstick blood glucose analysis provides a rapid means of hypoglycemia diagnosis. In the instance of insulinoma, elevated serum insulin levels are found with hypoglycemia. CT scan is effective in detecting insulinomas.

Treatment

a.

b.

V

Sweating is important to recognize because the DKA patient is dehydrated with dry skin. Other signs and symptoms include tachycardia, tremulousness, and palpitations secondary to adrenergic stimulation. Symptoms may then progress to somnolence, confusion, and coma.

Laboratory findings

a.

4.

Hypoglycemic coma must be rapidly differentiated from DKA or hyperglycemic nonketotic coma. This condition often occurs secondary to excess insulin, delayed ingestion of meals, or excess physical activity. Less commonly, it may be secondary to an insulinoma.

Fifty milliliters of 50% glucose is given intravenously over 3–5 minutes, followed by a constant infusion of 5% or 10% glucose at a rate sufficient to maintain serum glucose levels >100 mg/dL. Therapy may be required for several days, depending on the duration of action of insulin or the oral hypoglycemic agent involved.

Adrenal Gland Dysfunction A. DISORDERS AFFECTING THE ADRENAL CORTEX include Cushing syndrome, Addison disease, primary aldosteronism, and congenital adrenal hyperplasia; pheochromocytoma affects the adrenal medulla. B. CUSHING SYNDROME 1.

General characteristics

a.

Cushing syndrome is most commonly caused by administration of large doses of steroids for treatment of a primary disease.

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b.

c. 2.

If not iatrogenic, this syndrome is most commonly caused by increased levels of pituitary ACTH, which leads to adrenal gland hyperplasia and increased serum cortisol levels (known as Cushing disease). Cushing syndrome also may be caused by adrenal adenoma or carcinoma or ectopic ACTH production from tumors such as oat cell carcinoma of the lung.

Clinical features

a.

Patients exhibit central obesity, facial plethora, buffalo hump, supraclavicular fat pads, and purple striae (linear marks) on the abdomen. b. Mild hypertension secondary to the vascular effects of cortisol and sodium retention may occur. c. Patients have impaired glucose tolerance; 20% have overt diabetes. d. Androgen excess leads to acne, hirsutism, and oligomenorrhea; however, men may complain of impotence and loss of libido. e. Catabolic changes occur, including muscle weakness and breakdown. f. Patients bruise easily secondary to enhanced capillary fragility. g. Increased bone catabolism leads to osteoporosis. h. Depression is not an uncommon association. 3.

Laboratory findings

a. b. c. d.

e.

f.

4.

Diurnal variation in serum cortisol is absent. Twenty-four-hour urinary free cortisol excretion is often variable and is therefore not a useful screening test, but it may show increased cortisol excretion. Serum glucose levels are elevated, and leukocytosis is present (nonspecific findings). The overnight dexamethasone suppression test is a useful screening tool. i. When taken at night, dexamethasone normally suppresses ACTH secretion and hence decreases the morning serum cortisol level. ii. Morning cortisol levels of 5–10 g/dL suggest Cushing syndrome, but further testing is required because false-positive results can occur. The standard dexamethasone suppression test analyzes the response to low-dose and high-dose dexamethasone. i. Patients who have Cushing syndrome (adrenal hyperplasia) will exhibit suppressed adrenal function with high-dose dexamethasone only. ii. Patients who have adrenal tumors or ectopic ACTH production will not have a response to dexamethasone suppression (Table 6-5). CT scan of the adrenal glands reveals adrenal hyperplasia but does not distinguish between ACTH stimulation from a pituitary source or ectopic source; CT of the head may reveal pituitary adenoma producing ACTH.

Treatment

a.

Adrenal adenoma i. Surgical resection of the tumor often results in cure.

TABLE 6-5 Patient Type

Normal Adrenal tumor Ectopic ACTH production Cushing disease ACTH, adrenocorticotropic hormone.

STANDARD DEXAMETHASONE SUPPRESSION TEST RESULTS Suppression With Low Dose

Suppression With High Dose

   

   

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b.

c.

d.

113

ii. Postoperative cortisol replacement is required for a few months until the remaining normal adrenal tissue resumes function. Adrenal carcinoma i. Surgical resection is often not possible; once the diagnosis is made, surgery is associated with a poor outcome. ii. Symptomatic relief may be achieved through the use of adrenal steroid production-inhibiting drugs (mitotane, metyrapone, aminoglutethimide). Ectopic ACTH-producing tumors i. The tumor itself is usually of greater clinical significance than the resulting cortisol excess. ii. These tumors are usually not resectable. Cushing disease i. Transsphenoidal pituitary surgery is the treatment of choice, with success rates approaching 95%. ii. Pituitary irradiation is effective in children but not as effective in adults. iii. Bilateral adrenalectomy results in the need for permanent steroid replacement and may result in rapid growth of the pituitary adenoma due to the removal of the negative feedback stimulus (Nelson syndrome).

C. ADDISON DISEASE 1.

General characteristics

a.

b. c. 2.

Clinical features

a.

b.

c.

3.

Addison disease is an adrenocortical insufficiency most commonly caused by an idiopathic atrophy of the adrenal cortex, which is believed to be autoimmune related. Tuberculosis, bilateral adrenalectomy, or adrenal suppression after steroid therapy are potential causes of Addison disease. A less common cause is hypopituitarism (i.e., secondary adrenal insufficiency). Cortisol deficiency–related symptoms such as weakness, fatigue, anorexia, and weight loss are seen in virtually all affected patients. i. Skin hyperpigmentation occurs secondary to increased melanocytestimulating hormone (MSH); increased MSH is caused by an increase in ACTH due to a lack of negative feedback stimulus from cortisol. ii. Orthostatic hypotension results from a loss of cortisol’s pressor effects on the vasculature. iii. Hypoglycemia occurs because cortisol has anti-insulin effects on glucose homeostasis. Aldosterone deficiency–related symptoms include hyponatremia due to lack of aldosterone-mediated sodium retention at the distal tubule; hyperkalemia occurs in association with the hyponatremia and can lead to potentially fatal cardiac arrhythmias. Adrenal crisis is an acute, potentially fatal exacerbation of adrenal insufficiency that presents with fever, vomiting, decreased sensorium, abdominal tenderness, and vascular collapse.

Laboratory findings

a.

b. c.

Serum analysis indicates hyperkalemia, hyponatremia, hypoglycemia, increased eosinophil count (cortisol lowers peripheral eosinophil count), and decreased cortisol and aldosterone levels. Chest radiographic studies may reveal a small heart. Definitive diagnosis relies on ACTH testing.

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d. 4.

i. A 250-g dose of ACTH fails to induce a significant increase in serum cortisol and urinary corticoid levels in primary adrenal insufficiency. Endogenous ACTH is elevated. ii. In secondary adrenal insufficiency, the response to ACTH stimulation occurs in 3 or more days, and endogenous ACTH levels are low. Electrocardiogram (ECG) shows characteristic changes of hyperkalemia, including high-peaked T waves, prolonged PR interval, heart block, and atrial asystole.

Treatment

a.

b. c.

Glucocorticoid replacement, usually 20 mg each morning and 10 mg each evening, is required; increased dosages are required during stressful periods (e.g., surgery or illness). Mineralocorticoid replacement (fludrocortisone, 0.05–0.2 mg/d) is required in patients who have persistent hyponatremia, hyperkalemia, and hypotension. Adrenal crisis is treated with 100 mg of cortisol infused over 5–10 minutes, followed by approximately 300 mg over the next 24 hours. i. Intravenous saline is also required to replenish lost electrolytes and volume. ii. Mineralocorticoids may be necessary if hypotension and dehydration persist.

D. PRIMARY ALDOSTERONISM 1.

General characteristics

a. b. c.

2.

Clinical features

a. b. c.

d. 3.

Primary aldosteronism is characterized by autonomous production of aldosterone by the adrenal gland (Conn syndrome). The disease is most commonly caused by a benign adrenal adenoma but can also occur secondary to bilateral adrenal hyperplasia. Autonomous aldosterone production by the adrenal gland causes increased sodium retention in exchange for potassium and hydrogen excretion at the distal tubule. Hypertension occurs as a result of volume expansion secondary to sodium retention. Edema does not typically occur because a new steady state is achieved once the retained excess sodium begins to spill over into the renal filtrate. Potassium loss may produce muscle weakness, tetany, paresthesias, and dilute urine (due to hypokalemia-induced nephropathy, which impairs the kidney’s ability to concentrate urine). Metabolic alkalosis occurs secondary to renal hydrogen ion loss.

Laboratory findings

a. b.

c.

d. e. f.

Hypokalemia may be detected. Plasma levels of aldosterone that remain elevated despite sodium loading (saline infusion) indicate hyperaldosteronism but do not differentiate between primary and secondary (due to increased renin activity) aldosteronism. Plasma renin activity is decreased in primary aldosteronism but increased in the secondary form; the combination of elevated aldosterone and reduced renin activity confirms the diagnosis of primary aldosteronism. The biochemical changes are more pronounced if they are caused by an adenoma versus adrenal hyperplasia. CT scan may enable visualization of the adenoma. If the diagnosis of primary hyperaldosteronism is made but an obvious adenoma cannot be seen on CT, adrenal vein sampling will reveal which gland is secreting excess aldosterone.

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115

Treatment

a. b.

For adenoma, patients respond best to surgical removal. For hyperplasia, patients respond best to medical treatment, specifically spironolactone (a potassium-sparing diuretic that inhibits aldosterone’s effects on the distal nephron). Surgery is reserved for patients refractory to medical therapy.

E. CONGENITAL ADRENAL HYPERPLASIA (CAH) 1.

General characteristics

a. b.

c. d.

2.

Clinical features

a. b. c. 3.

Urinary 17-ketosteroids and pregnanetriol levels are elevated. Serum testosterone, androstenedione, and 17-hydroxyprogesterone (cortisol precursor) levels are elevated.

Treatment

a. b. c. F.

Androgen excess produces ambiguous genitalia in the female fetus (female pseudohermaphroditism) and macrogenitosomia in the male fetus. Androgen excess may not manifest until later in childhood, resulting in virilization and amenorrhea in females and precocious puberty in males. Mineralocorticoid deficiency leads to hyperkalemia, hyponatremia, dehydration, and hypotension.

Laboratory findings

a. b. 4.

CAH is caused by a congenital lack of the enzyme necessary for cortisol synthesis. The enzyme deficiency causes ACTH levels to increase, which in turn stimulates the adrenal gland to produce excess steroids not affected by the enzyme deficiency (i.e., androgens); this leads to adrenal hyperplasia. Cortisol deficiency is usually minimal, and therefore is not clinically apparent. The most common enzyme deficiency is 21-hydroxylase. i. The deficiency may be mild, leading only to virilization. ii. If deficiency is severe, mineralocorticoid production (salt-losing form) is impaired.

Cortisol administration suppresses ACTH-mediated adrenal hyperplasia. Mineralocorticoid replacement (fludrocortisone) is prescribed for the saltlosing form. Surgical reconstruction of external genitalia may be performed.

PHEOCHROMOCYTOMA 1.

General characteristics

a. b. c.

d. 2.

Clinical features

a. b. 3.

Pheochromocytoma is a catecholamine-producing adrenal tumor. This tumor is a rare cause of hypertension. Pheochromocytoma occurs within families, such as part of MEN type II syndrome (pheochromocytoma, hyperparathyroidism, and medullary carcinoma of the thyroid gland); it is also associated with neurofibromatosis. Pheochromocytoma is usually not malignant (
10%); 10% are bilateral and 10% are extra-adrenal. Signs and symptoms include episodic hypertension, headache, sweating, palpitations, and nervousness occurring with abdominal palpation or exercise. Weight loss and hyperglycemia may also occur.

Laboratory findings

a.

Analysis of urinary catecholamine metanephrines and vanillylmandelic acid levels is most useful in making the diagnosis.

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b.

4.

VI

Serum catecholamine concentrations are highly variable and therefore less useful diagnostically. c. CT scan of the abdomen detects the majority of these tumors. d. Positron emission tomography or MRI may be needed to localize smaller extraadrenal tumors. Treatment. Because of the dangers of catecholamine excess, pheochromocytomas should be removed surgically. Patients should first receive -receptor blockage (e.g., phenoxybenzamine) for 2 weeks before surgery. After blood pressure is controlled, -blockage is initiated (e.g., propranolol) to prevent catecholamine crisis during surgery.

Female Reproductive Disorders A. Reproductive disorders that have an endocrinologic basis include primary amenorrhea, secondary amenorrhea, and androgen excess syndromes. B. PRIMARY AMENORRHEA 1.

General characteristics

a. b. c. 2.

Primary amenorrhea is defined as the absence of menarche after 16 years of age (i.e., patient has never had a menstrual period). Gonadal causes include gonadal dysgenesis (Turner syndrome), testicular feminization syndrome (androgen resistance), and resistant ovary syndrome (rare). Extragonadal causes include hypogonadotropic hypogonadism, CAH (see adrenal gland dysfunction, V), and physical abnormalities.

Turner syndrome

a.

b.

c.

d.

General characteristics i. Turner syndrome is the most common cause of primary amenorrhea. ii. Individuals who have this syndrome have a 45X chromosomal arrangement. iii. Turner syndrome is not familial and is not correlated with advanced maternal age. iv. Primary amenorrhea in Turner syndrome is caused by failure of ovarian development → no estrogen → increased FSH/LH (due to absence of negative feedback). Clinical features i. Persons who have Turner syndrome are of short stature, between 4 and 5 feet tall. ii. Individuals have a short, webbed neck, epicanthal folds, low-set ears, and widely spaced nipples. iii. Renal and cardiac abnormalities may also occur. iv. Estrogen deficiency leads to absence of development of secondary sexual characteristics (e.g., breast, pubic, and axillary hair); therefore, these patients often present in adolescence. Laboratory findings i. Serum FSH/LH levels are elevated; estrogen is absent. ii. Chromosomal analysis reveals 45X (most commonly), mosaic 46XX/45X, or mosaic 46XY/45X. Treatment i. Secondary sexual characteristics develop with estrogen therapy. ii. If estrogen is given cyclically with progesterone (e.g., oral contraceptives), menstrual cycles will ensue. iii. Fertility is impossible because ovaries are nonfunctioning.

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iv. Streak gonads associated with the 46XY/45X mosaic chromosomal arrangement must be removed because of the increased incidence of gonadoblastoma in this population; karyotyping is therefore necessary. 3.

Testicular feminization syndrome (androgen resistance)

a.

b.

c. d.

4.

General characteristics i. Individuals are 46XY but have female external genitalia. ii. Peripheral tissues are resistant to androgens; therefore, male genitalia fail to develop. iii. Presence of Y chromosome leads to production of müllerian duct inhibitory factor, which exerts its normal effect of inhibiting the development of internal female reproductive organs. iv. These individuals are often raised as girls and present most often at adolescence with the complaint of primary amenorrhea. Clinical features i. Individuals are phenotypic females and have a vagina that ends in a blind pouch. ii. Hypoplastic male ducts and testes are found in the abdomen, inguinal canal, or labia majora. iii. Normal breast development occurs at puberty because of the action of endogenous estrogens. Laboratory findings. Pelvic ultrasound easily reveals the anatomic abnormalities. Treatment i. Because the testes may become malignant, removal is necessary. ii. Estrogen therapy maintains secondary sexual characteristics, but menses and fertility are not possible due to lack of female reproductive organs.

Hypogonadotropic hypogonadism

a.

b.

c.

General characteristics i. Hypogonadotropic hypogonadism may be associated with panhypopituitarism that occurs before the onset of menses, and therefore, patients will have been seen previously with other symptoms of hypopituitarism. ii. The condition is also caused by isolated gonadotropin-releasing hormone (Gn-RH) deficiency; Gn-RH deficiency most commonly occurs secondary to stress such as infection, death of a loved one, excessive exercise and dieting, and anorexia nervosa. iii. The condition may be caused by a prolactinoma; the patient presents with amenorrhea and galactorrhea (see disorders of the pituitary gland, I B 2 b). Laboratory findings i. Low circulating estrogens and FSH/LH levels are found. ii. Patients show no response to the progesterone withdrawal test. a. In the test, progesterone is administered for 5 days; menstrual bleeding should occur after progesterone is withdrawn if sufficient estrogens are present to induce uterine proliferation. b. Patients show a positive response (i.e., menses) to estrogen priming followed by progesterone withdrawal; this result is indicative of functioning end organs. Treatment i. Condition may resolve if the stressful event is reversed. ii. Estrogen therapy induces menses and maintains secondary sexual characteristics. iii. Cyclic estrogen–progesterone therapy induces menses but suppresses ovulation. iv. Gonadotropin hormone can be administered if pregnancy is desired.

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5.

Physical abnormalities

a.

b.

Physical abnormalities that can lead to primary amenorrhea include: i. Labial agglutination (fusion); this condition, often associated with ambiguous genitalia, may be seen in disorders such as CAH. ii. Congenital defects of the vagina or imperforate hymen iii. Transverse vaginal septae These patients are seen with cyclic abdominal pain because menstrual outflow is impeded.

C. SECONDARY AMENORRHEA 1. Secondary amenorrhea is defined as the cessation of menses for 3–6 months in a normally menstruating woman. 2. Causes of secondary amenorrhea include: a. Pregnancy followed by hypothalamic (functional) amenorrhea, in which Gn-RH levels are decreased, often secondary to psychological stress (most common cause of secondary amenorrhea) b. Anorexia nervosa and excessive exercise (e.g., marathon runners) c. Postpill amenorrhea, defined as the absence of menses 6 months after discontinuation of oral contraceptives (uncommon) d. Primary ovarian failure (early menopause), which occurs before 40 years of age secondary to a decline in ovarian function (caused by autoantibodies) and leads to decreased estrogen and increased gonadotropin levels e. Granulosa–theca ovarian tumor, which may inhibit menses through excess production of estrogens; less common D. ANDROGEN EXCESS SYNDROMES: POLYCYSTIC OVARY DISEASE 1. Androgen excess syndromes include polycystic ovary syndrome, androgen-producing ovarian tumors, adrenal tumors, and CAH. Only polycystic ovary disease is discussed here because the other clinical entities occur relatively infrequently. 2.

General characteristics

a. b. c. d. e.

f. 3.

Clinical features

a. b. c. 4.

Polycystic ovary disease causes chronic anovulation associated with androgen excess and obesity. Approximately 5% of reproductive-age women have polycystic ovary disease. Ovary produces excess androstenedione (androgenic steroid), which is converted in the periphery to estrone. Excess androgenic steroids prevent follicular maturation, which leads to anovulation. Increased levels of circulating estrone have positive feedback on LH secretion and inhibit FSH secretion, which leads to enlarged ovaries with small follicular cysts. Unopposed estrogens (i.e., no ovulation and therefore no progesterone) may increase the risk of endometrial cancer in this population. Chronic anovulation leads to infertility and menstrual irregularities such as oligomenorrhea or amenorrhea. Oily skin, hirsutism, and acne occur because of androgen excess. Obesity is often present.

Laboratory findings

a. b.

LH:FSH ratio is increased (2), LH level is elevated, and FSH level is low to normal. Serum testosterone and androstenedione levels are elevated.

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119

Estrone (estrogen formed in peripheral tissues) level is elevated; estradiol level is normal.

Treatment

a.

b.

Signs and symptoms of androgen excess can be alleviated with estrogen– progestin combinations that decrease androgen levels. i. Glucocorticoids may also be used because they suppress adrenal-derived androgens. ii. Spironolactone, a potassium-sparing diuretic, also decreases androgen synthesis and hair follicle stimulation. If fertility is desired, clomiphene can be used; clomiphene blocks negative feedback of estrogen, increasing FSH and LH levels and thereby stimulating follicular growth and ovulation.

E. DIAGNOSTIC EVALUATION OF THE AMENORRHEIC PATIENT 1. Pregnancy test [serum -human chorionic gonadotropin (HCG) level] should be performed before any other diagnostic procedure, even in primary amenorrhea. 2. Progesterone withdrawal test (10 mg medroxyprogesterone daily for 5 days) is the second diagnostic test for amenorrhea. a. Withdrawal bleeding suggests that sufficient estrogen production is present for uterine proliferation and that the lack of menses is due to anovulation. b. If withdrawal bleeding does not occur, proceed to Diagnostic Step 3. 3. Estrogen–progesterone withdrawal test is the third diagnostic test for amenorrhea (Premarin [a conjugated estrogen] 1.25 mg for 21 days followed by the progesterone withdrawal test). a. This test induces menses if the endometrium and outflow tract are normal (physical abnormalities should be readily detectable by physical examination before diagnostic evaluation). b. If no bleeding occurs, the patient should be referred to a gynecologist for further investigation. c. Bleeding suggests either ovarian dysfunction or hypothalamic–pituitary disease, which can be distinguished by Diagnostic Step 4. 4. Measurement of serum gonadotropin levels is the fourth diagnostic test for amenorrhea. a. Elevated levels indicate ovarian disease. b. Low gonadotropin level indicates hypothalamic–pituitary dysfunction, which may be secondary to a prolactinoma; hence, prolactin levels should also be measured (especially if galactorrhea is also present). c. Elevated LH:FSH ratio suggests polycystic ovary disease. VII

Male Reproductive Disorders A. The major reproductive disorders in men include hypogonadism and gynecomastia. B. HYPOGONADISM 1.

General characteristics

a. b.

c.

Hypogonadism results in inadequate testosterone and sperm production. Hypogonadotropic hypogonadism indicates that the testes lack stimulation from a diseased hypothalamic–pituitary axis; this condition may manifest as delayed puberty. Hypergonadotropic hypogonadism indicates a disorder within the testes themselves, and that negative feedback on the hypothalamic–pituitary axis is absent.

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i. Klinefelter syndrome (47XXY karyotype) results in congenital testicular damage, eunuchoidism, and gynecomastia. ii. Testicular agenesis results in failure of pubertal development and absence of testes (although testes were present during embryogenesis, because these individuals have male genitalia). iii. Mumps orchitis affects both testes and results in hypergonadotropic hypogonadism. 2.

Treatment

a. b.

Depo-Testosterone is necessary for full virilization. Infertility cannot be corrected in primary testicular damage; however, Gn-RH is effective for individuals who have hypogonadotropic hypogonadism.

C. GYNECOMASTIA 1. Gynecomastia is a group of disorders that cause male breast development and may involve estrogen excess, decreased levels of androgens, or both. 2. Gynecomastia in newborns is common and subsides spontaneously in weeks to months. 3. Two thirds of normal boys develop some degree of gynecomastia during puberty that subsides in 1–2 years; therefore, no diagnostic studies are indicated. 4. Hypogonadism may be associated with gynecomastia. 5. Liver diseases such as cirrhosis lead to increased estrogen and breast development (results of liver function tests are abnormal). 6. Tumors such as testicular choriocarcinoma (which secretes chorionic gonadotropin) cause testicular estrogen production, which leads to gynecomastia (diagnosis should be suspected from elevated -HCG level). 7. Gynecomastia can be drug-induced, as from marijuana, phenothiazines, tricyclic antidepressants, digitalis, and cimetidine. VIII

Disorders of Bone Metabolism A. OSTEOPOROSIS 1.

General characteristics

a. b. c. d. e. 2.

Clinical features

a. b. 3.

Osteoporosis is characterized by decreased bone volume; bone structure is normal. This disease is familial and predominates in Caucasian postmenopausal women. Calcium deficiency can increase bone resorption and osteoporosis. Estrogen has a protective effect on bone; therefore, osteoporosis is more common in postmenopausal women. Osteoporosis may be secondary to malabsorption syndromes, steroid therapy, or multiple myeloma. Vertebral compression fractures in the lower thoracic and lumbar vertebrae occur, the initial symptoms of which may be acute back pain. Femur fractures (at the neck) are also common.

Laboratory findings

a. b. c.

Radiography reveals decreased bone density if bone loss is more than 30%. Wedge-shaped deformities are characteristic of vertebral compression fractures (Figure 6-1). Bone marrow density measurement is now the diagnostic standard used.

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● Figure 6-1. Classic appearance of a vertebral wedge-shaped deformity associated with vertebral compression fracture in a patient with severe osteoporosis.

4.

Treatment

a.

b. c. d.

Estrogen replacement therapy (ERT) in the postmenopausal woman can prevent or slow the rate of osteoporosis development; ERT is contraindicated in women who are at high risk for endometrial or breast cancer. Therapy should start if bone marrow density is 2.5 standard deviations below the mean for young adults. Calcium supplementation is essential to maintain bone mass (1,500 mg/day) and prevent or slow osteoporosis. Weight-bearing exercise and an active lifestyle may help prevent osteoporosis. Recently, selective estrogen response modulators (e.g., tamoxifen) have increased bone density and may be beneficial for those at risk for breast cancer who have osteoporosis.

B. OSTEOMALACIA 1.

General characteristics

a. b.

c.

Osteomalacia is a disease of inadequate mineralization of bone matrix. Osteomalacia is caused by vitamin D deficiency (vitamin D is necessary for normal calcium metabolism, and deficiency of this vitamin causes rickets in children); vitamin D deficiency is now uncommon in the United States. Liver and renal diseases can impair vitamin D metabolism and therefore lead to decreased bone mineralization.

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d. 2.

Clinical features

a. b. c. 3.

Pain and tenderness are felt in the spine, ribs, and lower extremities. Proximal muscle weakness results in a waddling gait. Lower extremities are bowed and prone to fractures.

Laboratory findings

a. b. 4.

GI disorders that impair absorption interfere with vitamin D absorption and normal calcium metabolism.

Radiography reveals decreased bone density and a coarsened trabecular pattern. Serum analysis indicates low serum phosphate and calcium levels and an elevated alkaline phosphatase level.

Treatment

a. b. c.

Therapy should treat the primary disorder affecting the abnormal calcium metabolism. Vitamin D benefits individuals who have a lack of or impairment in metabolism of the vitamin. Supplemental calcium is of little benefit because the disorder is not caused by calcium deficiency; however, during bone reformation, calcium supplements may be necessary.

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7

Rheumatic Diseases I

Osteoarthritis and Rheumatoid Arthritis A. OSTEOARTHRITIS (OA) (ALSO CALLED DEGENERATIVE JOINT DISEASE) 1.

General characteristics

a. b. c.

d. e.

2.

OA is the most common rheumatic disease. Incidence increases with age, wear and tear, and obesity. OA is characterized by degeneration of cartilage, with reactive changes and new bone formation that leads to bony spurs; subchondral cysts may also form in the juxta-articular bone. OA may be classified as primary OA or secondary OA, depending on the absence or presence of an underlying etiologic factor. Some causes for secondary OA include previous trauma to the involved joint, congenital hip dysplasia, avascular necrosis of the capital femoral epiphysis, postinflammatory disorders (rheumatoid or infective arthritis), and metabolic disorders (calcium pyrophosphate deposition disorder, Wilson disease, hemochromatosis).

Clinical features

a.

3.

4.

Symptoms include gradual onset of deep pain that worsens with activity and is relieved by rest, morning stiffness that lasts
30 minutes, and painful range of motion. b. Signs and symptoms of late-stage OA include tenderness, crepitus, and joint deformity. c. In the hand, Heberden nodes (enlarged distal interphalangeal [DIP] joints) and Bouchard nodes (enlarged proximal interphalangeal [PIP] joints) may form. d. In the knee, a disproportionate loss of cartilage from medial or lateral compartments may give rise to genu valgus or varus. e. In the hip, pain occurs in the groin, inner thigh, knee, or buttocks, and internal rotation and extension are lost. f. In the foot, the first metatarsophalangeal joint is commonly affected. g. In the spine, the L3–4 intervertebral disc is commonly affected, and cauda equina syndrome with sphincter dysfunction may occur. Differential diagnosis includes seronegative rheumatoid arthritis, psoriatic arthritis or Reiter syndrome, chronic infective arthritis, and tendonitis and/or bursitis. Unlike rheumatoid arthritis, OA affects distal interphalangeal joints. Laboratory findings

a. b.

Results of hematologic studies are usually normal, including the erythrocyte sedimentation rate (ESR). Synovial fluid aspiration indicates mild inflammation (
2,000 cells per mm3,
30% neutrophils), no crystals, and good mucin clot formation (unlike inflammatory aspirates). 123

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c. 5.

Radiography indicates joint space narrowing, marginal osteophytes, and subchondral cysts; erosions are usually not present.

Treatment

a. b.

c.

d.

e. f.

Joint preservation can be achieved through weight reduction, physical therapy, and mechanical devices (canes, braces). Estrogen replacement therapy (ERT) may reduce hip and knee OA in postmenopausal women, although its use should be balanced with the risks of hormonal therapy. Acetaminophen, aspirin, and other nonsteroidal anti-inflammatory drugs (NSAIDs) are beneficial. COX–2 inhibitors are an alternative if no renal dysfunction exists; however, there is increasing concern regarding cardiovascular side effects with COX-2 inhibitors. Systemic corticosteroids are contraindicated, and intra-articular steroid injections provide only short-term relief. Intra-articular hyaluronan injection has shown equivocal benefit in recent studies. Glucosamine may reduce pain and may be chondroprotective. In severely affected joints, surgery to correct severe deformity or complete joint replacement may be indicated.

B. RHEUMATOID ARTHRITIS (RA) 1.

General characteristics

a. b.

c. 2.

RA is a chronic, systemic, inflammatory disorder that more commonly begins in women during their childbearing years. RA involves an inflammation and hypertrophy of the synovium, with infiltration by lymphocytes; the resulting immune complex formation leads to an immune reaction. The inflammatory process eventually leads to ulcerations in the cartilage, surrounding ligaments, and bone.

Clinical features

a.

Symptoms include fatigue, malaise, and generalized musculoskeletal pain over weeks to months, followed by specific joint pain, tenderness, redness, and swelling. b. Symmetric joints of the hands, wrists, elbows, shoulders, and feet are frequently affected. Patients may initially be seen with prolonged morning stiffness (30 minutes), with symptoms being aggravated by movement. c. In the hand, metacarpophalangeal (MCP) joints and PIPs are affected; DIPs are not affected (unlike OA); ulnar deviation of fingers and palmar subluxation of the PIPs are common; swan-neck deformities (hyperextension of PIP and flexion of DIP) or boutonniere deformities (flexion of PIP and extension of DIP) occur later in the disease process. d. In the wrists, decreased dorsiflexion, carpal tunnel syndrome, and atrophy of the thenar eminence occur. e. In the elbows, flexion contractures tend to occur early in the disease process. f. In the neck, pain and stiffness associated with cervical vertebral erosion may progress to atlantoaxial subluxation. g. In the knee, patellar tap reveals effusion, which may yield to a Baker cyst. h. In the feet, cocking up of toes and subluxation of metatarsal heads result in a clawlike appearance. i. Subcutaneous nodules at the elbows, occiput, and sacrum develop in 20%–25% of patients and are associated with seropositive disease.

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j.

3.

b. c. d. e. f.

Systemic lupus erythematosus often involves joints symmetrically but is usually not deforming. Spondyloarthropathies are distinguished from RA by their sacroiliac and axial spine involvement. Systemic sclerosis is characterized by short-lived joint inflammation and characteristic skin changes. Rheumatic fever, uncommon in adults, should be considered if an associated pharyngitis and migratory arthritis are present. Polymyalgia rheumatica is distinguished from RA by intermittent, nondeforming arthritis, which is rheumatoid factor negative. Lyme disease is difficult to distinguish from RA without the history of a tick bite and characteristic skin, cardiac, or central nervous system (CNS) changes. The arthritis usually only involves one joint (usually the knee).

Laboratory findings

a.

b.

c.

5.

Clinical course i. Sporadic course with periods of remission has a favorable prognosis. ii. Insidious progression with periodic debilitating flare-ups as well as joint subluxation and joint contractures with fibrosis has a variable prognosis. iii. “Malignant” rapid progressive deterioration is characterized by systemic symptoms of weight loss, synovitis, rheumatoid nodules, high levels of rheumatoid factor, vasculitis, scleritis, pulmonary nodules, neuropathy, and myopericarditis.

Differential diagnosis

a.

4.

125

Hematologic studies indicate normochromic-normocytic or hypochromicmicrocytic anemia, thrombocytosis (500–700  109/L), and elevated ESR; positive results for rheumatoid factor are sensitive but not specific. Rheumatoid factors (autoantibodies) are present in two-thirds of cases but are not specific to RA. High levels are indicative of more severe disease. Synovial fluid aspiration reveals 5,000–40,000 cells/mm3 with 50%–70% polymorphonuclear neutrophils (PMNs), decreased complement, and poor mucin clot formation. Radiography indicates evidence of joint deformities as described previously as well as the presence of cysts, loss of cartilage, and erosive changes (Figure 7-1). Radiography is usually the most specific test.

Treatment

a.

First-line treatment involves education, rest, exercise, and relief of joint pain and inflammation with NSAIDs. b. Second-line treatment is oral glucocorticoids. c. Intra-articular corticosteroids may be beneficial for treating flare-ups, involving only one or two joints. d. Methotrexate, gold, and penicillamine have been used in aggressive refractory cases. e. Anti–tumor necrosis factor (TNF) agents (e.g., infliximab and etanercept) produce substantial improvement in symptoms with tolerable side effects. f. Orthopedic surgery may be beneficial for impending or severe joint deformities. g. Medications used to treat RA may cause side effects. i. Salicylates may cause gastrointestinal (GI) ulcers, hearing loss and other CNS side effects, platelet function inhibition, and liver function test abnormalities and renal dysfunction.

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● Figure 7-1. A patient with rheumatoid arthritis who has marked protrusion of the acetabula and joint space narrowing. A hallmark of this disease is symmetric joint involvement.

ii. Gold may cause pruritic skin rash, mouth ulcers, and transient leukopenia. iii. Penicillamine may cause thrombocytopenia, leukopenia, nephrotic syndrome, GI upset, obliterative bronchitis, and alterations in taste perceptions. II

Crystal-Related Joint Diseases A. GOUT 1.

General characteristics

a. b. c.

d.

2.

Gout occurs secondary to a disorder of purine metabolism that leads to hyperuricemia, and therefore to intra-articular and extra-articular urate deposition. Gout commonly affects middle-aged men. Ninety percent of gout patients are underexcreters of uric acid (
700 mg/dL) usually as a result of renal disease secondary to volume-depleted states (e.g., adrenal insufficiency, diabetes insipidus); drugs such as acetylsalicylic acid (ASA), which decrease uric acid excretion; or organic acid accumulation (e.g., ketones, lactic acid, which compete with uric acid for renal excretion). Ten percent of gout patients are overproducers of uric acid who excrete 750 mg/dL on a normal diet due to a purine metabolic enzyme deficiency or secondary to increased nucleic acid turnover (e.g., myeloproliferative disorders, psoriasis, chemotherapy).

Clinical features

a.

There are two clinical stages of gout: i. In asymptomatic hyperuricemia, urate deposition is absent but increased serum uric acid concentration puts the patient at risk for acute gouty arthritis. ii. In acute gouty arthritis, lower-extremity monoarticular arthritis (50% of cases affect the first metatarsophalangeal joint) produces sudden tenderness, erythema, warmth, and swelling that resolves in a few days.

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b. c. d.

3.

4.

A mild fever may be present in the acute phase. Attacks may be triggered by trauma, alcohol, stress, or acute medical illness. Chronic tophaceous gout develops in advanced cases in which urate crystals deposit within the subcutaneous tissues, which can therefore be mistaken for the rheumatoid nodules of RA. e. A common complication of gout is acute obstructive uropathy leading to acute renal failure. Differential diagnosis includes septic arthritis, other crystal deposition diseases, and rheumatoid arthritis, especially in the presence of gouty tophi, which can be mistaken for rheumatoid nodules. Laboratory findings

a. b. c.

d. e.

5.

Hematologic studies indicate mild leukocytosis and a mildly elevated ESR. Elevated serum uric acid levels are helpful but not diagnostic because more than 10% of patients have normal serum uric acid levels during an acute attack. Synovial fluid aspiration indicates the presence of monosodium urate crystals (needle-shaped and negatively birefringent in polarized light) in the synovial fluid; cell count is 10,000–60,000 cells/mm3 (70% PMNs). Aspiration of gouty tophi reveals urate crystals, which differentiate the gouty tophi from rheumatoid nodules. Radiography is usually of little value during the acute attack because radiographs reveal only soft-tissue swelling. i. However, radiography may help exclude septic arthritis from the differential diagnosis because gout is characteristically accompanied by destructive changes. ii. In the case of chronic tophaceous gout, radiographs may show punchedout erosions in the subchondral bone.

Treatment

a.

NSAIDs such as indomethacin are effective in relieving the pain of an acute attack. b. Colchicine may be used early in the acute attack, especially if the patient has a history of gastric ulcer or conditions associated with decreased renal perfusion (contraindications for the use of NSAIDs). c. Intra-articular corticosteroids may be effective treatment if the aforementioned therapies are poorly tolerated or if the patient has severe monoarticular disease. d. Uric acid–lowering agents should not be used during the acute attack phase because they can prolong the duration of the attack. e. Acetylsalicylic acid should not be given for relief of pain during the acute attack because it interferes with uric acid excretion. f. Prophylaxis of attacks can be achieved with daily low-dose colchicine or NSAIDs. g. Patients who have persistent gout, visible tophi, or recurrent uric acid renal calculi should be treated with uric acid–lowering agents after the acute phase. h. Uricosuric drugs, such as probenecid and sulfinpyrazone, lower uric acid levels by decreasing tubular uric acid reabsorption; this effect is blocked by ASA. i. Allopurinol is a xanthine oxidase inhibitor (xanthine oxidase is an enzyme that converts hypoxanthine and xanthine to uric acid) and therefore lowers serum uric acid levels. i. This drug is appropriate for patients with a history of uric acid renal calculi (contraindication to the use of uricosuric agents) or patients with decreased renal function who would therefore gain little benefit from uricosuric agents.

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ii. Allopurinol toxicity is characterized by fever, leukocytosis, decreased renal function, and pruritic rash, which may occur in up to 5% of treated patients; therefore, allopurinol should be used only if uricosuric agents are contraindicated or are likely to be ineffective. B. CALCIUM PYROPHOSPHATE DIHYDRATE DEPOSITION DISEASE (CPPD) 1.

General characteristics

a. b. 2.

CPPD is also known as pseudogout. CPPD may be hereditary (autosomal dominant), idiopathic, or associated with other metabolic disorders (e.g., hemochromatosis and hyperparathyroidism).

Clinical features

a. b.

3. 4.

Attacks are common after surgery, trauma, or medical illness. Acute onset of warmth, erythema, swelling, and tenderness occurs most commonly in the knee as well as in the first metatarsophalangeal joint. c. Attacks last for a few days and are self-limited. d. Signs and symptoms may spread to adjacent joints. e. Fever and leukocytosis may also be present. f. CPPD crystals may be found in synovial fluid, tendons, ligaments, and cartilage. Differential diagnosis includes septic arthritis, gout, and OA. Laboratory findings

a. b.

5.

Synovial fluid aspiration reveals rhomboid crystals that show weakly positive results for birefringence in polarized light. Radiography indicates punctate and linear densities in the articular hyaline cartilage. i. Calcific deposits may be seen in tendons, ligaments, and articular cartilage. ii. Hooklike osteophytes and subchondral cysts are not uncommon. iii. Although these changes can suggest OA, their presence in joints such as the wrist, elbow, and shoulder (where OA is uncommon) suggests CPPD.

Treatment

a. b. c.

Repeated aspiration of synovial fluid can shorten the duration of attacks. NSAIDs, intra-articular corticosteroids, or a combination of these are useful in alleviating painful symptoms. An effective therapy for removing CPPD crystals is currently unavailable, but colchicine may help to reduce the frequency of attacks.

C. HEMOCHROMATOSIS 1.

General characteristics

a. b. c. 2.

Clinical features

a. b. 3.

Hemochromatosis is an inherited disorder of iron metabolism associated with excessive body iron stores. Hemochromatosis may occur secondary to repeated blood transfusions. Hemosiderin accumulates in the synovial lining and articular cartilage. Hemochromatosis primarily affects the second and third MCP joints. Other joints may secondarily become affected in association with CPPD deposition.

Laboratory findings

a. b. c.

Serum analysis indicates elevated serum iron and ferritin levels. Synovial fluid aspiration indicates
1,000 cells/mm3, good mucin clot formation, and iron levels that reflect those of serum. Radiography reveals chondrocalcinosis in 50% of cases.

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4.

Treatment

a. b. III

129

Phlebotomy to decrease body iron stores does not seem to affect already established arthropathy. NSAIDs may provide symptomatic relief.

Spondyloarthropathies A. GENERAL CHARACTERISTICS 1. Spondyloarthropathies are a group of inflammatory arthritides that are distinct from RA and are therefore seronegative. 2. They are distinguished from RA by predominant, asymmetric involvement of the axial skeleton and the sacroiliac joints. 3. Types of spondyloarthropathies discussed here include ankylosing spondylitis, Reiter syndrome, psoriatic arthritis, and enteropathic arthropathies. B. ANKYLOSING SPONDYLITIS 1.

General characteristics

a. b. c. 2.

Clinical features

a.

b. c. d. 3.

Mechanical low backache usually worsens with activity and is relieved by rest. Other spondyloarthropathies can be distinguished from ankylosing spondylitis on the basis of associated symptoms described later in this chapter.

Laboratory findings

a.

b.

5.

Symptoms include fatigue, weight loss, low-grade fever, insidious onset of lower back discomfort that persists for several months, and morning stiffness that improves with exercise and worsens with rest. Patients experience decreased spinal mobility, loss of lumbar lordosis, and increased thoracic kyphosis. Peripheral joint involvement and pulmonary fibrosis are features of severe disease. Transient uveitis (pain, redness, and photophobia) develops in up to 25% of patients.

Differential diagnosis

a. b. 4.

Ankylosing spondylitis primarily involves the sacroiliac joints and spine. Human leukocyte antigen (HLA)-B27 is associated with ankylosing spondylitis; therefore, a positive family history is often present. Onset usually occurs in the second and third decades of life.

HLA-B27 testing, although highly suggestive of the diagnosis, is costly and should not be performed unless the diagnosis is uncertain. C-reactive protein is usually increased. Radiography indicates squaring of the superior and inferior margins of the vertebral bodies, which leads to “bamboo” spine (Figure 7-2); destruction of cartilage and subchondral erosions gives the appearance of widened sacroiliac joints.

Treatment

a. b. c. d. e.

Physical therapy is critical to preserve function and prevent further deformity. NSAIDs provide relief of pain so that patients can achieve maximum function. Anti-TNF antibodies are being used more frequently, yielding rapid improvement in disease progression (e.g., infliximab). Bisphosphonates and sulfasalazine in men have modest results. Due to thoracic deformities and the risk of fibrosis, smoking is severely discouraged in this population.

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● Figure 7-2. Radiograph showing a characteristic feature of ankylosing spondylitis, that is, squaring of the anterior surface of the vertebrae in the thoracolumbar region (the so-called bamboo spine).

C. REACTIVE ARTHRITIS 1.

General characteristics

a. b. c. d. 2.

Occurs secondary to chlamydial urethritis or gastrointestinal infections by Shigella, Salmonella, Yersinia, and Campylobacter. Because organisms are not cultured from arthritic joints, this is a reactive arthritis. The disease often occurs in young adulthood. HLA-B27 is seen in the majority of patients, suggesting a general predisposition.

Clinical features

a. b. c.

d.

Signs and symptoms usually occur 2–4 weeks after the initial infection. Acute onset is characterized by asymmetric arthritis in knees and ankles. Three typical features include: i. Diffuse swelling of finger(s) or toe(s), which gives rise to the “sausage digit” ii. Tenderness of the Achilles tendon insertion iii. Low back pain associated with sacroiliitis Forty percent of patients develop mild, noninfectious, transient conjunctivitis, and 3%–5% develop disabling iritis, uveitis, or corneal ulceration.

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e.

f. 3.

Mucocutaneous lesions include balanitis circinata (small, shallow, painless ulcers of the glans penis) and keratoderma blennorrhagicum (hyperkeratotic scaling skin lesions similar to psoriasis) on the palms and soles. The majority of patients experience recurrent episodes of arthritis, but severe disability is rare.

Laboratory findings

a. b. c. d.

4.

131

Hematologic studies indicate elevated ESR and leukocytosis. Reactive arthritis is HLA-B27–linked. Synovial fluid aspiration indicates 500–75,000 cells/mm3 with a predominance of PMNs. Radiography reveals erosions and periosteal changes at the ischial tuberosities, greater trochanter, and Achilles tendon insertion. i. Radiography also reveals sacroiliitis. ii. Asymmetric syndesmophytes are found along the spine (unlike ankylosing spondylitis, in which they are symmetric and contiguous).

Treatment

a. b. c. d. e.

NSAIDs are the primary line of therapy. No evidence exists showing that antibiotics alter the disease course. Systemic corticosteroids are ineffective, but intra-articular steroids for severe monoarthritic disease produce relief. Topical corticosteroids may be prescribed for keratoderma blennorrhagicum and conjunctivitis. Sulfasalazine is the second line of therapy if NSAIDs are inadequate.

D. PSORIATIC ARTHRITIS 1.

General characteristics

a. b. c. 2.

Clinical features

a. b. c. d. e. f. g. 3.

Disease onset occurs in the 30s and 40s, with skin lesions followed by arthritis. The majority of patients have peripheral, asymmetric joint involvement; spinal involvement is not uncommon. Approximately 25% of patients have a symmetric polyarthritis similar to that of RA. Patients may develop sausage digits as in reactive arthritis. Psoriatic lesions are commonly found on the extensor surfaces. Nail involvement may include pitting and longitudinal ridges. Conjunctivitis or anterior uveitis may occur in up to 30% of patients.

Laboratory findings

a. b. c.

4.

Psoriatic arthritis is an inflammatory arthritis associated with psoriasis. Approximately 7% of patients who have psoriasis have some form of inflammatory arthritis. Several HLA types have been associated with this form of arthritis.

Serum analysis reveals mildly elevated ESR; hyperuricemia may be present with cases of severe psoriasis. Synovial fluid aspiration reveals mild inflammation, with 2,000–15,000 cells/mm3 and a predominance of PMNs. Radiography indicates distal interphalangeal erosions progressing to telescoping joints. i. Asymmetric sacroiliitis progressing to fusion is also common. ii. Isolated axial syndesmophytes may be seen at any level.

Treatment

a. b.

NSAIDs such as indomethacin are effective in relieving joint symptoms. Severe disease may require intra-articular corticosteroid treatment.

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c. d.

Methotrexate, penicillamine, gold, and hydroxychloroquine are effective second-line agents. Recent studies show anti-TNF antibodies (e.g., infliximab) to be effective in resolving the arthritis and psoriatic lesions.

E. ENTEROPATHIC ARTHROPATHIES 1.

Clinical features

a. b. c. d. 2.

Laboratory findings

a. b.

3.

Synovial fluid aspiration reveals effusions that are mildly to severely inflammatory and nonspecific. Radiography indicates that: i. Sacroiliitis is symmetric, as in ankylosing spondylitis ii. No destructive changes are present in the peripheral arthritis form

Treatment

a. b. c.

IV

Enteropathic arthropathies are forms of polyarticular arthritis and are associated with ulcerative colitis or Crohn disease. Peripheral (lower extremity) arthritis exists in approximately 20% of patients, whereas sacroiliitis predominates in another 20%. HLA-B27 is not linked with lower extremity arthritic syndrome, but HLA-B27 linkage is present in the sacroiliitis form. Peripheral arthritis tends to exacerbate with flare-ups of the bowel disease, whereas sacroiliitis tends to progress independent of the bowel disease.

Successful management of the inflammatory bowel disease alleviates the peripheral arthritis. Therapy for the sacroiliitis form is identical to that for ankylosing spondylitis. Anti-TNF antibodies are being used for treatment more routinely (e.g., infliximab).

Systemic Lupus Erythematosus (SLE) A. GENERAL CHARACTERISTICS 1. SLE is most common in women during their reproductive years, especially in African Americans. 2. SLE is an acute and chronic inflammatory process with multiple-organ involvement. The disease is linked to both HLA-DR2 and HLA-DR3. 3. SLE is believed to occur secondary to increased lymphocyte activity, which leads to formation of autoantibodies → immune complex deposition → tissue damage → fibrinoid necrosis. 4. A variety of symptoms may be present at any one time, and symptoms may develop over months to years. 5. SLE may be drug-induced (e.g., hydralazine, procainamide). B. CLINICAL FEATURES 1. Common constitutional symptoms include fatigue, weight loss, and fever. 2. Skin signs and symptoms include facial butterfly rash, alopecia, and photosensitivity. 3. Nervous system signs and symptoms include personality disorders, seizures, psychoses, and mononeuritis multiplex. 4. Cardiac signs and symptoms include pericardial effusions and myocarditis. 5. Pulmonary signs and symptoms include pleuritis, pleural effusions, and pneumonitis.

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6.

Common GI tract signs and symptoms include nonspecific abdominal complaints; less common signs and symptoms include infarction, perforation, and hemorrhage occurring secondary to bowel vasculitis. 7. Renal signs include any type of glomerulonephropathy. 8. Common musculoskeletal signs include symmetrical peripheral arthralgias (which are easily confused with RA); damage is limited to tendons and ligaments, with relatively no articular deformities. 9. A common reticuloendothelial sign is hepatosplenomegaly with lymphadenopathy; some patients develop functional hyposplenism, which results in an increased risk of bacterial infection. 10. Vasculitic complications include purpuric lesions (which may progress to necrosis) on fingertips, toes, and extensor surfaces. 11. Note that patients need only present with a few of the above features to be considered to have SLE. C. DIFFERENTIAL DIAGNOSIS includes RA, mixed connective tissue diseases, vasculitic syndromes (see VIII), and drug-induced SLE. D. LABORATORY FINDINGS 1. Hematologic studies reveal anemia characteristic of chronic disease (normochromicnormocytic) or Coombs’ positive hemolytic anemia, lymphopenia secondary to autoantibodies (more common than leukopenia), thrombocytopenia, and an elongated thromboplastin time (not corrected by addition of normal plasma to serum because clotting factors are inhibited by autoantibodies). 2. Serum analysis reveals positive results for the presence of antinuclear antibodies (ANA); this test is the standard screening test for SLE but is not specific for the disease. a. Antibodies to double-stranded DNA (anti-dsDNA) and a small nuclear ribonucleoprotein (anti-Sm) are specific to SLE but are not sensitive. b. ANAs to histones are present in 95% of patients. c. Hypocomplementemia (C3 and C4) is highly suggestive of the diagnosis. d. Antiphospholipid antibodies may be detected in up to one-third of patients. They are: i. Biological false test for syphilis ii. Lupus anticoagulant—actually is associated with increased risk of thrombosis iii. Anticardiolipin antibody E. TREATMENT 1. Patients should receive education to cope with a chronic illness. 2. NSAIDs, in anti-inflammatory doses, are a useful treatment for serositis, fever, and joint pain. 3. Corticosteroids are used topically for treating cutaneous manifestations and systemically for treating multiple organ involvement, specifically thrombocytopenic purpura, hemolytic anemia, myocarditis, pericarditis, nephritis, and convulsions. 4. Hydroxychloroquine or chloroquine has been used for cutaneous manifestations and milder forms of the disease; these medications may cause neuropathy. 5. Severe forms of the disease require immunosuppressive therapy with cyclophosphamide (which may cause bone marrow suppression, bladder carcinoma, or myeloproliferative and lymphoproliferative malignancies) or azathioprine (which is less toxic).

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Systemic Sclerosis (Scleroderma) A. GENERAL CHARACTERISTICS 1. Systemic sclerosis is a generalized disorder of connective tissue. 2. Inflammation and fibrosis with small vessel obliteration affect skin, blood vessels, musculoskeletal system, GI tract, lungs, heart, and kidneys. 3. Two clinical syndromes exist: a. Diffuse systemic sclerosis is characterized by widespread proximal skin involvement and early visceral involvement. b. CREST syndrome is characterized by subcutaneous calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia (visceral involvement is less common, and skin involvement is distal). 4. Age of onset is between 30 and 60 years. B. CLINICAL FEATURES 1. Disease usually begins with Raynaud phenomenon (vasospasm in hands or feet due to cold that produces triphasic color change from pallor to cyanosis to hyperemia), swelling of the hands, or distal polyarthralgias. 2. Thickening of the skin occurs several months after initial signs and symptoms. a. Areas of hypopigmentation and hyperpigmentation, loss of normal skinfolds, and shiny skin are common. b. Telangiectasias are present on the fingers, face, lips, and tongue. c. Subcutaneous calcinosis develops late in the CREST syndrome in the fingers, forearms, legs, and knees. 3. Musculoskeletal signs and symptoms include palpable friction over extensor surfaces, polyarthritis affecting both small and large joints, and muscle atrophy. 4. Common GI signs and symptoms include distal esophageal motor dysfunction, which leads to dysphagia for solid foods and reflux esophagitis; small bowel hypomotility is not uncommon, producing diarrhea, malabsorption, and occasionally, bacterial overgrowth syndrome. 5. Pulmonary signs and symptoms include shortness of breath on exertion secondary to pulmonary fibrosis, but pleuritis is uncommon (unlike in SLE). 6. Cardiac signs and symptoms are less common, but arrhythmias and congestive heart failure (CHF) may occur; pericarditis is rare (unlike in SLE). 7. Renal involvement is the leading cause of death in these patients; fibrosis of renal arterioles leads to malignant arterial hypertension and microangiopathic hemolytic anemia. C. LABORATORY FINDINGS 1. Results of routine laboratory tests are usually normal. a. Serum analysis indicates positive test results for ANAs (not specific) and anticentromere antibodies (if present, they are more diagnostic than are positive results for ANAs); hypocomplementemia and anti-dsDNA are rare (in contrast to SLE). b. Anti-scleroderma antibody (SCL-70), present in a minority of patients, is associated with a worse prognosis. c. Anti-RNA polymerases are associated with more frequent cardiac and renal involvement. 2.

Radiography

a. b.

Barium esophagrams can effectively show dysmotility and reflux. Osteopenia is usually the only bony abnormality associated with systemic sclerosis.

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D. TREATMENT 1.

2. 3. 4. 5. 6.

VI

Frequent evaluations are necessary to assess the multiple systems affected by

this disease, for example, barium swallows to assess esophageal motility; pulmonary function tests, cardiac ultrasound, and Holter monitoring to assess ventricular function and rhythm disturbances; and routine urinalysis to assess renal function. Penicillamine inhibits collagen cross-linking, which leads to decreased skin thickening. Captopril is effective in treating renal hypertensive disease. Calcium channel blockers may provide relief of Raynaud phenomenon. Corticosteroids are generally not effective except for the treatment of polymyositis and pulmonary complications. Sucralfate, ranitidine, or omeprazole may be beneficial for the symptoms of esophageal reflux, whereas metoclopramide (a smooth muscle stimulant) may improve intestinal motility.

Polymyositis and Dermatomyositis A. GENERAL CHARACTERISTICS 1. Polymyositis and dermatomyositis are inflammatory myopathies. 2. A cardinal sign of dermatomyositis is a characteristic rash. B. CLINICAL FEATURES 1. 2. 3. 4. 5.

6. 7. 8.

Symmetric proximal muscle weakness occurs after an insidious onset of malaise, weakness, and weight loss. Neck flexion weakness is also present. Facial or ocular weakness is not present (unlike myasthenia gravis). Affected muscles may be tender on palpation. Dermatomyositis is associated with erythematous smooth or scaly patches over elbows, knees, and medial malleoli, as well as heliotrope eyelids (violet discoloration of the eyelids). There is an increased incidence of ovarian, breast, and colon cancer; melanoma; and lymphoma. Cardiac involvement may lead to arrhythmias or CHF. Swallowing difficulties (dysphagia) are not uncommon. There is an increased risk of occult ovarian cancer in those with dermatomyositis.

C. LABORATORY FINDINGS 1. Results of routine laboratory tests are usually normal. 2. Serum analysis indicates elevated levels of creatine kinase, lactate dehydrogenase (LDH), and aldolase; test results for ANAs may be positive. 3. Electromyography (EMG) and nerve conduction studies show polyphasic potentials, fibrillations, and high-frequency action potentials. 4. Muscle biopsy is the only specific test, showing lymphoid inflammatory infiltrates in both cases. D. TREATMENT 1. 2. 3. 4.

High-dose oral corticosteroids are prescribed for a 3-month trial period. Azathioprine, cyclophosphamide, and methotrexate are second-line agents. Hydroxychloroquine may be beneficial for resistant skin manifestations.

In refractory cases, intravenous immunoglobulin promotes short-term improvement.

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Sjögren Syndrome A. GENERAL CHARACTERISTICS 1. Sjögren syndrome is an inflammation and destruction of salivary and lacrimal glands. 2. The disease may be primary (an isolated condition) or secondary (usually associated with RA or SLE). 3. Sjögren syndrome primarily affects women in their 50s. B. CLINICAL FEATURES 1. The disease is characterized by the insidious onset of dry eyes (keratoconjunctivitis sicca), which creates a gritty sensation, or dry mouth (xerostomia), which increases the frequency of dental caries and creates difficulties in chewing and swallowing. 2. In time, reduced visual acuity and photosensitivity occur. 3. Dryness of the nasopharynx and tracheobronchial tree may lead to epistaxis, hoarseness, and bronchitis. 4. Salivary gland enlargement may occur. 5. Constipation and pancreatic insufficiency may occur due to mucosal gland involvement of these organs. 6. The disease is strongly associated with lymphoma. C. LABORATORY FINDINGS 1. Hematologic studies indicate normochromic-normocytic anemia and leukopenia; mild eosinophilia is seen in approximately one-third of patients. 2. Serum analysis indicates the following: a. Results of tests for rheumatoid factor and ANAs are often positive but are not specific for Sjögren disease. b. Anti-nucleoprotein (anti–SS-A and anti–SS-B) antibodies are fairly specific to the disease. c. Lip or salivary gland biopsy and a consistent ophthalmologic examination confirm the diagnosis. D. TREATMENT 1. 2. 3.

VIII

Artificial tears for xerophthalmia should be prescribed; topical corticosteroids should be avoided because they may cause corneal thinning. Xerostomia can be relieved with water, and scrupulous dental care is necessary. Treatment with cyclophosphamide and corticosteroids is reserved for patients who have severe disease.

Vasculitic Syndromes A. GENERAL CHARACTERISTICS 1. The main pathologic feature of these diseases is inflammation of blood vessels. 2. Common vasculitic syndromes discussed here include hypersensitivity angiitis, Henoch-Schönlein purpura, Churg-Strauss syndrome, polyarteritis nodosa, Wegener granulomatosis, Goodpasture syndrome, and giant cell arteritis. B. HYPERSENSITIVITY ANGIITIS 1.

General characteristics

a. b.

Hypersensitivity angiitis is the most common form of vasculitis. The disease is localized to skin involvement.

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c. d. 2.

Fever and arthralgias may occur. Palpable purpura is the primary skin feature, usually first seen on the lower extremities.

Laboratory findings

a. b. 4.

Infiltration of dermal capillaries with PMNs occurs. The disease tends to occur after drug exposure.

Clinical features

a. b. 3.

137

Skin biopsy is the only diagnostic test. Serum complement levels may be low or normal.

Treatment

a. b.

The causative agent should be discontinued. Corticosteroids are useful in treating widespread disease.

C. HENOCH-SCHÖNLEIN PURPURA 1.

General characteristics

a. b. c. 2.

Clinical features

a. b.

c. 3.

First signs of the disease are palpable purpura on the lower extremities, which may coalesce and ulcerate; purpura subsides in several weeks. Abdominal pain, upper or lower GI bleeding, and lower-extremity arthritis may occur with the skin lesions or afterward; these signs and symptoms subside spontaneously. Renal involvement occurs in more than half of patients and is self-limiting.

Laboratory findings

a. b. c. 4.

Henoch-Schönlein purpura is also known as anaphylactoid or allergic purpura, which involves the small vessels. The disease occurs in children or young adults. The disease occurs secondary to streptococcal infections, insect stings, or administration of drugs.

Hematologic studies indicate mild anemia, leukocytosis, and elevated ESR. Serum immunoglobulin (Ig) A levels are raised in 50% of patients. Urinalysis indicates hematuria, red blood cell casts, and proteinuria, which indicate renal involvement. The presence of IgA in tissue biopsy confirms the diagnosis in patients who have appropriate symptomatology.

Treatment

a. b.

Therapy is supportive for mild disease. Corticosteroids are prescribed for treating arthralgias and renal disease.

D. CHURG-STRAUSS SYNDROME 1.

General characteristics

a.

b. 2.

Churg-Strauss syndrome is characterized by the triad of asthma or allergic rhinitis, peripheral eosinophilia, and systemic vasculitis involving small and medium arteries. The disease primarily affects men.

Clinical features

a. b. c. d.

Allergic rhinitis usually precedes asthma. Second phase of the disease involves eosinophilic tissue infiltration. Third phase is characterized by systemic necrotizing vasculitis, weight loss, and fever. Vasculitis leads to nonprogressive glomerulonephritis, palpable purpura, and a nondeforming arthritis.

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3.

Laboratory findings

a. b. c. d. 4.

Hematologic studies indicate leukocytosis with  eosinophils, elevated levels of serum IgE, and normochromic anemia. Tissue biopsy reveals small-vessel vasculitis and eosinophilic infiltration. Visceral angiography may reveal tortuous vessels with areas of obliteration or partial occlusion. Chest radiograph may show nodular opacities.

Treatment

a. b.

Systemic corticosteroids are usually sufficient. Azathioprine or cyclophosphamide may be necessary to treat unremitting disease or to allow for tapering of corticosteroids.

E. POLYARTERITIS NODOSA 1.

General characteristics

a. b. c. 2.

Clinical features

a. b. c.

d. e. f.

g. 3.

Polyarteritis nodosa involves small and medium-sized muscular arteries that form aneurysms and areas of occlusion. The disease primarily affects middle-aged men. The disease commonly affects skin, joints, nerves, GI tract, and kidneys. Fever, malaise, and weight loss occur frequently. Seventy percent of patients have renal involvement, which may lead to renal insufficiency and hypertension. Peripheral neuropathy occurs in 50%–70% of patients, beginning with sudden radicular pain and paresthesias, followed by motor deficits involving that peripheral nerve. In the skin, palpable purpura, ulcerations, and digital tip infarcts may occur. In the joints, nondeforming arthritis involving any number of joints may occur. GI signs and symptoms include generalized abdominal pain and distention that is suggestive of mesenteric artery involvement and may lead to obstruction, perforation, and GI bleeds. Rupture of aneurysms may lead to hemorrhagic shock and death.

Laboratory findings

a.

Hematologic studies indicate elevated ESR, leukocytosis, thrombocytosis, and anemia (from blood loss or renal failure). b. Serum analysis indicates hepatitis B surface antigen in 10%–50% of patients and hypocomplementemia (C3 and C4) in one-fourth of patients. c. Urinalysis reveals proteinuria, hematuria, and red blood cell casts, which indicate renal involvement. d. Tissue biopsy reveals vasculitis. e. Visceral angiography reveals microaneurysms and narrowing of segmental arteries of the kidney, liver, and mesentery. 4. Treatment consists of a combination of steroid and immunosuppressive therapy (cyclophosphamide). F.

WEGENER GRANULOMATOSIS 1.

General characteristics

a. b. c.

Wegener granulomatosis involves small arteries and veins. The disease is characterized by granulomatous vasculitis of the upper and lower respiratory tract and a necrotizing glomerulonephritis. The disease primarily affects middle-aged men.

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2.

Clinical features

a. b.

c. d. e. 3.

139

Fever, anorexia, and weight loss are common. Ulcerations of respiratory tract mucosa lead to chronic purulent sinusitis and saddle-nose deformity, as well as pneumonitis, cavity formation, cough, and hemoptysis. Progressive renal disease can be fatal. Eye inflammation with episcleritis occurs in over half of patients. GI tract and peripheral nerves are less commonly involved (unlike in polyarteritis nodosa).

Laboratory findings

a.

4.

Hematologic studies indicate normochromic anemia, leukocytosis without eosinophilia, and thrombocytosis. b. Serum analysis indicates elevated IgE and IgA levels; results are positive for antiprotenase-3 antineutrophic cytoplasmic antibodies (ANCA). c. Urinalysis reveals red blood cell casts, proteinuria, and hematuria, which indicate glomerular disease. d. Pulmonary biopsy shows a granulomatous vasculitis. Treatment consists of combined corticosteroid and cyclophosphamide therapy, which has markedly improved outcomes in this disease.

G. GOODPASTURE SYNDROME 1.

General characteristics

a.

2. 3.

Goodpasture syndrome is characterized by pulmonary hemorrhage and glomerulonephritis. b. Antiglomerular basement membrane antibodies are present and may also bind to lung basement membranes, which gives rise to disease manifestations. c. The disease primarily affects young men. Clinical features include an initial flulike prodrome, followed by renal and lung manifestations (cough and hemoptysis). Laboratory findings

a. b. c. d.

e. 4.

Hematologic studies indicate microcytic, hypochromic anemia and low serum iron levels. Urinalysis reveals proteinuria, hematuria, and red blood cell casts, which indicate glomerular involvement. Immunohistologic studies of renal biopsy tissue show linear deposits of antibodies along the glomerular basement membrane. Lung biopsy reveals alveolar hemorrhage and hemosiderosis; immunologic studies show linear deposits of antibodies along the alveolar basement membrane. Renal biopsy shows crescents in the glomeruli. Antiglomerular basement membrane antibodies to type IV collagen is diagnostic.

Treatment

a. b.

High-dose corticosteroids, cyclophosphamide, and emergent plasmapheresis, if started early, can prevent permanent renal failure. Hemodialysis may be necessary.

H. GIANT CELL ARTERITIS (TEMPORAL ARTERITIS) 1.

General characteristics

a. b.

Giant cell arteritis is a granulomatous medium- and large-artery vasculitis that affects persons older than 50 years of age. The disease may coexist with polymyalgia rheumatica (characterized by aching extremities, stiffness, fatigue, and headache).

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2.

Clinical features

a. b. c. d. e.

3.

Laboratory findings

a.

4.

Symptoms include those of claudication (pain, pallor, paresthesias, pulselessness), headache, visual changes, and scalp tenderness. Common sites of claudication include jaw (indicating temporal arteritis), tongue, and extremities. Visual changes include blurring, ptosis, diplopia, and partial or complete blindness (due to ophthalmic vessel arteritis). New onset of headache in an elderly person with fever and anemia suggests the diagnosis. Tenderness over the affected portion of the temporal artery may be elicited, and this area should undergo biopsy immediately because of the risk of blindness.

Hematologic studies indicate normochromic anemia, leukocytosis, thrombocytosis, and elevated ESR (which is highly suggestive of the diagnosis in an elderly person who has the appropriate symptoms). b. Temporal arteriography often gives false-positive results; therefore, biopsy remains the mainstay of diagnosis. Treatment consists of corticosteroids, which should be administered if the diagnosis is highly suspected on the basis of clinical symptoms, to avert the complication of blindness (even if biopsy has not yet been performed).

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8

Oncologic Diseases The American Joint Committee on Cancer has devised the TNM staging system for most cancers, which stages the degree of tumor size and invasiveness (T0–T4), the level of lymph nodes metastasis (N0–N2 or N3) and metastasis (M0 or M1). In general, tumors that are smaller, have less nodal involvement, and no distant metastasis are classified lower on the TNM stage (e.g., T1 N1 M0), as opposed to metastatic disease with larger, more invasive tumors (e.g., T3 N1 M1) I

Head and Neck Carcinoma A. GENERAL CHARACTERISTICS 1. Head and neck cancer may involve oral cavity, larynx, oropharynx, or salivary glands. 2. Incidence of these cancers increases with tobacco and alcohol consumption. 3. These cancers are often squamous cell tumors, except for adenocarcinomas of the salivary glands. B. CLINICAL FEATURES 1. 2. 3.

Signs and symptoms include dysphagia, hoarseness, and swelling in the neck. White plaques may be evident within the oral cavity. Neck swellings must be differentiated from simple lymphadenopathy through

4.

assessment of size, firmness, and adherence to adjacent tissues. Occasionally, patients may present with persistent cervical lymphadenopathy.

C. LABORATORY FINDINGS 1. Biopsy confirms the diagnosis. 2. 3.

Computed tomography (CT) scan or magnetic resonance imaging may be helpful in delineating the extent of the lesion. In persistent cervical lymphadenopathy with no obvious tumor on physical examination, lymph node biopsy should be performed. If it reveals squamous cell carcinoma, endoscopy of the nasopharynx and the oropharynx as well as the proximal esophagus and trachea to identify the primary tumor is required.

D. TREATMENT 1. 2.

Localized lesions (T1 or T2) are treated with surgical removal or radiotherapy. Radiation for small laryngeal cancer is preferred to preserve voice. For locally or regionally advanced disease, preoperative chemotherapy with cisplatin and 5-fluorouracil (FU) usually allows for organ preservation by shrinking the tumor preoperatively. Surgery is followed by chemoradiation to reduce recurrence.

141

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II

CHAPTER 8

Renal and Bladder Carcinoma A. GENERAL CHARACTERISTICS 1. Renal tumors are usually clear-cell carcinomas (adenocarcinomas). 2. Bladder carcinomas are composed of transitional cells. B. CLINICAL FEATURES 1. 2.

Signs and symptoms of renal cancer include flank pain, hematuria, abdominal mass that may be palpable, fatigue, anemia, and weight loss. Patients who have bladder cancer commonly have hematuria that is usually painless; bladder irritability and infections may be present initially.

C. LABORATORY FINDINGS 1. Renal tumors may be detected with intravenous pyelography that may differentiate the lesion from an obstructing renal calculus. a. Ultrasound is a rapid, inexpensive test that effectively detects renal masses. b. CT scan is effective in detecting renal masses and is the diagnostic modality of choice. c. Biopsy is required to confirm the histopathology. d. A chest x-ray should be obtained to rule out pulmonary metastasis. 2. Bladder tumors are best diagnosed with cystoscopy and then confirmed with biopsy. D. TREATMENT 1.

2. 3.

III

Renal cancer is primarily treated with radical nephrectomy for stage I and II disease and if the tumor involves the renal vein (stage III A), but not for nodal (stage III B) or metastatic disease (stage II) because a cure is not possible in these stages. Cystoscopic resection of superficial lesions not invading muscle is possible for bladder cancer, but more extensive lesions require cystectomy with urinary diversion. After cystoscopic removal, intravesical treatment with bacillus Calmette-Guérin (BCG) can prevent recurrence.

Prostatic Carcinoma A. GENERAL CHARACTERISTICS 1. Incidence of prostatic cancer increases with age. 2. The carcinoma is now often localized at the time of diagnosis due to more effective screening. 3. The Gleason Grading System is used to grade the degree of differentiation of cancers found on biopsy. 4. Most patients with prostate cancer do not die of their disease because it is slow growing. B. CLINICAL FEATURES 1. Patients who have prostatic cancer are often asymptomatic. 2. Signs and symptoms include dysuria, increased urinary frequency with difficulty voiding, and back or hip pain. 3. Hematuria may occur. 4. An elderly man with the aforementioned signs and symptoms who does not have urethral discharge should raise the clinician’s index of suspicion for this diagnosis.

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5.

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A palpable nodule or an enlarged, firm, and irregularly shaped prostate may be felt on digital rectal examination.

C. LABORATORY FINDINGS 1. Although ultrasound is effective in identifying prostate cancer, it is not sensitive enough to be used as a screening test. 2. Diagnosis must be confirmed with a biopsy (transrectal ultrasound guided biopsy). If prostate-specific antigen (PSA)
4 and biopsy is negative, a repeat biopsy should be done to ensure that the cancer was not missed. 3. Serum levels of PSA and acid phosphatase may be elevated; PSA should be measured yearly along with digital rectal examination for men
50 (normal PSA 4 ng/mL). PSA velocity is used when PSA levels are increasing but are still in the normal range because this is associated with cancer (rate of increase
0.75 ng/mL per year). 4. Bone marrow acid phosphatase levels may be elevated when metastatic disease is present. 5. Radionuclide bone scans are required to detect bone metastasis but are usually not present if PSA 10 ng/mL. 6. PSA is used to follow up for recurrence after treatment. D. TREATMENT 1. 2.

Surgery or radiotherapy may result in a cure in early-stage disease. Advanced disease often requires palliative treatment that may involve orchiec-

tomy or administration of exogenous estrogen (tumors are androgen sensitive). IV

Testicular Cancer A. GENERAL CHARACTERISTICS 1. Most are germ cell tumors arising from within the testicle. 2. Most occur in the second to fourth decade of life. Testicular masses in men age 50 or older are more likely to be lymphoma until proven otherwise. 3. Disease is more common in Caucasians. 4. Undescended testes are at a greater risk. 5. Tumors are classified as seminomas or nonseminomas. The nonseminomas may be subclassified as embryonic, teratoma, choriocarcinoma, or yolk sac. B. CLINICAL FEATURES 1. Painless testicular mass is pathognomonic. 2. May present with mild discomfort and swelling suggestive of epididymitis. If symptoms persist despite antibiotics, a cancer must be ruled out. C. LABORATORY FINDINGS 1. Ultrasound is indicated to confirm the diagnosis. 2. Serum
-fetoprotein (AFP), HCG, and LDH are the tumor markers used to differentiate nonseminomas from seminomas. Nonseminomas may produce AFP and/or HCG. Seminomas only produce HCG. Elevated LDH suggests metastatic disease. 3. Chest x-ray and CT of the abdomen/pelvis are necessary for staging. D. TREATMENT 1. Nonseminoma a. Orchiectomy is followed by assessment of tumor markers. If the tumor is confined to the testicle without invasion (T1) and markers are reduced, no further

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2.

V

treatment is necessary, but patients must be followed up with tumor markers for at least 2–3 years. If the tumor has invasion (T2–T4) or markers increase, then retroperitoneal lymph node dissection is required to remove nodal metastasis. b. If staging shows multiple enlarged retroperitoneal nodes, then surgical resection is followed by chemotherapy (e.g., etoposide, cisplatin,  bleomycin). c. If staging shows metastatic disease outside of the abdomen, then chemotherapy without retroperitoneal lymph node dissection is used. Seminoma a. Orchiectomy is followed by radiation regardless of stage and has a 98% cure rate. b. Chemotherapy (as above) is added for significant nodal metastases or distant metastatic disease.

Ovarian Cancer A. GENERAL CHARACTERISTICS 1. There is a lower risk in patients on oral contraceptives, who have had multiple pregnancies, who are breastfeeding, or who have no family history of ovarian cancer. 2. Estrogen replacement therapy in postmenopausal women does not increase risk. 3. Patients usually present after age 40 and are usually diagnosed after the disease has spread. B. CLINICAL FEATURES 1. Symptoms of abdominal pain, bloating, and urinary symptoms indicate advanced disease. 2. Localized disease is usually asymptomatic. 3. Routine pelvic examination may detect an enlarged adnexal mass. C. LABORATORY FINDINGS 1. CA-125 is elevated (35 U/mL) in about 85% of patients with ovarian cancer. 2. CT scan or transvaginal ultrasound will show an enlarged ovarian mass. The presence of ascites suggests metastatic disease. 3. Chest x-ray should be obtained to rule out metastatic disease. D. TREATMENT 1. Laparotomy to remove the primary cancer (hysterectomy and bilateral oophorectomy) and debulk for metastatic disease improves survival if the amount of residual tumor after resection is minimal. 2. For disease outside of the ovary, patients require platinum-based chemotherapy.

VI

Gastric Carcinoma A. GENERAL CHARACTERISTICS 1. Incidence increases with low dietary intake of fruits and vegetables and high intake of starches. High dietary nitrates are also a risk factor. Helicobacter pylori may be associated with an increase. 2. Incidence in Japan is high, whereas incidence in the United States has declined. 3. 4.

Gastric cancer is twice as common in men as in women.

The tumor is almost always an adenocarcinoma. Other types include primary gastric lymphoma and gastrointestinal stromal tumors.

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5.

145

Gastric adenocarcinoma is subdivided into: a. Diffuse: Tumor involves the entire stomach, thickening the walls. b. Intestinal: Tumor is usually confined to the antrum or lesser curve and is usually ulcerative.

B. CLINICAL FEATURES 1. An early symptom is vague postprandial heaviness that becomes more frequent. 2. Patients are anorexic (anorexia may be pronounced for meat products). 3. Weight loss is the most common sign. 4. Vomiting may be a prominent symptom if pyloric obstruction occurs; coffeeground vomitus is associated with a bleeding tumor. 5. Lesions occurring at the cardia of the stomach may cause dysphagia. 6. An epigastric mass may be palpable. 7. Virchow node (left supraclavicular node) may be present if metastasis has occurred. 8. Intra-abdominal masses may be palpable, depending on the degree and location of metastases. C. LABORATORY FINDINGS 1. Anemia (iron deficiency) is present in approximately half of the patients. 2. Stool analysis is positive for occult blood. 3. Carcinoembryonic antigen (CEA) level is elevated in two-thirds of patients; this result usually indicates extensive metastases. 4. Upper gastrointestinal (GI) series may be diagnostic, but the false-negative rate is approximately 20%. 5. Diagnosis is confirmed by gastroscopy with multiple biopsies. D. TREATMENT 1. 2. 3. 4. 5.

VII

Surgery offers the only chance for cure; approximately 50% of patients have resectable lesions, and half of these patients are potentially curable (i.e., 25%). Adjuvant chemotherapy has proved to be of little value. Radiation therapy is only used palliatively and does not improve survival. Combined chemoradiation after surgical resection has a small improvement in survival. Treatment of gastric lymphoma involves eradication of H. pylori (causes regression of 75% of cases). If there is no response, chemotherapy is usually used (CHOP [cyclophosphamide, doxorubicin, vincristine, and prednisone]).

Pancreatic Carcinoma A. GENERAL CHARACTERISTICS 1. Pancreatic cancer is the third leading cause of death due to cancer (after lung and colon) in men between ages 35 and 54. 2. Increased risk occurs with smoking, fried meat and fat consumption, and African American descent; coffee and alcohol intake are less strongly associated with increased incidence. 3. Peak incidence occurs in the fifth and sixth decades of life. 4. The tumor is most commonly located at the head of the gland. 5. Tumor type is usually ductal adenocarcinoma with a poorly differentiated cell pattern. Islet cell tumors make up 5%–10% of pancreatic cancers. 6. Pancreatic cancer is characterized by early local extension and metastasis to regional lymph nodes and the liver.

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B. CLINICAL FEATURES 1. 2.

3. 4. 5. 6. 7.

Signs and symptoms include weight loss, obstructive jaundice (if tumor is located at the head of the pancreas), and deep-seated abdominal pain. Pain may radiate to the back in 25% of patients and is associated with a worse prognosis; pain may be relieved by sitting up with the spine flexed and is aggravated by recumbency. Hepatomegaly may be present. An epigastric mass may be palpated and is usually indicative of a nonresectable lesion. A palpable, nontender gallbladder in a patient who has jaundice suggests neoplastic obstruction of the common bile duct (seen in 50% of patients). Jaundice is associated with pruritus. Ascites may be present.

C. LABORATORY FINDINGS 1. 2. 3. 4.

5.

6.

Serum bilirubin level (average is 18 mg/dL) is much higher than that found in benign disease of the biliary tree. Aspartate aminotransferase and alanine aminotransferase are usually not significantly elevated. Elevated alkaline phosphatase level occurs when bile duct obstruction is present and/or liver metastasis has occurred. Although a serum CEA level
9 ng/dL is usually associated with extrapancreatic spread, tumor markers are otherwise not useful in diagnosis because of their lack of sensitivity. CA 19-9
37 U/mL has a sensitivity of 86% and specificity of 87%; a normal CA 19-9 does not rule out cancer, and an elevated level does not automatically denote cancer. CT scan reveals a pancreatic mass in nearly all patients; pancreatic and bile duct dilatation is strong evidence of the disease despite the absence of an apparent pancreatic mass. Endoscopic retrograde cholangiopancreatography should also be performed to visualize the ductal system. Brushings may be negative in the face of cancer in 30% of cases.

D. TREATMENT

VIII

1. 2.

Surgical resection is indicated for resectable tumors (only 20%). Jaundice and pruritus are relieved by choledochojejunostomy or placement of

3.

a biliary stent in patients who have unresectable lesions. Although radiotherapy and chemotherapy can provide some palliation, these therapies are not curative.

Colorectal Carcinoma A. CANCER OF THE COLON AND RECTUM 1.

General characteristics

a. b. c. d.

Colorectal cancer is the second leading cause of death due to cancer (after lung cancer). Incidence increases with age, peaking in the 70s and 80s. Carcinoma of the right colon is more common in women, whereas carcinoma of the rectum is more common in men. The majority of colorectal tumors are adenocarcinomas.

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e.

2.

Other conditions associated with an increased risk of colorectal cancer include positive family history, ulcerative colitis, Crohn disease, decreased intake of dietary fiber with an increased fat intake, and colorectal polyps.

Clinical features

a.

b.

c.

d.

e.

3.

147

Signs and symptoms of right colon cancer include fatigue, weakness, and anemia. i. Patients report a vague, right-sided abdominal discomfort that may be postprandial. ii. Obstruction is uncommon because of the large caliber of the right colon and the liquidity of the stool (hence, alteration in bowel habits is not a common symptom). iii. Gross blood may not be evident in the stool. iv. Occasionally, a mass may be palpable on abdominal examination. Symptoms of left colon cancer include increased frequency of defecation (not true watery diarrhea) alternating with constipation due to the semisolid nature of the stools and the small caliber of the left colon. i. Patients may initially be seen with partial or complete obstruction. ii. Stool may be streaked with blood/clots. iii. A mass may be palpable on abdominal examination. Patients who have rectal cancer are most often seen with hematochezia. i. Tenesmus may be present. ii. Digital rectal examination may reveal a flat, hard, oval, or encircling mass. Inguinal and supraclavicular nodes should be palpated in all bowel carcinoma patients because enlargement of these nodes is evidence of metastasis; an enlarged node may also provide an accessible site for biopsy. Colorectal cancer patients initially may be seen with symptoms of obstruction, including nausea; vomiting; severe, cramping abdominal pain; and absence of flatus and bowel movements. Fever and tachycardia may also occur.

Laboratory findings

a. b.

Patients have hypochromic, microcytic anemia. Urinalysis should be performed to assess for urinary tract infections that may result from an enterovesical fistula formed via extension and invasion of the colonic tumor. c. Renal function should be assessed via measurement of serum creatinine level. d. Liver function should be assessed because colonic cancer may metastasize to the liver (i.e., measurement of albumin, bilirubin, and transaminase levels). e. Alkaline phosphatase level should be measured to assess for early bone metastasis. f. Measurement of CEA levels is only useful in detecting recurrence of disease after curative surgical resection; it should not be used as a screening test because of its lack of sensitivity. g. Barium enema is effective in delineating the lesions but is no longer used in most centers (see Figure 4-7); chest radiographic studies should also be obtained to assess for metastasis as well as free air under the diaphragm (which suggests intestinal perforation from the colonic tumor). h. Barium swallow should not be performed because it may precipitate acute large-bowel obstruction in a patient with suspected large-bowel cancer. i. Colonoscopy with biopsy confirms the diagnosis and should be performed to assess the entire colon; colonoscopy without barium enema is now standard practice in most centers.

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j. k. 4.

Radiographic studies are unreliable for diagnosis of rectal cancer; rectal carcinomas are best diagnosed with a sigmoidoscopy. CT scans are not essential for diagnosis of colorectal cancer but may assist in assessment of disease extent.

Treatment

a.

b.

c.

d.

For colonic cancer, surgical resection of the affected colon is often performed even if metastasis is present, because removal of the lesion can prevent obstruction and hemorrhage. For rectal cancer, surgical resection is performed with an attempt to preserve anal sphincter function when possible; neoadjuvant chemotherapy and radiotherapy can significantly reduce the surgical resection necessary for tumor removal. Follow-up should include CEA determinations every 6 months and fecal occult blood testing biannually; colonoscopy should be performed 1 year after resection of the tumor. Patients with nodal metastases should receive chemotherapy (e.g., 5-FU and leucovorin).

B. COLONIC AND RECTAL POLYPS 1.

General characteristics

a. b. c.

d. e. f. 2.

Polyps may be sessile or pedunculated. Polyps may be benign or malignant. Most polyps are adenomatous and are either tubular, tubulovillous, or villous, and have neoplastic potential; sessile lesions are more likely to become malignant than are pedunculated lesions. At least half of all polyps occur in the sigmoid colon or rectum. Other polyp types include hyperplastic and inflammatory polyps; both are nonneoplastic. Familial polyposis syndromes are a rare group of diseases summarized in Table 8-1.

Clinical features

a. b. c. d. e.

Most patients who have polyps are asymptomatic; most polyps are discovered by routine sigmoidoscopy. Rectal bleeding is the most common complaint; the bleeding is usually intermittent (rarely profuse). Generally, patients do not report a change in bowel habits unless the polyp is large. Peristaltic cramps occasionally may be caused by polypoid tumors. Rectal polyps may be felt on digital rectal examination.

TABLE 8-1

FAMILIAL POLYPOSIS SYNDROMES

Syndrome

Symptoms/Signs

Malignant Potential

Familial adenomatous polyposis


100 polyps in colon and rectum

Yes

Gardner syndrome

Polyposis, desmoid tumors, osteomas, sebaceous cysts

Yes

Turcot syndrome

Polyposis, medulloblastoma/glioma

Yes

Peutz-Jeghers syndrome

Multiple hamartomatous polyps, melanotic pigmentation of skin andmucous membranes

Small

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3.

Laboratory findings

a. b. c. 4.

Anemia usually is not present because bleeding is typically not extensive unless the polyp is malignant. Barium enemas may reveal a filling defect associated with the polyp(s); however, polyps 5 mm are generally difficult to detect. Colonoscopy is the most reliable means of detecting and treating small polypoid lesions.

Treatment

a. b.

IX

149

Polyps should be removed because they are either symptomatic (e.g., bleeding) or have malignant potential. Colonoscopy is an effective means of polyp removal. After polyps have been removed, colonoscopy should be performed yearly until no polyps are found, and then can be done at 3- to 5-year intervals.

Lung Carcinoma A. GENERAL CHARACTERISTICS 1. Lung cancer is the most common cause of cancer deaths. 2. Lung cancer is typically seen in the sixth decade of life. 3. Smoking is the most common cause, but asbestos exposure is also associated with this condition. 4. Asymptomatic individuals have the best chance of survival (75% of symptomatic patients are incurable). 5. Mean survival time is 9 months from time of diagnosis. 6. The majority of lung cancers fall into two categories (non–small-cell squamous cell carcinoma, adenocarcinoma) and small-cell (oat cell) carcinoma. Large-cell carcinoma is a less common and more aggressive form not discussed here. a. Squamous cell carcinoma i. Accounts for 30% of lung cancers ii. Tends to occur centrally, near the hilum iii. Has slower growth and metastatic rates relative to other lung cancers b. Adenocarcinoma i. Accounts for 50% of lung cancers ii. May be mucus-secreting (acinar adenocarcinoma) iii. May be bronchioalveolar carcinoma (scar-like carcinoma) c. Small-cell (oat cell) carcinoma i. Accounts for 20% of lung cancers ii. Occurs centrally iii. Metastasizes early iv. Is the most resistant to combined modality treatment B. CLINICAL FEATURES 1.

Intrathoracic signs and symptoms include cough, hemoptysis, wheezing, recurrent pneumonia, and pleuritic pain. a. Hoarseness occurs due to recurrent laryngeal nerve involvement. b. Neck or facial swelling occurs due to superior vena cava obstruction. c. Diaphragmatic paralysis occurs due to phrenic nerve involvement. d. Pancoast syndrome, characterized by pain of the ipsilateral arm, and Horner syndrome (ptosis, miosis, ipsilateral anhydrosis) are caused by a tumor of the upper lobe of the lung.

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2.

3.

Extrathoracic signs and symptoms may be due to metastasis or paraneoplastic syndromes. a. Metastasis commonly occurs to the liver, adrenal glands, brain, and bone. b. Paraneoplastic syndromes include Cushing syndrome, hypercalcemia, syndrome of inappropriate antidiuretic hormone, neuropathies, clubbing, and hypertrophic pulmonary osteoarthropathy. Nonspecific signs and symptoms include weight loss, anorexia, weakness, and malaise.

C. LABORATORY FINDINGS 1. 2. 3.

4. 5. 6. 7.

8. 9.

Microscopic analysis of sputum may reveal atypical cells; however, cell yields are

often inconsistent. Some patients may have anemia that is consistent with chronic disease. An atypical chest radiograph may be the first indication of lung cancer. a. Cavitation and obstructive pneumonitis are more commonly seen with squamous cell carcinomas and tend to occur near the hilum. b. Adenocarcinoma is often seen at the periphery. CT scan of the chest is used to determine resectability potential based on appearance of the tumor and nodal spread. Bronchoscopy with biopsy/brushings establishes the diagnosis in the majority of patients. CT-guided transthoracic biopsy may be necessary if bronchoscopy is negative. Patients experiencing signs and symptoms of paraneoplastic syndromes should be evaluated. Patients must be assessed preoperatively for new neurologic signs and symptoms, bone pain/tenderness, and an elevated alkaline phosphatase level;

if these signs and symptoms are not present, routine bone and CT scans are not indicated. Ventilation-perfusion scan can be used to preoperatively assess pulmonary reserve. Positron emission tomography (PET) is used for patients who have resectable disease on CT scan to determine whether there is metastatic disease not visible on CT.

D. TREATMENT 1.

2. 3. 4. 5. 6.

X

Patients who have resectable lesions, that is, no distant metastases, and adequate cardiopulmonary reserve when the affected area of the lung is removed require surgery for cure. Nodes within the mediastinum must be assessed; if nodes are 1 cm in size, they are positive for metastases in 5% of patients. Patients who have small-cell lung carcinomas have better survival rates than patients who have other carcinoma types. Radiotherapy is used palliatively for unresectable tumors and has some benefit in conjunction with chemotherapy after surgical resection. Chemotherapy (e.g., cisplatin) has some benefit in combination with radiation after surgery. Contraindications to surgery includes recent myocardial infarction, FEV1 (forced expiratory volume in one second) 1 L, PCO2
45.

Multiple Myeloma A. GENERAL CHARACTERISTICS 1. Multiple myeloma is a malignant proliferation of plasma cells derived from a single clone.

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2. 3.

151

Incidence increases with age (rare in patients 40 years of age). Malignant myeloma is twice as common in African Americans.

B. CLINICAL FEATURES 1. Bone pain is the most common symptom (usually occurs in the back and ribs). 2. Persistent localized pain in a patient who has myeloma usually indicates a pathologic fracture. 3. Patients may have signs and symptoms of spinal cord compression secondary to vertebral fractures. 4. Masses associated with lytic lesions of the skull may be palpated. 5. Patients have an increased susceptibility to bacterial infections, that is, pneumonia and pyelonephritis; Streptococcus pneumoniae, Staphylococcus aureus, and Klebsiella species commonly cause pneumonia, whereas Escherichia coli is predominant in the urinary tract. 6. Patients may become edematous secondary to renal failure, which commonly occurs as a result of hypercalcemia. 7. Hypercalcemia may cause confusion, weakness, and lethargy. 8. Hepatosplenomegaly rarely occurs. C. LABORATORY FINDINGS 1. Patients have normochromic-normocytic anemia. 2. Urine contains Bence-Jones (M-chain) proteins. 3. Chest and long bone radiographic studies reveal lytic lesions or diffuse osteopenia. 4. Elevated levels of blood urea nitrogen and creatinine indicate renal failure. 5. Serum calcium level is elevated. 6. M component is increased on protein electrophoresis (usually immunoglobulin G). D. TREATMENT 1. 2. 3. 4. 5.

XI

Radiotherapy to solitary bone plasmacytomas often is curative; radiotherapy may be used palliatively as well. Chemotherapy is also useful, for example, cyclophosphamide and prednisone. Corticosteroids, hydration, and natriuresis are indicated for hypercalcemia. Uric acid nephropathy may occur during chemotherapy (from lysis of tumor burden) and cause renal failure; nephropathy can be treated with allopurinol. Pneumococcal vaccines are of little use in preventing infection.

The Lymphomas A. HODGKIN LYMPHOMA 1.

General characteristics

a. b. c.

d. 2.

In the United States, Hodgkin lymphoma has a bimodal incidence that peaks at ages 15–35 and also over age 50. The disease is more common in men, especially within the younger age group. Incidence increases in patients who have immunodeficiencies as well as patients who have autoimmune diseases. The B-lymphocyte is the cell that predominates. Table 8-2 lists the four histologic subtypes.

Clinical features

a. b.

Patients are usually first seen with a mass or group of lymph nodes that are firm, nonfixed, and nontender. Adenopathy is common in the neck and/or supraclavicular area.

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TABLE 8-2

REY CLASSIFICATION OF HODGKIN LYMPHOMA

Subtype

Proportion

Pathology

Prognosis

Lymphocyte-predominant

5–10

Predominantly normalappearing lymphocytes

Very good

Lymphocyte-depleted

10–15

Few lymphocytes, pleomorphic cells, fibrosis

Poor

Mixed cellularity

25–40

Pleomorphic cells

Good

Nodular sclerosis

50–80

Lymphoid nodules, collagen bands

Good

c. d.

Approximately 50%–60% of patients have mediastinal lymphadenopathy. Two to five percent of patients report that the lymph nodes are painful after alcohol ingestion. e. Patients who have constitutional signs and symptoms are designated as having stage B disease, which is associated with a less favorable prognosis than that for patients who have stage A disease, which is the designation given when there are no constitutional signs and symptoms. i. Up to 40% of patients have low-grade fever with recurrent night sweats (more common in older patients and those who have more advanced disease). ii. Weight loss occurs in more than 10% of patients. f. Pruritus may be present. g. Generally, patients do not have opportunistic infections because humoral immunity is usually intact. h. Hepatosplenomegaly may be present. 3.

Laboratory findings

a. b. c.

d. e. 4.

Patients who have lymph nodes
1 cm for more than 4–6 weeks should undergo biopsy. Presence of Reed-Sternberg cells confirms the diagnosis. Hematologic analysis reveals normochromic-normocytic anemia, with elevated iron stores and low iron-binding capacity consistent with anemia of chronic disease. A marked leukemoid reaction is evident. Staging is done with CT of the chest/abdomen/pelvis, and PET scan is frequently being used after treatment to document remission.

Treatment

a.

Radiotherapy (localized disease: stages I and II) and chemotherapy (disseminated disease: stages III and IV) should be used with the intention of cure. Chemotherapy (e.g., doxorubicin, bleomycin, vinblastine, and dacarbazine) is frequently used for localized disease in conjunction with radiation.

B. NON-HODGKIN LYMPHOMA 1.

General characteristics

a. b. c.

Peak incidence occurs in individuals between ages 20 and 40. This disease may be associated with viral infection and immunosuppression (e.g., iatrogenic or acquired immunodeficiency syndrome). The majority of subtypes are of B-cell lineage (except for the high-grade lymphoblastic subtype, which has a T-cell origin).

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2.

Clinical features

a. b. c. d. e. 3.

c.

Biopsy of suspicious nodes is required for diagnosis. Suggested workup includes complete blood count, liver function tests, renal function tests, determination of alkaline phosphatase level, CT scan of the abdomen and pelvis, and bone marrow biopsy to determine the extent of the disease. PET scans are increasingly being used for staging and following up treatment responses. Hypergammaglobulinemia is not present because the overproduced B cell is typically in a resting state (unlike in multiple myeloma).

Treatment

a. b. c. d.

XII

Persistent, painless, peripheral lymphadenopathy is common. Epitrochlear and mesenteric node involvement are more suggestive of nonHodgkin than Hodgkin lymphoma. Patients are less likely to have constitutional signs and symptoms (compared with Hodgkin lymphoma). Site-specific signs and symptoms associated with lymphadenopathy may occur. Hepatosplenomegaly may be present.

Laboratory findings

a. b.

4.

153

Treatment is based on histologic subtype (low-, intermediate-, or high-grade lymphoma). Radiotherapy has a limited role. Chemotherapy is the most common treatment modality. Most involve some form of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone). Bone marrow transplantation is of some benefit for patients whose conditions are refractory to standard chemotherapy.

The Leukemias A. GENERAL CHARACTERISTICS 1. The leukemias are classified according to cell type and may be either acute or chronic, myeloid or lymphoid. 2. Risk factors include a family history, radiation exposure, and treatment with certain chemotherapeutic agents (alkylating agents). 3. The four main subtypes are acute lymphocytic leukemia (ALL), acute myelogenous leukemia (AML), chronic lymphocytic leukemia (CLL), and chronic myelogenous leukemia (CML). B. ACUTE LEUKEMIAS 1. Acute leukemias include acute lymphocytic leukemia and acute lymphoblastic leukemia. 2. ALL may be T-cell type (20%), null-type (non-T, non-B cell), or less commonly, B-cell type. a. ALL typically occurs in children. b. The presence of an enzyme, terminal deoxynucleotidyl transferase, is relatively specific for ALL. 3. AML is characterized by larger myelogenous cells (relative to lymphoblastic cells) that may contain Auer bodies (abnormal primary granules, which are a diagnostic finding). a. AMLs are rare in children. b. AMLs are not uncommon in persons receiving radiotherapy for Hodgkin disease.

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4.

Clinical features

a. b.

Signs and symptoms of ALL and AML are similar. Fatigue is the most common presenting symptom and may be associated with pallor and dyspnea on mild exertion (symptoms of anemia). c. Fever may be present, with no obvious sign of infection. d. Bone pain occurs secondary to marrow infiltration. e. Thrombocytopenia leads to bleeding abnormalities (petechiae and easy bruising). f. Oral and GI hemorrhages begin to occur when the platelet count is below 20  109/L. g. Decreasing levels of polymorphonuclear neutrophils (PMNs) occurring secondary to marrow infiltration may cause frequent infections. i. Infecting organisms may be gram-positive cocci, gram-negative organisms, and Candida species. ii. Mucosal breakdown leads to infection of the skin, gingiva, perirectal tissue, and lung and urinary tracts. h. Hepatosplenomegaly may be present and produce signs and symptoms of early satiety. i. An anterior mediastinal mass is usually indicative of T-cell type ALL and is not typically found in other forms of leukemia. j. Soft-tissue masses of leukemic cells can develop in any area (chloromas). k. Generalized lymphadenopathy may be present. l. Neurologic signs and symptoms associated with leukemic meningitis can occur (headache and nausea, followed by seizures and decreased mentation) but are usually not present at the time of diagnosis. 5.

Laboratory findings

a.

b. c. d. e. f. 6.

Signs typical of pancytopenia (normochromic-normocytic anemia) are present, with the exception of large numbers of lymphoblasts (ALL) or myeloblasts (AML). White blood cell count (WBC) may be
50  109/L or may be as low as 5  109/L; in either case, blastic cells predominate. Serum lactate dehydrogenase and uric acid levels may be increased due to increased cell turnover. Cerebrospinal fluid may reveal leukemic blast cells, increased protein levels, and decreased glucose levels in leukemic meningitis. Bone marrow biopsy confirms the diagnosis. CT scan may be useful in delineating extramedullary sites that are impinging on other structures.

Treatment

a. b.

c.

d. e.

Patients should receive transfusion with the appropriate blood products; platelet count should be maintained above 20  109/L. Fever must be evaluated, and the patient should be placed on broad-spectrum antibiotics until the cause of the fever can be found and infection is either ruled out or appropriately treated. Because fungal infections may also exist, a patient whose condition is unresponsive to antibiotics should receive a trial of amphotericin B; daily serum creatinine levels should be evaluated for the possible nephrotoxicity that occurs with this agent. The use of granulocyte transfusions remains controversial. Fifty percent of children who have ALL are cured with chemotherapy (cytarabine, anthracycline).

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155

f.

Because treatment often leads to increased serum urate levels, allopurinol (which decreases formation of uric acid) and diuretics may be necessary to prevent the formation of urate renal calculi. g. Only 10%30% of patients who have AML survive for more than 5 years disease-free despite treatment with chemotherapy. h. Acute promyelocytic leukemia (a subtype of AML) is often associated with disseminated intravascular coagulopathy; patients who have this subtype often require prophylactic heparin therapy during chemotherapy.

C. CHRONIC LYMPHOCYTIC LEUKEMIA 1.

General characteristics

a.

b. c. d. 2.

Clinical features

a. b. c. d. e. f. 3.

CLL may be discovered incidentally. Patients may initially be seen with signs and symptoms of anemia such as fatigue, pallor, and dyspnea on exertion. Lymphadenopathy may be present. Intercurrent infection (decreased levels of mature PMNs) may be present. Patients who have advanced disease may have easy bruising and gingival bleeding (thrombocytopenia). Hepatosplenomegaly may be noted.

Laboratory findings

a. b. c. d. 4.

CLL is characterized by accumulation of mature-appearing lymphocytes in the peripheral blood and infiltration of these lymphocytes into the marrow, spleen, and lymph nodes. This disease usually occurs in individuals over age 50. The disease is more common in men and is the most common form of chronic leukemia in the United States. CLL is most often caused by a clonal expansion of B cells.

Normochromic-normocytic anemia is present. WBC count ranges between 15 and 200  109/L, with a predominance of mature-appearing lymphocytes. Lymph node biopsy may be necessary to distinguish a normal reactive lymphocytosis from CLL. An M spike shown on protein electrophoresis similar to that seen in multiple myeloma may be present.

Treatment

a. b. c.

d.

Cure is usually not achieved despite chemotherapy. The goal of treatment is palliative. Because progression of the disease is typically slow, patients do not receive therapy unless cytopenia (e.g., significant anemia or thrombocytopenia) or marked systemic symptoms exist. Patients may live 10–15 years after diagnosis of the disease.

D. CHRONIC MYELOGENOUS LEUKEMIA 1.

General characteristics

a. b. c.

CML is characterized by increased numbers of granulocytes (neutrophils). The disease generally runs a mild course (chronic phase) until the development of the blastic phase. CML can occur at any age, but peak incidence occurs between the third and fourth decades of life.

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2.

Clinical features

a. b. c. d. e. f. 3.

Patients may initially be seen with upper left quadrant abdominal discomfort associated with splenomegaly (often palpable on physical examination). Patients have signs and symptoms of anemia, such as pallor, fatigue, and dyspnea on exertion. Lymphadenopathy is typically not present during the chronic phase of the disease. Weight loss and fever may be present. Meningeal leukemia is rare. Blastic phase is associated with marked anemia, thrombocytopenia (easy bruising), and predominance of blasts.

Laboratory findings

a. b.

Normochromic-normocytic anemia is present. Leukocytosis is prominent; myelocytes and metamyelocytes are present (unlike a physiologic leukemoid reaction). c. Basophilia is often prominent. d. Serum vitamin B12 levels and vitamin B12–binding capacity are elevated; this reflects an increase in transcobalamin I that is produced by the leukemic cells. e. Leukocyte alkaline phosphatase level is decreased; this feature distinguishes CML from other myeloproliferative disorders. f. Hyperuricemia occurs due to increased cell turnover. g. Philadelphia chromosome is present in more than 95% of CML patients. h. Bone marrow biopsy reveals a myeloid infiltrate.

4.

Treatment

a. b.

Allogenic stem cell transplant is curative and reasonable in patients with good end-organ function. Imatinib induces apoptosis in leukemic cells and can induce remission in 60% of patients.

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Hematologic Diseases I

Anemias A. GENERAL CHARACTERISTICS 1. Anemias occur because of lack of red blood cell formation, increased red blood cell destruction, blood loss, or an association with a primary disease (Table 9-1). 2. Anemias are best evaluated in terms of red blood cell indices. Anemia types are characterized by a mean corpuscular volume (MCV) as follows: hypochromicmicrocytic anemia (MCV
80), normochromic-normocytic anemia (MCV 80–100), and macrocytic anemia (MCV 100) (Table 9-2). B. CLINICAL FEATURES 1. Anemia types vary in rapidity of onset. 2. Rapid blood loss or hemolysis leads to tachycardia, postural hypotension, faintness, and peripheral vascular constriction (cold, pale extremities). 3. If anemia occurs gradually, the plasma volume expands to accommodate the blood loss or hemolysis, in which case the patient may notice only exertional dyspnea. 4. Pronounced anemia may cause pallor of skin and mucous membranes; jaundice; chelosis (fissuring of the angles of the mouth); beefy red, smooth tongue; and koilonychia (spoon-shaped nails). 5. Additional signs include systolic murmurs and bounding pulses with widened pulse pressures. C. HYPOCHROMIC-MICROCYTIC ANEMIAS 1.

General characteristics

a. b. c.

2.

These anemias are caused by an abnormality in heme or globin synthesis (Figure 9-1). The most common cause is iron deficiency secondary to chronic blood loss or low dietary intake (seen mainly in children or pregnant women). Other causes include anemia of chronic disease, which results in poor iron utilization; sideroblastic anemia, which leads to a block in heme synthesis; and hemoglobinopathies such as sickle-cell disease or defective globin synthesis as seen in the thalassemias.

Iron deficiency

a.

General characteristics i. Iron deficiency is most often secondary to chronic bleeding of the gastrointestinal (GI) tract. ii. It may also be secondary to partial gastrectomy (which impairs iron absorption) or malabsorption syndromes. iii. Patients have the aforementioned clinical features in addition to pica (cravings for ice, clay, or starch). 157

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TABLE 9-1

NORMAL BLOOD MEASUREMENTS

Important Values

Male

Female

Hemoglobin Red blood cells Hematocrit

13.7–17.5 g/dL 4.5–6.5  1012/L 40%–52%

11.5–15.5 g/dL 3.9–5.6  1012/L 35%–47%

b.

c.

3.

Anemia of chronic disease

a.

b.

c.

4.

Laboratory findings i. Red blood cell smear reveals hypochromic-microcytic cells. ii. Increased platelet count may be noted if chronic bleeding is the cause (Table 9-3). iii. Serum iron level is decreased, and total iron binding capacity (TIBC) is elevated; that is, transferrin saturation is
15%, ferritin is decreased, and free erythrocyte protoporphyrin (a precursor of heme that requires iron for formation) is increased. Treatment i. An underlying cause should always be investigated; menstruation should never be assumed to cause a woman’s iron deficiency. ii. Iron salts (e.g., ferrous sulfate), 325 mg three times per day, are indicated. iii. Adequate therapy results in an increase of 1 g of hemoglobin (Hgb) in 2 weeks; therefore, noncompliance or continued bleeding may be the cause if the patient is unresponsive to therapy. General characteristics i. Anemia of chronic disease may be normochromic-normocytic or hypochromic-microcytic. ii. Development of this anemia type occurs 1–2 months after onset of chronic disease. iii. Chronic disease leads to decreased availability of iron for erythropoiesis. Laboratory findings i. Serum iron is decreased. ii. Unlike iron deficiency, serum ferritin level is elevated, and TIBC is decreased. Treatment i. Usually, the anemia is mild and requires no treatment. ii. Anemia resolves when the underlying disease is treated.

Sideroblastic anemia

a.

General characteristics i. Sideroblastic anemia is caused by a defect in heme synthesis that leads to iron overload secondary to ineffective erythropoiesis. ii. This type of anemia is most often secondary to agents such as alcohol or lead.

TABLE 9-2

NORMAL RED CELL INDICES

Red Blood Cell Indices

Value

Mean corpuscular Hgb Mean corpuscular volume Mean corpuscular Hgb concentration

27–34 pg 80–100 fL 30–35 g/dL

Hgb, hemoglobin

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Peripheral smear

Red blood cell indices

MACROCYTIC

NORMOCYTIC

MICROCYTIC

Are reticulocytes increased?

Are reticulocytes increased?

Is iron low?

no

yes

HEMORRHAGE

no

yes

IRON DEFICIENCY

Megaloblastic marrow?

ANEMIA OF CHRONIC DISEASE

HEMOLYSIS yes

B12 OR FOLATE DEFICIENCY

POSTHEMORRHAGIC ANEMIA

no HYPOPLASTIC MARROW

yes

PRIOR HEMOLYSIS

SIDEROBLASTIC ANEMIA

HEMOGLOBINOPATHIES

no

Bone marrow aspiration and biopsy

PRIOR HEMORRHAGE

Abnormal marrow

MYELOMA METASTASES MYELOFIBROSIS LEUKEMIA RENAL FAILURE (hypoplastic marrow)

Normal marrow

HYPOTHYROID

LIVER DISEASE

ANEMIA OF CHRONIC DISEASE ● Figure 9-1. Diagnostic approach to anemias.

THALASSEMIA

159

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TABLE 9-3

NORMAL CONCENTRATIONS OF BLOOD COMPONENTS

Other Parameters

Values

Platelets Reticulocyte count Segmented neutrophils Bands Lymphocytes Monocytes Eosinophils Basophils

150–440 109/L 0.5%–2.0% (of normal RBCs) 2.5–7.5  109/L (50%–70%) 0.1–0.6  109/L (2%–6%) 1.0–5.0  109/L (20%–45%) 0.1–1.0  109/L (2%–9%) 0.0–0.4  109/L (0%–4%) 0.0–0.2  109/L (0%–2%)

RBC, red blood cells.

b.

c.

5.

Laboratory findings i. Peripheral smear reveals hypochromic-microcytic red blood cells and rings within the red blood cells (ringed sideroblasts). ii. Serum iron and ferritin levels are elevated. Treatment i. The offending agents should be discontinued. ii. Transfusions may be necessary if the degree of anemia is significant.

Sickle-cell disease

a.

b.

c.

d.

General characteristics i. Sickle-cell disease is caused by a mutated form of the -globin chain (Hgb S), which is insoluble under deoxygenated conditions and causes sickle-shaped red blood cells. ii. The disease is most common in African Americans. iii. Individuals may be homozygous for the defective gene and have severe anemia, or they may be heterozygous and have mild anemia. Clinical features i. Signs and symptoms begin in infancy when fetal hemoglobin (Hgb F) levels decrease. ii. Signs include painful crises, swelling of extremities and spleen, and bony, pulmonary, and cerebral infarctions. iii. Microvascular occlusion from abnormally shaped red blood cells (RBCs) leads to infarction of virtually any organ. iv. Chronic hemolysis leads to increased incidence of cholelithiasis with bilirubin stones. v. Splenic infarction leads to increased susceptibility to encapsulated organisms (e.g., Streptococcus pneumoniae). Laboratory findings i. Peripheral smear reveals sickle-shaped cells, elevated reticulocyte count (20%), and nucleated RBCs. ii. Serum analysis reveals elevated bilirubin level (mainly conjugated) and a low free haptoglobin (hemoglobin-binding protein) level. iii. Hemoglobin electrophoresis reveals the abnormal Hgb S. Treatment i. Treatment is largely symptomatic. ii. Painful crises are managed with oxygen therapy, fluids, correction of acidosis, and analgesics. iii. Because sickle-cell crisis itself does not cause fever, infection must be suspected in a patient who has fever, because the infection can precipitate a crisis.

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iv. Pneumococcal vaccine must be administered to all patients. v. Although acute crises are not alleviated by transfusions, chronic exchange transfusions may decrease iron overload, reduce anemia, and lessen the degree of sickling. vi. Hydroxyurea increases fetal Hgb and improves symptoms. 6.

Thalassemias

a.

b.

c.

General characteristics i. Two types of thalassemias exist: -thalassemia and -thalassemia; both are congenital. ii. Each type may occur homozygously (more severe disease) or heterozygously (minor disease). iii. The minor forms are typically benign and require no therapy. -Thalassemia major i. General characteristics (a) Virtually all patients die before the third decade of life. (b) A defect in the  subunit of hemoglobin → precipitation of  chains → hemolytic red blood cell destruction → ineffective erythropoiesis → hyperplastic bone marrow, liver, and spleen. (c) This type of thalassemia is most common in individuals of Mediterranean descent. ii. Clinical features (a) Signs and symptoms do not occur until age 4–6 months, when the switch from fetal to adult hemoglobin occurs. (b) Patients have signs and symptoms of severe anemia. (c) Patients have marked wasting and a malnourished appearance. (d) Chipmunk facies are present. (e) Marked hepatosplenomegaly occurs. (f) Growth retardation and fractures occur secondary to excessive bone marrow expansion. iii. Laboratory findings (a) Hemoglobin analysis reveals persistence of Hgb F. (b) Peripheral smear reveals hypochromic-microcytic anemia, many nucleated red blood cells, and anisocytosis. (c) Hgb level is usually between 3 and 6 mg/dL in the untreated state. iv. Treatment (a) Treatment of major disease involves transfusion therapy. (b) Desferrioxamine may be required to prevent iron overload from repeated transfusions. (c) Splenectomy may be required to decrease red blood cell destruction. -Thalassemia i. Two clinically significant forms of the disease exist: Hgb H disease and Bart Hgb (4 chains). ii. Bart Hgb leads to hydrops fetalis; in utero, the total absence of  chains leads to 100% -Hgb, which binds oxygen tightly and therefore deprives tissues of oxygen. iii. Hgb H disease is characterized by 4 chains that tend to precipitate within the red blood cells (Heinz bodies), which leads to hemolytic anemia. (a) Signs and symptoms are similar to -thalassemia, but they are often less severe. (b) Treatment is similar to that for -thalassemia.

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D. NORMOCHROMIC-NORMOCYTIC ANEMIAS 1.

General characteristics

a. b. c. d.

2.

Aplastic anemia

a.

b.

c.

d.

3.

These disorders can be classified as anemias in which bone marrow production is impaired and anemias in which red blood cell production is normal. Anemias in which bone marrow production is impaired include aplastic anemia, myelophthisic syndromes, and red blood cell aplasia. Normochromic-normocytic anemias may also occur as a result of anemia of chronic disease (see hypochromic-microcytic anemias, I C). Anemias in which erythropoietic response is normal include anemia of hemorrhage and hemolytic anemias (may be macrocytic due to the predominance of reticulocytes; see macrocytic anemias, I E). General characteristics i. Aplastic anemia produces a peripheral pancytopenia, but bone marrow architecture is unaffected. ii. This form of anemia may be inherited (Fanconi anemia), secondary to viral infection (hepatitis, Epstein-Barr virus [EBV]), or drug-induced (cytosine arabinoside, chloramphenicol, phenylbutazone). Clinical features i. Severity of signs and symptoms reflects the progression of the disease. ii. Neutropenia predisposes patients to infection. iii. Patients with thrombocytopenia may have petechiae and purpura. Laboratory findings i. Corrected reticulocyte count is
1%, platelet count is
20.0  109/L, and polymorphonuclear neutrophil (PMN) count is
0.5  109/L. ii. Bone marrow aspiration reveals a hypoplastic marrow without evidence of infiltration. Treatment i. Blood transfusions should be given as required. ii. Bone marrow transplantation may also be effective if the appropriate donor is found.

Myelophthisic syndromes (myelofibrosis)

a.

b.

c.

d.

General characteristics i. Myelophthisic syndromes are caused by invasion of the bone marrow by infection (tuberculosis), tumor (breast, lung, prostate, thyroid, leukemia, lymphoma, myeloma), or fibrosis. ii. Invasion leads to anemia, thrombocytopenia, and leukocytosis. Clinical features i. Patients experience an insidious onset of weight loss, weakness, and pallor. ii. Splenomegaly → platelet trapping → bleeding and petechiae. Laboratory findings i. Peripheral smear reveals normochromic-normocytic cells, normoblasts, teardrop cells, inappropriately decreased reticulocyte count, and elevated white blood cell (WBC) count with a “shift to the left” (immature WBCs). ii. Bone marrow aspiration yields a dry tap due to the infiltration by abnormal tissue. iii. Bone marrow biopsy must therefore be performed to reveal the abnormal marrow architecture. Treatment i. The primary pathologic process must be treated. ii. Blood transfusions may be necessary.

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Red blood cell aplasia

a. b. c. d. e. f.

Red blood cell aplasia is characterized by anemia with no evidence of reticulocytosis. Platelet and WBC counts are normal; bone marrow is also normal, except for the absence of erythroid precursors. Red blood cell aplasia is associated with immunologic deficiency states (including thymoma). It may also be drug-induced (chlorpropamide, gold, isoniazid). Clinical features are similar to those of anemia. Treatment involves red blood cell transfusions.

E. MACROCYTIC ANEMIAS 1. Macrocytic anemias include anemias caused by reticulocytosis, that is, acute hemorrhage and hemolytic anemias, as well as the megaloblastic anemias. 2.

Acute hemorrhage

a. b. c. d. 3.

An acute hemorrhage is characterized by a clinically apparent site of bleeding (trauma, GI tract). Patients develop compensatory reticulocytosis. Patients have signs and symptoms of acute blood loss, that is, tachycardia, hypotension, sweating, pallor, and cold and clammy extremities. Rapid replacement of blood products may be required if hemorrhage is significant.

Hemolytic anemias

a.

Intravascular hemolytic anemia i. General characteristics (a) This type of anemia is caused by acute transfusion reactions (antibody-mediated), prosthetic heart valve dysfunction, cold agglutinin disease, or clostridial infection. (b) RBC destruction → free hemoglobin binding to haptoglobin, hemopexin, and/or albumin (methemoglobin) → clearance by the liver; the binding capacity of haptoglobin/albumin is often exceeded, which leads to hemoglobinuria. (c) Chronic hemolysis leads to renal tubular cells filled with hemosiderin that is sloughed into urine, which leads to iron deficiency. ii. Clinical features (a) Patients have signs and symptoms of anemia. (b) Restlessness, anxiety, flushing, fever and chills, headache, chest or lumbar pain, tachypnea, and nausea may indicate an acute transfusion reaction. (c) The transfusion reaction may progress to shock, renal failure, and disseminated intravascular coagulation (DIC). iii. Laboratory findings (a) Serum free haptoglobin and hemopexin levels are decreased. (b) Plasma and urine hemoglobin levels are elevated, lactate dehydrogenase (LDH) level is elevated, and total and indirect (unconjugated) bilirubin levels are elevated. (c) Peripheral smear reveals macrocytic anemia with reticulocytosis, nucleated red blood cells, and cell fragments. (d) Coombs test (which detects the presence of RBC antibodies) is positive if the anemia is antibody-mediated; the test is negative if the anemia is secondary to shearing from prosthetic valve dysfunction.

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b.

c.

iv. Treatment (a) Immediate therapy with an osmotic diuretic to decrease the risk of renal damage is necessary. (b) Patients should be hospitalized for appropriate management of shock and DIC. Extravascular hemolysis i. General characteristics (a) This disease is caused by the abnormally early removal of RBCs by the spleen and liver. (b) Because only a small amount of Hgb is released into the blood vessels to bind with other proteins, iron deficiency is less likely to occur. (c) Extravascular hemolysis is often associated with antibodies to the Rhesus factor. ii. Clinical features (a) Signs and symptoms usually include malaise and fever. (b) Shock and renal failure almost never occur. (c) Patients have mild-to-moderate splenomegaly. iii. Laboratory findings (a) Haptoglobin level is only slightly decreased (in contrast to intravascular hemolysis), and hemoglobinemia or hemoglobinuria does not occur. (b) Indirect (unconjugated) bilirubin level is elevated if the hemolysis is brisk. (c) Serum LDH level is elevated. (d) Reticulocytosis is present. iv. Treatment is conservative and usually does not include transfusion. Intracorpuscular abnormalities i. Hereditary spherocytosis (a) General characteristics (i) Hereditary spherocytosis is the most common RBC membrane defect. (ii) This disease is most common in Europeans; the severe form is autosomal dominant (therefore, the disease is often linked to a prominent family history). (iii) Increased splenic destruction of RBCs occurs secondary to altered sodium cell membrane permeability and RBC shape; because RBCs are destroyed by the spleen, this disease is considered to be a form of extravascular hemolysis. (iv) Cells have a decreased surface-to-volume ratio. (b) Clinical features (i) Patients who have the severe form are first seen in childhood with jaundice and fatigue. (ii) Splenomegaly is present. (iii) Patients have a high incidence of gallstones secondary to increased bilirubin turnover. (iv) Aplastic crisis can develop. (c) Laboratory findings (i) Peripheral smear reveals reticulocytosis and spherocytes. (ii) Serum analysis indicates indirect hyperbilirubinemia. (iii) During the osmotic fragility test, spherocytes lyse at lower concentrations of sodium chloride than do normal RBCs.

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(d) Treatment (i) Transfusions are necessary during aplastic crisis. (ii) Splenectomy decreases hemolysis and therefore restores the RBC life span to nearly normal; pneumococcal vaccine is required due to increased susceptibility in splenectomized patients. ii. Glucose-6-phosphate dehydrogenase (G6PD) deficiency (a) General characteristics (i) G6PD is the most common RBC enzyme defect. (ii) Incidence is higher in African American individuals and persons of Mediterranean descent. (iii) This X-linked disorder causes a buildup of intracellular methemoglobin, which precipitates in the RBC → these precipitates are cleared in the spleen via microcytosis of red blood cell membrane → microspherocytes. (iv) Lack of this enzyme also leads to a buildup of intracellular oxidants that causes cell lysis (intravascular hemolysis). (v) Exacerbations are brought on by infection, certain drugs (antimalarials, sulfonamides), and fava beans. (b) Clinical features (i) Patients have splenomegaly and an increased incidence of cholelithiasis. (ii) Clinical features of intravascular hemolysis may occur. (c) Laboratory findings (i) Peripheral smear reveals microspherocytes (not normal-sized as seen in hereditary spherocytosis), reticulocytosis, and Heinz bodies. (ii) Serum analysis reveals decreased haptoglobin levels, hemoglobinemia, and indirect bilirubinemia. (iii) Decreased intracellular G6PD activity is evident. (d) Treatment (i) Therapy is symptomatic; fluids and transfusions are given as required. (ii) Patients should avoid oxidants. 4.

Megaloblastic anemias

a.

b.

General characteristics i. These anemias are commonly caused by B12 and/or folate deficiency. ii. Impaired deoxyribonucleic acid synthesis → pancytopenia. iii. Destruction of developing cells by hemolysis leads to ineffective erythropoiesis. iv. Folate deficiency may be secondary to a poor diet (commonly seen in alcoholics), malabsorption syndromes, or certain drugs (phenytoin); body stores of folate last 2–4 months; therefore, folate deficiency occurs before B12 deficiency. v. B12 deficiency is often associated with pernicious anemia (indicated by the presence of anti–intrinsic factor [IF] antibodies), previous gastrectomy, or small bowel disease (Crohn disease, tropical sprue); B12 deficiency causes subacute combined degeneration of the spinal cord. Clinical features i. B12 and folate deficiencies lead to sore tongue, diarrhea, and anorexia. ii. Lack of B 12 leads to peripheral nerve and spinal neuron demyelination, which causes paresthesias, weakness, diminished position,

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c.

d.

II

and vibration sense and ataxia; effects on the cerebrum may lead to dementia. iii. Signs and symptoms of anemia are seen in both deficiencies. Laboratory findings i. Serum B12 or folate levels are decreased, and LDH level is elevated; hyperbilirubinemia is present. ii. Peripheral smear reveals macrocytic anemia with decreased reticulocyte response, leukopenia, hypersegmented PMNs, and large platelets with thrombocytopenia. iii. Schilling test result is positive in pernicious anemia (B12 deficiency). (a) In this test, the patient is given a dose of nonlabeled vitamin B12, followed by an oral dose of radiolabeled vitamin B12; a 48-hour urine sample is then collected. (b) If
5% labeled vitamin B12 is found in the urine, malabsorption of vitamin B12 is suggested. (c) The defect is corrected with oral administration of intrinsic factor if the patient has pernicious anemia. (d) If no correction occurs with IF treatment, malabsorption within the small bowel is likely. iv. Bone marrow changes (increased marrow iron and hyperplasia, with increased mitotic figures) are evident, but their presence is not necessary for diagnosis. Treatment i. Administration of the appropriate vitamin leads to bone marrow changes within 24–48 hours, reticulocytosis within 3–4 days, normalization of leukopenia and thrombocytopenia within 10 days, decreased bilirubin and LDH levels within 1–3 weeks, correction of anemia within 1–2 months, and correction of neurologic deficits (in B12 deficiency) within 6–12 months if neuronal death has not occurred. ii. In pernicious anemia, administration of vitamin B12 must be intramuscular because oral absorption is defective. iii. The clinician must not assume that a megaloblastic anemia is due to folate deficiency without checking for B12 deficiency; folate therapy will not correct the neuronal damage caused by a lack of vitamin B12.

Hematocrit Disorders A. GENERAL CHARACTERISTICS 1. These disorders result from increased red blood cell mass, that is, elevated hematocrit. 2. Elevated hematocrit may be secondary to stress (relative) erythrocytosis or absolute erythrocytosis. B. STRESS ERYTHROCYTOSIS 1.

General characteristics

a. b. 2.

Stress erythrocytosis typically affects obese, hypertensive, tense men. This condition is not a true erythrocytosis because red blood cell mass is normal (plasma volume is contracted).

Clinical features

a. b.

Signs and symptoms include dizziness, headache, epistaxis, and a characteristic “ruddy” cyanosis. Splenomegaly is absent (unlike polycythemia vera).

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167

Laboratory findings

a. b. 4.

Hematocrit is between 55% and 60%. Platelets, leukocytes, and red blood cell mass are normal. Treatment is unnecessary because the condition is generally benign.

C. ABSOLUTE ERYTHROCYTOSIS 1.

General characteristics

a. b.

2.

Polycythemia vera

a.

b.

c.

III

This condition is characterized by a definite increase in RBC mass. Causes include chronic hypoxia (lung disease, heart failure), erythropoietinsecreting tumors (renal tumors), and polycythemia vera (which is caused by autonomous bone marrow). Clinical features i. This condition causes hyperviscosity, which leads to decreased cerebral blood flow; patients have tinnitus, light-headedness, and (rarely) stroke. ii. Congestive heart failure may be present. iii. Thrombosis may be present. Laboratory findings i. RBC mass is elevated, and arterial oxygen saturation is 92% (i.e., the erythrocytosis is not secondary to hypoxia); splenomegaly is present. ii. Alkaline phosphatase and serum vitamin B12 levels are elevated; leukocytosis and thrombocytosis are also present. iii. Erythropoietin is nearly absent. Treatment i. Repeated phlebotomies are necessary to bring the hematocrit to
50%. ii. Chemotherapy (hydroxyurea) may be necessary for resistant cases.

Leukocyte Disorders A. LYMPHOPENIA 1.

General characteristics

a. b.

c. d. 2.

Clinical features

a. b.

c. 3.

Lymphopenia may be secondary to another condition (acute infection, elevated cortisol level), but antibody production is not affected. Lymphopenia that causes immunodeficiency is most likely secondary to human immunodeficiency virus infection or a congenital disease (if signs and symptoms appear in infancy). Lymphopenia is usually caused by a lack of T cells (thymic hypoplasia). B cells may also be deficient (Bruton agammaglobulinemia). T-cell deficiency may be associated with rashes, eczema, and mucocutaneous candidiasis. In acquired immunodeficiency syndrome, opportunistic viral, fungal, and protozoal infections predominate (Pneumocystis carinii pneumonia, Mycobacterium avium-intracellulare pneumonia or disseminated disease, hepatitis, cytomegalovirus, herpes). B-cell deficiency is associated with repeated infections by encapsulated organisms (S. pneumoniae).

Laboratory findings

a. b.

Lymphocyte count
1.5  109/L (or
10%). Bone marrow is usually normocellular (5%–20% of bone marrow cells are lymphocytes).

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c. d. 4.

T-cell count is decreased. Quantitation of immunoglobulins is useful in detecting B-lymphocyte deficiencies.

Treatment

a. b.

Thymic transplantation for thymic hypoplasia has some benefit. Therapy is supportive with appropriate antibiotics.

B. LYMPHOCYTOSIS 1.

General characteristics

a. b. 2.

Clinical features

a. b. c. 3.

Malaise, fever, exanthem, and pharyngitis are common. If the cause is reactive, duration is
6 weeks. Lymphadenopathy, usually cervical, may be present.

Laboratory findings

a. b. c. 4.

Lymphocytosis may be caused by infection, that is, a reactive lymphocytosis caused by EBV, hepatitis, or cytomegalovirus. Lymphocytosis can also be caused by leukemias and lymphomas.

Peripheral smear that reveals anisocytotic, atypical lymphocytes indicates a reactive process; morphologic monotony suggests neoplastic disease. Serologic testing for viral causes can help differentiate between reactive and neoplastic disease. T- and B-cell immunocytochemistry may identify malignant markers present on lymphocytes.

Treatment

a. b.

For reactive lymphocytosis, treatment is supportive, because the disease resolves spontaneously. Chemotherapy for neoplasms may be required (see Chapter 8, Oncologic Diseases).

C. NEUTROPHILIA 1.

General characteristics

a. b. c. d. 2.

Clinical features

a. b. 3.

Neutrophilia is usually secondary to infection (neutrophil count is usually 20  109/L). Neutrophilia may also be present in inflammatory diseases. The most common malignancy associated with neutrophilia is chronic myelogenous leukemia (CML). Neutrophilia can also be drug-induced (e.g., heparin, digitalis). If the cause is infectious, patients have signs and symptoms of infection, that is, fever, localized pain, swelling, and purulent exudates. Splenomegaly is present in CML.

Laboratory findings

a. b. c.

d.

WBC count is elevated in CML. Serum alkaline phosphatase level is decreased in CML. Bone marrow aspiration is indicated if WBC 20  109/L or increased intracellular granules are noted. i. Bone marrow cellularity is normal if neutrophilia is secondary to acute infection. ii. The presence of a significant number of blasts suggests CML. Karyotyping should be performed to look for the Philadelphia chromosome (marker for CML).

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169

Peripheral WBC count 100  109/L occurs with CML, as does thrombocytosis.

Treatment

a. b.

Infection is treated with appropriate antibiotic therapy. CML should be treated appropriately (see Chapter 8, Oncologic Diseases).

D. NEUTROPENIA 1.

General characteristics

a.

b. c. 2.

Clinical features

a. b. c. d. 3.

Neutropenia is apparent in agranulocytosis (neutrophil count
0.5  109/L). Signs and symptoms include high fever, necrotic pharyngitis, regional lymphadenopathy, and proctitis. Cellulitis, pneumonia, and urinary tract infections ensue. Mortality is high without treatment.

Laboratory findings

a. b.

c. 4.

Neutropenia is most commonly secondary to exogenous factors such as infections (hepatitis, influenza) or certain drugs (phenothiazines, antithyroid drugs, chemotherapeutic agents). Neutropenia is often a feature of collagen vascular diseases (e.g., systemic lupus erythematosus). Neutropenia is also a feature of leukemias, lymphomas, or myelofibrosis.

Peripheral neutrophil count is
1.5  109/L. Hypocellular marrow revealed after bone marrow aspiration and biopsy suggests chemical-induced toxicity; evidence of neoplastic disease or myelofibrosis may be apparent. Presence of antinuclear antibodies indicates that collagen vascular diseases may be present.

Treatment

a. b. c.

Patients should discontinue possible toxic agents. Infection is treated with broad-spectrum antibiotics (ampicillin and gentamicin are common choices). Granulocyte transfusions are usually of little benefit.

E. DYSFUNCTIONAL NEUTROPHILS 1.

General characteristics

a. b. c. d.

2.

Clinical features

a. b. 3.

Although these conditions are rare, they have serious clinical effects. These conditions include chronic granulomatous disease (CGD) and myeloperoxidase deficiency. CGD is X-linked recessive; in this disease, PMNs lack superoxide, which causes increased susceptibility to Staphylococcus, gram-negative organisms, and fungi. Myeloperoxidase deficiency is autosomal recessive; in this disease, patients have an increased susceptibility to catalase-positive organisms (e.g., Staphylococcus aureus). Clinical features are secondary to infection. Patients may have fever, regional lymphadenopathy, and eczematoid skin eruptions.

Laboratory findings

a. b.

Granulocytosis indicates infection. Bone marrow aspiration reveals granulomas in CGD and hyperplasia in infection.

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c.

4.

IV

In the nitroblue tetrazolium dye test, normal PMNs digest the dye, which causes blue granule formation; digestion and granule formation do not occur in CGD. d. Myeloperoxidase stain is not apparent in myeloperoxidase deficiency. Treatment with penicillin, vancomycin, or trimethoprim-sulfamethoxazole can decrease duration and frequency of recurrent infections.

Hemostasis and Coagulation Disorders A. THROMBOCYTOPENIA 1. Thrombocytopenia is the most common cause of abnormal bleeding. 2. Bleeding time is prolonged when platelet count is
100  109/L; petechiae and purpura may occur when the platelet count is 20–50  109/L, and risk of severe hemorrhage increases if platelet count is
20  109/L. 3. Bleeding occurs at superficial sites, for example, skin, mucous membranes, and genitourinary and GI tracts. 4. Thrombocytopenia is caused by impaired platelet production, abnormal platelet pooling, or increased peripheral destruction. a. Increased peripheral destruction i. Increased peripheral destruction is the most common cause of thrombocytopenia and may be immune-mediated (or idiopathic) or due to thrombocytopenic purpura (discussed next), sepsis, platelet transfusions, or certain drugs (e.g., heparin). ii. Idiopathic thrombocytopenic purpura (ITP) (a) General characteristics (i) No exogenous cause for platelet destruction is found in the patient’s history. (ii) Acute form is associated with viral infection in children and resolves spontaneously. (iii) Adult form is chronic, does not resolve spontaneously, and may be associated with other autoimmune diseases. (iv) Patients develop mucosal bullae and purpura, with mucocutaneous bleeding. (b) Laboratory findings (i) Peripheral smear reveals thrombocytopenia with large platelets; other cell lines are normal. (ii) Bone marrow aspiration/biopsy reveals increased megakaryocytes. (iii) Platelet-associated immunoglobulin G indicates immunemediated disease. (c) Treatment (i) Patients should avoid drugs that act as platelet antagonists (e.g., aspirin). (ii) Corticosteroids are recommended for severe thrombocytopenia. (iii) Transfusions are reserved only for patients who have severe bleeding because the survival time of transfused platelets is short. (iv) Plasmapheresis is generally not effective. (v) Cyclophosphamide or azathioprine may be necessary for refractory ITP.

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b.

c.

171

iii. Heparin-induced thrombocytopenia (a) Type I causes mild thrombocytopenia through direct agglutination of platelets and is short-lived, requiring no treatment. (b) Type II results from antibody to platelet factor 4–heparin complex, which causes platelet activations. This may lead to thrombosis and tissue necrosis. Treatment requires cessation of heparin and use of argatroban (thrombin inhibitor that does not cross-react with heparin). Abnormal platelet pooling i. General characteristics (a) Abnormal platelet pooling is most commonly due to splenic sequestration. (b) Splenomegaly (often due to cirrhosis with portal hypertension) leads to increased platelet sequestration. ii. Laboratory findings (a) Thrombocytopenia in a patient with hypersplenism suggests the diagnosis. (b) Bone marrow aspiration/biopsy reveals an adequate number of marrow megakaryocytes. iii. Treatment (a) Usually, no treatment is required because the degree of thrombocytopenia is not severe. (b) Platelet transfusion is of little value because the transfused platelets will also be sequestered. (c) Splenectomy may be of benefit, especially if splenic enlargement causes discomfort. Impaired platelet production i. General characteristics (a) Impaired platelet production commonly occurs secondary to administration of certain drugs (e.g., ethanol, thiazide diuretics, chemotherapy). (b) The condition is also associated with vitamin B12 and folate deficiency or may be secondary to bone marrow disease (e.g., myelofibrosis or bone marrow aplasia), therefore affecting other cell lines. ii. Laboratory findings (a) Bone marrow biopsy is necessary if no obvious drug or vitamin deficiency is present that reveals bone marrow disease. (b) Thrombocytopenia is evident on peripheral smear. iii. Treatment (a) Patients should discontinue the offending agent or receive treatment for the underlying disease. (b) Platelet transfusion is indicated if bleeding is present. (c) Vitamin B12 and/or folate supplementation is indicated if required.

B. PLATELET DYSFUNCTION 1.

General characteristics

a. b. 2.

Platelet dysfunction is most commonly caused by certain drugs (e.g., acetylsalicylic acid and other nonsteroidal anti-inflammatory drugs [NSAIDs]). This condition is also seen in uremia and is therefore not uncommon in chronic renal failure.

Laboratory findings

a. b.

Peripheral smear is normal (normal number of platelets). Platelet function study results are abnormal.

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3.

Treatment

a. b.

The offending agent should be discontinued. Dialysis may benefit patients who have uremia.

C. PLATELET CONSUMPTION SYNDROMES 1.

Thrombotic thrombocytopenic purpura (TTP)

a.

b.

c.

d. 2.

Hemolytic uremic syndrome (HUS)

a. b. c. 3.

General characteristics i. TTP usually affects young women. ii. A viral prodrome is common. iii. Presence of hyaline thrombi in arterioles without vessel wall inflammation (i.e., not a vasculitis) → microvascular disease. iv. Extensive activation of the coagulation system does not occur. Clinical features include a pentad of symptoms and signs: thrombocytopenia, microangiopathic hemolytic anemia, neurologic abnormalities, renal dysfunction, and fever. Laboratory findings i. Peripheral smear reveals severe thrombocytopenia, schistocytes, fragmented RBCs (due to hemolysis), and increased reticulocytes. ii. Coombs test is negative (the hemolysis is not immune-related). iii. Signs of intravascular hemolysis are present, including elevated serum LDH and bilirubin levels, hemoglobinemia, and hemoglobinuria. iv. Gingival biopsy may reveal diagnostic histopathologic changes characteristic of the disease. Treatment involves exchange transfusion or plasmapheresis coupled with fresh frozen plasma; this therapy has improved outcome. HUS is similar to TTP. HUS occurs in children. Because this disease is localized to the kidney, no neurologic abnormalities occur; otherwise, HUS has the same clinical picture as TTP.

Disseminated intravascular coagulation

a.

b.

c.

General characteristics i. In DIC, an activated coagulation system leads to abnormal formation of excessive thrombin within the circulation → consumption of coagulation factors and platelet, with activation of the fibrinolytic system. ii. DIC occurs secondary to other conditions (e.g., amniotic fluid emboli, meningococcemia, sepsis, metastatic malignancy, trauma). Clinical features i. Clinical features depend on balance between intravascular coagulation and fibrinolysis. ii. Extensive skin and mucous membrane bleeding and shock occur if coagulation predominates. iii. Less frequently, thrombosis predominates, which leads to extensive clotting and peripheral acrocyanosis. Laboratory findings i. Peripheral smear reveals thrombocytopenia, schistocytes, and fragmented red blood cells consistent with intravascular traumatic hemolysis. ii. Prothrombin (PT), partial thromboplastin (PTT), and bleeding times are prolonged (Table 9-4). iii. Serum analysis indicates decreased fibrinogen levels, elevated fibrin degradation products, and decreased clotting factors.

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TABLE 9-4

173

DIAGNOSTIC SUMMARY OF BLEEDING PARAMETERS

Platelet Count

Bleeding Time

PTT

PT

Likely Diagnosis

Decreased Normal Normal Normal Normal

Increased Increased Normal Increased Normal

Normal Normal Increased Increased Increased

Normal Normal Normal Normal Increased

Thrombocytopenia Thrombocytopathia Hemophilia A VWD Liver disease, lack of vitamin K, heparin therapy

PT, prothrombin time; PTT, partial thromboplastin time; VWD, von Willebrand disease.

d.

Treatment i. The primary cause should be reversed if possible; for example, antibiotics for sepsis. ii. Fresh frozen plasma to replace clotting factors and platelets to correct thrombocytopenia are indicated in patients who have excessive bleeding. iii. Patients in whom thrombosis predominates need prompt anticoagulation therapy with intravenous heparin.

D. HEREDITARY COAGULOPATHIES 1.

Hemophilia A

a.

b.

c.

d.

2.

General characteristics i. Hemophilia A is the most common hereditary coagulopathy. ii. The disease is X-linked recessive. iii. In hemophilia A, VIIIpro (the procoagulant portion of the factor VIII molecule) is deficient, whereas VIIIag (the antigenic portion of the factor VIII molecule) is present in normal amounts. Clinical features i. Patients have a positive family history. ii. Patients are usually men because the disease is X-linked recessive. iii. Bleeding occurs into soft tissues, muscles, and weight-bearing joints. iv. Bleeding occurs hours or days after injury and may persist for days to weeks, which may lead to compartment syndromes. v. Hematuria may also occur. Laboratory findings i. Bleeding parameters: PTT is prolonged (reflects function of the intrinsic coagulation pathway), PT is normal (reflects function of extrinsic and common pathways), and bleeding times are normal (reflects platelet function). ii. Levels of VIIIpro are decreased, and VIIIag levels are normal. Treatment i. Patients should avoid platelet-inhibiting drugs (e.g., NSAIDs). ii. Factor VIII concentrates or cryoprecipitates are effective in treating bleeding and should be given before any surgical or dental procedure.

von Willebrand disease

a.

General characteristics i. This disease is autosomal dominant with variable penetrance. ii. Both VIIIpro and VIIIag levels are decreased. iii. Because VIIIag is necessary for normal platelet aggregation, lack of VIIIag causes signs and symptoms similar to those conditions with defective platelet function.

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b.

c.

d.

Clinical features i. Both males and females are affected. ii. Patients have a mixed bleeding picture, with both mucocutaneous bleeding and soft-tissue bleeding with hemarthrosis. Laboratory findings i. PTT and bleeding time are prolonged; PT is normal. ii. Serum VIIIag and VIIIpro levels are decreased. Treatment involves cryoprecipitate therapy because factor VIII concentrates are rich in VIIIpro but poor in VIIIag.

E. ACQUIRED COAGULOPATHIES 1.

General characteristics

a. b. c. 2.

Acquired coagulopathies usually involve multiple coagulation factor deficiencies. The common deficiencies are the vitamin K–dependent factor deficiencies. Other causes include DIC (see IV C 3), presence of lupus inhibitor, and antifactor VIII antibody–mediated coagulopathy.

Vitamin K–dependent factor deficiencies

a.

b.

c.

d.

General characteristics i. Vitamin K acts as a cofactor in the final step of the synthesis of factors II, VII, IX, and X by the liver. ii. This deficiency can occur secondary to liver failure; malabsorption of vitamin K (as with biliary obstruction that impairs absorption of fat-soluble vitamins A, D, E, and K); malnutrition (common in intensive care unit patients); and the use of certain drugs (sodium warfarin). Clinical features i. Features of the primary disorder typically predominate. ii. Soft-tissue bleeding with hemarthrosis may occur if deficiencies are severe. Laboratory findings i. PT and PTT are prolonged; bleeding time is normal. ii. Evidence of liver disease may be present (e.g., elevated liver enzyme levels). iii. Serum levels of vitamin K and factors II, VII, IX, and X are decreased. Treatment i. The underlying cause must be treated. ii. A dose of 10 mg of parenteral vitamin K restores production of clotting factors within 8–10 hours. iii. Severe hemorrhage can be treated with fresh frozen plasma.

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10

Neurologic Diseases I

Cerebrovascular Disease A. STROKE 1.

General characteristics

a.

b.

c. d. e.

2.

May be ischemic (arterial thrombosis, venous thrombosis, and arterial embolism) or hemorrhagic (intracerebral hemorrhage or subarachnoid hemorrhage) (Figure 10-1). A stroke can cause permanent or temporary neurologic deficits. i. Patient may have a permanent neurologic deficit. ii. Patient may have transient ischemic attacks (TIA, defined as a neurologic deficit that persists for
24 hours). iii. Patient may have a reversible ischemic neurologic deficit (RIND, defined as a neurologic deficit that slowly resolves over days to weeks). Stroke incidence increases with age. Risk factors are divided into major and minor contributors (Table 10-1). Lacunar strokes are caused by occlusion of small, penetrating intracerebral arteries and are most commonly associated with hypertension or diabetes mellitus.

Clinical features

a.

b.

c.

d. e. f.

g.

Any of the following signs and symptoms may be present: sudden onset of neurologic deficit, headache, loss of consciousness, speech disturbance such as dysarthria and aphasia, homonymous hemifield visual deficits, and contralateral motor and/or sensory deficits. Signs and symptoms associated with the brain stem or cerebellum include dysarthria, dysphagia, ataxia, diplopia, vertigo, nausea, nystagmus, ipsilateral numbness, and contralateral motor deficits. Infarcts involving the middle cerebral artery can result in aphasia if the dominant hemisphere is affected, along with contralateral muscle weakness that is more pronounced in the face and arm than in the leg. Infarcts involving the anterior cerebral artery distribution typically cause more significant weakness in the contralateral leg than in the contralateral arm and face. Infarcts involving the contralateral posterior cerebral artery distribution typically cause an isolated homonymous hemianopia. Transient monocular blindness indicates involvement of the carotid system (as opposed to the vertebrobasilar system); monocular blindness is often caused by an embolus from a carotid plaque that occludes the retinal artery. A pure motor stroke usually results from a small infarct in the posterior limb of the internal capsule that causes equal one-sided loss of face, arm, and leg strength (no sensory loss or cortical dysfunction). 175

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Stroke

Primary ischemic (80%)

Cerebral thrombosis (50%)

Large artery thrombosis (30%)

Primary hemorrhagic (20%)

Cerebral embolus (30%)

Intracerebral hemorrhage (15%)

Subarachnoid hemorrhage (5%)

Lacunar infarct (20%)

● Figure 10-1. The majority of strokes are secondary to an ischemic event; for example, they are associated with a thrombus or an embolic phenomenon rather than a primary hemorrhagic event.

h. Bilateral visual loss suggests ischemia of the vertebrobasilar system. i. Patients who have an intracerebral hemorrhage may or may not experience acute onset of severe headache; if the hemorrhage is severe, the patient may develop signs and symptoms of increased intracranial pressure, including vomiting, decreased level of consciousness, pupillary asymmetry, and posturing of the extremities. j. Carotid bruit may be detected. k. Irregular heartbeat suggests atrial fibrillation, which can result in thrombus formation that leads to a cerebral embolic event. l. Heart murmurs may suggest endocarditis as the origin of the embolus. m. The presence of multiple vascular areas of infarction strongly suggests cerebral embolus (multiple emboli).

TABLE 10-1

RISK FACTORS FOR STROKE

Major

Minor

Age Male gender Race (African American) Family history Diabetes Smoking Hypertension Prior stroke TIAs Cardiac disease (e.g., atrial fibrillation with thrombus) Asymptomatic bruit

Hypercholesterolemia Obesity Physical inactivity Oral contraceptive use Alcohol consumption

TIA, transient ischemic attack.

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3.

177

Laboratory findings

a.

Complete blood count (CBC), prothrombin time/partial thromboplastin time, and platelet count should be performed to look for evidence of coagulation problems and hyperviscosity. b. Increased white blood cells (WBCs) suggest endocarditis as the cause of the embolus that leads to stroke. c. Electrocardiogram (ECG) should be obtained because atrial fibrillation with mural thrombus formation can be the origin for emboli. d. Results of a computed tomographic (CT) scan of the head can differentiate a hemorrhagic from a thromboembolic stroke. i. Lacunar strokes typically appear as a small area of infarction in the subcortical area (usually
1 cm); however, the CT scan may not reveal any area of infarction until the infarction has evolved over 48 hours. ii. An initially ischemic area that becomes hemorrhagic suggests an embolic etiology. iii. The presence of intraventricular blood is associated with a hemorrhagic stroke and a poor prognosis. e. Serum cholesterol level may be elevated and suggests a stenotic artery as the origin of the thromboembolus. f. Doppler studies of the carotid arteries are often warranted in a patient who has TIAs originating from the carotid artery circulation; these studies are effective in detecting stenotic vessels. g. Lumbar puncture is not routinely indicated and, in fact, is contraindicated due to the risk of herniation in patients who have mass effects associated with the stroke; indications for lumbar puncture include suspected syphilis, meningeal irritation, or an unexplained fever. h. Blood cultures should be performed if bacterial endocarditis is suspected or if the patient has an unexplained fever. i. Magnetic resonance imaging (MRI) is not required in the initial evaluation of a patient who has stroke because the CT scan effectively distinguishes hemorrhagic stroke from a thromboembolic stroke. 4.

Treatment

a.

b.

c.

d. e.

f.

Patients who have lacunar strokes typically have a good prognosis for recovery. i. Patients require hypertension and diabetic control (if applicable). ii. Patients also require intensive rehabilitation therapy. Early, vigorous treatment of hypertension immediately after a nonhemorrhagic stroke is not indicated because hypotension may lead to further ischemic insult; gradual lowering of the blood pressure is desirable unless the patient is in hypertensive crisis. Patients presenting within 3 hours of the onset of symptoms should have an immediate head CT to rule out hemorrhagic stroke. Intravenous t-PA should then be given because it reduces the neurologic deficit. A stroke that is progressing should be heparinized once hemorrhage is excluded. Anticoagulation therapy (e.g., sodium warfarin) is indicated for a cardiogenic source of emboli if the stroke is nonhemorrhagic. Patients who experience TIAs or are at increased risk for stroke may take daily doses of aspirin. If taken within 48 hours of stroke, the recurrences of stroke and mortality are reduced. For hemorrhagic stroke, mannitol, intubation for airway protection, intracranial pressure (ICP), monitoring and elevation of the head of the bed may be warranted if the patient has signs and symptoms of increased ICP.

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i. Aggressive control of elevated blood pressure also decreases elevated intracranial pressure. ii. Cerebellar hematomas are particularly responsive to surgical evacuation if they are surgically accessible. g. Blood sugar 200 mg/dL and fever increase cerebral metabolism and should be treated. h. Early rehabilitation, including physical, occupational, and speech therapy, improves outcome. B. SUBARACHNOID HEMORRHAGE 1.

General characteristics

a.

b. c.

2.

Clinical features

a. b. c. d. e. 3.

Patients experience acute onset of severe, localized headache. Meningismus may be present. Focal neurologic deficits may or may not be present. Seizure may be the first sign of an AVM. Cerebral vagoplasm occurs in 30% of patients about 1–2 weeks after the bleed, producing clinical symptoms of stroke depending on the vessels involved.

Laboratory findings

a.

b.

c.

4.

The most common nontraumatic causes of subarachnoid hemorrhage include ruptured intracranial aneurysm and bleeding of an arteriovenous malformation (AVM). AVMs usually occur in persons under the age of 40; AVMs are congenital and twice as common in men. Intracranial aneurysms may bleed at any time but are more likely to bleed during periods of stress with increased blood pressure; intracranial aneurysms are usually congenital.

CBC and coagulation studies should be performed to assess the patient’s coagulation ability because surgical intervention is often immediately necessary. Serum Na must be monitored because cerebral salt wasting leading to increased Na excretion can cause profound hyponatremia. Cerebral angiography remains diagnostic for both AVM and cerebral aneurysm; cerebral artery vasospasm may become evident 2–3 days after a bleed. Initial CT scan should be performed to localize the lesion and confirm or rule out the presence of subarachnoid/intracerebral blood. CT angiography with arterial reconstruction is increasingly being used and is taking the place of angiography.

Treatment

a. b. c. d. e. f. g.

Neurosurgical consultation is necessary. The aneurysm should be clipped surgically or coiled angiographically by interventional radiology. Appropriate antiseizure therapy should be administered if the patient has seizure; therapy includes phenytoin and ventilatory support, if needed. Increased intracranial pressure should be managed, for example, with elevation of the head of the bed, mannitol, intubation, and hyperventilation. Airway protection may be necessary if the patient is obtunded. Raised intracranial pressure may be due to hydrocephalus from blood obstructing normal CSF flow and will require ventricular drainage. Vasospasm is treated with calcium channel blockers (e.g., nimodipine), volume expansion, and increasing blood pressure. Hyponatremia should be treated with hypertonic saline.

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II

179

Disorders of Higher Cognitive Function A. GENERAL CHARACTERISTICS 1. Lesions in specific cortical areas of the brain produce recognizable clinical symptoms. 2. Lesions of the frontal, parietal, temporal, and occipital lobes as well as anterior, posterior, and conductive aphasia are discussed here. B. FRONTAL LOBE LESIONS 1.

General characteristics

a. b. c. d. e. f.

Frontal lobe contusions often result from head injury. These lesions may be infarcted by anterior communicating artery aneurysm rupture or compressed by a meningioma arising from the olfactory groove. Patients exhibit lack of social appropriateness and inhibitions, which may lead to urination or masturbation in public. Perseveration is present. Stroking the hand from lateral to medial aspect leads to the sustained grasping reflex. Stroking the thenar eminence leads to twitching of the ipsilateral corner of the mouth (palmo-mental reflex).

C. TEMPORAL LOBE LESIONS 1.

General characteristics

a. b. c. 2.

Temporal lobe lesions often produce seizures. Aphasia may occur if the lesion progresses posteriorly on the dominant hemisphere. Superior quadrantic hemianopia occurs when Meyer loop is involved.

Clinical features

a. b. c. d.

Patients exhibit brief, repetitive behaviors (e.g., lip smacking, eye twitching, chewing). Seizures are preceded by an aura that may be olfactory or gustatory. Patients may experience an intense feeling of unfamiliarity or familiarity with their surroundings. Patients appear to be in a daze and rarely lose consciousness.

D. OCCIPITAL LOBE LESIONS 1.

Bilateral occipital lobe involvement produces cortical blindness in which the pupil-

2. 3.

lary response (which involves brain stem nuclei only) is maintained, but vision is lost. A single affected occipital lobe leads to a crossed homonymous hemianopia. Occipital lobe lesions may occur secondary to basilar artery occlusion.

E. PARIETAL LOBE LESIONS 1. Parietal lobe lesions are characterized by a visual field attention deficit in the contralateral visual field; a left-sided parietal lobe lesion produces an inability to see movement of fingers in the patient’s right visual field when fingers in both visual fields are moved. 2. Patients exhibit contralateral astereognosis (inability to recognize objects by feeling their shape) and neglect of contralateral body parts. 3. If the lesion is present on the dominant side, finger agnosia may be present (inability to name fingers). 4. Lower homonymous hemianopia may occur. 5. Acalculia may be present.

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F.

APHASIA 1.

Expressive aphasia (Broca aphasia)

a. b. c. d. e. f.

Spontaneous language production is slow. Patients often overuse and repeat nouns. Little intonation is present in speech. Comprehension of language is good. Proximity of the lesion to the facial motor strip may lead to associated contralateral facial palsy. Patients often appear distressed about the inability to clearly express themselves because they comprehend their disability.

2. Receptive aphasia (Wernicke aphasia)

a. b. c. d. 3.

Conduction aphasia

a. b. c.

III

Patients can generate speech, but it contains few nouns and lacks meaning. Patients may use unknown meaningless words (neologisms). Comprehension is impaired. Patients often have poor insight into their deficit. Patients’ speech contains semantic confusions. Patients exhibit little dysphasia and good comprehension. Patients have poor ability to repeat heard words.

Dementia A. GENERAL CHARACTERISTICS 1. Dementia is an acquired, persistent, and progressive impairment of intellectual function. 2. Dementia may cause compromise in language, memory, visuospatial skills, or cognition (calculation, abstraction, judgment). 3. Sixty to seventy percent of senile dementia cases are due to Alzheimer disease; 15%–20% are multi-infarct dementias. 4. Multi-infarct dementia is more common in men and is associated with hypertension. a. Drugs that commonly cause dementia include sedatives, ranitidine and cimetidine, neuroleptic agents, anticholinergics, and nonsteroidal anti-inflammatory drugs (NSAIDs). b. Chronic alcohol abuse can also produce signs and symptoms of dementia. B. CLINICAL FEATURES 1.

Signs and symptoms of dementia include:

a. b. c. d. e.

2. 3. 4. 5.

Forgetfulness in the absence of depression Loss of computational ability Word-finding and concentration problems (e.g., inability to read a paragraph) Difficulties with daily activities, such as dressing or balancing a checkbook Progression to severe memory loss, disorientation, and social withdrawal. Patients who have Alzheimer disease experience an insidious onset and steady progression of signs and symptoms. Patients who have multi-infarct dementia exhibit a stepwise deterioration. Rapid onset and short duration of dementia suggest a treatable cause such as infection or drug-associated dementia. Normal-pressure hydrocephalus is associated with the triad of dementia, urinary incontinence, and gait instability.

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6.

181

Depression can be mistaken for dementia.

a. b.

These patients also perform poorly on mental status examinations, may be irritable, and exhibit short attention spans. The depressed patient is more likely to complain about difficulty answering mental status examination questions, whereas the demented patient is usually oblivious to his or her errors.

C. LABORATORY FINDINGS 1. Analysis of serum electrolyte, glucose, calcium, thyroid-stimulating hormone (TSH), and vitamin B12 levels should be performed to exclude curable causes. 2. Elevated cholesterol level may be seen in patients who have multi-infarct dementia (nonspecific). 3. If hypoxemia is suspected, an arterial blood gas analysis should be performed to confirm the presence of this condition. 4. Urinalysis should also be performed because an ongoing urinary tract infection can produce symptoms of dementia. 5. If it is difficult to differentiate between multi-infarct dementia and Alzheimer disease from history and physical examination, a CT scan or MRI can detect the presence of multi-infarct dementia; no clear changes on CT scan or MRI are associated with Alzheimer disease. D. TREATMENT 1.

2.

3. 4.

IV

Reversible causes should be treated; for example, discontinue any suspected medications known to have a side effect of dementia; correct any electrolyte, mineral, and/or vitamin deficiencies; and treat any apparent infections. If no reversible cause is found and Alzheimer disease is strongly suspected, a small percentage of patients have shown improvement with the use of donepezil; occupational therapy and social services help the patient and family cope with this disease. Vitamin C may slow progression. Cessation of smoking and treatment of hypertension may alter the natural course of multi-infarct dementia. Treatment of depression (psychiatric referral) should be initiated if the diagnosis is established.

Seizure Disorders A. GENERAL CHARACTERISTICS 1. Seizures may be caused by: a. Metabolic disorders (e.g., hypocalcemia, hypoglycemia, alcohol withdrawal) b. Trauma (usually manifests within 2 years after a head injury) c. Tumors (especially if the seizure occurs after age 30) d. Cerebrovascular disease most commonly causes seizures after age 60. e. Infectious disease i. History of supratentorial brain abscess carries a high risk of seizures. ii. Infectious causes must be ruled out if the physical examination reveals signs and symptoms of meningitis or cerebral abscess. 2. Seizures may also be idiopathic or congenital. 3. Types of seizures include simple partial, complex partial, generalized, and febrile. a. In simple partial seizures, no loss or disturbance in consciousness occurs; seizure activity depends on the portion of the brain affected (e.g., a motor

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b. c.

d.

seizure involving the left leg indicates seizure activity originating in the right cortical motor strip associated with leg function). Complex partial seizures resemble simple partial seizures except that an associated disturbance or loss of consciousness occurs. Generalized seizures may be absence seizures (i.e., petit mal), myoclonic, or tonic-clonic (grand mal). i. Generalized seizures are associated with loss of consciousness or loss of responsiveness/awareness; no focal origin is suggested by the seizure’s appearance (i.e., the seizure involves the entire body rather than initiating in one particular limb). ii. Generalized seizures may arise from a partial seizure; a generalized seizure may begin in, for example, the arm and then become generalized over the entire body. iii. Urinary/fecal incontinence may occur. iv. Confusion, fatigue, headache, and disorientation may occur after the seizure (postictal state). v. These seizures may be unrelenting (status epilepticus). Febrile seizures typically occur between ages 18 months and 5 years. i. Febrile seizures can occur in normally healthy children. ii. These seizures usually last no longer than a few moments and occur after an increase in body temperature.

B. CLINICAL FEATURES 1. 2.

3. 4. 5. 6. 7.

No relationship typically exists between postural changes and the onset of seizures (compared with vasovagal syncope). The neurologic examination is often normal in patients who have seizures; the exception is the patient who has sustained developmental delay from recurrent seizures during infancy. Lateralizing signs may be seen immediately after focal seizures that may point out the affected area. Temporal lobe seizures are often preceded by an aura (often of an odor or a feeling of strange, intense familiarity with the surroundings). Petit mal seizures typically last
15 seconds. It is important to differentiate seizure from syncope (a patient experiencing syncope usually does not bite the tongue, which is commonly seen in generalized seizures). Pseudoseizures are seizure-like episodes of psychogenic origin. a. Pseudoseizures can be distinguished from true seizure disorders by variations in the seizure types described by the patient and by the clinician’s observation of a tight association between seizures and stressors or significant personal events. b. Patients who have pseudoseizures may report an awareness of their surroundings during a “grand-mal” seizure (this awareness does not occur in a true grand-mal seizure).

C. LABORATORY FINDINGS 1. CT scan/MRI should be ordered for patients who have seizures of focal origin (i.e., partial seizures) and for patients more than 30 years of age with new onset of seizures, because these individuals may have an underlying neoplasm. 2. Electroencephalogram (EEG) may be helpful in classifying the seizure disorder and may thereby assist in guiding therapy; EEG may be useful intraoperatively when removing epileptogenic foci.

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TABLE 10-2

COMMONLY USED ANTICONVULSANTS

Seizure Type

Drug

Grand mal and/or partial

Phenytoin Carbamazepine Valproic acid Ethosuximide Valproic acid Valproic acid

Petit mal Myoclonic

3.

183

CBC, glucose, and renal and liver function tests should be performed if the patient is older than age 10 to rule out metabolic causes as well as provide a baseline for organ function monitoring and side effects of anticonvulsants.

D. TREATMENT 1. Patients should be referred to a neurologist. 2. Patients are treated with anticonvulsive therapy appropriate to the seizure type (Table 10-2). 3. If the maximum dose of one anticonvulsant has been reached, but no improvement is noted in the seizure disorder, then a second anticonvulsant may be added to the regimen while the first drug is tapered. 4. Plasma drug levels must be monitored to ensure compliance and adequate dosing regimens. 5. Status epilepticus is managed with maintenance of the airway; 25–50 mL of 50% dextrose is administered if hypoglycemia is the cause. Intravenous phenytoin drip is given and repeated if there is no resolution in 20 minutes. Phenobarbital or propofol are used if there is no resolution. 6. Surgery may be effective in patients resistant to medical therapy. Resection of the temporal lobe or placement of a vagal nerve stimulator has been effective. V

Headaches A. GENERAL CHARACTERISTICS 1. Headaches may be chronic or acute. 2. Acute onset of headache in a previously healthy patient suggests an organic cause. 3. Headache types include classic migraine, common migraine, tension headache, cluster headache, trigeminal neuralgia, and giant cell arteritis. B. CLINICAL FEATURES 1. Classic migraine is associated with a prodromal aura, which is usually a transient visual, motor, or sensory phenomenon. a. Headache is typically unilateral and pulsating. b. Headache is preceded by a prodrome. c. Headache may persist for 1–2 days. d. Pain may vary from mild to severe. e. Some prodromal symptoms may be severe and produce transient hemiplegia, aphasia, or hemisensory deficits. 2. Common migraine is not associated with a prodromal aura. a. Pain is unilateral or bilateral and is usually intense. b. Pain usually affects the eyes, frontal regions, and temples.

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c. d.

3.

4.

5.

6.

Headache typically lasts for a day or longer. Both types of migraines tend to begin in adolescence or early adulthood and may be associated with vomiting. Tension headache is characterized by a feeling of tightness, pressure, and constriction. a. These headaches are often associated with stressors. b. Pain is commonly suboccipital and nonthrobbing. c. Tension headaches may be associated with prolonged positioning of the head and neck. Cluster headaches recur over periods of weeks to months, followed by periods with no headache. a. Cluster headaches are most common in middle-aged men with leonine facies and a history of heavy smoking or drinking. b. Each headache typically lasts 30 minutes to 2 hours. c. Pain is unilateral and occurs around the eye. d. Horner syndrome may be present. e. Headache may be associated with nasal congestion/rhinorrhea. f. Pain radiates to the ipsilateral neck or jaw. g. Ipsilateral conjunctival injection and ipsilateral facial redness may be seen. h. Alcohol is a common trigger. Trigeminal neuralgia appears in the middle to later part of life and is more common in women. a. Trigeminal neuralgia is characterized by momentary, sudden, lancinating facial pain. b. Pain typically arises on one side of the mouth and then radiates to the eye, ear, and/or nostril on the ipsilateral side. c. Pain may be precipitated by touch, movement, breezes, or eating. d. Attacks tend to increase in frequency. e. Neurologic examination is usually normal unless an underlying disease is present (e.g., multiple sclerosis). Giant cell (temporal) arteritis (see Chapter 7 VIII H) is another type of headache.

C. LABORATORY FINDINGS 1.

2.

3.

If a patient has neurologic findings, behavioral changes, or a chronic persistent headache, then WBC count, TSH/thyroxine analysis, CT scan, and EEG should be ordered to rule out a possible infectious, hormonal, or cerebral tumor etiology. In a young patient who has trigeminal neuralgia, multiple sclerosis must be suspected; cerebrospinal fluid (CSF) and nerve conduction studies may corroborate this suspicion (see multiple sclerosis, XI). CT scan may be necessary to rule out posterior fossa tumor.

D. TREATMENT 1.

Migraine treatment consists of:

a. b. c. d.

Resting in a quiet, dark room Initial treatment with aspirin Ergotamine and caffeine combination Sumatriptan (a drug with an affinity for serotonin receptors) i. Sumatriptan is injected subcutaneously and is effective in many patients who are refractory to the aforementioned therapies. ii. This drug is contraindicated in pregnant patients.

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e.

2.

3.

4.

5.

VI

Prophylactic treatment if patients experience migraines more than 2–3 times per month (e.g., amitriptyline) f. Calcium channel blockers (e.g., nifedipine) Cluster headache treatment consists of: a. Inhalation of 100% oxygen for 15 minutes b. Ergotamine tartrate aerosol (may be given prophylactically as well) c. Amitriptyline for prophylaxis Trigeminal neuralgia treatment consists of: a. Carbamazepine (most often effective) b. Neurosurgery consultation if patients are refractory to therapy i. A significant number of refractory patients may have an impinging vascular structure adjacent to the trigeminal nerve root. ii. Multiple sclerosis must be excluded. Tension headache treatment consists of: a. Stress relief exercises b. Aspirin or acetaminophen c. Antimigrainous agents if patient is refractory to simple analgesics For treatment of giant cell arteritis, see Chapter 7, Rheumatic Diseases, VIII H 4.

Movement Disorders A. BENIGN ESSENTIAL TREMOR 1.

General characteristics

a. b. c. 2.

Benign essential tremors commonly occur after age 40; incidence increases with age. These tremors may be familial related. Diagnosis should be distinguished from Parkinson disease (see VI B).

Clinical features

a. b.

3. 4.

Postural tremor is often seen in the hands. Tremor attenuates with movement but becomes more obvious when the target is reached (e.g., when a patient attempts to grab a glass, the tremor is initially minimal but becomes more pronounced just before picking up the glass). c. Frequency of the tremor is typically between 7 and 11 cycles per second (c/s). Laboratory findings are typically not used in the diagnosis, which is most often made by history and physical examination. Treatment

a. b. c.

One or two ounces of alcohol may improve the tremor. If tremor is disabling, propranolol or primidone may be effective in reducing the severity. Thalamotomy or deep brain stimulator implantation is used for patients refractory to medical therapy.

B. PARKINSON DISEASE 1.

General characteristics

a. b. c.

Parkinson disease is the most frequently encountered extrapyramidal movement disorder. This neurodegenerative disease begins most often in the fifth and sixth decades of life. Parkinson disease is characterized by low dopamine levels in the corpus striatum.

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2.

Clinical features

a.

Patients exhibit a resting tremor that usually is initially seen in one extremity. i. Frequency of the tremor is typically 4–7 c/s. ii. Tremor may be pill-rolling in nature. iii. Tremor decreases with movement of the affected limb. b. Patients have difficulty in buttoning shirts and dressing and in cutting food; alterations in handwriting are noted. c. Patients report a feeling of stiffness and overall slowness in movement (bradykinesia). d. Rising from a low sitting position is difficult. e. Patients exhibit propulsion (inability to stop walking forward). f. Masked facies is present. g. Posture is stooped and flexed. h. Cogwheel rigidity may be present unilaterally or bilaterally. i. Patients have impaired postural reflexes (seen when a patient turns around and must take several small shuffling steps to maintain balance). j. The duration and rate of onset of signs and symptoms is important because Parkinson disease is a slow, progressive disease that develops over months to years; acute onset of parkinsonian symptoms suggests intoxication (e.g., carbon monoxide).

3.

Laboratory findings

a. b. c. 4.

Diagnosis is based on history and physical examination. CT scan of the head may be used to rule out other diagnostic possibilities such as normal pressure hydrocephalus. Apomorphine (a short-acting dopamine agonist) can be used as a therapeutic challenge; if symptoms improve, Parkinson disease is confirmed.

Treatment

a. b. c.

d.

e. f.

No cure exists. Amantadine is often used for patients who have mild symptoms. Anticholinergic drugs (e.g., benztropine) tend to alleviate tremor and rigidity rather than bradykinesia; these drugs are contraindicated in patients who have narrow-angle glaucoma. Levodopa (a drug that is converted into dopamine in situ) alleviates the signs and symptoms but does not stop the progression of the disease. i. Dyskinesia, a major side effect, necessitates “drug holidays.” ii. Patient response to levodopa is unpredictable. iii. Carbidopa is an inhibitor of the enzyme that breaks down peripheral dopamine in the body; therefore, it is used to decrease the dose of dopamine administered. Bromocriptine acts on dopamine receptors and can be used synergistically with levodopa/carbidopa. Deep brain stimulator implantation has provided significant improvement and provides an alternative to the side effects of medical therapy.

C. HUNTINGTON DISEASE 1.

General characteristics

a. b. c. d.

Huntington disease is characterized by chorea and dementia. The disease is autosomal dominant. Onset is delayed until after age 30 (usually after the patient has had children). The disease is caused by decreased
-aminobutyric acid and cholinergic activity relative to dopamine activity.

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2.

Clinical features

a. b. c. d. e. f. g. h. i. 3.

Huntington disease is progressive, with a fatal outcome within 15–20 years. Early changes include irritability, moodiness, and antisocial behavior. Subsequent dementia occurs. Dyskinesia may begin as restlessness and progress to choreiform movements. Patients exhibit irregular, involuntary hand and facial movements. Reflexes are typically brisk. Smooth eye pursuit movements are absent. Stance is wide with variable cadence. Patients are unable to maintain tongue protrusion.

Laboratory findings

a. b.

4.

187

Diagnosis is based on history and physical examination. Recombinant deoxyribonucleic acid testing is used to diagnose family members of patients with Huntington disease (particularly children of affected individuals); test is 99% accurate.

Treatment

a. b. c. d.

No cure exists. Dopamine-blocking agents such as phenothiazines or haloperidol may control dyskinesia and behavioral problems. Reserpine, which blocks neurotransmitter reuptake and therefore depletes stores of dopamine, has provided some benefit. Genetic counseling is recommended for children of patients.

D. TOURETTE SYNDROME 1.

General characteristics

a. b. 2.

Signs and symptoms begin before age 15. Tourette syndrome is a chronic, lifelong disorder with relapses and remissions.

Clinical features

a.

3. 4.

Motor tics are usually the first sign; tics commonly involve the face and may include sniffing, blinking, or frowning. b. Phonic tics may also occur. i. Phonic tics consist of barking, grunting, throat-clearing, or coughing. ii. Coprolalia (obscene speech) or echolalia (repeating the speech of others) may be present. Laboratory findings are usually unnecessary because the diagnosis is based on history and physical examination. Treatment

a. b. c.

Clonazepam and clonidine are used as first-line drug therapy. Haloperidol is effective but has extrapyramidal side effects. Reserpine appears to be effective and better tolerated than the typical antipsychotics.

E. WILSON DISEASE 1.

General characteristics

a. b. c. d.

Wilson disease is characterized by hepatolenticular degeneration. The disease is rare autosomal recessive. Onset occurs between the first and third decades of life. Excessive deposition of copper in the liver and brain is an important feature of this disease. i. Excess copper deposition is caused by increased absorption of copper from the bowel and decreased excretion by the liver.

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ii. This feature is important because it is a reversible cause of neurologic and hepatic dysfunction. 2.

Clinical features

a. b. c. d. e. f.

3.

Laboratory findings

a. b. 4.

Urine copper level is 100 g/24 h. Ceruloplasmin level is decreased (
20 g/dL).

Treatment

a. b. c. d. e. f.

VII

Patients may exhibit rigidity and parkinsonian tremor. Dysarthria is a consistent finding. Neurologic symptoms progress slowly over years. Psychiatric disorders may be present and vary from adjustment disorder to depression to schizophrenia. Kayser-Fleischer rings (fine, pigmented, brownish deposits in the cornea) may be present. Hepatitis is often the earliest sign of the disease (occurring before the neurologic signs and symptoms). i. Patients with hepatitis have jaundice, malaise, and anorexia, which usually spontaneously resolve. ii. Cirrhosis may be detected.

Early treatment is necessary to prevent permanent hepatic and neurologic damage. Penicillamine enhances urinary excretion of chelated copper. Pyridoxine is given in conjunction with penicillamine treatment because penicillamine is a pyridoxine antimetabolite. Patients should restrict their intake of dietary copper (shellfish, legumes). Oral zinc decreases gastrointestinal absorption of copper and may be used as maintenance therapy. Screening tests for family members of affected individuals are recommended.

Spinal Cord Syndromes A. TRAUMATIC INJURY TO THE SPINAL CORD 1.

General characteristics

a. b. 2.

Clinical features

a. b. c. d. 3.

Traumatic spinal cord injuries usually occur in the prime of life. These injuries are commonly associated with motor vehicle accidents, diving accidents, and falls. If conscious, the patient reports a lack of feeling and paralysis below the level of the injury. If the patient is unconscious, a spinal cord injury must be assumed; care must be taken when placing this patient in a cervical spinal collar. The cervical, thoracic, and/or lumbar spines are often tender to palpation when a vertebra is fractured. Reflexes may be brisk below the level of the lesion.

Laboratory findings

a.

b.

Anterior, lateral, and open-mouth radiographic views should be obtained in any patient suspected of having a spinal cord injury; if necessary, flexion, extension, and a swimmer’s view should also be obtained. If clinical suspicion exists and radiographs are equivocal, CT scan or MRI can be used to assess for cervical spine fracture.

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c.

4.

189

If clinical suspicion is high for a spinal cord injury, but radiographs are unrevealing, immobilization must be continued until the presence or absence of neurologic injury can be confirmed clinically.

Treatment

a. b. c. d.

Spinal immobilization must be maintained. Neurosurgical consultation is necessary. Methylprednisolone may be of benefit if given within 8 hours of the injury. Long-term management requires transfer to a center equipped to care for spinal cord injury patients.

B. CERVICAL SPINAL AND RADICULAR SYNDROMES 1.

General characteristics

a. b. 2.

Clinical features

a.

b. c.

d.

3.

Whiplash usually occurs during a motor vehicle accident commonly involving a rear-end collision. i. Patient is usually in the vehicle and is wearing a seat belt. ii. Commonly, neck pain begins a few hours after the injury, although it is not uncommon for neck pain to begin immediately after the collision. iii. Pain is exacerbated by movement. iv. Pain may be accompanied by occipital headache. v. Severe injury, especially in individuals with pre-existing spondylotic degenerative disease, may produce cervical radicular syndromes (see next). Spondylotic degenerative changes most commonly affect C6–C7. In C6 injury: i. Deep, boring pain is referred to the upper arm and shoulder. ii. Pain is exaggerated with neck movement. iii. Tingling and numbness occur in the index finger and thumb. iv. Biceps reflex is depressed. v. Biceps and brachioradialis muscles weaken (weak supination and flexion at the elbow). In C7 injury: i. Pain is referred to the arm and forearm. ii. Sensory disturbance occurs in the middle finger. iii. Triceps reflex is depressed and weakened.

Laboratory findings

a. b. c. 4.

Whiplash injury is a common cause of these syndromes. Spondylotic degenerative cervical spine changes are another common cause.

In patients who have spondylotic degenerative changes, radiographic study may reveal osteophyte formation and narrowing of the intervertebral disk space. MRI is particularly effective in detecting disk propulsion into the spinal cord. Whiplash injury typically does not appear in radiographic studies because it typically involves the ligaments.

Treatment

a. b. c.

A soft collar may provide some comfort. Analgesics such as NSAIDs may be of benefit. Continued pain and weakness may necessitate a neurosurgical decompression of the affected nerve root.

C. LUMBAR SPINAL AND RADICULAR SYNDROMES 1.

General characteristics

a. b.

These syndromes are most often due to prolapsed intervertebral lumbar disks. Patients may have a history of awkward lifting or straining.

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c.

2.

Injury most commonly arises at the L5–S1 level (70%), which causes compression of the first sacral root, followed by injury at L4–L5 (25%), which causes compression of the fifth lumbar root.

Clinical features

a. b.

Patients experience sciatica, or pain in the buttock and down the back of the thigh and leg. S1 compression causes tingling along the outer aspect of the foot, with numbness corresponding over the S1 dermatome (Figure 10-2). i. Ankle tendon reflex is decreased. ii. If compression is severe, the gastrocnemius muscle may begin to atrophy.

● Figure 10-2. Dermatomes of the leg. L2, gray shading; L3, clear; L4, dotted; L5, lined; S1, black.

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c.

3.

L5 compression causes weakness of the extensor hallucis longus (extension of the great toe), with varying degrees of footdrop; sensory deficit occurs along the outer aspect of the leg and dorsum of the foot.

Laboratory findings

a. b. c. 4.

191

Radiographs may reveal narrowing of lumbar disk spaces. MRI may show herniated disk material and a compressed nerve root. These studies are necessary if the patient requires surgery (i.e., the patient does not respond to conservative management).

Treatment

a. b. c.

Conservative management includes bed rest and NSAIDs. Steroid injections are not beneficial. Surgical consultation is necessary if signs and symptoms do not subside after 2–4 weeks of conservative management and radiography reveals evidence of nerve root compression.

D. EXTRAMEDULLARY LESIONS 1.

General characteristics

a. b.

c. 2.

Clinical features

a. b. c. d. e. f.

3.

Presence of fever suggests infectious etiology. History of prostatic, breast, or lung cancer should prompt a search for bony metastasis. Radicular pain is felt at the dermatomal level of the lesion. Ipsilateral extremity weakness and sensory deficits eventually progress to the contralateral extremity as the lesion expands. Patients may experience urgency of micturition and impotency. Cauda equina syndrome occurs if a lesion compresses the sacral and lumbar roots as these roots stream caudally (e.g., central L4–L5 disk herniation). i. This compression causes loss of sphincter control. ii. Patients experience numbness in the buttocks and the back of the thighs. iii. Weakness/paralysis of dorsiflexion of the foot (L4) and toes (L4–L5) and plantar flexion (S1) occur.

Laboratory findings

a. b. c. 4.

Lesions occur outside the dura but cause signs and symptoms due to spinal cord compression. The lesions may be caused by metastatic spread of a tumor to vertebral bodies (e.g., breast, lung, or prostatic metastasis), vertebral infection (e.g., tuberculosis), or extradural hematoma (associated with anticoagulant therapy). Primary tumors such as meningiomas and neurofibromas (more common than intramedullary tumors) may also cause cord compression.

Radiographs may reveal calcification associated with a tumor mass. CT scan and MRI are often more revealing of the nature and extent of the lesion. Bone scans are often performed on patients who have prostatic or breast carcinoma to rule out bony metastases.

Treatment

a.

b.

If the lesion is caused by an infection, the abscess must be surgically drained, and the patient should be started on appropriate antibiotic therapy (e.g., isoniazid for tuberculosis). Neurosurgical consultation is necessary.

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E. INTRAMEDULLARY LESIONS 1.

General characteristics

a. b.

2.

Clinical features

a.

b.

3.

These lesions occur within the spinal cord. Types of intramedullary lesions include astrocytomas, ependymomas, syringomyelia, vascular infarcts, or plaque demyelination in association with multiple sclerosis. Syringomyelia or a centrally located ependymoma impairs pain and temperature sensation and spares pinprick sensation and proprioception (dissociated sensory loss); sacral sparing is typical (this sign differentiates an intramedullary lesion from an extramedullary lesion). A lesion involving the left portion of the spinal cord causes ipsilateral weakness and contralateral lack of pain and temperature sensation below the lesion.

Laboratory findings

a. b.

4.

VIII

CT scan and MRI are required for delineation of the lesion. CSF may reveal the presence of malignant cells. Treatment requires a neurosurgical consultation regarding surgical resectability versus chemotherapy/radiotherapy.

Neurocutaneous Syndromes A. TUBEROUS SCLEROSIS 1.

General characteristics

a. b. 2.

Clinical features

a. b. c. 3.

This disease may be sporadic or autosomal dominant with variable penetrance. Tuberous sclerosis is a multiple intracerebral hamartoma. Patients are initially seen in early childhood to have seizures and psychomotor retardation. Reddened nodules on the face appear between ages 5 and 10. CT scan/MRI reveals the intracranial lesions.

Treatment

a. b.

No specific treatment is available. Anticonvulsant drugs may control the seizures.

B. NEUROFIBROMATOSIS 1.

General characteristics

a. b.

2.

Clinical features

a. b. 3.

The disease may be sporadic or autosomal dominant with variable penetrance. Two types exist: i. Type I (Recklinghausen disease) is characterized by multiple hyperpigmented macules and neurofibromas. ii. Type II is characterized by intraspinal, intracranial tumors and a high incidence of multiple, bilateral, acoustic neuromas.

Café au lait spots (patches of cutaneous pigmentation) appear. CT scan/MRI is used for diagnosis and to follow up on the growth of lesions. Treatment involves surgical resection of symptomatic tumors.

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C. STURGE-WEBER SYNDROME 1. General characteristics: This congenital syndrome is caused by a unilateral cutaneous capillary angioma involving the upper face and leading to leptomeningeal angiomatosis. 2.

Clinical features

a. b. c. 3.

Treatment

a. b.

IX

Patients may have focal or generalized seizures secondary to the leptomeningeal angiomatosis. Contralateral hemiparesis and hemisensory disturbance may be present. Radiographs taken after age 2 usually reveal gyriform intracranial calcification in the parieto-occipital region beneath the intracranial angioma. Treatment is aimed at controlling seizures pharmacologically (see seizure disorders, IV). If seizures are refractory to medical therapy, surgical excision may be necessary.

Peripheral Neural Disorders A. POLYNEUROPATHIES 1.

General characteristics

a. b. 2.

Clinical features

a. b. c. d. e. f. g.

3.

Patients have unpleasant paresthesias (prickling or burning sensations) in the tips of the toes or on the soles of feet. Paresthesias may then spread to fingertips. Muscle weakness is usually not prominent if the onset of the disease is slow. Ankle and knee jerks are decreased. Patients lose vibration sensation before losing light-touch sensation. Positive Romberg sign and ataxia may be present. Guillain-Barré syndrome is characterized by an ascending paralysis. i. This syndrome occurs at any age. ii. It is often preceded by a viral prodrome. iii. Patients have weak, rubbery, painful legs. iv. Ascending weakness with quadriparesis and ventilatory insufficiency may ensue within 48 hours or develop over a period of up to 3 weeks. v. Cranial nerve VII is often affected, causing bilateral facial motor weakness.

Laboratory findings

a. b. c. d. e. 4.

Subacute polyneuropathy may occur secondary to a primary process, such as diabetes mellitus, chronic renal failure, deficiency in vitamin B12, or alcoholism. Polyneuropathy may occur as a primary process (e.g., Guillain-Barré syndrome).

Evaluation is primarily based on patient history and physical examination to narrow the diagnostic possibilities. Elevated blood sugar level suggests a diabetic etiology. Elevated blood alcohol level and decreased serum vitamin B12 level often coexist in alcoholics. Elevated serum creatinine and blood urea nitrogen levels exist in individuals who have chronic renal failure. CSF analysis reveals an elevated protein level and often a normal or increased lymphocyte count in Guillain-Barré syndrome.

Treatment

a.

Treatment is based on etiology.

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b. c. d.

Progression of diabetic neuropathy can be decreased with strict diabetic control; pain often spontaneously resolves after a period of 1 year. Vitamin B12 deficiency is treated with replacement of the vitamin through regular injections or oral supplements. Guillain-Barré syndrome is managed with respiratory support. i. The disease spontaneously resolves. ii. Plasmapheresis may hasten recovery if performed within 7 days of onset of the disease.

B. MONONEUROPATHIES 1.

Carpal tunnel syndrome

a.

b.

c.

2.

Radial nerve injury

a. b. c. 3.

The radial nerve is commonly injured at the axilla due to the pressure of crutches or when the arm hangs over the back of a chair. The injured nerve causes weakness or paralysis of the arm extension at the elbow, wrist extension, metacarpophalangeal joint extension, and thumb extension. A secondary sensory deficit may occur at the dorsolateral aspect of the hand (see Figure 10-3).

Ulnar nerve injury

a. b. c. 4.

General characteristics i. Carpal tunnel syndrome is caused by compression of the median nerve beneath the carpal ligament secondary to synovitis of the tendon sheaths or a poorly healed fracture. ii. Carpal tunnel syndrome may also be caused by repetitive use of the hands (often seen in typists). Clinical features i. Patients experience burning and tingling in the lateral aspect of the hand (first three fingers) along the palmar aspect and the dorsal aspect of the second and third fingers distal to the middle interphalangeal joint (Figure 10-3). ii. Pain may radiate into the forearm and is exacerbated by manual activity, especially with flexion and extension of the wrist. iii. Sensation is impaired in the median nerve distribution. iv. Tinel sign may be positive (pain on percussion of the volar aspect of the wrist). v. Abductor pollicis brevis atrophy occurs later. vi. Electromyography (EMG) may show conduction delay in the median nerve. Treatment i. Splinting of the hand and forearm may sufficiently reduce signs and symptoms. ii. Individuals who have synovitis of the wrist may benefit from steroid injection into the carpal tunnel. iii. Refractory or severely affected individuals should undergo surgical division of the carpal tunnel ligament.

Trauma or pressure typically occurs behind the medial epicondyle (may be seen in persons undergoing surgery who have been improperly positioned). Sensory changes occur in the medial 1.5 fingers and along the medial border of the hand (see Figure 10-3). Wrist inversion (flexor carpi ulnaris function), palmar abduction, and thumb adduction may be weak.

Sciatic nerve palsy

a.

Sciatic nerve palsy is commonly caused by a misplaced intramuscular injection in the buttock or trauma to the buttock or hip area.

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● Figure 10-3. Cutaneous innervation of the hand. Dark gray, median nerve sensory distribution; light gray, radial nerve sensory distribution; hatched, ulnar nerve sensory distribution.

b. c. 5.

Weakness of dorsiflexion and eversion of the foot are present. Sensory deficit occurs along the anterolateral aspect of the calf and dorsum of the foot.

Bell facial palsy

a.

b.

c.

General characteristics i. Bell facial palsy is an idiopathic facial paresis and may be associated with the herpes simplex virus. ii. This palsy affects the lower motor neuron and lasts a few days. Clinical features i. Patients experience a sudden onset of paresis that is often accompanied by ear pain. ii. Patients are unable to completely close the ipsilateral eye. iii. Disturbance of taste due to involvement of chorda tympani fibers may also be present. Treatment i. Sixty percent of patients recover completely without treatment. ii. Individuals who have a complete palsy are less likely to fully recover and require treatment.

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iii. Recommended treatment is oral prednisone for 4–5 days, followed by a tapering dose. iv. If eye closure is affected, lubricating eye drops and an eye patch may be helpful. v. Surgical procedures to decompress the facial nerve have not proven to be beneficial.

X

Neuromuscular Disorders A. AMYOTROPHIC LATERAL SCLEROSIS (ALS) 1.

General characteristics

a. b. c. 2.

Clinical features

a. b. c. d. e. f. g. 3.

Patients experience asymmetric weakness and atrophy. Footdrop and/or clawhand deformity are common. Fasciculations and/or spasticity may be seen. Hyperreflexia in an atrophic fasciculating extremity strongly suggests the diagnosis. Spread to virtually all muscle groups may occur over weeks to months. Facial and eye movements tend to be spared. Most patients succumb to respiratory insufficiency or infection within 2–3 years.

Laboratory findings

a. b. c. d. 4.

ALS is a degeneration of anterior horn cells (lower motoneurons) and pyramidal neurons (upper motoneurons). Most cases occur sporadically. The cause of ALS remains unknown.

EMG is most diagnostic because it reveals abnormal spontaneous activity in resting muscles. Sensory conduction studies are normal. CSF is normal. Serum creatine kinase level may be slightly elevated but not to the degree seen in muscular dystrophies.

Treatment

a. b. c. d. e. f.

Treatment is symptomatic. Stretching exercises prevent contractures. Adaptive equipment and bracing are required. Swallowing dysfunction may lead to aspiration or choking; the patient must be closely watched. Diazepam may relieve a degree of spasticity. Riluzole appears to increase survival.

B. MYASTHENIA GRAVIS 1.

General characteristics

a. b. c. d. e.

Myasthenia gravis may occur at any age. This disease can be associated with thymic tumors or thyrotoxicosis. Disease occurs most commonly in young women with human leukocyte antigen-DR3. Onset is usually insidious, but may be unmasked by a coincidental infection that exacerbates symptoms. The disease has an autoimmune etiology.

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2.

Clinical features

a. b. c. d. 3.

Signs and symptoms include ptosis, diplopia, difficulty chewing or swallowing, respiratory difficulties, and limb weakness. Weakness may be localized to only a few muscle groups, especially the extraocular muscles, or may be generalized. Weakness improves after rest. Sensation and reflexes are normal.

Laboratory findings

a.

b. c. d. 4.

197

Diagnosis is confirmed by marked improvement in muscle strength that lasts approximately 5–10 minutes after a therapeutic challenge with edrophonium (an anticholinesterase inhibitor). Posteroanterior and lateral films of the chest (or CT scan) should be obtained to rule out a possible thymoma. Serum acetylcholine receptor antibody titer is elevated. Decremental muscle response to repetitive stimulation of motor nerves occurs.

Treatment

a. b. c. d. e.

Patients should avoid aminoglycosides, which exacerbate signs and symptoms. Anticholinesterase drugs (neostigmine and/or pyridostigmine) provide symptomatic relief. Corticosteroids may benefit patients who are refractory to anticholinesterase drugs. Patients who have severe signs and symptoms may benefit from plasmapheresis. Thymectomy usually leads to symptomatic relief or remission and should be considered in patients under age 60.

C. BOTULISM 1.

General characteristics

a. b. c. 2.

Botulism is caused by ingesting Clostridium botulinum toxin or infection with the bacterium. The toxin prevents the release of acetylcholine at the neuromuscular junction. Botulism often results from ingestion of contaminated home-canned food.

Clinical features

a.

Botulism is characterized by sudden, fluctuating, and severe weakness in a previously healthy person. b. Signs and symptoms begin within 72 hours of ingestion of the contaminated food. c. Signs and symptoms include diplopia, ptosis, facial weakness, and dysphagia. d. Respiratory difficulty and weakness in extremities follow. e. Weakness progresses from head to foot. f. Vision is blurred, and the pupils are dilated and unreactive. g. Dry mouth, constipation, and postural hypotension also may be present. h. Sensation and reflexes remain normal. 3.

Laboratory findings

a. b. 4.

EMG shows normal nerve conduction velocities. Repetitive stimulation of a motor nerve may show a posttetanic increase in amplitude of the evoked muscle response.

Treatment

a. b. c.

Patients must be hospitalized if ventilatory support is required. Polyvalent antitoxin should be administered. Antibiotic therapy is not used because it may produce large quantities of toxin release as a result of bacterial death.

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D. DUCHENNE-TYPE MUSCULAR DYSTROPHY 1.

General characteristics

a. b. 2.

Duchenne muscular dystrophy is an inherited disease. Because it is an X-linked recessive disorder, the disease typically affects boys.

Clinical features

a. b. c. d.

Affected toddlers have a waddling, clumsy gait. The abdomen protrudes due to increased lumbar lordosis. Pseudohypertrophy of the calves is present. Children push themselves up with their hands against their legs in order to stand. e. Eye movements, swallowing, and sensation are normal. f. Mental retardation is common. g. Independent walking is impossible by age 12. h. Progressive kyphoscoliosis and weak respiratory muscles are contributing factors to death, usually by the early 20s. 3.

Laboratory findings

a. b. 4.

Treatment

a. b. c.

XI

Creatine kinase level (20–100 times normal) is elevated before the disease is clinically evident. Muscle biopsy is diagnostic. No cure exists. Early rehabilitation prevents the progression of contractures, and strength maintenance exercises can improve the quality of life. Parents should receive genetic counseling.

Multiple Sclerosis (MS) A. GENERAL CHARACTERISTICS 1. MS is an immune-mediated destruction of myelin sheaths. 2. MS is twice as common in women as in men. 3. MS occurs predominantly in young adults of northern European origin. B. CLINICAL FEATURES 1. Diagnosis is based on clinical findings. The following diagnostic criteria must be met: a. Two attacks and clinical evidence of two separate lesions, or b. Two attacks with clinical evidence of one lesion and paraclinical evidence of another separate lesion. c. The two attacks must involve separate parts of the nervous system. d. If the patient has had only one attack, and the CSF is consistent with the diagnosis, the patient meets the diagnostic criteria for multiple sclerosis. 2. Attacks may be variable. 3. A young person may initially complain of being unable to walk along an uneven surface. 4. Numbness or tingling may be present in any limb. 5. Spastic paresis may develop. 6. Diplopia occurs. 7. Tremor may develop. 8. Nystagmus occurs. 9. Urinary urgency or hesitancy (sphincter disturbance) occurs.

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10. Signs and symptoms spontaneously resolve, but relapses occur and become

more frequent with disease progression and eventually cause permanent deficits. C. LABORATORY FINDINGS 1. MRI is more helpful than CT scan in visualizing the multiple lesions. 2. Visual and auditory evoked responses may show prolonged latencies. 3. CSF analysis reveals elevated immunoglobulin G titer, which is oligoclonal in nature; this finding is highly suggestive of multiple sclerosis in the appropriate clinical setting but is not specific. D. TREATMENT 1. 2. 3.

Progression of the disorder cannot be prevented. Corticosteroids may hasten recovery from relapses. Interferon therapy of exacerbations reduces their number.

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Index Page numbers in italics denote figures; those followed by a t denote tables.

A Abdominal pain in aortic aneurysm, 15 in appendicitis, 65 in cholangitis, 74 in cholecystitis, 73 in pancreatic carcinoma, 73 in pancreatitis, 72 in pelvic inflammatory disease (PID), 89 in peptic ulcer disease, 57 Abdominal radiography. See Radiography ABG. See Arterial blood gas Abscess hepatic, 79 intracranial, 83–84, 85 supratentorial brain, 181 Acalculia, 179 ACE inhibitors. See Angiotensin-converting enzyme (ACE) inhibitors Acetaminophen for headache, 185 for osteoarthritis, 124 Acetone breath, in ketoacidosis, 110 Acetylcholine receptor antibody titer, 197 Acetylsalicylic acid (ASA) gastritis from, 54 for gout, 127 for ischemic heart disease, 4 for ulcerative colitis, 68 Achalasia, 55–56, 56 Acid-base disorders, 49, 50, 51, 51–52 Acid phosphatase, in prostatic carcinoma, 143 Acidosis anion-gap acidosis in chronic renal disease, 40 ketoacidosis, 110 metabolic, 49, 50, 110, 111 respiratory, 49 Acquired immunodeficiency syndrome (AIDS) clinical features, 95–96, 95t general characteristics, 95 laboratory findings, 96 lymphopenia in, 167 treatment, 96 Acromegaly, 99 ACTH. See Adrenocorticotropic hormone (ACTH) Acute lymphocytic leukemia (ALL), 153–155 Acute myelogenous leukemia (AML), 153–155 Acute promyelocytic leukemia, 155 Acute renal failure (ARF), 38–39, 39t Acyclovir for genital herpes, 90 for herpes simplex virus (HSV), 70, 96 for HSV encephalitis, 83 Addison disease, 113–114 Adenocarcinoma biliary, 75 colonic, 70

200

lung, 34, 149, 150 pancreatic, 73 ADH. See Antidiuretic hormone (ADH) Adrenal cortex diseases, 111–115 Adrenal crisis, 113, 114 Adrenal gland dysfunction Addison disease, 113–114 congenital adrenal hyperplasia, 115 Cushing syndrome, 111–113, 112t pheochromocytoma, 115–116 primary aldosteronism, 114–115 Adrenal hyperplasia, congenital, 115 Adrenal medulla diseases, 115–116 Adrenalectomy, 113 Adrenergic agonists for asthma, 20t for COPD, 21 Adrenocortical insufficiency, 113–114 Adrenocorticotropic hormone (ACTH) deficiency, 98 excess and Cushing syndrome, 112, 113 increase in congenital adrenal hyperplasia, 115 secretion by pituitary tumors, 97 testing for Addison disease, 113–114 Adult respiratory distress syndrome (ARDS), 27–28 AFP (
-fetoprotein), 80, 143 AIDS. See Acquired immunodeficiency syndrome (AIDS) Alanine aminotransferase (ALT) in alcoholic liver disease, 78 in viral hepatitis, 76 Albuterol, for asthma, 20 Alcohol abuse dementia from, 180 pancreatitis associated with, 72 Alcoholic liver disease, 78–79 Aldosterone deficiency, 113 Aldosteronism, primary, 114–115 Alkaline phosphatase in alcoholic liver disease, 78 in biliary obstruction, 74 in choledocholithiasis, 74 in chronic myelogenous leukemia (CML), 156, 168 in colorectal cancer, 147 in hepatoma, 80 in lung carcinoma, 150 in pancreatic carcinoma, 146 Alkalosis metabolic, 49, 51, 114 respiratory, 49 ALL (acute lymphocytic leukemia), 153–155 Allergic purpura, 137 Allergic rhinitis, in Churg-Strauss syndrome, 137 Allopurinol for gout, 127–128 for nephropathy, 151 for renal calculi, 43 toxicity, 128
-blockers, for hypertension, 17

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INDEX
-fetoprotein (AFP), 80, 143
-thalassemia, 161 ALS (amyotrophic lateral sclerosis), 196 ALT. See Alanine aminotransferase (ALT) Alzheimer disease, dementia in, 180–181 Amantadine, for Parkinson disease, 186 Amebicides, for hepatic abscess, 79 Amenorrhea diagnostic evaluation of patients, 119 hypothalamic (functional), 118 in pituitary hyperfunction, 99 primary general characteristics, 116 hypogonadotropic hypogonadism, 117 physical abnormalities, 118 testicular feminization syndrome, 117 Turner syndrome, 116–117 secondary, 118 Aminoglutethimide, for Cushing syndrome, 113 Aminoglycosides for cystic fibrosis, 24 for pneumonia, 87 Amiodarone, for atrial fibrillation, 5 Amitriptyline, for headache, 185 AML (acute myelogenous leukemia), 153–155 Amoxicillin for otitis, 84 for peptic ulcer disease, 59 for sinusitis, 84 Ampicillin for bacterial overgrowth syndrome, 63 for hepatic abscess, 79 for meningitis, 82 petechial rash from, 92 pseudomembranous colitis from, 70 for urinary tract infection, 91 Ampicillin/sulbactam, for appendicitis, 66 Amylase level in pancreatitis, 72 in pleural effusion, 29 Amyotrophic lateral sclerosis (ALS), 196 Anaphylactoid purpura, 137 Anaplastic carcinoma, thyroid, 105 ANAs. See Antinuclear antibodies (ANAs) Androgen excess in congenital adrenal hyperplasia, 115 syndromes, 118–119 Androstenedione, excess production of, 118 Anemia from acute hemorrhage, 163 aplastic, 162 of chronic disease, 158 in chronic lymphocytic leukemia, 155 in chronic myelogenous leukemia, 156 in chronic renal disease, 39 clinical features, 157 in colorectal polyps, 149 in Crohn disease, 64 diagnostic approach to, 157–158, 159 in gastric cancer, 145 general characteristics, 157, 158t hemolytic, 163–165 hypochromic-microcytic, 157–161 iron deficiency, 70, 157–158 in lung carcinoma, 150 macrocytic, 163–166 in malabsorption, 63 megaloblastic, 165–166 in multiple myeloma, 151 myelophthisic syndromes, 162 normochromic-normocytic, 162–163 in peptic ulcer disease, 57 pernicious, 54 red blood cell aplasia, 163 sickle-cell disease, 160–161 sideroblastic, 158, 160 thalassemias, 161

Aneurysms aortic, 15–16 intracranial, 178 in polyarteritis nodosa, 138 Angiitis, hypersensitivity, 136–137 Angina, 3–4 in aortic stenosis, 6 in hypertrophic obstructive cardiomyopathy, 10 Angiography in aortic aneurysms, 16 cerebral, 178 in choledocholithiasis, 74 in Churg-Strauss syndrome, 138 in gastrointestinal bleeding, 81 in polyarteritis nodosa, 138 in pulmonary embolus, 14 in subarachnoid hemorrhage, 178 Angiomatosis, leptomeningeal, in Sturge-Weber syndrome, 193 Angioplasty for hypertension, 18 for renovascular disease, 44 Angiotensin-converting enzyme (ACE) inhibitors for heart failure, 2 for hypertension, 17, 18 for ischemic heart disease, 4 Anion-gap acidosis, in chronic renal disease, 40 Ankylosing spondylitis, 129, 130 Anorexia, in appendicitis, 65 Anorexia nervosa, amenorrhea and, 117, 118 Antacids for gastritis, 54 for peptic ulcer disease, 58 for reflux esophagitis, 53 Anthracycline, for acute leukemia, 154 Anti-dsDNA, in systemic lupus erythematosus, 133 Anti-nucleoprotein antibodies, in Sjögren syndrome, 136 Anti-RNA polymerases, 134 Anti-scleroderma antibody (SCL-70), 134 Anti-Sm, in systemic lupus erythematosus, 133 Anti-tumor necrosis factor (TNF) agents for ankylosing spondylitis, 129 for enteropathic arthropathies, 132 for psoriatic arthritis, 132 for rheumatoid arthritis, 125 Antibiotic therapy for acute leukemia, 154 for adult respiratory distress syndrome (ARDS), 28 for appendicitis, 66 for bronchiectasis, 23 for cholangitis, 75 for choledocholithiasis, 74 for chronic myelogenous leukemia (CML), 169 for cystic fibrosis, 24 for diverticular disease, 66 for endocarditis, 7 for hepatic abscess, 79 for intracellular abscess, 84 for joint infections, 92 for Lyme disease, 95 for lymphopenia, 168 for mediastinitis, 31 for meningitis, 82 for osteomyelitis, 92 for otitis, 84 for pancreatitis, 72 for pelvic inflammatory disease (PID), 89 for peptic ulcer disease, 58–59 for pharyngitis, 86 for pneumonia, 87 pseudomembranous colitis from, 70 for renal calculi, 43 for sinusitis, 84 for toxic shock syndrome (TSS), 94 for urethritis, 89 for urinary tract infection, 91 Anticentromere antibodies, in systemic sclerosis, 134

201

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INDEX

Anticholinergic drugs for esophageal dysmotility, 56 for Parkinson disease, 186 Anticholinesterase drugs, for myasthenia gravis, 197 Anticoagulant therapy for aortic regurgitation, 7 for atrial fibrillation, 5 for deep venous thrombosis, 13–14 for DIC, 173 for ischemic heart disease, 4 for mitral regurgitation, 8 for mitral stenosis, 7 for pulmonary embolus, 15 for stroke, 177 Anticonvulsants, 183, 183t Antidiuretic hormone (ADH) in diabetes insipidus, 99–100, 100t in SIADH, 100–101 Antiglomerular basement membrane antibodies, 36, 139 Antinuclear antibodies (ANAs) in polymyositis, 135 in Sjögren syndrome, 136 in systemic lupus erythematosus, 133 in systemic sclerosis, 134 Antiphospholipid antibodies, in systemic lupus erythematosus, 133 Antiretroviral therapy, in AIDS, 96 Antithyroid antibodies (thyroid peroxidase antibodies), 104 Anuria, in acute renal failure, 38 Aortic aneurysms, 15–16 Aortic regurgitation, 6–7 Aortic stenosis, 5–6 AP. See Alkaline phosphatase Aphasia, 179, 180 Aplastic anemia, 162 Apomorphine, for Parkinson disease, 186 Appendicitis, 65–66 ARDS (adult respiratory distress syndrome), 27–28 ARF (acute renal failure), 38–39, 39t Arrhythmias atrial fibrillation, 5 in ischemic heart disease, 3–4 in polymyositis, 135 in sarcoidosis, 26 Arterial blood gas in adult respiratory distress syndrome (ARDS), 27 in asthma, 20 in dementia, 181 in pulmonary embolus, 14 Arteriography in giant cell arteritis, 140 in renovascular disease, 44 Arteriovenous malformation (AVM), 178 Arteritis, giant cell arteritis, 139–140, 184, 185 Arthritis acute gouty, 126 in AIDS, 96 gonococcal, 92 in Henoch-Schönlein purpura, 137 in Lyme disease, 94 osteoarthritis, 123–124 peripheral, 63, 132 in polyarteritis nodosa, 138 rheumatoid, 124–126, 126 in sarcoidosis, 26 spondyloarthropathies, 129–132 ankylosing spondylitis, 129, 130 enteropathic arthropathies, 132 general characteristics, 129 psoriatic arthritis, 131–132 reactive arthritis, 130–131 Artificial tears, for xerophthalmia, 136 ASA. See Acetylsalicylic acid (ASA) Asbestos exposure, 25 Ascites in alcoholic liver disease, 78 in hepatoma, 80 in pancreatic carcinoma, 146

Aspartate aminotransferase (AST) in alcoholic liver disease, 78 in viral hepatitis, 76 Aspiration pneumonia, 86–87, 88 Aspirin for headache, 184, 185 for osteoarthritis, 124 for stroke, 177 for thromboembolism prevention, 5 AST. See Aspartate aminotransferase (AST) Astereognosis, 179 Asthma, 19–20, 20t Atherosclerotic disease aortic aneurysms from, 15 ischemic heart disease from, 3 renovascular hypertension from, 17 Atrial fibrillation, 5 Atropine, for ischemic heart disease, 4 Auer bodies, in acute myelogenous leukemia, 153 Aura, seizure, 182 AVM (arteriovenous malformation), 178 Azathioprine for Churg-Strauss syndrome, 138 for polymyositis, 135 for pulmonary fibrosis, 25 for systemic lupus erythematosus, 133 for thrombocytopenia, 170 Azithromycin for chancroid, 90 for urethritis, 89 Azotemia, in Goodpasture syndrome, 36

B B-cell deficiency, 167 Back pain in aortic aneurysm, 15 in pancreatic carcinoma, 73 in renal calculi, 42 Bacterial food poisoning syndromes, 62t Bacterial overgrowth syndrome, 63 Barium enema in colonic neoplastic disease, 69, 69, 70 in colorectal cancer, 147 in colorectal polyps, 149 diverticular disease, 66, 67 for ulcerative colitis, 67, 68 Barium swallow in esophageal neoplasms, 54 in reflux esophagitis, 53 Barrett esophagus, 54, 55 Bart Hgb, 161 Basophilia, in chronic myelogenous leukemia, 156 Bell facial palsy, 195–196 Bence-Jones (M-chain) proteins, in multiple myeloma, 151 Benign essential tremor, 185 Benztropine, for Parkinson disease, 186 Beta-adrenergic agonists for asthma, 20t for COPD, 21 -blockers for atrial fibrillation, 5 for heart failure, 3 for hypertension, 17 for hyperthyroidism, 102 for hypertrophic obstructive cardiomyopathy, 10 for ischemic heart disease, 4 for pheochromocytoma, 18 for thyroiditis, 103, 104 -thalassemia major, 161 Bezoars, gastric, 57 Bile duct adenocarcinoma, 75 Biliary tract disease acute cholecystitis, 73–74 ascending cholangitis, 74–75 choledocholithiasis, 74 tumors, 75

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INDEX Bilirubin in biliary tumors, 75 in cholangitis, 74 in choledocholithiasis, 74 in pancreatic carcinoma, 146 in viral hepatitis, 76 Biopsy in alcoholic liver disease, 78 in bladder carcinoma, 142 in chronic lymphocytic leukemia, 155 in Churg-Strauss syndrome, 138 in colonic neoplastic disease, 70 in giant cell arteritis, 140 in head and neck carcinoma, 141 in Henoch-Schönlein purpura, 137 in mediastinal masses, 32 in non-Hodgkin lymphoma, 153 in pancreatic carcinoma, 73 in peptic ulcer disease, 58 in pneumothorax, 31 in polyarteritis nodosa, 138 in prostatic carcinoma, 143 in pseudomonas colitis, 71 in reflux esophagitis, 53 in renal carcinoma, 142 in sarcoidosis, 26 in Sjögren syndrome, 136 in Wegener granulomatosis, 37, 139 Bisphosphonates for ankylosing spondylitis, 129 for hypercalcemia, 107 Bladder carcinoma, 142 Bleeding. See also Hemorrhage gastrointestinal, 80–81 rectal, 148 in reflux esophagitis, 53 variceal, 78, 79 Bleeding disorders, 170–174, 173t Bleeding time, 172, 173t Bleomycin for Hodgkin lymphoma, 152 for testicular cancer, 144 Blindness in giant cell arteritis, 140 monocular, in stroke, 175 Blood components, normal concentrations of, 160t Blood gases. See Arterial blood gas Blood measurements, normal, 158t Blood pressure. See Hypertension Blood urea nitrogen, in multiple myeloma, 151 Blue bloaters, 21 Bone marrow aspiration/biopsy in acute leukemia, 154 in aplastic anemia, 162 in chronic myelogenous leukemia (CML), 156, 168 in dysfunctional neutrophil disorders, 169 in lymphopenia, 167 in myelophthisic syndromes, 162 in neutropenia, 169 in thrombocytopenia, 170, 171 Bone marrow transplantation for aplastic anemia, 162 for non-Hodgkin lymphoma, 153 Bone metabolism disorders osteomalacia, 121–122 osteoporosis, 120–121 Bone pain in leukemia, 154 in multiple myeloma, 151 Bone scan in osteomyelitis, 91 in spinal extramedullary lesions, 191 Borrelia burgdorferi, 94 Botulism, 197 Bouchard nodes, in osteoarthritis, 123 Boutonniere deformities, in rheumatoid arthritis, 124

203

Bowel obstruction, 59–62 in cystic fibrosis, 23 Bradykinesia, in Parkinson disease, 186 Brain lesions aphasia from, 181 frontal lobe, 180 occipital lobe, 180 parietal lobe, 180 temporal lobe, 180 Breath sounds in pleural effusion, 28 in pneumothorax, 30 Broca aphasia, 180 Bromocriptine for Parkinson disease, 186 for pituitary hyperfunction, 99 for pituitary tumors, 98 Bronchial washings, in pneumonia, 87 Bronchiectasis, 22–23, 23 Bronchitis, 21 Bronchodilators, for cystic fibrosis, 24 Bronchogram, 23 Bronchoscopy in bronchiectasis, 22 in lung neoplasia, 35, 150 Brucella cereus food poisoning, 62t

C Cabergoline, for pituitary hyperfunction, 99 Café au lait spots, in neurofibromatosis, 192 Caffeine, for headache, 184 CAH (congenital adrenal hyperplasia), 115 Calcinosis, subcutaneous, in systemic sclerosis, 134 Calcitonin, for hypercalcemia, 107 Calcium for chronic renal disease, 40 metabolism disorders hypercalcemia, 106–107 hypocalcemia, 107–108 laboratory findings, 108t in multiple myeloma, 151 renal calculi, 42 supplementation for osteoporosis, 121 Calcium channel blockers for esophageal dysmotility, 56 for headache, 185 for hypertrophic obstructive cardiomyopathy, 10 for Raynaud phenomenon, 135 Calcium pyrophosphate dihydrate deposition disease (CPPD), 128 Calculi, renal, 42–43 Calymmatobacterium granulomatis, 90 Campylobacter, diarrhea from, 60t Cancer, 141–156. See also specific cancers biliary, 75 colorectal, 68–70, 69, 146–149 esophagus, 54–55 gastric, 55, 144–145 head and neck carcinoma, 141 hepatic, 79–80 leukemia, 153–156 lung, 33–36, 34, 36, 149–150 lymphoma, 151–153 multiple myeloma, 150–151 ovarian cancer, 144 pancreatic, 72–73, 145–146 pleural, 31 prostatic carcinoma, 142–143 renal and bladder carcinoma, 142 testicular cancer, 143–144 thyroid, 104–105 TNM staging, 141 Candidiasis, in AIDS, 96 Captopril for renal hypertension, 135 renography in renovascular disease, 44

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INDEX

Carbamazepine for headache, 185 for seizure, 183t Carbidopa, for Parkinson disease, 186 Carcinoembryonic antigen (CEA) in colonic neoplastic disease, 70 in gastric cancer, 145 in gastric neoplasms, 55 in pancreatic carcinoma, 73 Cardiac catheterization in congestive cardiomyopathy, 9 in constrictive pericarditis, 13 in heart failure, 1 in hypertrophic obstructive cardiomyopathy, 10 in mitral stenosis, 7 in restrictive cardiomyopathy, 10 Cardiac tamponade, 11 Cardiomyopathy congestive (dilated), 9 hypertrophic obstructive, 10 restrictive, 10–11 Cardiovascular disease, 1–18 aortic aneurysms, 15–16 atrial fibrillation, 5 cardiomyopathy, 9–11 congestive heart failure, 1–3 deep venous thrombosis, 13–14 hypertension, 16–18 ischemic heart disease, 3–4 pericardial disease, 11–13 pulmonary embolus, 14–15 valvular heart disease, 5–9 Cardioversion, for atrial fibrillation, 5 Carotid bruit, in stroke, 176 Carpal tunnel syndrome, 194 in rheumatoid arthritis, 124 Cauda equina syndrome, 191 with osteoarthritis, 123 CEA. See Carcinoembryonic antigen (CEA) Cefotaxime, for meningitis, 82 Cefoxitin, for pelvic inflammatory disease (PID), 89 Ceftriaxone for chancroid, 90 for gonorrhea, 70 for meningitis, 82 for urethritis, 89 Celiac disease, 63 Central nervous system infections, 82–84 in AIDS, 95 encephalitis, 82–83 intracranial abscess, 83–84, 85 meningitis, 82, 83t Cephalosporin for cystic fibrosis, 24 for intracellular abscess, 84 for pneumonia, 87 pseudomembranous colitis from, 70 Cerebellar hematoma, 178 Cerebral angiography, 178 Cerebral artery vasospasm, 178 Cerebrospinal fluid (CSF) analysis in acute leukemia, 154 in amyotrophic lateral sclerosis, 196 in encephalitis, 83, 83t in Guillain-Barré syndrome, 193 in headache, 184 in meningitis, 82 in multiple sclerosis, 199 in spinal intramedullary lesions, 192 Cerebrovascular disease stroke, 175–178 subarachnoid hemorrhage, 178 Ceruloplasmin level, in Wilson disease, 188 Cervical spinal syndromes, 189 Chancroid, 89–90 Charcot triad, in cholangitis, 74 Chemoembolization, for hepatoma, 80

Chemotherapy for absolute erythrocytosis, 167 for acute leukemia, 154 for colorectal cancer, 148 for gastric neoplasms, 55, 145 for head and neck carcinoma, 141 for Hodgkin lymphoma, 152 for lung carcinoma, 150 for multiple myeloma, 151 for non-Hodgkin lymphoma, 153 platinum-based, 144 for testicular cancer, 144 Chest pain in pericarditis, 11 in pleural effusion, 28 in pleural neoplasia, 31 in pneumothorax, 30 Chest physiotherapy, for cystic fibrosis, 24 Chest radiography. See Radiography Chest wall disorders, 32–33, 33 Chlamydia, 88, 89, 91 Chloroma, 154 Chloroquine, for systemic lupus erythematosus, 133 Chlorpropamide for diabetes insipidus, 100 for diabetes mellitus, 109 Cholangiocarcinoma, 75 Cholangiography, in choledocholithiasis, 74 Cholangitis, ascending, 74–75 Cholecystitis, acute, 73–74 Choledocholithiasis, 74 Cholelithiasis, in glucose-6-phosphate dehydrogenase (G6PD) deficiency, 165 Cholesterol level in dementia, 181 in stroke, 177 Chorea, in Huntington disease, 186 Chronic disease, anemia of, 158 Chronic granulomatous disease (CGD), neutrophil dysfunction in, 169 Chronic lymphocytic leukemia (CLL), 155 Chronic myelogenous leukemia (CML), 155–156, 168 Chronic obstructive pulmonary disease (COPD), 20, 21–22 Chronic renal insufficiency, 39–40 Churg-Strauss syndrome, 137–138 Chvostek sign, 107 Cimetidine, for reflux esophagitis, 53 Ciprofloxacin, for chancroid, 90 Cirrhosis, alcoholic, 78–79 Cisplatin for head and neck carcinoma, 141 for lung neoplasia, 35 for mediastinal masses, 32 for testicular cancer, 144 Clarithromycin, for peptic ulcer disease, 59 Claudication in giant cell arteritis, 140 intermittent, in renovascular disease, 43 Clindamycin for pelvic inflammatory disease (PID), 89 pseudomembranous colitis from, 70 CLL (chronic lymphocytic leukemia), 155 Clomiphene, for androgen excess syndrome, 119 Clonazepam, for Tourette syndrome, 187 Clonidine for hypertension, 17 for Tourette syndrome, 187 Clopidogrel, for ischemic heart disease, 4 Clostridium botulinum, 197 food poisoning, 62t Clostridium difficile, 70–71 food poisoning, 62t Clostridium perfringens, food poisoning from, 62t Clubbing in bronchiectasis, 22 in lung neoplasia, 34 Cluster headaches, 184, 185 CML (chronic myelogenous leukemia), 155–156, 168

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INDEX Coagulation disorders, 170–174, 173t disseminated intravascular, 172–173 Coagulopathies acquired, 174 hereditary, 173–174 Cognitive disorders, 180–181 Cogwheel rigidity, in Parkinson disease, 186 Colchicine, for gout, 127 Cold-air challenge test, in asthma, 19 Colectomy, for ulcerative colitis, 68 Colitis pseudomembranous, 70–71 ulcerative, 66–68, 68 Collagen vascular disease, 11 Colonic and rectal polyps, 148–149, 148t Colonic neoplastic disease, 68–70, 69 Colonoscopy in colorectal cancer, 147, 148 in colorectal polyps, 149 in diverticular disease, 66 in gastrointestinal bleeding, 81 in ulcerative colitis, 67 Colorectal cancer, 68–70, 69, 146–148 Colorectal polyps, 68–69, 148–149 Coma hyperosmolar nonketotic, 110–111 hypoglycemic, 111 myxedema, 103 Community-acquired pneumonia, 86–87 Complement deficiency, in systemic lupus erythematosus, 133 Computed tomography (CT) in acute leukemia, 154 in alcoholic liver disease, 78 in aldosteronism, 114 in appendicitis, 65 in bronchiectasis, 22 in Cushing syndrome, 112 in dementia, 181 in encephalitis, 83 in esophageal neoplasms, 55 in head and neck carcinoma, 141 in headache, 184 in hepatic abscess, 79 in hepatoma, 80 in insulinoma, 111 in intracellular abscess, 84 in lung carcinoma, 150 in lung neoplasia, 35 in mediastinal masses, 32 in neurofibromatosis, 192 in osteomyelitis, 91 in ovarian cancer, 144 in pancreatic carcinoma, 73, 146 in pancreatitis, 71, 72 in Parkinson disease, 186 in pheochromocytoma, 18, 116 in pituitary tumors, 97 in pleural effusions, 29 in primary hyperparathyroidism, 106 in pulmonary embolus, 14 in renal calculi, 43 in renal carcinoma, 142 in seizure, 182 in spinal cord injury, 188 in spinal extramedullary lesions, 191 in spinal intramedullary lesions, 192 in stroke, 177 in subarachnoid hemorrhage, 178 in tuberous sclerosis, 192 Conduction aphasia, 180 Congenital adrenal hyperplasia (CAH), 115 Congestive (dilated) cardiomyopathy, 9 Congestive heart failure (CHF). See Heart failure Conjunctivitis in psoriatic arthritis, 131 in reactive arthritis, 130

Conn syndrome, 114 Constipation, 65 Coombs test, in hemolytic anemia, 133, 163 COPD (chronic obstructive pulmonary disease), 20, 21–22 Copper deposition, in Wilson disease, 187–188 Coprolalia, in Tourette syndrome, 187 Cor pulmonale in bronchiectasis, 22 in COPD, 21 in cystic fibrosis, 23 Corticosteroids for asthma, 20 for calcium pyrophosphate dihydrate deposition disease, 128 for Churg-Strauss syndrome, 138 for COPD, 21 for Crohn disease, 64 for giant cell arteritis, 140 for Goodpasture syndrome, 37, 139 for gout, 127 for Henoch-Schönlein purpura, 137 for hypersensitivity angiitis, 137 for hypersensitivity pneumonitis, 26 for multiple myeloma, 151 for multiple sclerosis, 199 for myasthenia gravis, 197 for polyarteritis nodosa, 138 for polymyositis, 135 for psoriatic arthritis, 131 for pulmonary fibrosis, 25 for reactive arthritis, 131 for rheumatoid arthritis, 125 for sarcoidosis, 27 for Sjögren syndrome, 136 for systemic lupus erythematosus, 133 for thrombocytopenia, 170 for ulcerative colitis, 68 for Wegener granulomatosis, 37, 139 Cortisol for congenital adrenal hyperplasia, 115 in Cushing syndrome, 112 deficiency in congenital adrenal hyperplasia, 115 Cough in achalasia, 55 in asthma, 19 in bronchiectasis, 22 in COPD, 21 in Goodpasture syndrome, 139 in hypersensitivity pneumonitis, 26 in pneumoconiosis, 25 in pulmonary fibrosis, 25 CPPD (calcium pyrophosphate dihydrate deposition disease), 128 Crackles in bronchiectasis, 22 in heart failure, 1 in hypersensitivity pneumonitis, 26 Creatine kinase in amyotrophic lateral sclerosis, 196 in Duchenne muscular dystrophy, 198 in ischemic heart disease, 4 Creatinine in acute renal failure, 38 in chronic renal disease, 40 in multiple myeloma, 151 CREST syndrome, 134 Crohn disease, 63–64, 64 Cromolyn sodium, for asthma, 20 Cryoprecipitate therapy for hemophilia A, 173 for von Willebrand disease, 174 Cryptococcal meningitis, 95 Crystal-related joint disease, 92 CSF. See Cerebrospinal fluid (CSF) analysis CT. See Computed tomography (CT) Cullen sign, in pancreatitis, 71

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Cushing syndrome, 111–113, 112t Cutaneous innervation of the hand, 195 Cyclophosphamide for Churg-Strauss syndrome, 138 for Goodpasture syndrome, 139 for polyarteritis nodosa, 138 for polymyositis, 135 for pulmonary fibrosis, 25 for Sjögren syndrome, 136 for systemic lupus erythematosus, 133 for thrombocytopenia, 170 for Wegener granulomatosis, 37, 139 Cystic fibrosis (CF), 23–24, 24 pancreatitis associated with, 72 Cytarabine, for acute leukemia, 154 Cytoscopy, in bladder carcinoma, 142

D Dacarbazine, for Hodgkin lymphoma, 152 DDAVP (desmopressin), for diabetes insipidus, 100 Deep venous thrombosis (DVT), 13–14 Degenerative joint disease, 123–124 Dehydration, 44 Demeclocycline, for syndrome of inappropriate antidiuretic hormone, 101 Dementia in AIDS, 95 clinical features, 180–181 general characteristics, 180 in Huntington disease, 186, 187 laboratory findings, 181 treatment, 181 Depo-Testosterone, for hypogonadotropic hypogonadism, 120 Depression, dementia confused with, 181 Dermatomes of the leg, 190 Dermatomyositis, 135 Desferrioxamine, for thalassemias, 161 Desmopressin, for diabetes insipidus, 100 Dexamethasone suppression test, 112, 112t Dextrose, for hypoglycemia, 183 Diabetes insipidus, 99–100, 100t Diabetes mellitus clinical features, 108–109 diarrhea in, 59 general characteristics, 108 hyperosmolar nonketotic coma, 110–111 ketoacidosis, 110 laboratory findings, 109 pancreatitis associated with, 72 treatment, 109, 109t Diabetic neuropathy, 194 Dialysis for acute renal failure, 39 for chronic renal disease, 40 for Goodpasture syndrome, 37 for platelet dysfunction, 172 Diaphragmatic paralysis, in lung cancer, 149 Diarrhea in AIDS, 96 clinical features, 59 general characteristics, 59 infectious, 60t laboratory findings, 59 osmotic, 59 secretory, 59 workup for acute, 61 Diazepam, for amyotrophic lateral sclerosis, 196 Dicloxacillin, for osteomyelitis, 92 Diffuse esophageal spasm, 55–56 Diffuse interstitial lung disease, 24–27 Digital subtraction renal arteriography, in renovascular disease, 44 Digitalis for aortic regurgitation, 7 for congestive cardiomyopathy, 9

for mitral regurgitation, 8 for restrictive cardiomyopathy, 11 Digoxin for atrial fibrillation, 5 for heart failure, 2 Disseminated intravascular coagulation (DIC), 172–173 Diuresis, for hypercalcemia, 107 Diuretic drugs for aortic regurgitation, 7 for congestive cardiomyopathy, 9 for heart failure, 2 for hemolytic anemia, 164 for hypertension, 17 for mitral regurgitation, 8 for mitral stenosis, 7 for renal calculi, 43 for restrictive cardiomyopathy, 11 Diverticular disease, 66, 67 DNA testing, in Huntington disease, 187 Donepezil, for Alzheimer disease, 181 Dopamine, for Parkinson disease, 186 Dopamine-blocking agents, for Huntington disease, 187 Doppler studies in deep venous thrombosis, 13 in stroke, 177 Doxorubicin, for Hodgkin lymphoma, 152 Doxycycline for chlamydia, 70 for pelvic inflammatory disease (PID), 89 for urethritis, 89 Duchenne-type muscular dystrophy, 198 DVT (deep venous thrombosis), 13–14 Dyskinesia, in Huntington disease, 187 Dysphagia in esophageal neoplasms, 54 in polymyositis, 135 Dyspnea in asthma, 19 in bronchiectasis, 22 in constrictive pericarditis, 13 in COPD, 21 in Goodpasture syndrome, 36 in hypersensitivity pneumonitis, 26 in hypertension, 16 in hypertrophic obstructive cardiomyopathy, 10 in kyphoscoliosis, 32 in mitral regurgitation, 8 in mitral stenosis, 7 in pleural effusions, 28 in pneumoconiosis, 25 in pneumothorax, 30, 31 in pulmonary embolus, 14 in pulmonary fibrosis, 24

E Ear infection, 84 EBV. See Epstein-Barr virus (EBV) ECG. See Electrocardiogram (ECG) Echocardiography in acute pericarditis, 11 in aortic regurgitation, 7 in aortic stenosis, 6 in congestive cardiomyopathy, 9 in constrictive pericarditis, 13 in heart failure, 1 in hypertrophic obstructive cardiomyopathy, 10 in mitral regurgitation, 8 in mitral stenosis, 7 in pericardial effusion, 11 in restrictive cardiomyopathy, 10 in tricuspid regurgitation, 9 Echolalia, in Tourette syndrome, 187 Ectopic pregnancy, 89 Edrophonium challenge, for myasthenia gravis, 197 EEG. See Electroencephalogram (EEG)

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INDEX Electrocardiogram (ECG) in acute pericarditis, 11 in Addison disease, 114 in aortic regurgitation, 6 in aortic stenosis, 6 in atrial fibrillation, 5 in congestive cardiomyopathy, 9 in constrictive pericarditis, 13 in heart failure, 1 in hypertrophic obstructive cardiomyopathy, 10 in ischemic heart disease, 4 in mitral regurgitation, 8 in mitral stenosis, 7 in pericardial effusion, 11, 12 in pulmonary embolus, 14 in restrictive cardiomyopathy, 10 in stroke, 177 in tricuspid regurgitation, 9 Electroencephalogram (EEG) in encephalitis, 83 in headache, 184 in seizure, 182 Electrolyte disorders acid-base disorders, 49, 50, 51, 51–52 hyperkalemia, 45 hypernatremia, 45, 47 hypokalemia, 45, 48 hyponatremia, 44–45, 46 osmolar gap, 45, 45t Electromyography (EMG) in amyotrophic lateral sclerosis, 196 in botulism, 197 in carpal tunnel syndrome, 194 in polymyositis, 135 Embolization, for gastrointestinal bleeding, 81 EMG. See Electromyography (EMG) Emphysema, 21 Emphysematous bullous disease, pneumothorax secondary to, 21 Encephalitis, 82–83 Encephalopathy, hepatic, 78 End-stage renal disease, 39–40 Endocrinologic and metabolic disorders adrenal gland, 111–116 bone metabolism disorders, 120–122 female reproductive disorders, 116–119 glucose homeostasis, 108–111 male reproductive disorders, 119–120 parathyroid gland, 106–108 pituitary gland, 97–101 thyroid gland, 101–106 Endoscopic retrograde cholangiopancreatography (ERCP) in cholangitis, 75 in pancreatic carcinoma, 73, 146 in pancreatitis, 72 Endoscopy in colonic neoplastic disease, 69, 70 in Crohn disease, 64 in esophageal neoplasms, 54 in gastric emptying disorders, 57 in gastric neoplasms, 55 in gastritis, 54 in gastrointestinal bleeding, 81 in peptic ulcer disease, 57–58 in reflux esophagitis, 53 Entamoeba histolytica, 79 Enteropathic arthropathies, 132 Eosinophilia-associated infections, 93–94 Ependymoma, 192 Epigastric pain. See Abdominal pain Episcleritis, in Wegener granulomatosis, 139 Epstein-Barr virus (EBV) infectious mononucleosis, 92–93 pharyngitis, 86 Ergotamine, for headache, 184, 185 ERT. See Estrogen replacement therapy (ERT) Erythema chronicum migrans, in Lyme disease, 94

207

Erythrocytosis absolute, 167 stress, 166–167 Erythromycin for Lyme disease, 95 for lymphogranuloma venereum, 90 for pharyngitis, 86 Erythropoietin therapy, for chronic renal disease, 40 Escherichia coli diarrhea from, 60t food poisoning, 62t osteomyelitis, 91 Esophageal dysmotility, 55–56, 56 Esophageal manometry in esophageal dysmotility, 56 in reflux esophagitis, 53 Esophageal neoplasms, 54–55 Esophageal perforation, 31 Esophagram, in esophageal dysmotility, 55, 56 Estrogen deficiency in Turner syndrome, 116 for hypercalcemia, 107 for hypogonadotropic hypogonadism, 117 for prostatic carcinoma, 143 for testicular feminization syndrome, 117 for Turner syndrome, 116 Estrogen-progesterone withdrawal test, for amenorrhea diagnosis, 119 Estrogen-progestin combinations, for androgen excess syndrome, 119 Estrogen replacement therapy (ERT) for osteoarthritis, 124 for osteoporosis, 121 Estrone, increase in androgen excess syndrome, 118, 119 Etanercept, for rheumatoid arthritis, 125 Ethambutol, for tuberculosis, 93 Ethanol, gastritis from, 54 Ethosuximide, for seizure, 183t Etoposide, for testicular cancer, 144 Exophthalmos, in Graves disease, 101 Expressive aphasia, 180 Exudative fluid, 28t

F Facial palsy, 195–196 Familial polyposis syndromes, 68, 148, 148t Fanconi anemia, 162 Farmer’s lung, 25 Fasciculations, in amyotrophic lateral sclerosis, 196 Fat malabsorption, 63 Febrile seizures, 182 Fecal fat analysis, in malabsorption, 63 Fecal occult blood, in Crohn disease, 63 Female reproductive disorders, 116–119 amenorrhea, primary, 116–118 amenorrhea, secondary, 118 androgen excess syndrome, 118–119 diagnostic evaluation, 119 Fever in alcoholic liver disease, 78 in chronic myelogenous leukemia, 156 in CPPD, 128 in dysfunctional neutrophil disorders, 169 in gastric emptying disorders, 57 in gout, 127 in hypersensitivity angiitis, 137 in hypersensitivity pneumonitis, 26 in leukemia, 154 in polyarteritis nodosa, 138 in pulmonary fibrosis, 24 in renal calculi, 42 in Wegener granulomatosis, 139 5-ASA. See Acetylsalicylic acid (ASA) Fluconazole, for candidiasis, 96

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Fludrocortisone for Addison disease, 114 for congenital adrenal hyperplasia, 115 Fluoroquinolone for pneumonia, 87 for renal calculi, 43 for urethritis, 89 Fluorouracil, for head and neck carcinoma, 141 Folate for alcoholic liver disease, 78 deficiency, 165–166, 171 Follicular carcinoma, thyroid, 105 Food poisoning, bacterial, 62t Footdrop, in amyotrophic lateral sclerosis, 196 Fremitus, vocal, in pleural effusion, 28 Friction rub, pericardial, 11 Frontal lobe lesions, 179 FSH/LH levels in androgen excess syndrome, 118–119 in hypogonadotropic hypogonadism, 117 in Turner syndrome, 116 Furosemide for heart failure, 2 for hypercalcemia, 107

G Galactorrhea, 99 Gallbladder. See also Biliary tract disease adenocarcinoma, 75 cholecystitis, 73–74 perforation, 73 surgical removal, 74 Gallstones, 73, 74 in hereditary spherocytosis, 164 pancreatitis from, 71 -glutamyltransferase, in alcoholic liver disease, 78 Gastric bezoars, 57 Gastric carcinoma, 144–145 Gastric emptying disorders, 56–57 Gastric manometry, in gastric emptying disorders, 57 Gastric neoplasms, 55 Gastric volvulus, 57 Gastritis acute, 54 chronic, 54 Gastroesophageal reflux disease (GERD), 53 Gastrointestinal disorders biliary tract disease, 73–75 bleeding, 80–81 colon, rectum, and anus, 65–71, 67–69 esophagus and stomach, 53–59, 56, 58 infections, 88 liver diseases, 75–80, 76t, 77 pancreatic disorders, 71–73 small intestine, 59–64, 60t, 61, 62t Gastroparesis, 57 Genital infections, 88–90 Genital ulcer and lymphadenopathy syndromes, 89–90 Gentamicin for hepatic abscess, 79 for otitis, 84 for pelvic inflammatory disease (PID), 89 for pneumonia, 87 for urinary tract infection, 91 GERD (gastroesophageal reflux disease), 53 Giant cell arteritis, 139–140, 184, 185 Giardia lamblia, diarrhea from, 60t Gigantism, 99 Glipizide, for diabetes mellitus, 109 Glomerulonephritis in Goodpasture syndrome, 36 poststreptococcal, 41, 42t Glomerulonephropathy general characteristics, 41 nephritic versus nephrotic syndromes, 42t

nonproliferative, 41–42 proliferative, 41 proteinuria in, 40 Glucocorticoids for Addison disease, 114 for androgen excess syndrome, 119 for hypercalcemia, 107 for rheumatoid arthritis, 125 Glucosamine, for osteoarthritis, 124 Glucose for diabetic ketoacidosis, 110 homeostasis diabetes mellitus, 108–109 diabetic ketoacidosis, 110 hyperosmolar nonketotic coma, 110–111 hypoglycemic coma, 111 insulin types, 109t for hypoglycemia, 111 Glucose-6-phosphate dehydrogenase (G6PD) deficiency, 165 Glucose tolerance in Cushing syndrome, 112 impaired, 112 in pituitary hyperfunction, 99 Glucose tolerance test, 109 Glyburide, for diabetes mellitus, 109 Glycoprotein IIb/IIIa inhibitors, for ischemic heart disease, 4 Glycosylated hemoglobin levels, 109 Goiter diffuse toxic, 101 nodular toxic, 101 Gold therapy for psoriatic arthritis, 132 for rheumatoid arthritis, 125 side effects, 126 Gonadotropin releasing hormone (Gn-RH), for hypogonadotropic hypogonadism, 120 Gonadotropin releasing hormone (Gn-RH) deficiency, in hypogonadotropic hypogonadism, 117 Gonococcal infection, 88 Goodpasture syndrome, 36–37, 139 Gout, 126–128 Granuloma inguinale, 89–90 Graves disease, 101–102 Grey-Turner sign, in pancreatitis, 71 Group A streptococci, 86 Growth hormone assessing secretion of, 98 deficiency, 98 secretion by pituitary tumors, 97 Guaiac test, in diarrhea, 59 Guillain-Barré syndrome, 193, 194 Gynecomastia, 120

H H2-receptor blockers for gastritis, 54 for peptic ulcer disease, 58 for reflux esophagitis, 53 Haemophilus ducreyi, 90 Haemophilus influenzae, 82, 83t, 84, 86 Haloperidol for Huntington disease, 187 for Tourette syndrome, 187 Hashimoto thyroiditis, 102, 104 Head carcinoma, 141 infections, 84 Headache clinical features, 183–184 cluster, 184, 185 general characteristics, 183 in giant cell arteritis, 184, 185 laboratory findings, 184 migraine, 183–185 in pituitary tumors, 97

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INDEX Headache (continued) tension, 184, 185 treatment, 184–185 in trigeminal neuralgia, 184, 185 Heart failure clinical features, 1 general characteristics, 1 laboratory findings, 1, 2 treatment, 2–3 Heart murmur aortic regurgitation, 6 in hypertrophic obstructive cardiomyopathy, 10 in ischemic heart disease, 3 in mitral regurgitation, 8 in stroke, 176 in tricuspid regurgitation, 8 Heartburn, 53 Heberden nodes, in osteoarthritis, 123 Helicobacter pylori gastric neoplasia and, 55, 145 peptic ulcer disease and, 58 Heliotrope eyelids, 135 Heller myotomy, 56 Hematemesis clinical features, 80 in gastritis, 54 Hematochezia clinical features, 80 in colorectal cancer, 70, 147 in infectious proctitis, 70 Hematocrit disorders, 166–167 Hematologic diseases, 157–174 anemias, 157–166 hematocrit disorders, 166–167 hemostasis and coagulation disorders, 170–174 leukocyte disorders, 167–170 Hematoma in aneurysm, 16 extradural, 191 Hematuria, 40–41 in bladder cancer, 142 in prostatic carcinoma, 142 in renal calculi, 43 Hemianopia, 179 Hemochromatosis, 128–129 Hemodialysis, for Goodpasture syndrome, 139 Hemoglobin electrophoresis, 160 Hemoglobin H disease, 161 Hemolytic anemias, 163–165 extravascular hemolysis, 164 glucose-6-phosphate dehydrogenase (G6PD) deficiency, 165 hereditary spherocytosis, 164–165 intracorpuscular abnormalities, 164–165 intravascular, 163–164 Hemolytic uremic syndrome (HUS), 172 Hemophilia A, 173 Hemoptysis in Goodpasture syndrome, 36, 139 in mitral stenosis, 7 Hemorrhage. See also Bleeding in acquired coagulopathies, 174 anemia from acute, 163 in gastritis, 54 intra-alveolar in Goodpasture syndrome, 36 intracerebral, in stroke, 175, 176 in peptic ulcer disease, 57 subarachnoid, 178 Hemorrhagic stroke, 175–177 Hemosiderosis, idiopathic pulmonary, 37 Hemostasis disorders, 170–174, 173t Henoch-Schönlein purpura, 137 Heparin for acute promyelocytic leukemia, 155 for deep venous thrombosis, 13 for DIC, 173 for ischemic heart disease, 4 for pulmonary embolus, 14–15

Heparin-induced thrombocytopenia, 171 Hepatitis alcoholic, 78–79 viral, 75–76, 76t, 77 in Wilson disease, 188 Hepatoma, 80 Hepatomegaly in alcoholic liver disease, 78 in pancreatic carcinoma, 146 Hepatosplenomegaly in acute leukemia, 154 in chronic lymphocytic leukemia, 155 in Hodgkin lymphoma, 152 in multiple myeloma, 151 in non-Hodgkin lymphoma, 153 in systemic lupus erythematosus, 133 Herpes simplex virus (HSV) encephalitis, 82 genital, 89–90 Hgb H disease, 161 Histoplasmosis, 31 HIV, 95–96 HLA-B27 testing, 129 Hodgkin lymphoma, 151–152, 152t Horner syndrome in lung cancer, 149 from Pancoast tumor, 34 Hospital-acquired pneumonia, 87 HSV. See Herpes simplex virus (HSV) Human immunodeficiency virus (HIV), 95–96 Huntington disease, 186–187 HUS (hemolytic uremic syndrome), 172 Hyaluronan injection, for osteoarthritis, 124 Hydralazine for hypertension, 17 SLE induced by, 132 Hydrocephalus, normal-pressure, 180 21-hydroxylase deficiency, 115 Hydroxychloroquine for polymyositis, 135 for psoriatic arthritis, 132 for systemic lupus erythematosus, 133 Hydroxyurea, for absolute erythrocytosis, 167 Hypercalcemia, 106–107, 108t in multiple myeloma, 151 Hypergammaglobulinemia, in non-Hodgkin lymphoma, 153 Hyperglycemia in diabetes mellitus, 109 in hyperosmolar nonketotic coma, 110 in ketoacidosis, 110 Hypergonadotropic hypogonadism, 119 Hyperkalemia, 45 in Addison disease, 113 in chronic renal disease, 39 Hyperosmolar nonketotic coma, 110 Hyperparathyroidism primary, 106–107, 108t secondary, 106, 108t Hyperpigmentation, in Addison disease, 113 Hyperprolactinemia, 99 Hyperreflexia, in ALS, 196 Hyperresonance, in pneumothorax, 30 Hypersensitivity angiitis, 136–137 Hypersensitivity pneumonitis, 25–26 Hypertension in aldosteronism, 114 essential (primary), 16–17 from pheochromocytoma, 18 renovascular, 17–18 in renovascular disease, 43 secondary, 17–18, 43 Hyperthyroidism, 101–102 diarrhea in, 59 hypercalcemia in, 107 Hypertonic saline, for SIADH, 100–101 Hypertrophic obstructive cardiomyopathy, 10 Hyperuricemia, 126

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Hypoalbuminemia, hypocalcemia in, 107 Hypocalcemia, 107–108, 108t Hypochromic-microcytic anemia, 157–161 Hypochromic-microcytic anemias, 157–161 Hypocomplementemia, in systemic lupus erythematosus, 133 Hypoglycemia, in Addison disease, 113 Hypoglycemic agents, for diabetes mellitus, 109 Hypoglycemic coma, 111 Hypogonadism gynecomastia with, 120 hypogonadotropic, 117 in males, 119–120 Hypogonadotropic hypogonadism, 117, 119–120 Hypokalemia, 45, 48 in aldosteronism, 114 in renovascular disease, 44 Hypomagnesemia, 108 Hyponatremia, 44–45, 46 in Addison disease, 113 in SIADH, 100 Hypoparathyroidism, 107–108, 108t Hypopituitarism in Addison disease, 113 in hypogonadotropic hypogonadism, 117 Hypotension, orthostatic in acute renal failure, 38 in Addison disease, 113 in pheochromocytoma, 18 Hypothyroidism, 102–103 Hypovolemia, in acute renal failure, 38 Hypoxemia, in dementia, 181 Hypoxia, in COPD, 21

I ICD (implantable cardioverter defibrillator), 3 Idiopathic pulmonary hemosiderosis, 37 Idiopathic thrombocytopenic purpura (ITP), 170 Ileus, adynamic, in small bowel obstruction, 60, 61 Imatinib, for chronic myelogenous leukemia, 156 Imipenem, for pancreatitis, 72 Immunoglobulin A (IgA) nephropathy, 41 Immunosuppressive therapy for Goodpasture syndrome, 37 for polyarteritis nodosa, 138 for systemic lupus erythematosus, 133 Implantable cardioverter defibrillator (ICD), 3 Impotency, in spinal cord syndromes, 191 Indomethacin, for gout, 127 Infarction in dementia, 180–181 in frontal lobe lesions, 179 stroke, 175, 176 Infection, 82–96. See also specific diseases AIDS, 95–96 central nervous system (CNS), 82–84 eosinophilia-associated, 93–94 gastrointestinal, 88 genital and sexually transmitted, 88–90 head and neck, 84 infectious mononucleosis, 92–93 joint, 92 Lyme disease, 94–95 osteomyelitis, 91–92 respiratory tract, 84–88 seizures from, 181 toxic shock syndrome, 94 tuberculosis, 93 urinary tract, 90–91 Infectious mononucleosis, 92–93 Infliximab for ankylosing spondylitis, 129 for Crohn disease, 64 for enteropathic arthropathies, 132 for psoriatic arthritis, 132 for rheumatoid arthritis, 125

Inner ear infection, 84 Insulin, 109–110, 109t Insulin-induced hypoglycemia test, 98 Insulinoma, 111 Interferon therapy for Kaposi sarcoma, 96 for multiple sclerosis, 199 Intermittent claudication, 43 Interstitial lung disease, 24–27 Intervertebral disks, prolapse of, 189–191 Intracranial abscess, 83–84, 85 Intracranial pressure, increased in stroke, 177–178 in subarachnoid hemorrhage, 178 Intravenous immunoglobulin, for polymyositis, 135 Intravenous pyelography, in renal carcinoma, 142 Intravenous urography, in urinary tract infections, 91 Intrinsic factor, 54 Iodine deficiency, 102 Ion gap, in diarrhea, 59 Ipratropium bromide, for COPD, 21 Iron deficiency anemia, 157–158 in Goodpasture syndrome, 37 Irritable bowel syndrome, 59 Ischemia heart disease, 3–4 in small bowel obstruction, 60 in stroke, 175–177 Isoniazid, for tuberculosis (TB), 93 ITP (idiopathic thrombocytopenic purpura), 170

J Jaundice in alcoholic liver disease, 78 in cholangitis, 74 in cholecystitis, 73 in choledocholithiasis, 74 in pancreatic carcinoma, 73, 146 in pancreatitis, 72 Joint disease. See also Arthritis crystal related, 126–129 calcium pyrophosphate dihydrate deposition disease (CPPD), 128 gout, 126–128 hemochromatosis, 128–129 degenerative, 123–124 infections, 92

K Kaposi sarcoma, 95, 96 Karyotyping, in Turner syndrome, 117 Kayser-Fleischer rings, in Wilson disease, 188 Ketoacidosis, diabetic, 110 Klinefelter syndrome, 120 Kussmaul respirations, in ketoacidosis, 110 Kussmaul sign, in restrictive cardiomyopathy, 10 Kyphoscoliosis, 32–33, 33, 198

L L-thyroxine for hypothyroidism, 103 for thyroid cancer, 105 for thyroiditis, 104 Lactase deficiency, 63 Lactate dehydrogenase (LDH) in acute leukemia, 154 in ischemic heart disease, 4 in pericardial effusion, 12 in pleural effusions, 29

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INDEX Lactulose, 79 Lacunar strokes, 175, 177 Lateral sclerosis, amyotrophic, 196 LDH. See Lactate dehydrogenase (LDH) Leptomeningeal angiomatosis, in Sturge-Weber syndrome, 193 Leukemia acute, 153–155 chronic lymphocytic, 155 chronic myelogenous, 155–156, 168–169 general characteristics, 153 lymphocytosis in, 168 neutropenia in, 169 Leukocytic disorders dysfunctional neutrophils, 169–170 lymphocytosis, 168 lymphopenia, 167–168 neutropenia, 169 neutrophilia, 168–169 Leukocytosis in asthma, 19 in chronic myelogenous leukemia, 156 Levodopa, for Parkinson disease, 186 LH/FSH levels in androgen excess syndrome, 118–119 deficiency, 98 in hypogonadotropic hypogonadism, 117 in Turner syndrome, 116 Listeria monocytogenes, 83t Lithotripsy, for renal calculi, 43 Liver biopsy in alcoholic liver disease, 78 in hepatoma, 80 Liver diseases, 75–80 abscess, 79 alcoholic, 78–79 tumors, 79–80 viral hepatitis, 75–76, 76t, 77, 78 Lobectomy, for cystic fibrosis, 24 Lumbar puncture in intracellular abscess, 84 in meningitis, 82 in stroke, 177 Lumbar spinal syndromes, 189–191 Lung biopsy in Goodpasture syndrome, 139 in hypersensitivity pneumonitis, 26 in lung neoplasia, 35 in pulmonary fibrosis, 25 cancer clinical features, 149–150 general characteristics, 149 laboratory findings, 150 treatment, 150 neoplasms, 33–36, 34, 36 Lung disease. See Pulmonary diseases Lupus, 132–133 Lyme disease, 94–95 Lymph node biopsy in chronic lymphocytic leukemia, 155 in lung neoplasia, 35 Lymphadenopathy in acute leukemia, 154 in chronic lymphocytic leukemia, 155 in chronic myelogenous leukemia, 156 in dysfunctional neutrophil disorders, 169 in head and neck carcinoma, 141 in Hodgkin lymphoma, 152 in lymphocytosis, 168 in non-Hodgkin lymphoma, 153 in systemic lupus erythematosus, 133 Lymphocytic leukemia acute, 153–155 chronic, 155 Lymphocytosis, 168 Lymphogranuloma venereum, 89–90

Lymphoma Hodgkin, 151–152, 152t non-Hodgkin lymphoma, 152–153 Sjögren syndrome association with, 136 Lymphopenia, 167–168

M Macrocytic anemia, 163–166 Magnesium ammonium sulfate, renal calculi, 42 Magnetic resonance imaging (MRI) in cervical spinal syndromes, 189 in dementia, 181 in encephalitis, 83 in head and neck carcinoma, 141 in lumbar spinal syndromes, 191 in multiple sclerosis, 199 in neurofibromatosis, 192 in osteomyelitis, 91 in pituitary tumors, 97 in seizure, 182 in spinal cord injury, 188 in spinal extramedullary lesions, 191 in spinal intramedullary lesions, 192 in stroke, 177 in tuberous sclerosis, 192 Malabsorption, 62–63 Male reproductive disorders, 119–120 gynecomastia, 120 hypogonadism, 119–120 Malignant hypertension, proteinuria in, 40 Mannitol, for stroke, 177 Mast cell stabilizer, for asthma, 20 Mebendazole, for pinworm, 94 Meconium ileus, in cystic fibrosis, 23 Mediastinal masses, 31–32 Mediastinal shift, in pneumothorax, 30 Mediastinitis, 31 Medullary carcinoma, thyroid, 105 Megacolon, toxic, 67, 68, 68 Megaloblastic anemia, 165–166 Melena, 80 MEN syndromes, 97, 106, 115 Meningitis, 82, 83t leukemic, 154 in Lyme disease, 94 Metabolic acidosis, 49, 50 in hyperosmolar nonketotic coma, 111 in ketoacidosis, 110 Metabolic alkalosis, 49, 51 in aldosteronism, 114 Metaproterenol, for asthma, 20 Methacholine, in asthma, 19 Methimazole, for hyperthyroidism, 102 Methotrexate for polymyositis, 135 for psoriatic arthritis, 132 for rheumatoid arthritis, 125 Methyldopa, for hypertension, 17 Methylene blue staining, of stools, 59 Methylprednisolone, for spinal cord injury, 189 Metoclopramide for gastric emptying disorders, 57 for intestinal motility, 135 Metronidazole for Crohn disease, 64 for hepatic abscess, 79 for intracellular abscess, 84 for peptic ulcer disease, 59 for pseudomonas colitis, 71 Metyrapone, for Cushing syndrome, 113 Metyrapone test, 98 Microscopy, polarizing, 92 Midabdominal bruit, in renovascular disease, 44 Middle ear infection, 84

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Migraine, 183–185 Milwaukee brace, for kyphoscoliosis, 33 Mineralocorticoid deficiency in congenital adrenal hyperplasia, 115 replacement for Addison disease, 114 for congenital adrenal hyperplasia, 115 Minoxidil, for hypertension, 17 Mitotane, for Cushing syndrome, 113 Mitral regurgitation, 8 Mononeuropathies, 194–196 Morphine, for heart failure, 2 Motor stroke, 175 Movement disorders benign essential tremor, 185 Huntington disease, 186–187 Parkinson disease, 185–186 Tourette syndrome, 187 Wilson disease, 187–188 MRI. See Magnetic resonance imaging (MRI) MS. See Multiple sclerosis (MS) Mucolytics, for COPD, 21 Multiple endocrine neoplasm (MEN), 97, 106, 115 Multiple myeloma, 150–151 Multiple sclerosis (MS) clinical features, 198–199 general characteristics, 198 laboratory findings, 199 treatment, 199 Mumps orchitis, 120 Muscle biopsy in Duchenne muscular dystrophy, 198 in polymyositis, 135 Muscular dystrophy, Duchenne, 198 Myasthenia gravis, 196–197 mediastinal mass in, 31 Mycoplasma, 86–87, 88 Myelogenous leukemia acute, 153–155 chronic, 155–156, 168 Myeloperoxidase deficiency, 169–170 Myelophthisic syndromes (myelofibrosis), 162 Myocardial infarction, 1 Myocardial ischemia, 3–4 Myocarditis, in Lyme disease, 94 Myotomy for esophageal dysmotility, 56 for gastric emptying disorders, 57 Myxedema coma, 103

N N-acetylcysteine, for COPD, 21 Nafcillin for osteomyelitis, 92 for toxic shock syndrome (TSS), 94 Narcotics, for pancreatitis, 72 Natriuresis, in SIADH, 100 Nausea, in appendicitis, 65 Neck carcinoma, 141 Neck infections, 84 Neisseria gonorrhoeae, 88, 89, 92 Neisseria meningitidis, 82, 83t Neoplasia, 141–156. See also specific cancers biliary, 75 colonic, 68–70, 69 colorectal cancer, 146–149 esophagus, 54–55 gastric, 55, 144–145 head and neck carcinoma, 141 hepatic, 79–80 leukemia, 153–156 lung, 33–36, 34, 36, 149–150 lymphoma, 151–153 multiple myeloma, 150–151

ovarian cancer, 144 pancreatic, 72–73, 145–146 pleural, 31 prostatic carcinoma, 142–143 renal and bladder carcinoma, 142 testicular cancer, 143–144 thyroid, 104–105 TNM staging, 141 Neostigmine, for myasthenia gravis, 197 Nephrectomy, for renal cancer, 142 Nephritic versus nephrotic syndromes, 42t Nephropathy, diabetic, 108 Nephrotic syndrome, proteinuria in, 40 Nerve conduction studies in headache, 184 in polymyositis, 135 Neurocutaneous syndromes neurofibromatosis, 192 Sturge-Weber syndrome, 193 tuberous sclerosis, 192 Neurofibromatosis, 192 Neurological diseases, 175–199 amyotrophic lateral sclerosis (ALS), 196 aphasia, 180 benign essential tremor, 185 botulism, 197 cerebrovascular disease, 175–178 dementia, 180–181 disorders of higher cognitive function, 179–180 headaches, 183–185 Huntington disease, 186–187 movement disorders, 185–188 multiple sclerosis, 198–199 muscular dystrophy, Duchenne-type, 198 myasthenia gravis, 196–197 neurocutaneous syndromes, 192–193 neurofibromatosis, 192 neuromuscular disorders, 196–198 Parkinson disease, 185–186 peripheral neural disorders, 192–196 seizures, 181–183 spinal cord syndromes, 188–192 stroke, 175–178 Sturge-Weber syndrome, 192 subarachnoid hemorrhage, 178 Tourette syndrome, 187 tuberous sclerosis, 192 Wilson disease, 187–188 Neuromuscular disorders amyotrophic lateral sclerosis (ALS), 196 botulism, 197 muscular dystrophy, Duchenne-type, 198 myasthenia gravis, 196–197 Neuropathy, in diabetes mellitus, 109 Neutropenia, 169 Neutrophilia, 168–169 Neutrophils, dysfunctional, 169–170 Nissen fundoplication, for reflux esophagitis, 53 Nitrates, for esophageal dysmotility, 56 Nitroblue tetrazolium dye test, 170 Nitroglycerin for angina, 2 for ischemic heart disease, 4 Nocturia, in heart failure, 1 Non-Hodgkin lymphoma, 152–153 in AIDS, 95 Nonsteroidal anti-inflammatory drugs (NSAIDs) for acute pericarditis, 11 for ankylosing spondylitis, 129 for calcium pyrophosphate dihydrate deposition disease, 128 gastritis from, 54 for gout, 127 for hemochromatosis, 129 for infectious mononucleosis, 93 for osteoarthritis, 124

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INDEX Nonsteroidal anti-inflammatory drugs (NSAIDs) (continued) for psoriatic arthritis, 131 for reactive arthritis, 131 for rheumatoid arthritis, 125 for spinal syndromes, 189, 191 for systemic lupus erythematosus, 133 for thyroiditis, 103 Normochromic-normocytic anemia, 162–163 Norwalk agent, diarrhea from, 60t NSAIDs. See Nonsteroidal anti-inflammatory drugs (NSAIDs) Nuclear medicine scan, in gastrointestinal bleeding, 81 Nystagmus, in multiple sclerosis, 198

O Obstruction colonic, 70 small bowel, 59–62 Obstructive lung disease, 19–24 Obturator sign, in appendicitis, 65 Occipital lobe lesions, 179 Oliguria, in acute renal failure, 38 Omeprazole for esophageal reflux, 135 for reflux esophagitis, 53 Oncologic diseases, 141–156 colorectal cancer, 146–149 gastric cancer, 144–145 head and neck carcinoma, 141 leukemia, 153–156 lung carcinoma, 149–150 lymphoma, 151–153 multiple myeloma, 150–151 ovarian cancer, 144 pancreatic cancer, 145–146 prostatic carcinoma, 142–143 renal and bladder carcinoma, 142 testicular cancer, 143–144 TNM staging, 141 Opportunistic infections, in AIDS, 95–96, 95t Orthophosphate, for renal calculi, 43 Orthopnea in constrictive pericarditis, 13 in heart failure, 1 in mitral regurgitation, 8 in mitral stenosis, 7 Orthostatic hypotension in acute renal failure, 38 in Addison disease, 113 in pheochromocytoma, 18 Osmolality, in diabetes insipidus, 100 Osmolar gap, 45, 45t Osmotic fragility test, in hereditary spherocytosis, 164 Osteitis fibrosa cystica, 107 Osteoarthritis, 123–124 Osteoblastic metastasis, 108 Osteodystrophy, in chronic renal disease, 39 Osteomalacia, 121–122 Osteomyelitis, 91–92 Osteoporosis, 120–121, 121 Otitis, 84 Ovary cancer, 144 failure to develop in Turner syndrome, 116 granulosa-theca tumor, 118 ovarian failure, primary, 118 polycystic, 118–119 Oxacillin, for osteomyelitis, 92 Oxygen therapy for adult respiratory distress syndrome (ARDS), 28 for cystic fibrosis, 24 for headache, 185 for heart failure, 3 for pneumoconiosis, 25 for pulmonary embolus, 14

P Pain in aortic aneurysm, 15 in appendicitis, 65 in cholangitis, 74 in cholecystitis, 73 in leukemia, 154 in multiple myeloma, 151 in pancreatic carcinoma, 73 in pancreatitis, 72 in pelvic inflammatory disease (PID), 89 in peptic ulcer disease, 57 in pericarditis, 11 in pleural effusion, 28 in pleural neoplasia, 31 in pneumothorax, 30 in renal calculi, 42 Palsy Bell facial, 195–196 sciatic nerve, 194–195 Pancoast syndrome, 149 Pancoast tumor, 34, 34 Pancreatic carcinoma, 72–73, 145–146 Pancreatic enzyme for bacterial overgrowth syndrome, 63 for cystic fibrosis, 24 for pancreatitis, 72 Pancreatic stimulation tests, 72 Pancreatitis acute, 71–72 chronic, 72 Pancytopenia in acute leukemia, 154 in aplastic anemia, 162 Papillary carcinoma, thyroid, 105 Paraneoplastic syndromes in lung carcinoma, 150 in pancreatic carcinoma, 73 Parathyroid gland disorders hypoparathyroidism, 107–108 primary hyperparathyroidism, 106–107 Paresthesias, in polyneuropathies, 193 Parietal lobe lesions, 179 Parkinson disease, 185–186 Parkinsonian tremor, in Wilson disease, 188 Partial thromboplastin (PTT) time, 172, 173t Pelvic inflammatory disease (PID), 89 Penicillamine for psoriatic arthritis, 132 for rheumatoid arthritis, 125 side effects, 126 for systemic sclerosis, 135 for Wilson disease, 188 Penicillin for cystic fibrosis, 24 for dysfunctional neutrophil disorders, 170 for joint infections, 92 for Lyme disease, 95 for pharyngitis, 86 for pneumonia, 87 for sinusitis, 84 for syphilis, 90 Peptic ulcer disease, 57–59, 58 Percutaneous needle aspiration, in lung neoplasia, 35 Pericardial effusion, 11–12 Pericardiocentesis, 12 Pericarditis acute, 11, 12 constrictive, 12–13 Peripheral neural disorders mononeuropathies, 194–196 polyneuropathies, 193–194 Peripheral neuropathy, in polyarteritis nodosa, 138 Peritonitis, in appendicitis, 65 Pernicious anemia, 54 PET (positron emission tomography), in lung carcinoma, 150

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Pharyngitis, 86 Phenothiazines, for Huntington disease, 187 Phenoxybenzamine, for hypertension, 17 Phenytoin, for seizure, 178, 183, 183t Pheochromocytoma, 18, 115–116 Philadelphia chromosome, 156, 168 Phlebotomy, for hemochromatosis, 129 Phosphate, for hypercalcemia, 107 Phosphate binders, for chronic renal disease, 40 Pica, iron deficiency anemia and, 157 PID (pelvic inflammatory disease), 89 Pigeon-breeder’s lung, 25 Pink puffers, 21 Pinworm infection, 93–94 Piperacillin for cholangitis, 75 for pneumonia, 87 Pituitary gland disorders diabetes insipidus, 99–100, 100t general characteristics, 97 hyperfunction, 99 hypofunction, 98 SIADH (syndrome of inappropriate antidiuretic hormone secretion), 100–101 tumors, 97–98 Plasmapheresis for Goodpasture syndrome, 37, 139 for Guillain-Barré syndrome, 194 for myasthenia gravis, 197 Platelets consumption syndromes, 172–173 dysfunction, 171–172 thrombocytopenia, 170–171 Pleural diseases pleural effusions, 28–29, 28t, 29t pleural neoplasia, 31 pneumothorax, 29–31, 30 Pleural effusions, 28–29, 28t, 29t Pleural neoplasia, 31 Pleurodesis, chemical for pleural effusion, 29 for pneumothorax, 30 Plummer disease, 101 Pneumatic dilatation, for achalasia, 56 Pneumoconiosis, 25–26 Pneumomediastinum, 31 Pneumonia community-acquired, 86–87 hospital-acquired, 87 radiography, 87, 87, 88 Pneumonitis hypersensitivity, 25–26 in lung carcinoma, 150 Pneumothorax, 29–31, 30 in emphysematous bullous disease, 21 Polyarteritis nodosa, 138 Polycystic ovary disease, 118–119 Polymyalgia rheumatica, 139 Polymyositis, 135 Polyneuropathies, 193–194 Polyposis syndromes, familial, 68, 148, 148t Polyps, colonic and rectal, 68–69, 148–149, 148t Polyuria, in diabetes insipidus, 100 Positron emission tomography (PET), in lung carcinoma, 150 Poststreptococcal glomerulonephritis, 41, 42t Potassium hyperkalemia, 45 hypokalemia, 45, 48 in ketoacidosis, 110 loss in aldosteronism, 114 Prazosin, for hypertension, 17 Prednisone for Bell facial palsy, 196 for thyroiditis, 103 Pregnancy test, 119 Primidone, for benign essential tremor, 185 Probenecid, for gout, 127

Procainamide for atrial fibrillation, 5 SLE induced by, 132 Proctitis infectious, 70 ulcerative, 66 Progesterone withdrawal test for amenorrhea diagnosis, 119 in hypogonadotropic hypogonadism, 117 Prolactin deficiency, 98 secretion by pituitary tumors, 97 Prolactinoma, 117 Propranolol for benign essential tremor, 185 for hypertension, 17 for hypertrophic obstructive cardiomyopathy, 10 Propylthiouracil, for hyperthyroidism, 102 Prostate-specific antigen (PSA), 143 Prostatic carcinoma, 142–143 Protein electrophoresis in chronic lymphocytic leukemia, 155 in multiple myeloma, 151 Proteinuria, 40 Prothrombin (PT) time, 172, 173t Proton pump inhibitors for peptic ulcer disease, 58 for reflux esophagitis, 53 Proctoscopy, 67 Pruritus, in Hodgkin lymphoma, 152 PSA (prostate-specific antigen), 143 Pseudogout, 128 Pseudomembranous colitis, 70–71 Pseudomonas, 84, 92 Pseudoseizures, 182 Psoas sign, in appendicitis, 65 Psoriatic arthritis, 131–132 PT (prothrombin) time, 172, 173t PTT (partial thromboplastin) time, 172, 173t Pulmonary angiography, in pulmonary embolus, 14 Pulmonary diseases adult respiratory distress syndrome (ARDS), 27–28 chest wall disorders, 32–33 diffuse interstitial lung disease, 24–27 mediastinal diseases, 31–32 neoplasms, 33–36 obstructive lung disease, 19–24 pleural disease, 28–31 of unknown etiology, 36–37 Pulmonary edema, secondary to heart failure, 2 Pulmonary embolus, 14–15, 15 Pulmonary fibrosis, 24–25 in ankylosing spondylitis, 129 Pulmonary function tests in asthma, 19 in bronchiectasis, 22 in COPD, 21 in cystic fibrosis, 23 in Goodpasture syndrome, 37 in hypersensitivity pneumonitis, 26 in pneumoconiosis, 25 in pulmonary fibrosis, 25 in sarcoidosis, 26, 27 Pulsus paradoxus, in asthma, 19 Purpura anaphylactoid (allergic), 137 Henoch-Schönlein, 137 in hypersensitivity angiitis, 137 idiopathic thrombocytopenic, 170 palpable, 82 thrombotic thrombocytopenic, 172 Pyelogram, intravenous, in renal calculi, 43 Pyelonephritis, 90, 91 Pyloric stenosis, 57 Pyrazinamide, for tuberculosis, 93 Pyridostigmine, for myasthenia gravis, 197 Pyridoxine, for Wilson disease, 188

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Q Quinolone, for urinary tract infection, 91

R Radial nerve injury, 194 Radicular syndromes cervical, 189 lumbar, 189–191 Radioactive iodine scintigraphy, in thyroid nodule disease, 105 Radioactive iodine therapy for hyperthyroidism, 102 for thyroid cancer, 105 Radioactive iodine uptake test, 101 Radiography in Addison disease, 113 in adult respiratory distress syndrome (ARDS), 27 in AIDS, 96 in ankylosing spondylitis, 129, 130 in aortic regurgitation, 6 in appendicitis, 65 in asthma, 19 in bronchiectasis, 22, 23 in cervical spinal syndromes, 189 in cholecystitis, 73 in colonic neoplastic disease, 69, 69, 70 in colorectal cancer, 147–148 in congestive cardiomyopathy, 9 in constrictive pericarditis, 13 in COPD, 21, 22 in CPPD, 128 in Crohn disease, 64, 64 in cystic fibrosis, 23, 24 in enteropathic arthropathies, 132 in esophageal dysmotility, 55, 56 in gastric cancer, 145 in gastric emptying disorders, 57 in gastric neoplasms, 55 in Goodpasture syndrome, 37 in gout, 127 in heart failure, 1, 2 in hemochromatosis, 128 in hypersensitivity pneumonitis, 26 in kyphoscoliosis, 33 in lumbar spinal syndromes, 191 in lung carcinoma, 150 in malabsorption, 63 in mediastinal masses, 32 in mediastinitis, 31 in mitral regurgitation, 8 in mitral stenosis, 7 in multiple myeloma, 151 in myasthenia gravis, 197 in osteoarthritis, 124 in osteomalacia, 122 in osteomyelitis, 91 in osteoporosis, 120, 121 in pancreatitis, 72 in peptic ulcer disease, 57–58, 58 in pericardial effusion, 11 in pleural effusions, 28 in pneumoconiosis, 25 in pneumonia, 87, 87, 88 in pneumothorax, 30, 30, 31 in psoriatic arthritis, 131 in pulmonary embolus, 14, 15 in pulmonary fibrosis, 25 in reactive arthritis, 131 in reflux esophagitis, 53 in renal calculi, 43 in restrictive cardiomyopathy, 10 in rheumatoid arthritis, 125, 126 in sarcoidosis, 26, 27, 27 in sinusitis, 84

in small bowel obstruction, 60 in spinal cord injury, 188 in spinal extramedullary lesions, 191 in Sturge-Weber syndrome, 193 in systemic sclerosis, 134 in tricuspid regurgitation, 9 in ulcerative colitis, 67, 68 in urinary tract infections, 91 in Wegener granulomatosis, 37 Radionuclide biliary scan, in cholecystitis, 73 Radiotherapy for colorectal cancer, 148 for Cushing syndrome, 113 for esophageal neoplasms, 55 for gastric neoplasms, 55 for head and neck carcinoma, 141 for Hodgkin lymphoma, 152 for hyperthyroidism, 102 for lung carcinoma, 150 for multiple myeloma, 151 for non-Hodgkin lymphoma, 153 for pituitary hyperfunction, 99 for pituitary tumors, 98 for prostatic carcinoma, 143 Ranitidine for peptic ulcer disease, 58 for reflux esophagitis, 53, 135 Raynaud phenomenon, 134, 135 RBC casts, 40 Reactive arthritis, 130–131 Receptive aphasia, 180 Recklinghausen disease, 192 Red blood cell aplasia, 163 Red blood cell indices, 157, 158t Reed-Sternberg cells, in Hodgkin lymphoma, 152 Reflux esophagitis, 53 Reiter syndrome, 131 Renal artery stenosis, 43 Renal biopsy, in acute renal failure, 38 Renal calculi, 42–43 Renal carcinoma, 142 Renal failure acute, 38–39, 39t chronic, 39–40 Renovascular disease, 43–44 Renovascular hypertension, 17–18 Reproductive disorders female, 116–119 amenorrhea, primary, 116–118 amenorrhea, secondary, 118 androgen excess syndrome, 118–119 diagnostic evaluation, 119 male, 119–120 gynecomastia, 120 hypogonadism, 119–120 Reserpine for Huntington disease, 187 for Tourette syndrome, 187 Respiratory acidosis, 49 Respiratory alkalosis, 49 Respiratory tract infections, 84–88 pharyngitis, 86 pneumonia, 86–87, 87, 88 upper respiratory tract infections (URTIs), 84, 86 Restrictive cardiomyopathy, 10–11 Reticulocytosis, anemia from, 163 Retinitis, in AIDS, 96 Reversible ischemic neurologic deficit (RIND), 175 Rhabdomyolysis, hypercalcemia in, 107 Rheumatic diseases, 123–140 crystal-related joint diseases, 126–129 osteoarthritis, 123–124 polymyositis and dermatomyositis, 135 rheumatoid arthritis, 124–126, 126 Sjögren syndrome, 136 spondyloarthropathies, 129–132

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Rheumatic diseases (continued) systemic lupus erythematosus, 132–133 systemic sclerosis (scleroderma), 134–135 vasculitic syndromes, 136–140 Rheumatic fever mitral regurgitation from, 8 mitral stenosis from, 7 tricuspid regurgitation from, 8 Rheumatoid arthritis, 124–126, 126 Rhinitis, allergic in Churg-Strauss syndrome, 137 Rifampin for meningitis, 82 for tuberculosis, 93 Riluzole, for amyotrophic lateral sclerosis, 196 RIND (reversible ischemic neurologic deficit), 175 Rotavirus, diarrhea from, 60t Rovsing sign, in appendicitis, 65

S Sacroiliitis, 131, 132 Saddle-nose deformity, in Wegener granulomatosis, 139 Salicylates, side effects of, 125 Saline, intravenous for Addison disease, 114 for hypercalcemia, 107 Salmonella spp. diarrhea from, 60t food poisoning, 62t Sarcoidosis, 26–27, 27 hypercalcemia in, 106 mediastinal disease, 31 Schilling test, 54, 63, 166 Sciatic nerve palsy, 194–195 Sciatica, 90 Scleroderma, 134–135 Sclerosis, tuberous, 192 Seizure in arteriovenous malformation, 178 clinical features, 182 in encephalitis, 83 febrile, 182 general characteristics, 181–182 generalized, 182 in hyperosmolar nonketotic coma, 111 in intracranial abscess, 83 laboratory findings, 182–183 partial complex, 182 simple, 181–182 pseudoseizures, 182 status epilepticus, 182, 183 in Sturge-Weber syndrome, 193 in temporal lobe lesions, 179 treatment, 183, 183t in tuberous sclerosis, 192 Seminoma, 143–144 Sensory conduction studies, in amyotrophic lateral sclerosis, 196 Sexually transmitted infectious diseases, 88–90 Sheehan syndrome, 98 Shigella spp. diarrhea from, 60t food poisoning, 62t Shock, in gastritis, 54 Sickle-cell disease, 160–161 Sideroblastic anemia, 158, 160 Sigmoidoscopy, for pseudomonas colitis, 71 Silicosis, 25 Sinusitis, 84 in Wegener granulomatosis, 139 Sjögren syndrome, 136 Skin biopsy, in hypersensitivity angiitis, 137 SLE (systemic lupus erythematosus), 132–133 Small-cell carcinoma, lung, 34, 35, 149 Small intestine diseases bacterial food poisoning, 62t

Crohn disease, 63–64, 64 diarrhea, 59, 60t, 61 malabsorption, 62–63 obstruction, 59–62 Sodium hypernatremia, 45, 47 hyponatremia, 44–45, 46 Sodium restriction for congestive cardiomyopathy, 9 for hypertension, 17 Somatostatin analogues, for pituitary hyperfunction, 99 Spasticity, in amyotrophic lateral sclerosis, 196 Spherocytosis, hereditary, 164–165 Spinal cord cervical and radicular syndromes, 189 extramedullary lesions, 191 intramedullary lesions, 192 lumber and radicular syndromes, 189–191 traumatic injury, 188–189 Spirometry, in COPD, 21 Spironolactone for aldosteronism, 115 for androgen excess syndrome, 119 for heart failure, 3 Splenectomy for hereditary spherocytosis, 165 for thalassemias, 161 in thrombocytopenia, 171 Splenic infarction, in sickle-cell disease, 160 Splenomegaly in chronic myelogenous leukemia (CML), 156, 168 in glucose-6-phosphate dehydrogenase (G6PD) deficiency, 165 in hereditary spherocytosis, 164 in thrombocytopenia, 171 in viral hepatitis, 76 Spondyloarthropathies, 129–132 ankylosing spondylitis, 129, 130 enteropathic arthropathies, 132 general characteristics, 129 psoriatic arthritis, 131–132 reactive arthritis, 130–131 Spondylotic degeneration, cervical spine, 189 Sputum in asthma, 19 in bronchiectasis, 22 in lung carcinoma, 150 in lung neoplasia, 35 in sarcoidosis, 26 Squamous cell carcinoma, lung, 34, 34, 149 Staphylococcus aureus food poisoning, 62t MRSA, 84, 87 osteomyelitis, 91, 92 toxic shock syndrome, 94 Staphylococcus epidermidis, 92 Status asthmaticus, 19 Steatorrhea in cystic fibrosis, 23 in malabsorption, 63 in pancreatitis, 72 Stem cell transplant, for chronic myelogenous leukemia, 156 Stent therapy, for esophageal neoplasms, 55 Steroids. See also Corticosteroids for acute pericarditis, 11 Stomach disorders emptying disorders, 56–57 gastritis, 54 neoplasia, 55 peptic ulcer disease, 57–59, 58 Stool analysis in colonic neoplastic disease, 70 in diarrhea, 59 fecal fat analysis, in malabsorption, 63 fecal occult blood, in Crohn disease, 63 in pseudomonas colitis, 71 in ulcerative colitis, 67

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INDEX Streak gonads, 117 Streptococci, 83, 92 Streptococcus pneumoniae, 82, 83t, 86–87, 87 Streptococcus pyogenes, 84 Streptokinase for deep venous thrombosis, 13–14 for pulmonary embolus, 15 Stroke clinical features, 175–176 general characteristics, 175, 176 hemorrhage, 175–177 ischemic, 175–177 laboratory findings, 177 motor, 175 risk factors, 175, 176t treatment, 177–178 Sturge-Weber syndrome, 193 Subarachnoid hemorrhage, 178 Subcutaneous calcinosis, in systemic sclerosis, 134 Sucralfate for esophageal reflux, 135 for gastritis, 54 for peptic ulcer disease, 58 Sulfasalazine for ankylosing spondylitis, 129 for Crohn disease, 64 for reactive arthritis, 131 for ulcerative colitis, 68 Sulfinpyrazone, for gout, 127 Sumatriptan, for headache, 184 Swallowing dysfunction, in amyotrophic lateral sclerosis, 196 Swan-neck deformities, in rheumatoid arthritis, 124 Sweat test, in cystic fibrosis, 23 Sympathomimetics, for asthma, 20 Syncope in aortic regurgitation, 6 in aortic stenosis, 6 in pulmonary embolus, 14 seizure compared, 182 Syndesmophytes, in reactive arthritis, 131 Syndrome of inappropriate antidiuretic hormone secretion (SIADH), 100–101 Synovial fluid analysis in CPPD, 128 in enteropathic arthropathies, 132 in gout, 127 in hemochromatosis, 128 in osteoarthritis, 123 in psoriatic arthritis, 131 in reactive arthritis, 131 in rheumatoid arthritis, 125 Syphilis, 89–90 Syringomyelia, 192 Systemic hypertension. See Hypertension Systemic lupus erythematosus (SLE), 132–133 Systemic sclerosis, 134–135

T T-cell deficiency, 167 T3 resin uptake test, 102 Tachycardia, in heart failure, 1 Tachypnea, in chronic renal disease, 39 Tazobactam for cholangitis, 75 for pneumonia, 87 Telangiectasias, in systemic sclerosis, 134 Temporal arteritis, 139–140 Temporal lobe lesions, 179 Tension headache, 184, 185 Tension pneumothorax, 30, 30–31 Terminal deoxynucleotidyl transferase, 153 Testicular agenesis, 120 Testicular cancer, 143–144 Testicular choriocarcinoma, 120 Testicular feminization syndrome (androgen resistance), 117

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Tetany in hypokalemia, 44 latent, 107 overt, 107 Tetracycline for bacterial overgrowth syndrome, 63 for chemical pleurodesis, 29, 30 for granuloma inguinale, 90 for Lyme disease, 95 for lymphogranuloma venereum, 90 for pharyngitis, 86 Thalassemias, 161 Thiamine, for alcoholic liver disease, 78 Thiazides for diabetes insipidus, 100 for hypertension, 17 for renal calculi, 43 Thoracocentesis in pleural effusions, 29 in pneumothorax, 31 Thrombocytopenia, 170 in acute leukemia, 154 alcohol-induced, 78 Thrombocytosis, in chronic myelogenous leukemia (CML), 169 Thromboembolic stroke. See Stroke Thrombolytic agents for deep venous thrombosis, 13–14 for pulmonary embolus, 15 Thrombotic thrombocytopenic purpura (TTP), 172 Thymectomy, for myasthenia gravis, 197 Thyroid cancer, 104–105 Thyroid gland disorders, 101–106, 104t cancer, 104–105 hyperthyroidism, 101–102 hypothyroidism, 102–103 nodules, 105–106 thyroiditis, 103–104 Thyroid nodules, 105–106 Thyroid storm, 101 Thyroidectomy, subtotal, 102 Thyroiditis Hashimoto, 102, 104 lymphocytic, 104 painless, 104 subacute, 101, 103 Thyroxine for hypothyroidism, 103 for thyroid cancer, 105 for thyroiditis, 104 TIA (transient ischemic attack), 175, 177 Ticlopidine, for ischemic heart disease, 4 Tics, in Tourette syndrome, 187 Tissue plasminogen activator (t-PA) for deep venous thrombosis, 13–14 for ischemic heart disease, 4 for pulmonary embolus, 15 for stroke, 177 Tourette syndrome, 187 Toxic megacolon, 67, 68, 68 Toxic shock syndrome (TSS), 94 Toxoplasmosis, in AIDS, 95, 96 Transfusion for acute leukemia, 154 for aplastic anemia, 162 for glucose-6-phosphate dehydrogenase (G6PD) deficiency, 165 for hereditary spherocytosis, 165 for myelophthisic syndromes, 162 platelet, 170, 171 for red blood cell aplasia, 163 for sickle-cell disease, 161 for sideroblastic anemia, 160 for thalassemias, 161 for thrombocytopenia, 170 Transfusion reaction, hemolytic anemia from, 163 Transient ischemic attack (TIA), 175, 177 Transudative fluid, 28t

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Tremor benign essential, 185 in multiple sclerosis, 198 in Parkinson disease, 186 in Wilson disease, 188 Tricuspid regurgitation, 8–9 Trigeminal neuralgia, headache in, 184, 185 Trimethoprim-sulfamethoxazole (TMP-SMX) for dysfunctional neutrophil disorders, 170 for granuloma inguinale, 90 for otitis, 84 for toxoplasmosis, 96 for urinary tract infection, 91 Troponin, in ischemic heart disease, 4 Trousseau sign, 107 TSH deficiency, 98 TSS (toxic shock syndrome), 94 TTP (thrombotic thrombocytopenic purpura), 172 Tube thoracostomy, 30 Tuberculosis, 93 Tuberous sclerosis, 192 Tumor biliary, 75 hepatic, 79–80 mediastinal masses, 31–32 pheochromocytoma, 115–116 pituitary, 97–98 spinal cord, 191, 192 testicular, 120 Tumor necrosis factor. See Anti-tumor necrosis factor (TNF) agents Turner syndrome, 116–117 21-hydroxylase deficiency, 115 Tzanck test, 90

U Ulcer genital, 89–90 peptic, 57–59, 58 Ulcerative colitis, 66–68, 68 Ulnar nerve injury, 194 Ultrasound in alcoholic liver disease, 78 in aortic aneurysms, 16 in appendicitis, 65 in cholangitis, 75 in cholecystitis, 73 in choledocholithiasis, 74 in hepatic abscess, 79 in ovarian cancer, 144 in pancreatitis, 71 in pelvic inflammatory disease (PID), 89 in primary hyperparathyroidism, 106 in prostatic carcinoma, 143 in renal carcinoma, 142 in testicular cancer, 143 Upper GI series in gastric neoplasms, 55 in peptic ulcer disease, 57–58, 58 in reflux esophagitis, 53 Urea in acute renal failure, 38 in chronic renal disease, 40 Ureaplasma, 91 Uremic toxemia, in chronic renal disease, 39 Urethritis, 88–89 Uric acid in acute leukemia, 154 in gout, 126–127 nephropathy in multiple myeloma, 151 renal calculi, 42 Urinalysis abnormal hematuria, 40–41 proteinuria, 40

in acute renal failure, 38 in colorectal cancer, 147 in dementia, 181 in Goodpasture syndrome, 37, 139 in Henoch-Schönlein purpura, 137 in ketoacidosis, 110 in multiple myeloma, 151 in nonproliferative glomerulonephropathy, 42 in pheochromocytoma, 18 in polyarteritis nodosa, 138 in primary hyperparathyroidism, 106 in proliferative glomerulonephropathy, 41 in renal calculi, 43 in urinary tract infections, 91 in Wegener granulomatosis, 139 Urinary sodium excretion, in SIADH, 100 Urinary tract infections (UTIs), 90–91 Urine collection, 24-hour, in renal calculi, 43 Urine culture, 91 Uropathy, acute obstructive, 127 Uveitis in ankylosing spondylitis, 129 in psoriatic arthritis, 131 in sarcoidosis, 26

V Valproic acid, for seizure, 183t Valvular heart disease aortic regurgitation, 6–7 aortic stenosis, 5–6 mitral regurgitation, 8 mitral stenosis, 7 tricuspid regurgitation, 8–9 Valvuloplasty, balloon, for aortic stenosis, 6 Valvuloplasty, mitral, 7 Vancomycin for dysfunctional neutrophil disorders, 170 for joint infections, 92 for meningitis, 82 for osteomyelitis, 92 for pseudomonas colitis, 71 for toxic shock syndrome (TSS), 94 Vasculitic syndromes, 136–140 Churg-Strauss syndrome, 137–138 general characteristics, 136 giant cell arteritis, 139–140 Goodpasture syndrome, 139 Henoch-Schönlein purpura, 137 hypersensitivity angiitis, 136–137 polyarteritis nodosa, 138 Wegener granulomatosis, 138–139 Vasculitis, in Wegener granulomatosis, 37 Vasodilators for aortic regurgitation, 7 for hypertension, 17 for mitral regurgitation, 8 Vasopressin, for gastrointestinal bleeding, 81 Venography, contrast, in deep venous thrombosis, 13 Ventilation-perfusion scan in lung carcinoma, 150 in pulmonary embolus, 14 Verapamil, for hypertrophic obstructive cardiomyopathy, 10 Vertebral wedge-shaped deformity, in osteoporosis, 120, 121 Vibrio cholerae, food poisoning, 62t Vinblastine, for Hodgkin lymphoma, 152 Virchow node, 55, 145 Visceral angiography in Churg-Strauss syndrome, 138 in polyarteritis nodosa, 138 Visual and auditory evoked responses, in multiple sclerosis, 199 Visual disturbance, in pituitary tumors, 97 Vitamin B12 for Crohn disease, 64 deficiency, 165–166, 171 polyneuropathy from, 194

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INDEX Vitamin C, for Alzheimer disease, 181 Vitamin D for chronic renal disease, 40 deficiency, osteomalacia from, 121 intoxication, 106 for osteomalacia, 122 Vitamin K, for viral hepatitis, 78 Vitamin K-dependent factor deficiencies, 174 Vocal fremitus, in pleural effusion, 28 Volume and electrolyte disorders, 44–52 Vomiting, in appendicitis, 65 Von Willebrand disease, 173–174

W Warfarin for atrial fibrillation, 5 for mitral stenosis, 7

Water deprivation test, for diabetes insipidus, 100, 100t Wegener granulomatosis, 138–139 Wernicke aphasia, 180 Whiplash injury, 189 Wilson disease, 187–188 Wright staining, of stools, 59

X Xerophthalmia, 136 Xerostomia, 136 Xylose absorption test, in malabsorption, 63

Z Zinc, for Wilson disease, 188 Zoledronate, for hypercalcemia, 107

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