5580_FM_ppi-xii 8/28/06 11:22 AM Page i

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

2 Pulmonary Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .19

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

3 Renal, Fluid, and Electrolyte Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .38

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

4 Gastrointestinal Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .53

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

vii
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viii CONTENTS

5 Infectious Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .82

I. Central Nervous System (CNS) Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .82
II. Head and Neck Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .84
III. Respiratory Tract Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .84
IV. Gastrointestinal Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .88
V. Genital and Sexually Transmitted Infectious Diseases . . . . . . . . . . . . . . . . . . . . . . . .88
VI. Urinary Tract Infections (UTIs) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .90
VII. Osteomyelitis and Joint Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .91
VIII. Other Infectious Syndromes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .92

6 Endocrinologic and Metabolic Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .97

I. Disorders of the Pituitary Gland . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .97
II. Disorders of the Thyroid Gland . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .101
III. Disorders of the Parathyroid Gland . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .106
IV. Glucose Homeostasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .108
V. Adrenal Gland Dysfunction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .111
VI. Female Reproductive Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .116
VII. Male Reproductive Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .119
VIII. Disorders of Bone Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .120

7 Rheumatic Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .123

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

8 Oncologic Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .141

I. Head and Neck Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .141
II. Renal and Bladder Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .142
III. Prostatic Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .142
IV. Testicular Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .143
V. Ovarian Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .144
VI. Gastric Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .144
VII. Pancreatic Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .145
VIII. Colorectal Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .146
IX. Lung Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .149
X. Multiple Myeloma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .150
XI. The Lymphomas . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .151
XII. The Leukemias . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .153

9 Hematologic Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .157

I. Anemias . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .157
II. Hematocrit Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .166
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CONTENTS ix

III. Leukocyte Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .167

IV. Hemostasis and Coagulation Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .170

10 Neurologic Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .175

I. Cerebrovascular Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .175
II. Disorders of Higher Cognitive Function . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .179
III. Dementia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .180
IV. Seizure Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .181
V. Headaches . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .183
VI. Movement Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 185
VII. Spinal Cord Syndromes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .188
VIII. Neurocutaneous Syndromes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .192
IX. Peripheral Neural Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .193
X. Neuromuscular Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .196
XI. 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 re-
ceived 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 educa-
tion. 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 em-
ploys 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

xi
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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 ather-
osclerotic disease.
3. Other causes include myocarditis, cardiomyopathies, valvular insufficiency or steno-
sis, hypertension, constrictive pericarditis, and arrhythmias.

B. CLINICAL FEATURES
1. Left-sided CHF: Low cardiac output (if measured by Swan), hypotension and tachy-
cardia (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 pil-
lows 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. S4 may also occur.
9. Nocturia occurs due to increased renal blood flow during recumbency.
10. Acute CHF may present secondary to acute MI (see II.B.2).
11. 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 tak-
ing 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 symp-
toms, 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

g. 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.
3. If oxygenation fails to improve the patient’s deteriorating condition (e.g., persistent
cyanosis, obtundation), intubation is indicated with positive pressure ventilation.
4. Invasive hemodynamic monitoring is reserved for those cases of pulmonary
edema that do not resolve.
5. Implantable cardioverter defibrillators (ICDs) have been shown to reduce the risk
of death; about half of patients with CHF die of sudden ventricular arrhythmias.

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. 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 grad-
ual 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 dys-
function secondary to ischemia.
2. 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. Patients may develop CHF and pulmonary congestion.
3. Hypotension and cardiogenic shock may occur in significant infarction.
4. Acute onset of CHF in conjunction with holosystolic murmur after MI usually
indicates papillary muscle rupture with mitral valve insufficiency or ventricular
septal rupture.
5. Life-threatening ventricular arrhythmias are common in the first 24 hours
after MI.
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4 CHAPTER 1

6. Inferior wall MIs often produce sinus bradycardia and/or atrioventricular nodal
block.
7. Bundle-branch blocks are more likely with anterior MIs.
8. Left ventricular arrhythmias may lead to systemic emboli.
9. 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. 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 sig-
nificant changes.
2. 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.
3. Echocardiography confirms the diagnosis and can be used to quantitate the sever-
ity 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 reduc-
ing 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 thrombol-
ysis 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 anti-
coagulation with heparin or low-molecular-weight heparin followed by long-
term oral anticoagulation is needed.
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CARDIOVASCULAR DISEASES 5

III Atrial Fibrillation (AF)

A. GENERAL CHARACTERISTICS
1. The most common chronic arrhythmia
2. May be secondary to myocardial infarction, rheumatic heart disease, dilated or hyper-
trophic cardiomyopathy, atrial septal disease, trauma, hypothyroid surgery, hyperten-
sion, ethanol intoxication, or mitral valve prolapse, or it may be idiopathic.

B. CLINICAL FEATURES
1. Irregularly irregular rhythm with a rate <180 bpm.
2. Hypotension may occur if the rate is too high to allow for adequate filling.
3. CHF, MI, or stroke may occur as a result of AF.
4. Patients may report palpitations, shortness of breath, or dizziness.

C. LABORATORY FINDINGS. ECG is diagnostic, showing absent P-waves and an irreg-

ularly irregular rhythm. Elevated T3 or T4 levels may indicate thyroid dysfunction as the
cause.

D. TREATMENT OF ACUTE AF
1. Hemodynamically unstable or symptomatic: synchronized electrical cardioversion
with 100 J initially.
2. Hemodynamically stable: attempts to restore normal sinus rhythm should be under-
taken within 48 hours. If delayed, cardioversion becomes more difficult and mural
thrombus may develop and embolize during subsequent cardioversion.
a. An underlying cause should be sought and treated.
b. Amiodarone, β-blockers, procainamide, or digoxin have been useful in chem-
ical conversion.
c. Rate control can quickly be achieved with either calcium channel blockers or
β-blockers. Caution for hypotension, which may lead to electrical cardioversion.
d. Anticoagulation to an international normalized ratio (INR) of 2–3 with war-
farin to prevent thromboembolism is recommended unless there is a contra-
diction; aspirin is an alternative for patients who do not have other risk factors
for stroke (e.g., history of transient ischemic attack, valve replacement, previ-
ous stroke).

IV Valvular Heart Disease

A. The most common valvular disorders include aortic stenosis, aortic regurgitation,
mitral stenosis, mitral regurgitation, and tricuspid regurgitation.

B. AORTIC STENOSIS
1. General characteristics
a. Aortic stenosis is most commonly caused either by calcification of the aor-
tic valve or by a congenital bicuspid aortic valve that gradually thickens and
becomes stenotic during adulthood.
b. Aortic stenosis may occur secondary to rheumatic fever, but rarely without
coexistent mitral involvement, and is rarely seen in developed countries.
c. The condition affects more men than women (ratio of 3:1).
d. Aortic obstruction → increased left ventricular pressure → left ventricu-
lar hypertrophy (not dilatation, as in CHF).
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6 CHAPTER 1

2. Clinical features. Most patients are asymptomatic for years as the stenosis progresses.
a. Angina is a common symptom due to increased myocardial oxygen demands.
b. Syncope during exercise occurs due to the compensatory decrease in periph-
eral resistance combined with the inability of the heart to maintain adequate
stroke volumes across the stenotic aortic valve.
c. Prolonged, severe pressure overload occurs, which leads to CHF from myocar-
dial dysfunction.
d. Delayed carotid upstroke, soft S2 (due to decreased A2 sound), S4 sound (due
to ventricular hypertrophy), and systolic ejection murmur are present.
e. Severe stenosis puts the patient at risk for sudden death.
3. Laboratory findings
a. ECG reveals evidence of left ventricular hypertrophy (nonspecific).
b. Echocardiography provides assessment of the presence of valvular calcifica-
tion, peak jet velocity across the valve, and valve surface area, which are used
to predict the need for surgery. The combination of significant calcifications
and an increase in velocity of ≥0.3 m/s in serial echocardiograms within 1 year
is associated with the need for surgery or the occurance of sudden death.
4. Treatment
a. Patients with good left ventricular function have the lowest mortality during
aortic valve replacement; patients with poor ejection fractions who survive
surgery often respond well (i.e., poor left ventricular function is not a con-
traindication to surgery). Symptomatic patients with valve area ≤0.6 cm and/or
left ventricular hypertrophy should undergo surgical valve replacement.
b. Balloon valvuloplasty can be effective for patients who are poor surgical can-
didates (restenosis is common).

C. AORTIC REGURGITATION
1. General characteristics
a. Aortic regurgitation is commonly caused by prolapse of the aortic leaflet asso-
ciated with myxomatous, aortic valve ring ectasia, or aortic root dilation.
b. This condition may also occur secondary to infective endocarditis, hyper-
tension, syphilis, or collagen vascular diseases.
c. Aortic regurgitation → increased end-diastolic volume → ventricular
dilatation → mitral regurgitation.
2. Clinical features
a. Patients have signs and symptoms of left ventricular failure, including orthop-
nea, dyspnea, and nocturia.
b. Syncope may occur due to decreased diastolic pressures secondary to regurgi-
tation, but this is less common than in aortic stenosis.
c. Reduced diastolic pressures also compromise coronary blood flow and occa-
sionally present as angina.
d. Additional signs include laterally displaced point of maximal impulse, dia-
stolic blowing murmur, and widened pulse pressure.
e. Decreased S2 sounds and early diastolic murmur occur along the left sternal
border.
f. In patients with acute aortic regurgitation secondary to infective endocarditis,
fever and chills may indicate bacteremia.
3. Laboratory findings
a. ECG is usually not helpful, but may show left axis deviation.
b. Chest radiographic study reveals cardiac enlargement with or without signs
of pulmonary congestion; a dilated proximal aorta may be seen.
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CARDIOVASCULAR DISEASES 7

c. Echocardiography reveals enlarged left ventricle with mitral valve vibration

during diastole secondary to aortic regurgitation. Vegetations on valves indi-
cate endocarditis.
d. Blood cultures may be positive if endocarditis is the cause.
4. Treatment
a. Arterial vasodilators, diuretics, and digitalis (which increases cardiac contrac-
tility) may be used for symptomatic relief to reduce the degree of regurgitation.
b. Surgical valve replacement is indicated when signs of decompensation
occur.
c. Prosthetic valve replacement requires long-term anticoagulant therapy and
antibiotic prophylaxis for any operative procedure (including dental procedures).
d. Broad-spectrum antibiotics are needed for endocarditis.

D. MITRAL STENOSIS
1. General characteristics
a. Mitral stenosis is almost always due to rheumatic fever and usually occurs
in women.
b. Mitral stenosis → increased left atrial pressure and enlargement → pulmonary
venous congestion → pulmonary hypertension → right-sided failure.
2. Clinical features
a. When the primary cause is childhood rheumatic fever, age of onset of
mitral stenosis is usually between 24 and 45 years.
b. Dyspnea and orthopnea are common.
c. Right-sided failure leads to ascites, edema, anorexia, and fatigue.
d. Hemoptysis occurs secondary to increased pulmonary pressures and vessel
rupture.
e. Patients have an irregular pulse secondary to associated atrial fibrillation.
f. Systemic emboli occur due to thrombi formed in the fibrillating atrium.
g. Additional signs include increased S1, increased P2 (if pulmonary hyperten-
sion is present), opening snap following S2, diastolic rumble, and inspiratory
crackles (if pulmonary congestion is present).
3. Laboratory findings
a. ECG may reveal left atrial enlargement or atrial fibrillation.
b. Chest radiographic study reveals atrial enlargement, pulmonary congestion,
loss of retrosternal air space laterally (if right ventricular hypertrophy has
occurred secondary to pulmonary hypertension).
c. Echocardiogram often provides sufficient diagnostic imaging of the stenotic
mitral valve; however, cardiac catheterization is still performed to assess
other structures that may also be affected.
4. Treatment
a. Medical therapy includes diuretic drugs for patients who have pulmonary
congestion and digitalis and long-term anticoagulant therapy (warfarin) for
patients who have atrial fibrillation.
b. To reduce operative mortality, surgery should be performed before onset of
pulmonary hypertension.
i. Because hypertension does reverse on correction of the defect, it is not a
contraindication to surgery.
ii. Systemic embolization despite anticoagulant therapy is an indication for
surgery.
c. Mitral valvuloplasty should be performed on patients who are poor surgical
candidates (restenosis often occurs).
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8 CHAPTER 1

E. MITRAL REGURGITATION
1. General characteristics
a. Mitral regurgitation is most commonly caused by rheumatic fever and is
more common in men.
b. The condition can occur acutely with MI if papillary muscle rupture occurs.
c. Mitral regurgitation may also be seen in mitral valve prolapse and hyper-
trophic cardiomyopathy, or secondary to cardiac dilatation.
d. Mitral regurgitation → increased left atrial pressure → increased pulmonary
pressure → left ventricular dilatation (due to increased stroke volumes against
the low resistance of the regurgitant mitral valve).
2. Clinical features
a. Signs include dyspnea and orthopnea.
b. Pulmonary hypertension and right-sided failure occur if regurgitation is
severe and chronic.
c. Atrial fibrillation and systemic emboli may occur.
d. Additional signs include displaced point of maximal impulse, holosystolic api-
cal murmur radiating to the axilla, and an S3 sound (rapid filling of the left
ventricle from the overloaded atrium).
3. Laboratory findings
a. ECG reveals evidence of left ventricular hypertrophy and enlargement.
b. Chest radiographic study reveals cardiac enlargement with or without pul-
monary congestion.
c. Echocardiography shows a regurgitant mitral valve and enlarged left-sided
chambers.
4. Treatment
a. Because muscle dysfunction can occur, mitral valve replacement must be per-
formed early.
b. Medical therapy includes:
i. Digitalis for patients in atrial fibrillation or with cardiac muscle dysfunction
ii. Diuretic drugs for pulmonary congestion
iii. Arterial vasodilators to increase forward flow
iv. Anticoagulant drugs for patients with atrial fibrillation at risk of develop-
ing emboli

F. TRICUSPID REGURGITATION
1. General characteristics
a. Tricuspid regurgitation is usually secondary to right ventricular dilatation
from pulmonary hypertension and may therefore occur with rheumatic
fever.
b. This condition should be suspected in drug addicts who have infective
endocarditis.
c. Tricuspid regurgitation → increased right atrial pressure → venous hypertension.
2. Clinical features
a. Signs and symptoms are similar to those of right-sided failure (ascites and
edema).
b. Right upper quadrant pain may occur due to hepatic congestion if the con-
dition develops acutely.
c. Holosystolic murmur is detected along left sternal border.
d. An additional sign is elevated JVP during systole.
e. Patients have hepatojugular reflux and a pulsatile liver.
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CARDIOVASCULAR DISEASES 9

3. Laboratory findings
a. ECG may reveal right ventricular and atrial enlargement.
b. Chest radiographic study reveals loss of retrosternal air space laterally, which
indicates an enlarged right ventricle.
c. Echocardiography reveals enlarged right-sided chambers; Doppler flow studies
can reveal the significance of the regurgitant valve.
4. Treatment
a. Underlying disease must be treated.
b. Isolated tricuspid regurgitation is usually well tolerated and does not require
surgery.

V Cardiomyopathies and Pericardial Disease

A. GENERAL CONSIDERATIONS
1. These two clinical entities are considered together because they often produce a
similar clinical picture.
2. Cardiomyopathies include congestive cardiomyopathy, hypertrophic obstructive
cardiomyopathy, and restrictive cardiomyopathy.
3. Pericardial disease can present as acute pericarditis, pericardial effusion, or con-
strictive pericarditis.

B. CONGESTIVE (DILATED) CARDIOMYOPATHY

1. General characteristics
a. Congestive cardiomyopathy is a loss of cardiac muscle function in the
absence of pressure or volume overload and coronary artery disease; that
is, it is strictly caused by a malfunction of myocardium.
b. Prolonged ethanol abuse is the most common cause.
c. This condition may be idiopathic or may be caused by infections or drugs
other than ethanol (e.g., doxorubicin).
d. Cardiac dilatation → left and right systolic dysfunction → congestive heart
failure.
2. Clinical features
a. Signs and symptoms are similar to those of congestive heart failure.
b. Murmur of mitral regurgitation may be present secondary to dilatation.
3. Laboratory findings
a. ECG reveals nonspecific ST and T wave changes; left bundle-branch block is
also common.
b. Chest radiographic study reveals cardiomegaly with pulmonary vascular
congestion.
c. Echocardiography reveals dilated chambers with poor wall motion.
d. Cardiac catheterization is not required for diagnosis.
4. Treatment
a. If present, the offending agent (ethanol, other drugs) should be with-
drawn.
b. CHF should be treated with sodium restriction; diuretic drugs; and digi-
talis, which improves contractility.
c. In selected patients, cardiac transplantation is effective.
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10 CHAPTER 1

C. HYPERTROPHIC OBSTRUCTIVE CARDIOMYOPATHY

1. General characteristics
a. This condition is also known as idiopathic hypertrophic subaortic stenosis.
b. Hypertrophy of interventricular septum → left ventricular outflow obstruc-
tion and impaired diastolic filling due to stiff left ventricle → pulmonary
congestion.
c. Most cases are autosomal dominant.
2. Clinical features
a. Dyspnea is the most common sign and is secondary to pulmonary congestion.
b. Angina is often present.
c. Syncope after exercise occurs due to peripheral vasodilation, which decreases
afterload → decreased left ventricular size → increased outflow obstruction.
d. Carotid upstroke has a spike-and-dome configuration.
e. Systolic ejection murmur, usually nonradiating, is detected along the left
sternal border; murmur increases with maneuvers that decrease left ventricular
size (e.g., Valsalva maneuver or standing).
3. Laboratory findings
a. ECG reveals hypertrophy of the left ventricle.
b. Echocardiography is the best technique for visualizing the hypertrophic septum.
c. Cardiac catheterization is used in patients who require quantification of the
degree of obstruction before surgery or in a patient whose septum is not well
visualized by echocardiography.
4. Treatment
a. Medical therapy is the standard approach.
i. β-Blockers (e.g., propranolol) slow the heart rate and allow increased dia-
stolic filling time, which diminishes the obstruction.
ii. Calcium channel blockers (e.g., verapamil) improve ventricular compliance.
b. Surgical therapy involves myomectomy and/or mitral valve replacement
(the anterior leaflet of the mitral valve often produces obstruction); no evi-
dence exists that surgery prolongs life in these patients.

D. RESTRICTIVE CARDIOMYOPATHY
1. General characteristics
a. Myocardium composition changes → noncompliance → diastolic non-
compliance with elevated filling pressures → pulmonary congestion.
b. This condition is less common than dilated or hypertrophic cardiomyopathies.
c. Restrictive cardiomyopathy is often caused by an infiltrative process (e.g.,
amyloidosis, sarcoidosis, hemochromatosis).
2. Clinical features
a. Signs and symptoms are similar to those of CHF.
b. Kussmaul sign (an inspiratory increase in central venous pressure) may be
present.
3. Laboratory findings
a. ECG reveals low-voltage QRS complexes and nonspecific ST- and T-wave
abnormalities.
b. Chest radiographic study reveals pulmonary congestion without cardiomegaly.
c. Echocardiography often reveals left ventricular thickening (left ventricular
thickening in conjunction with low ECG voltages aids in diagnosis).
d. Cardiac catheterization reveals unequal pressures in all four chambers in
contrast to constrictive pericarditis.
e. Specific cause is diagnosed through tissue biopsy.
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CARDIOVASCULAR DISEASES 11

4. Treatment
a. The underlying cause must be treated, if possible.
b. Diuretic drugs may alleviate symptoms of CHF.
c. Digitalis may be used cautiously to increase contractility (these patients are
sensitive to the drug’s toxic effects).

E. ACUTE PERICARDITIS
1. General characteristics
a. Acute pericarditis is an inflammation of the pericardium.
b. The disease may be idiopathic or secondary to a viral infection (e.g., cox-
sackievirus B, hepatitis B, cytomegalovirus), bacterial infection (Staphylococcus
spp., Streptococcus spp., tubercle bacillus), post-MI complications, drugs (e.g.,
procainamide), malignancy (usually pulmonary or breast metastases), or collagen
vascular disease (e.g., systemic lupus erythematosus).
2. Clinical features
a. Patients report chest pain that worsens with deep breathing, coughing, and
lying down and is relieved by sitting and leaning forward.
b. Pericardial friction rub is heard in both systole and diastole; this finding is
diagnostic.
3. Laboratory findings
a. ECG reveals ST segment elevation in all precordial leads (Figure 1-2) with-
out reciprocal ST segment depression (which occurs in MI).
b. Echocardiography often reveals a pericardial effusion, which confirms the
diagnosis.
4. Treatment
a. The underlying cause must be treated.
b. Nonsteroidal anti-inflammatory drugs (NSAIDs) are usually effective in
relieving pain and inflammation.
c. Patients should be given steroids if they are unresponsive to NSAIDs.
d. Results of cardiac enzyme assays are usually normal, but they may be help-
ful in ruling out MI.

F. PERICARDIAL EFFUSION
1. General characteristics
a. Prolonged and/or severe inflammation leads to an effusion.
b. Rapid effusion leads to cardiac tamponade, but chronic accumulation is
accommodated by the expanding pericardium.
2. Clinical features
a. A small effusion produces no symptoms.
b. Large effusions lead to cardiac tamponade (hypotension, tachycardia, dis-
tended neck veins, indistinct heart sounds).
c. Heart sounds are diminished, and it is difficult to locate the point of maxi-
mal impulse.
d. Friction rub secondary to coexistent pericarditis is heard.
3. Laboratory findings
a. ECG reveals low-voltage QRS complexes and ST changes associated with
pericarditis.
b. Cardiac shadow has an enlarged “water-bottle” appearance on chest radi-
ograph.
c. Echocardiography may show an anechoic space between the layers of peri-
cardium; this sign is diagnostic of pericardial effusion.
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12 CHAPTER 1

aVF
I

Reciprocal ST
II aVR

V2 V3 V4

V5 V6

● Figure 1-2. ECG of a patient who has acute pericarditis showing ST-segment elevation in all precordial leads (heavy
arrow), but no reciprocal ST-segment depression.

d. Pericardiocentesis, the aspiration of fluid in the pericardial space, confirms

the diagnosis.
i. Fluid should be sent for culture: protein and LDH assays (LDH and pro-
tein determine if fluid is a transudate or exudate), cytology, and antinu-
clear antibody assay (if collagen vascular disease is suspected).
ii. If tap is bloody, then let it clot.
a. If it does not clot, then it is blood from the effusion.
b. If it does clot, then it is ventricular blood from a puncture during the
procedure.
4. Treatment
a. If symptoms are severe, pericardiocentesis is indicated to remove fluid.
b. Otherwise, therapy is the same as for acute pericarditis.

G. CONSTRICTIVE PERICARDITIS
1. General characteristics
a. Constrictive pericarditis is a thickening and fibrosis of the pericardium that
occurs long after an acute episode of pericarditis.
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CARDIOVASCULAR DISEASES 13

b. The condition can occur after bacterial, viral, fungal, or neoplastic peri-
carditis.
c. Constrictive pericarditis produces decreased diastolic filling.
2. Clinical features
a. Patients report dyspnea on exertion and orthopnea.
b. Edema, ascites, pulsatile liver, and elevated JVP are additional signs.
c. The volume of the carotid pulse is decreased.
d. Heart sounds are distant, and a pericardial knock is detected after S2.
3. Laboratory findings
a. ECG commonly reveals low voltage in limb leads and atrial arrhythmias.
b. Chest radiographic study reveals pericardial calcification.
c. Echocardiography is often unreliable diagnostically.
d. Cardiac catheterization reveals equal and elevated pressures in all four
chambers (unlike restrictive cardiomyopathy); ventricular pressure trac-
ings reveal the characteristic diastolic dip and systolic plateau (square
root sign).
4. Treatment is pericardiectomy.

VI Deep Venous Thrombosis, Pulmonary Embolus, and Aortic Aneurysms

A. DEEP VENOUS THROMBOSIS (DVT)
1. General characteristics
a. In DVT, a blood clot forms in the veins of the lower extremity or pelvis.
Proximal DVT forms in veins above the knee and has a higher risk of pul-
monary embolism than calf vein venous thrombosis.
b. DVT is most often associated with prolonged immobilization (e.g., extend-
ed postoperative period), hypercoagulable states (e.g., malignancies, estro-
gen use), CHF, and varicose veins (valvular insufficiency).
c. DVT may not manifest until the patient presents with the complication of
PE.
2. Clinical features include leg pain, swelling, warmth, and calf tenderness of the
affected limb.
3. Laboratory findings
a. Doppler studies are most effective in patients who have more proximal lesions;
because these studies are noninvasive, they should be performed first.
b. Contrast venography is the most effective method of delineating venous
occlusion, but is rarely necessary because it has been replaced with Doppler.
4. Treatment
a. Intravenous heparin to reach a partial thromboplastin time (PTT) between 60
and 90 seconds is followed by oral anticoagulation to reach an INR between 2
and 3. (Low-molecular-weight heparin may be used instead and is dosed based
on the patient’s weight.)
b. Oral anticoagulation is required for 6 months.
c. When switching to oral therapy, the patient must be maintained on intra-
venous heparin for 2–5 days after oral treatment is initiated because of the
lag that exists between the initiation of each therapy and attainment of its ther-
apeutic effect.
d. Thrombolytic agents (streptokinase, t-PA) have not been shown to signifi-
cantly alter morbidity, mortality, or recurrence rates; therefore, these agents are
generally not used.
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14 CHAPTER 1

e. Patients with below-knee DVT have a longer risk of PE and therefore should
be followed up with Doppler to determine whether they develop extension
into the proximal vein, which then requires therapy, unless the venous throm-
bosis is producing leg symptoms, in which case anticoagulation is appropriate.

B. PULMONARY EMBOLUS
1. General characteristics
a. Pulmonary embolus results when a thrombus from a DVT breaks off and
travels through the right-sided circulation and becomes lodged in the pul-
monary artery.
b. This condition produces ventilation–perfusion mismatching → hypoxemia.
c. An extensive embolus may produce pulmonary infarction and right ven-
tricular overload, with cardiovascular collapse.
2. Clinical features
a. Dyspnea is the most common sign.
b. Additional signs and symptoms include pleuritic chest pain, tachypnea, and
hemoptysis.
c. Syncope may occur if PE is extensive and compromises cardiac output.
d. Patients are tachycardic and have a low-grade fever (<38.0°C).
e. Splinting, wheezing, and a pleural effusion may be detected.
f. In massive PE, right-sided heart failure with hypotension and tachycardia
and a loud P2 are evident.
g. Evidence of a DVT may be present, which should alert the physician to the
diagnosis of PE.
3. Laboratory findings
a. ECG often reveals only sinus tachycardia, but may also show poor R-wave
progression in anterior leads.
b. Chest radiographic study may reveal decreased vascular markings in the
area of the obstruction; a wedge-shaped pleural-based density is a classic
sign if pulmonary infarction has occurred and may be associated with a pleu-
ral effusion (Figure 1-3).
c. Results of arterial blood gas studies may indicate hypoxia, hypocarbia (due
to hyperventilation), and respiratory alkalosis; however, these changes are not
specific to PE and may not necessarily be present.
d. Normal ventilation–perfusion scan results rule out the diagnosis of PE.
i. However, the results are often of intermediate probability (i.e., PE diagno-
sis cannot be confirmed or ruled out).
ii. Ventilation–perfusion scan should be performed if the situation is not
emergent, because this procedure carries less risk than pulmonary angiog-
raphy.
e. Pulmonary angiography (arteriography) was the gold standard for diagnosis
of PE; this procedure requires a pulmonary artery catheter and contrast mate-
rial and therefore carries some risk.
f. CT angiography is now the diagnostic tool of choice in most centers and has
largely replaced ventilation–perfusion scans and pulmonary angiography.
4. Treatment
a. Patients should receive oxygen by mask.
b. IV heparin should be given for 7–10 days to maintain the PTT between 1.5
and 2.0 times the normal value (60–90 sec); in patients who have clinical
symptoms that strongly suggest the diagnosis, heparin should be started before
diagnostic confirmation.
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CARDIOVASCULAR DISEASES 15

● Figure 1-3. The uncommonly seen appearance of pulmonary embolism on radiographic chest film. Note the opacity in
the right lower lobe. This nonspecific finding could represent an infectious infiltrate; however, this patient’s ventilation–
perfusion scan reveals that the patient has had a pulmonary embolism. (Reprinted with permission from Freundlich IM,
Bragg DG: A Radiologic Approach to Diseases of the Chest, 2nd ed. Baltimore, Williams & Wilkins, 1996, p 410.)

c. Oral anticoagulation therapy can be started before heparin is discontinued

to maintain PT at 1.3 to 1.5 times baseline (INR, 2.0–3.0), for approximately
6 months.
d. Patients who have massive embolus producing cardiovascular instability may
benefit from thrombolytic agents (streptokinase or t-PA) or embolectomy via
interventional radiology or surgical means.
e. If anticoagulation is contraindicated (e.g., recent or ongoing hemorrhage)
or if the patient shows evidence of recurrent PE despite heparin therapy in
the initial 24 hours, a venacaval interruption (with a Greenfield filter) may
be performed to prevent further episodes of PE.

C. AORTIC ANEURYSMS
1. General characteristics
a. Aortic aneurysms may occur in the ascending aorta, aortic arch, descending
aorta, or abdominal aorta.
b. The most common cause of aortic aneurysm is atherosclerotic disease lead-
ing to abdominal aortic aneurysm; this type is usually seen in older men.
2. Clinical features
a. The condition is usually asymptomatic until rupture occurs, or the
aneurysm may be perceived as an abdominal fullness or pulsation.
b. Back and epigastric pain may be present, which becomes severe before rup-
ture.
c. A pulsatile abdominal mass may be palpated.
d. Evidence of peripheral emboli may be present.
e. Symptoms of associated peripheral vascular disease (e.g., intermittent clau-
dication) are common.
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16 CHAPTER 1

f. Aneurysm may rupture into the gastrointestinal (GI) tract in the form of acute
massive GI hemorrhage.
i. Ruptures into the retroperitoneal space produce flank or groin
hematomas.
ii. Ruptures into the abdominal cavity produce abdominal distention.
3. Laboratory findings
a. Abdominal ultrasound is effective in detecting and measuring the diameter of
aortic aneurysms.
b. Angiography is necessary to define surgical anatomy.
4. Treatment
a. Surgery is recommended for aneurysms >6 cm in size and for patients whose
aneurysms have ruptured.
b. Poor surgical candidates with aneurysms between 4 and 6 cm can be fol-
lowed up closely because these aneurysms rupture less frequently than larger
aneurysms; however, these patients require surgery if the aneurysm expands
or signs of impending rupture occur.

VII Systemic Hypertension

A. GENERAL CHARACTERISTICS
1. Systemic hypertension is defined as blood pressure that is consistently >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 min-
utes before measurement.

B. ESSENTIAL (PRIMARY) HYPERTENSION

1. General characteristics
a. Essential hypertension is defined as hypertension that occurs without any
identifiable cause.
b. Ninety to ninety-five percent of hypertensive patients fall into this category.
c. Essential hypertension is usually detected during middle age.
d. If the condition is not treated, the mortality rate increases dramatically due
to stroke, coronary artery disease, and/or congestive heart failure.
e. Retinal hemorrhages indicate more severe disease.
f. Malignant hypertension is a rapidly progressive form of essential hyper-
tension with diastolic readings >120 mm Hg and widespread end-organ dys-
function.
2. Clinical features
a. Patients are often asymptomatic until they are seen with complications as
described previously.
b. 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 17

3. Laboratory findings
a. Patients who have hypertension should have baseline studies to give an indi-
cation of end-organ function.
b. 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.
4. Treatment
a. Treatment should be aimed at reducing diastolic pressures to <90 mm Hg.
b. Limiting dietary sodium to <2 g/day may be sufficient and should constitute
the first line of therapy unless more severe disease is present.
c. Diuretic drugs (thiazides) decrease plasma volume and vascular resistance;
diuretics may cause hypokalemia and hyperuricemia, which may necessitate
the use of potassium supplements.
d. β-Blockers (e.g., propranolol) reduce cardiac output and decrease renin-
angiotensin–mediated sodium and water reabsorption; side effects include
worsening CHF, occasional vascular incompetence, fatigue, depression, and
nightmares.
e. Vasodilators (hydralazine, minoxidil) are effective when used with
β-blockers; β-blockers inhibit the reflex tachycardia that can occur with
vasodilators.
f. Methyldopa and clonidine (centrally acting adrenergic agonists) may be
effective in cases in which β-blockers are relatively contraindicated.
g. Prazosin and phenoxybenzamine (α-blockers) are used less commonly.
h. Angiotensin-converting enzyme (ACE) inhibitors such as captopril are effec-
tive in reducing hypertension and may be cardioprotective; side effects
include leukopenia, rashes, cough, and proteinuria.
i. Therapeutic approach consists of first instituting dietary measures. If these
measures fail, institute diuretic drug therapy; then, add a β-blocker if
required, followed by a vasodilator, and then followed by captopril or an
α-blocker.

C. SECONDARY HYPERTENSION
1. General characteristics
a. Secondary hypertension is seen in 5% to 10% of patients who have hyper-
tension.
b. Secondary hypertension should be suspected if hypertension appears in a
young person or in a person who does not have a response to treatments
for primary hypertension.
c. Important treatable causes include renovascular hypertension and
pheochromocytoma.
d. Other causes include renal parenchymal disease (acute or chronic), oral
contraceptive use (hypertension occurs in 5% of users and is reversible on
discontinuation of the preparation), primary aldosteronism, Cushing syn-
drome, and hyperparathyroidism.
2. Renovascular hypertension
a. General characteristics
i. Obstruction of renal blood flow → perceived as volume depletion by
kidney → stimulation of the renin-angiotensin-aldosterone system →
increased sodium and water reabsorption → hypertension.
ii. This disease is often caused by atherosclerotic disease in the elderly or
fibromuscular disease of the renal artery in young women.
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18 CHAPTER 1

b. A clinical feature is abdominal bruit over the renal artery.

c. Laboratory findings
i. Renal arteriogram reveals a stenotic lesion, which is diagnostic.
ii. CT angiography has largely replaced standard arteriography.
iii. In cases in which renal insufficiency is a contradiction to contrast, magnetic
resonance angiography or a captopril test can be used to identify the stenosis.
iv. Renal vein renin tests show increased renin in samples drawn from renal
vein ipsilateral to the stenosis compared with samples drawn from the
contralateral side (if the contralateral side is unaffected). This is usually
unnecessary with improved imaging technology.
v. Elevated serum urea level is indicative of decreased renal perfusion.
d. Treatment
i. Medical therapy consisting of ACE inhibitors and other antihyperten-
sives is used in poor surgical candidates.
ii. Transluminal angioplasty or surgical revascularization is often curative
in operable candidates.
3. Pheochromocytoma is a tumor of the adrenal gland that produces norepinephrine.
a. Clinical features
i. Signs and symptoms include paroxysmal sweating, flushing, and palpi-
tations.
ii. Orthostatic hypotension with intermittent hypertension is present.
b. Laboratory findings
i. Urinalysis reveals increased catecholamine, metanephrine, and vanillyl-
mandelic acid levels.
ii. Computed tomographic scan of the abdomen often reveals the tumor.
c. Treatment is surgical removal of the tumor following preoperative blood
pressure control with β-blockers.
5580_Ch02_pp019-037 8/28/06 11:21 AM Page 19

Chapter 2
Pulmonary Diseases

I Obstructive Lung Disease

A. These diseases are characterized by decreased expiratory flow rates and include
asthma, chronic obstructive pulmonary disease, bronchiectasis, and cystic fibrosis.

B. ASTHMA
1. General characteristics
a. Chronic inflammatory disorder of airways → airway hyperresponsiveness.
b. Asthma occurs in 5% to 10% of the population.
c. Symptoms may be precipitated by exercise, respiratory infection, stress, weath-
er changes, or respirable particles (e.g., smoke, ozone).
d. Patients may have a spectrum from mild to severe disease (Table 2-1).
2. Clinical features
a. Patients experience episodic bouts of coughing, dyspnea, expiratory wheez-
ing, and chest tightness.
b. Symptoms worsen with exercise, inhaling cold air or irritating gases,
upper respiratory tract infections, and emotional stress.
c. Tachycardia, tachypnea with prolonged expiration, and overinflation of
chest occur during episodes.
d. Status asthmaticus is a prolonged, severe asthmatic attack that does not
respond to initial bronchodilator therapy.
i. Status asthmaticus leads to fatigue, cyanosis, tachycardia, and pulsus
paradoxus (decrease in systolic blood pressure
15 mm Hg with inspi-
ration).
ii. These patients are at risk for respiratory failure and death.
3. Laboratory findings
a. Pulmonary function tests reveal decreased forced expiratory volume in 1
second (FEV1), hyperinflation that improves with inhalation by a bronchodi-
lating drug, and increased total lung capacity (TLC) and residual lung vol-
ume (RV).
b. Methacholine and cold-air challenge tests produce bronchoconstriction in
patients who have asthma at doses lower than those that produce bron-
choconstriction in persons whose airways are functioning normally.
c. Sputum culture should be performed to rule out infectious etiology (espe-
cially Aspergillus fumigatus); sputum culture of asthma patients may contain
increased eosinophils.
d. Serum analysis reveals leukocytosis with increased eosinophils.
e. Chest radiographic findings reveal hyperinflation.

19
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20 CHAPTER 2

TABLE 2-1 ASTHMA SEVERITY CLASSIFICATION

Treatment
Night Pulmonary Acute Chronic
Symptoms Symptoms Function Exacerbation Therapy

Mild 2 times per week 2 times per FEV1  80% Short-acting β2 None
intermittent Normal month predicted agonist (e.g.,
pulmonary albuterol). If used
function between
2 times per
episodes week, need
additional chronic
therapy
Mild persistent
2 times per
2 times per FEV1  80% Short-acting β2 Inhaled steroid
week but 1 time month predicted agonist (if or cromolyn
per day increasingly used, daily
Episodes may then additional
affect activity chronic therapy
required)
Moderate 1 time per day
1 time per 60%  FEV1
Short-acting β2 Medium-dose
persistent Episodes affect week 80% predicted agonist (if inhaled steroid
activity increasingly used, OR low-dose
then additional inhaled steroid
chronic therapy and long-acting
required) β2 agonist
Severe Continual Frequent FEV1  60% Short-acting β2 High-dose
persistent symptoms predicted agonist (if inhaled steroid
Limited activity increasingly used, AND long-
then additional acting β2
chronic therapy agonist AND
required) systemic
steroids

f. Arterial blood gas (ABG) analysis usually indicates a decreased PaCO2

level (36 mm Hg) due to hyperventilation.
i Hypoxia still occurs despite hyperventilation due to ventilation–perfusion
mismatch.
ii Elevated PaCO2 level indicates severe obstruction; these patients will
develop a mixed respiratory and metabolic acidosis due to hypercapnia and
lactic acidosis caused by decreased oxygen delivery.
4. Treatment
a. Patients should be instructed to avoid trigger agents.
b. Cromolyn sodium (mast cell stabilizer) can prevent an attack if administered
before exposure to the trigger.
i. This drug is ineffective if the attack has begun.
ii. This drug is most effective in young patients who have the extrinsic
form of asthma.
c. Nebulized sympathomimetics (e.g., metaproterenol, albuterol) relax
bronchial smooth muscle and decrease airway obstruction; the “albuterol
puffer” is usually the first line of therapy.
d. Corticosteroids should be used for acute, severe exacerbations. Inhaled
steroids are useful in reducing frequency of attacks and improving pulmonary
function (see Table 2-1).
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PULMONARY DISEASES 21

C. CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)

1. General characteristics
a. COPD is a progressive airway obstruction.
b. COPD affects middle-aged and older individuals.
c. Emphysema (abnormal enlargement of air spaces with destruction of alveolar
walls) and chronic bronchitis (productive cough for at least 3 months during
each of 2 consecutive years) are hallmarks of the disease.
d. COPD is most commonly associated with a significant smoking history.
2. Clinical features
a. COPD has an insidious onset.
b. Chronic cough eventually progresses to dyspnea on exertion.
c. Unlike asthma, the degree of airway obstruction in COPD does not fluctuate
as widely.
d. Exacerbations can occur with respiratory tract infections, trauma, or surgery.
e. Signs of hyperinflation, use of accessory respiratory muscles, and diffuse
wheezing are present.
f. Two clinically distinct types of COPD patients exist.
i. “Pink puffers” often present in later years (
60 years of age) with pro-
gressive dyspnea and weight loss, but little cough or sputum; these patients
have mild hypoxia and hypocapnia with overinflation and show little
improvement with bronchodilator therapy.
ii. “Blue bloaters” present at an earlier age with chronic cough and expec-
toration, weight gain, and episodic dyspnea; these patients have severe
hypoxia that leads to polycythemia, and they respond well to bron-
chodilator therapy.
iii. Most patients are seen to have some combination of both entities.
g. Chronic hypoxia → pulmonary arterial constriction and pulmonary
hypertension → right-sided failure (cor pulmonale).
h. Patients may develop spontaneous pneumothorax secondary to emphyse-
matous bullous disease, especially secondary to mechanical ventilation.
3. Laboratory findings
a. Spirometry is a useful screening tool that reveals decreased FEV1 to forced
vital capacity (FVC) ratios.
b. Pulmonary function tests reveal decreased vital capacity and expiratory
flow rates with increased RV and TLC; improvement with bronchodilators
may occur, but improvement is often no more than 15% to 20% (less than
that seen with asthma).
c. ABG analysis indicates hypoxia with hypocapnia early in the disease and
hypercapnia as the disease becomes more severe.
d. Chest radiographic study reveals overinflation, bronchial thickening, and
emphysematous bullae (Figure 2-1).
4. Treatment
a. Prevention can be achieved with smoking cessation.
b. β-Adrenergic agonists (see asthma, I B 4 c) often provide short-term relief.
Addition of an inhaled (e.g., ipratropium bromide) anticholinergic to β2-agonists
can improve FEV1 and quality of life compared to β-agonists alone.
c. Oral corticosteroids are usually reserved for patients who have more severe
disease and/or exacerbations, and may be more effective than inhaled steroids.
d. Annual vaccinations for pneumococcal and influenza infection are neces-
sary to prevent respiratory tract infections, which can be fatal in such com-
promised patients. Mucolytics (e.g., N-acetylcysteine) reduce the frequency
and duration of COPD exacerbations.
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22 CHAPTER 2

● Figure 2-1. Chest film of a patient with longstanding chronic obstructive pulmonary disease. Note the hyperinflated
lungs and flattened diaphragm. This patient also has a right lower pneumothorax, which can occur spontaneously in
such patients. (Reprinted with permission from Freundlich IM, Bragg DG: A Radiologic Approach to Diseases of the
Chest, 2nd ed. Baltimore, Williams & Wilkins, 1996, p 357.)

e. Resection of emphysematous bullae can be performed in low-risk surgical

candidates.
f. Lung transplantation is a growing mode of therapy.
g. Home O2 for hypoxemic patients has increased survival.

D. BRONCHIECTASIS
1. General characteristics
a. Bronchiectasis is an abnormal dilatation of the bronchi.
b. This disease is usually secondary to severe necrotizing lung infection (usu-
ally gram-negative organisms) associated with aspiration, or anatomic dis-
ruption from a lung tumor leading to recurrent pulmonary infections.
2. Clinical features
a. Patients have a chronic cough with large amounts of foul-smelling, blood-
tinged sputum.
b. Progressive dyspnea occurs.
c. Persistent crackles are heard, and pleuritic pain is present over the affected
lung field(s).
d. Clubbing and cor pulmonale occur in longstanding disease.
3. Laboratory findings
a. Pulmonary function tests may reveal a restrictive pattern (increased FEV1 with
decreased lung volumes) or a mixture of restrictive and obstructive patterns.
b. Chest radiographic study reveals peribronchial thickening with collapsed
areas of lung in the regions of bronchiectasis (Figure 2-2).
c. Bronchoscopy provides direct visualization of the affected regions.
d. Computed tomographic (CT) scan is often sufficient to visualize the lesions.
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PULMONARY DISEASES 23

● Figure 2-2. A. Plain film of a patient with bronchiectasis. Some left lower lobe volume loss with hyperlucent areas is
evident. B. Bronchogram delineating cystic bronchiectasis in the same patient. (Reprinted with permission from Freundlich
IM, Bragg DG: A Radiologic Approach to Diseases of the Chest, 2nd ed. Baltimore, Williams & Wilkins, 1996, p 716.)

4. Treatment
a. Patients should receive appropriate antibiotic therapy on a regular basis
(ampicillin, tetracycline, erythromycin).
b. Associated abscesses should be drained.
c. Patients should receive annual pneumococcal and influenza vaccines.
d. Surgery is usually of little benefit.

E. CYSTIC FIBROSIS (CF)

1. General characteristics
a. CF is an autosomal recessive disease.
b. In CF, exocrine gland dysfunction → obstruction of secretory glands of the
lung, pancreas, and gastrointestinal tract.
c. CF is the most common cause of obstructive airway disease in persons
under 30 years of age.
2. Clinical features
a. The disease usually manifests itself in childhood as steatorrhea or bowel
obstruction.
b. CF is seen as meconium ileus in the neonate.
c. Additional signs include sinusitis, nasal polyps, and clubbing.
d. Later, recurrent lung infections with Staphylococcus aureus and Pseudomonas
aeruginosa are the major problem.
e. CF causes sterility in men.
f. Cor pulmonale (manifesting as right-sided heart failure) develops secondary
to pulmonary hypertension, which results from areas of hypoventilation.
3. Laboratory findings
a. Sweat test reveals elevated sweat chloride levels (
60 mEq/L).
b. Pulmonary function tests reveal an obstructive pattern with decreased expi-
ratory flow rates and increased RV.
c. Chest radiographic study reveals hyperinflation, cyst formation, bronchiec-
tasis, and atelectasis (Figure 2-3).
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24 CHAPTER 2

● Figure 2-3. Chest radiographic study of a patient who has cystic fibrosis. The upper lung zones show evidence of
fibrosis and bronchiectasis with peribronchial cuffing. The lower lung segments are commonly involved late in the
disease. (Reprinted with permission from Freundlich IM, Bragg DG: A Radiologic Approach to Diseases of the Chest,
2nd ed. Baltimore, Williams & Wilkins, 1996, p 19.)

4. Treatment
a. Salt depletion may occur; patients may require supplements.
b. Patients should receive pancreatic enzyme replacement.
c. Patients need chest physiotherapy to assist with clearing of secretions.
d. Antibiotics (cephalosporin or penicillin with an aminoglycoside) and oxygen
are given for acute, severe infections.
e. Bronchodilators are of some benefit when bronchospasm is prominent.
f. Lobectomy is occasionally required for localized infection or tissue destruction.
g. Lung transplantation in advanced disease has dramatically improved the quality
of life.

II Diffuse Interstitial Lung Disease

A. GENERAL CHARACTERISTICS
1. These disorders are characterized by an infiltration of the lung parenchyma that
eventually leads to pulmonary fibrosis.
2. The most common entities include idiopathic pulmonary fibrosis, pneumoconiosis,
hypersensitivity pneumonitis, and sarcoidosis.

B. IDIOPATHIC PULMONARY FIBROSIS

1. General characteristics
a. Idiopathic pulmonary fibrosis usually occurs in middle-aged persons.
b. No predisposing factor has been found.
c. The disease may progress rapidly or slowly.
2. Clinical features
a. Constitutional signs and symptoms of fatigue, fever, and weight loss are
common.
b. Patients experience dyspnea on exertion.
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PULMONARY DISEASES 25

c. A nonproductive cough is present.

d. Additional signs include tachypnea, inspiratory crackles, small tidal volumes,
and digital clubbing.
e. Evidence of right-sided heart failure and cyanosis occur in severe disease.
3. Laboratory findings
a. Pulmonary function tests reveal small lung volumes and increased expiratory
flow rates (increased FEV1-to-FVC ratio); these results are not specific to the
cause of the pulmonary fibrosis and only indicate the restrictive component
of the lung disease.
b. Chest radiographic study reveals a diffuse reticulonodular pattern.
c. Open-lung biopsy is required for definitive diagnosis.
4. Treatment
a. Corticosteroids are the mainstay of therapy.
b. Azathioprine or cyclophosphamide is used in steroid-resistant disease.

C. PNEUMOCONIOSIS
1. General characteristics
a. Pneumoconiosis results from inhalation of organic dust (e.g., asbestos, silica,
metals).
b. Asbestos exposure is associated with increased incidence of bronchogenic
carcinoma and mesotheliomas (especially if the patient smokes).
c. Often, the disease has a prolonged latency period after exposure.
d. Silicosis is associated with superinfection by Mycobacterium tuberculosis.
2. Clinical features
a. Patients usually have a progressive fibrosis of the lung that leads to increas-
ing dyspnea and cough.
b. Signs and symptoms similar to those of idiopathic pulmonary fibrosis occur.
3. Laboratory findings
a. Pulmonary function tests reveal a restrictive pattern, as in idiopathic pul-
monary fibrosis.
b. Chest radiographic study depends on the offending agent.
i. Diffuse reticulonodular pattern is seen in coal dust exposure.
ii. Perihilar eggshell calcifications are seen in silicosis.
iii. Calcified plaques and pleural thickening are seen in asbestos expo-
sure with or without evidence of bronchogenic carcinoma or mesothe-
lioma.
c. Tissue biopsy often reveals the offending agent.
4. Treatment
a. Patients should avoid exposure to the offending agent.
b. Patients should stop smoking.
c. Coexisting tuberculosis should be treated (e.g., with isoniazid).
d. Oxygen should be given if disease impairs oxygenation and/or progresses to
cor pulmonale.

D. HYPERSENSITIVITY PNEUMONITIS
1. General characteristics
a. Hypersensitivity pneumonitis occurs in persons who have an abnormal sen-
sitivity to an organic agent.
b. Examples include farmer’s lung (caused by exposure to Actinomyces in moldy
hay) and pigeon-breeder’s lung (caused by exposure to animal protein in bird
droppings).
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26 CHAPTER 2

2. Clinical features
a. Patients experience onset of cough, dyspnea, fever, and malaise several hours
after exposure; symptoms slowly resolve but recur on re-exposure.
b. Diffuse crackles can be heard, but wheezing usually is not present (unlike in
asthma).
c. Duration of symptoms may increase with repeated exposure, eventually lead-
ing to pulmonary fibrosis.
3. Laboratory findings
a. Chest radiographic study reveals reticulonodular infiltrates, with sparing of
the apices.
b. Hematology studies reveal leukocytosis after exposure (eosinophilia is not
seen).
c. Serum precipitins to the offending agent are often present (their presence is
not specific to the disease but does indicate exposure to the offending agent).
d. Pulmonary function tests may reveal a restrictive pattern.
e. Transbronchial biopsy or open-lung biopsy tissue may be required for
definitive diagnosis.
4. Treatment
a. Patient should avoid exposure to the offending agent.
b. Corticosteroids may be required in the acute phase and may be of some ben-
efit in patients who progress to chronic, severe fibrosis.

E. SARCOIDOSIS
1. General characteristics
a. Sarcoidosis is a condition in which noncaseating granulomas occur through-
out the body in association with a T-cell abnormality.
b. The disease is most common in African American patients in the third to
fourth decade of life.
2. Clinical features
a. Fifty percent of patients present with pulmonary disease consisting of pro-
gressive, nonproductive cough and shortness of breath, and/or laryngeal or
endobronchial obstruction.
b. Other patients present with constitutional symptoms (fever, malaise).
c. Pleurisy and hemoptysis are uncommon.
d. Other clinical features include:
i. Uveitis that may progress to blindness
ii. Various infiltrative lesions and erythema nodosum
iii. Polyarthritis and cystic destruction of bone
iv. Cranial neuropathies (e.g., Bell palsy) and peripheral neuropathies
v. Arrhythmias and conduction disturbances
vi. Increased formation of 1,25-dihydroxyvitamin D, which leads to hyper-
calcemia, hypercalciuria, and renal stones
3. Laboratory findings
a. Pulmonary function tests reveal a tendency toward a restrictive pattern and
impaired diffusing capacity.
b. Chest radiographic study reveals hilar lymphadenopathy, diffuse nodular
infiltrates, fibrosis, and honeycombing (Figure 2-4).
c. Transbronchial biopsy or tissue biopsy confirms the diagnosis by revealing
typical granulomas.
d. Sputum cultures should be obtained before biopsy to rule out infectious eti-
ology (e.g., tuberculosis).
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PULMONARY DISEASES 27

● Figure 2-4. Marked hilar and paratracheal lymphadenopathy in a patient who has sarcoidosis. Also note the bilater-
al reticulonodular pattern. (Reprinted with permission from Freundlich IM, Bragg DG: A Radiologic Approach to Diseases
of the Chest, 2nd ed. Baltimore, Williams & Wilkins, 1996, p 182.)

4. Treatment
a. Corticosteroids are first-line therapy if symptoms cause significant morbidity.
b. Patients must be followed up with regular pulmonary function tests and
chest radiographic studies in order to determine the need for continuation of
treatment.
c. Most patients have a good prognosis, with disease regression within 2 to 3 years.

III Adult Respiratory Distress Syndrome (ARDS)

A. GENERAL CHARACTERISTICS
1. ARDS is an acute respiratory failure characterized by hypoxemia, bilateral pul-
monary infiltrates, noncardiogenic pulmonary edema, and decreased lung compli-
ance without preceding lung disease.
2. ARDS may be seen in association with disseminated intravascular coagulopathy,
bacterial septicemia, trauma, blood transfusions, pancreatitis, and smoke inhalation.

B. CLINICAL FEATURES
1. Accumulation of pulmonary fluid leads to dyspnea and hyperventilation.
2. Without treatment, patients progress to respiratory failure within 24 hours.

C. LABORATORY FINDINGS
1. Chest radiographic study reveals a fine, diffuse, reticular infiltrate.
2. ABG analysis reveals hypoxia and hypocarbia initially and hypercarbia as respi-
ratory failure ensues.
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28 CHAPTER 2

3. No specific diagnostic test exists; the diagnosis is based on the clinical presenta-
tion and is achieved after infectious etiology is ruled out.
4. The accepted critical care definition of ARDS is a PaO2/FIO2 ratio 200 with
a pulmonary wedge pressure 18 mm Hg and bilateral pulmonary infiltrates
on chest radiograph.

D. TREATMENT
1. The underlying cause must be treated.
2. Patients should receive adequate oxygen (tracheal intubation if necessary) with
high FIO2 (inspired oxygen) initially.
a. High-concentration oxygen must be reduced as soon as possible due to the
theoretical toxicities associated with this oxygen therapy.
3. Positive pressure ventilation is often required due to reduced lung compliance.
4. Corticosteroids are not beneficial in the treatment of ARDS and are contraindi-
cated if the condition is secondary to bacterial sepsis.
5. Empiric antibiotic therapy should be started if no other etiology for the condition
is found.
6. Lung protective ventilation, using 6 mL/kg tidal volume to keep static pressures
low, have shown a survival benefit. Permissive hypercapnia (allowing PCO2 to
increase) is often used to reduce barotrauma from the ventilator.

IV Disorders of the Pleural Space, Mediastinum, and Chest Wall

A. PLEURAL DISEASES
1. Pleural effusions
a. General characteristics
i. Pleural effusions are either transudative or exudative.
ii. Determining whether an effusion is a transudate or an exudate allows the
clinician to narrow the diagnostic possibilities (Tables 2-2 and 2-3).
b. Clinical features
i. Dyspnea is a common sign.
ii. Patients report chest discomfort that is often pleuritic.
iii. Vocal fremitus and breath sounds are decreased over the effusion.
iv. Percussion is dull over the effusion.
v. Other signs and symptoms associated with the specific cause must be
sought (e.g., fever and productive cough suggest an infectious etiology).
c. Laboratory findings
i. If more than 250 mL of fluid is present, the fluid may appear on chest
radiographic study as blunting of the costophrenic angle or as a concave
meniscus.

TABLE 2-2 EXUDATIVE VERSUS TRANSUDATIVE FLUID

Exudate Transudate

Protein content
3 g/dL 3 g/dL

Pleural–serum protein ratio
0.5 0.5
LDH content
200 U/L 200 U/L
Pleural–serum LDH level
0.6 0.6
LDH, lactate dehydrogenase
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PULMONARY DISEASES 29

TABLE 2-3 DIFFERENTIAL DIAGNOSIS OF PLEURAL EFFUSIONS

Transudates Exudates

Congestive heart failure Bacterial infection (e.g., actinomyces, tuberculosis,

mycoplasma)
Hypoalbuminemia (e.g., nephrotic Malignancy (e.g., bronchogenic carcinoma,
syndrome, starvation, cirrhosis) mesothelioma, metastases)
Pulmonary embolus
Rheumatoid arthritis
Systemic lupus erythematosus
Drug-induced (e.g., quinidine)
Abdominal process (e.g., pancreatitis, subphrenic abscess)
Trauma (e.g., hemothorax, chylothorax, ruptured esophagus)

ii. A subpulmonic effusion may be mistaken for an elevated hemidiaphragm

(easily distinguished by a lateral decubitus film).
iii. CT scan may be necessary if the patient has coexisting parenchymal dis-
ease; coexisting disease makes it difficult to distinguish the presence of an
effusion.
iv. Aspirate from thoracocentesis should be sent for protein and lactate
dehydrogenase analysis (these analyses distinguish transudate from exu-
date—see Table 2-2), followed by further analyses, such as cytology (e.g.,
for suspected malignancy) and culture and sensitivity (e.g., for suspected
infection).
v. Special investigations can suggest specific diagnoses:
(a) Presence of leukoerythrogenic cells suggests systemic lupus erythe-
matosus (SLE).
(b) Presence of rheumatoid factor suggests rheumatoid arthritis.
(c) Glucose 20 mg/dL is consistent with rheumatoid arthritis.
(d) Amylase levels more than twice the normal value suggest
esophageal perforation or pancreatitis.
(e) Hematocrit
20% suggests hemothorax (suspect malignancy, trau-
ma, or pulmonary embolus).
(f) High lymphocyte count (
50% of white blood cells) suggests tuber-
culosis or malignancy.
(g) Pleural fluid pH measurements are usually of little clinical value.
d. Treatment
i. The underlying cause must be treated.
ii. Symptomatic improvement can be achieved with fluid aspiration, but
relief is only temporary.
iii. Empyemas must be drained.
iv. Repeated thoracocentesis should be avoided, because this procedure
results in significant protein depletion.
v. Chemical pleurodesis (intrapleural tetracycline) can benefit patients who
have malignant effusions.
2. Pneumothorax
a. General characteristics
i. Most common causes include chest trauma, emphysema, and iatrogenic
etiology (thoracocentesis, transthoracic lung biopsy, mechanical ventilation,
central line insertion). Pneumothorax may also be idiopathic.
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30 CHAPTER 2

● Figure 2-5. Tension pneumothorax in a patient who has penetrating chest trauma. Note the lack of pulmonary vas-
cular markings in the right hemithorax, the mediastinal shift to the left, and depression of the right hemidiaphragm.
(Reprinted with permission from Freundlich IM, Bragg DG: A Radiologic Approach to Diseases of the Chest, 2nd ed.
Baltimore, Williams & Wilkins, 1996, p 270.)

ii. A tension pneumothorax increases in size, which causes a shift of intratho-

racic structures.
b. Clinical features
i. Patients report dyspnea and chest pain.
ii. Hyperresonance is detected, and breath sounds are decreased over the
involved area.
iii. In the case of tension pneumothorax, there is tracheal deviation away from
the side of the pneumothorax, as well as distended neck veins.
c. Laboratory findings
i. Chest radiographic films taken during expiration may more clearly reveal
a pneumothorax because they provide more contrast between the lung
parenchyma and the air space (Figure 2-5).
ii. Chest radiographic study may reveal mediastinal shift if tension pneu-
mothorax exists.
d. Treatment
i. A small pneumothorax in an asymptomatic patient often requires no therapy.
ii. Pneumothoraces
20% usually require treatment.
(a) Tube thoracostomy is the treatment of choice.
(b) Patients who have a history of recurrence may benefit from pleurodesis
with intrapleural tetracycline.
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PULMONARY DISEASES 31

iii. Patients who have a tension pneumothorax require immediate therapy

with rapid needle thoracentesis immediately followed by the insertion of
a chest tube.
3. Pleural neoplasia
a. General characteristics
i. The most serious pleural neoplasm is diffuse malignant mesothelioma.
ii. Persons with a history of asbestos exposure have an increased risk of
malignant mesothelioma.
iii. This neoplasm has a prolonged latency period (
20 years).
b. Clinical features include chest pain and dyspnea.
c. Laboratory findings
i. Chest radiographic study may reveal pleural thickening and/or effusion.
ii. Pleural biopsy is necessary for the diagnosis.
d. Treatment includes radiotherapy or chemotherapy, but response to treat-
ment is poor.

B. MEDIASTINAL DISEASES
1. Mediastinitis
a. General characteristics
i. Acute mediastinitis is most commonly associated with esophageal per-
foration (either from endoscopy or an invading malignancy), traumatic
rupture of the airway, or cardiac surgery.
ii. Chronic disease is often secondary to histoplasmosis or sarcoidosis.
b. Clinical features
i. Signs and symptoms include fever, tachycardia, and tachypnea.
ii. Pneumomediastinum may lead to muffled heart sounds, decreased venous
return, and subcutaneous emphysema.
iii. Pneumothorax and pleural effusion may also occur.
c. Laboratory findings
i. Chest radiographic study reveals mediastinal widening, air in the medi-
astinum and soft tissues, and pneumothorax; fractures of the first three ribs
with traumatic bronchial rupture are commonly seen in the case of trau-
matic pneumomediastinum.
ii. Leukocytosis is common.
iii. Pleural fluid amylase levels are elevated if there is esophageal rupture.
d. Treatment
i. Patients should receive appropriate broad-spectrum antibiotics.
ii. Surgical drainage should be performed.
iii. The perforated viscus should be surgically closed.
2. Mediastinal masses
a. General characteristics
i. Most mediastinal masses are tumors.
ii. These tumors may be benign or malignant.
b. Clinical features
i. Benign tumors grow slowly and displace surrounding structures; these
tumors are often painless.
ii. Malignant lesions grow rapidly and invade and compress structures.
iii. Signs and symptoms of malignant lesions include dysphagia, hoarse-
ness, stridor, cough, dyspnea, and Horner syndrome (ptosis, anhidrosis,
and miosis ipsilateral to the lesion).
iv. Signs and symptoms of myasthenia gravis may be present in patients
who have an anterior mediastinal thymoma.
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32 CHAPTER 2

c. Laboratory findings
i. Chest radiographic study suggests the diagnosis when it reveals the pres-
ence of a mass.
(a) Lateral radiographic study is valuable because masses in the anteri-
or, middle, and posterior mediastinum have differential diagnoses.
(b) Anterior mediastinal masses include thymoma, thyroid mass, ger-
minal cell neoplasms, and lymphoma.
(c) Middle mediastinal masses include bronchogenic cysts, sarcoidosis,
and aneurysms.
(d) Posterior mediastinal masses include neurogenic tumors and cysts
and esophageal diverticula or neoplasms.
ii. CT scan defines the mass’s origin and its relationship to vascular structures
more clearly than does radiography.
iii. Biopsy is required for definitive diagnosis of a nonvascular mass.
d. Treatment depends on the etiology of the mass.
i. Thymomas should be excised and frequently improves symptoms of
myasthenia gravis. Radiation may be beneficial for recurrence or
incomplete resection. Cisplatin is used for metastatic and unresectable
tumors.
ii. Thyroid masses extending into the mediastinum are frequently benign
but may be symptomatic goiters, in which case they should be surgically
excised.
iii. Germinal cell neoplasms should be resected if not invading vital structures;
however, chemoradiation is used if the mass cannot be easily excised.
iv. Lymphomas typically will respond to chemoradiation and need not be
surgically removed.
v. Bronchogenic cysts should be excised to confirm the diagnosis.
vi. Sarcoidosis (see II E)
vii. Aneurysms of the descending thoracic aorta should be surgically repaired or
stented via endovascular techniques in appropriate candidates; aneurisms

6–7 cm should be repaired.
viii. Esophageal diverticular should be surgically or endoscopically repaired if
symptomatic. Results with surgery are superior to endoscopy for smaller
(3 cm) diverticula and are equivalent for larger diverticula. Esophageal
neoplasms should be resected if the disease is localized to the esophagus
such that the resection may be curative.
ix. Neurogenic tumors should be removed when possible because these may
be symptomatic or malignant; radiation and cisplatin are used for advanced
disease.

C. CHEST WALL DISORDERS are divided into mechanical disorders such as kyphosco-
liosis and neuromuscular disorders (see Chapter 10, Neurologic Diseases).
1. Kyphoscoliosis
a. General characteristics
i. Posterolateral curvature of the spine → decreased mobility of chest
wall → decreased ventilation.
ii. Kyphoscoliosis occurs predominantly in women.
b. Clinical features
i. Patients experience exertional dyspnea, especially if deformity is greater
than 70°.
ii. Pulmonary hypertension may develop after prolonged hypoventilation,
which leads to right-sided failure.
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PULMONARY DISEASES 33

● Figure 2-6. Note the extensive curvature of the thoracic spine in this patient who has kyphoscoliosis. (Reprinted with
permission from Slaby F, Jacobs ER: NMS Radiographic Anatomy. Baltimore, Williams & Wilkins, p 242.)

c. Laboratory findings
i. Anteroposterior view on chest radiographic study reveals curvature of the
spine, with crowding of the ribs on the convex side and widened inter-
costal spaces on the concave side of the curvature; lateral view reveals pos-
terior curvature (Figure 2-6).
ii. Pulmonary function tests are usually unnecessary unless a second dis-
order is suspected.
d. Treatment
i. Early detection and therapy during adolescence can greatly improve
outcome.
ii. Treatment is administered when angulation is greater than 40°.
iii. Patient should wear a Milwaukee brace to reduce further curvature.
iv. Surgical correction (Harrington procedure) with spinal fusion and metal-
lic rod insertion may help preserve remaining pulmonary function.

V Neoplasms of the Lung

A. GENERAL CHARACTERISTICS
1. Neoplasms of the lung are often malignant and may be primary or metastatic.
2. These neoplasms are most commonly associated with a history of cigarette
smoking.

B. PRIMARY PULMONARY NEOPLASMS

1. General characteristics
a. Primary pulmonary neoplasms have several primary histologic variants,
including non–small-cell (squamous cell carcinoma or adenocarcinoma) and
small-cell (oat) carcinoma.
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34 CHAPTER 2

● Figure 2-7. A large left apical mass has destroyed the posterior first to third ribs and merges with the pleura inferiorly.
This Pancoast tumor is formed by a squamous cell carcinoma of the lung. (Reprinted with permission from Freundlich
IM, Bragg DG: A Radiologic Approach to Diseases of the Chest, 2nd ed. Baltimore, Williams & Wilkins, 1996, p 553.)

b. Adenocarcinoma
i. Accounts for approximately 40% of all lung cancers
ii. Grows in the peripheral lung
iii. Is slower growing than squamous cell carcinoma
iv. Metastasizes early
c. Squamous cell carcinoma
i. Accounts for approximately 30% of all lung cancers
ii. Is seen in upper lobes and main stem bronchi
iii. Is a slow-growing tumor
iv. Is late to metastasize
d. Small-cell (oat) carcinoma
i. Accounts for 20% of lung cancers
ii. Has a peripheral origin
iii. Grows rapidly
iv. Has usually metastasized at time of diagnosis
2. Clinical features
a. Signs and symptoms include weight loss, a cough that has changed in char-
acter, dyspnea, and hemoptysis.
b. A sign of adenocarcinoma is increased sputum production.
c. Digital clubbing occasionally is seen.
d. Pancoast tumor is an apical tumor involving the brachial plexus; this tumor
leads to Horner syndrome (Figure 2-7). If the tumor obstructs the superior vena
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PULMONARY DISEASES 35

cava, patients develop neck and face swelling, dilated upper extremity head and
facial veins, and headaches (also known as superior vena cava syndrome).
e. Small-cell tumor is more frequently associated with superior vena cava syndrome.
f. Wheezing may be present if tumor partially obstructs a bronchus.
g. Recurrent pneumonias are common when a tumor completely obstructs a
bronchus.
h. Left hilar mass may involve the left recurrent laryngeal nerve and cause
hoarseness.
i. Mediastinal mass may produce diaphragmatic paralysis (phrenic nerve
entrapment), which may be detected during physical examination.
j. Common paraneoplastic syndromes seen with pulmonary neoplasm
include hypertrophic pulmonary osteoarthropathy, gynecomastia, syndrome of
inappropriate antidiuretic hormone, hypercalcemia associated with neoplastic
secretion of parathyroid hormone–like substance, and ectopic adrenocorticotropic-
producing Cushing syndrome.
k. Patients may present with metastatic disease rather than pulmonary signs and
symptoms; signs and symptoms of metastatic disease include:
i. Enlarged cervical lymph nodes
ii. Bone, pelvis, and back pain due to bony metastasis
iii. Seizure and/or altered mental status due to cerebral metastasis
3. Laboratory findings
a. Sputum cytology is an effective, inexpensive diagnostic test that may reveal
the diagnosis if the tumor involves the bronchi; for accurate results, the spu-
tum sample must have a high white blood cell to squamous cell ratio. Negative
sputum cytology, however, is not specific, and if the diagnosis is suspected, a
CT scan and/or bronchoscopy should be performed.
b. Chest radiographic study reveals multiple nodules of varying size, or occa-
sionally a solitary pulmonary nodule (see V C); cavitation may be evident.
c. Bronchoscopy is effective in detecting central lesions after sputum cytology.
d. Percutaneous needle aspiration with CT guidance is used to obtain samples
from small peripheral nodules.
e. Lymph node biopsy is the easiest biopsy technique; in the absence of lymph
node involvement, transbronchial CT-guided or open-lung biopsies may be
necessary.
f. Abnormal liver function results indicate liver metastases; abnormal bone scan
and elevated alkaline phosphatase and calcium levels indicate bone metastases.
4. Treatment
a. Surgical resection is indicated for patients without evidence of metastatic dis-
ease. This is usually for patients with non–small-cell cancer.
b. Inadequate FEV1 precludes surgery (predicted postoperative FEV1 must be

0.8 L).
c. Chemotherapy/radiotherapy is indicated for small-cell carcinoma because it
has usually metastasized by the time it presents.
d. In non–small-cell cancers that have metastasized, combined chemoradiation
therapy can improve survival to a small degree. Cisplatin is the chemotherapy
agent most frequently used.

C. SOLITARY PULMONARY NODULE

1. General characteristics
a. A solitary primary nodule is a rounded lesion with well-demarcated margins.
b. Between 5% and 40% of these nodules are malignant.
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36 CHAPTER 2

Nodule present

Non-calcified
Calcified Unclear previous chest radiograph
or doubling time > 20
and < 450 days

Repeat chest radiograph every Patient is good

High operative risk
6 months for 2 years operative candidate

BRONCHOSCOPIC
RESECT OR NEEDLE BIOPSY

● Figure 2-8. Decision algorithm for a pulmonary nodule.

2. Clinical features
a. Patients who have a solitary pulmonary nodule are usually asymptomatic.
b. Features associated with benign lesions include:
i. Diameter 2 cm
ii. Sharp borders
iii. Nonsatellite appearance
iv. “Popcorn” calcification
v. Age of patient 40 years
3. Treatment
a. Because of the potential for malignancy, the physician must follow up suspi-
cious lesions (Figure 2-8).
b. Therapy for malignant lesions includes surgical resection for good operative
candidates and bronchoscopic or needle biopsy for patients at high operative risk.

VI Pulmonary Disease of Unknown Etiology

A. GOODPASTURE SYNDROME
1. General characteristics
a. Goodpasture syndrome is characterized by intra-alveolar hemorrhage and
proliferative glomerulonephritis.
b. This syndrome primarily affects men.
c. Antiglomerular basement membrane antibodies also present in this syn-
drome react with alveolar basement membranes → linear deposition (type II
hypersensitivity).
2. Clinical features
a. Patients commonly present with hemoptysis and dyspnea.
b. Renal failure with azotemia may occur.
c. Patients may have a history of respiratory illness before hemorrhage.
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PULMONARY DISEASES 37

3. Laboratory findings
a. Chest radiographic study reveals bilateral alveolar infiltrates.
b. Pulmonary function tests indicate a restrictive pattern.
c. Iron deficiency anemia may be present secondary to ongoing pulmonary
hemorrhages.
d. Serum or tissue (renal or pulmonary) analysis indicates the presence of
antiglomerular basement membrane antibodies.
e. Urinalysis reveals the presence of red blood cell casts with proteinuria.
4. Differential diagnosis
a. SLE is distinguished from Goodpasture syndrome by the lack of antiglomeru-
lar basement membrane antibodies and the presence of antinuclear antibodies
and hypocomplementemia.
b. Idiopathic pulmonary hemosiderosis lacks the renal and immune system
involvement characteristic of Goodpasture syndrome.
c. Wegener granulomatosis is discussed next.
5. Treatment
a. Corticosteroids, immunosuppressive therapy with alkylating agents, and
plasmapheresis offer the best results.
b. Dialysis may be required.

B. WEGENER GRANULOMATOSIS
1. General characteristics
a. This disease commonly affects men.
b. Wegener granulomatosis is a systemic vasculitis commonly involving the res-
piratory tract and is associated with glomerulonephritis.
2. Clinical features (see Chapter 7, Rheumatic Diseases)
a. Signs and symptoms include paranasal sinus pain and drainage with purulent
or bloody nasal discharge.
b. Nasal septal perforation with saddle-nose deformity is often present.
c. Additional signs and symptoms include cough, hemoptysis, dyspnea, and
chest discomfort.
3. Laboratory findings
a. Chest radiographic study reveals the presence of single or multiple focal
lesions (unlike the diffuse infiltrates seen in Goodpasture syndrome).
b. Biopsy is necessary.
4. Treatment with cyclophosphamide with or without corticosteroids produces
rapid improvement.
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Chapter 3
Renal, Fluid, and Electrolyte Disorders

I Renal Failure
A. ACUTE RENAL FAILURE (ARF)
1. General characteristics
a. ARF is an abrupt reduction in kidney function that results from a variety of
causes (Table 3-1).
b. ARF is usually reversible.
2. Clinical features
a. Signs and symptoms of ARF depend on etiology.
b. Oliguria (
400 mL/day) or anuria (
100 mL/day) may be present; however,
patients may still produce urine and have ARF if acute azotemia is present.
c. Patient may be edematous and hypertensive if the cause is renal.
d. Orthostatic hypotension, tachycardia, and dry mucous membranes are
indicative of prerenal causes.
e. Tympanic lower abdomen may be present if bladder outflow is obstructed
(e.g., Foley catheter obstruction).
3. Laboratory findings
a. Serum urea and creatinine levels are elevated; if the ratio of blood urea
nitrogen to creatinine is more than 20:1, then the cause of the ARF is likely
prerenal.
b. In prerenal ARF, fractional excretion of sodium (FENa)
1%  (urineNa/
plasmaNa) (plasmaCr/urineCr), provided that the patient has not recently used
loop diuretics.
c. UrineOsm more than 400 mOsm/kg and urineNa
20 mmol/L are labora-
tory results usually consistent with prerenal causes.
d. Urinary sediment (urinalysis) reveals granular casts, which indicate acute
tubular necrosis or nephrotoxins.
i. White blood cells and/or white blood cell casts suggest interstitial nephri-
tis (as seen with drug allergies or infections).
ii. Red blood cells (RBCs) (or more specifically, RBC casts) suggest glomeru-
lonephritis.
e. If urinalysis indicates renal parenchymal disease, a renal biopsy may be indi-
cated to differentiate conditions that may respond to steroid or immunosup-
pressive therapy.
4. Treatment
a. Treatment depends on the cause of ARF.
b. Hypovolemia should be treated with rehydration.
c. Obstruction may require catheterization and removal if obstruction (e.g., calculi)
has been present for more than 5 days.

38
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RENAL, FLUID, AND ELECTROLYTE DISORDERS 39

TABLE 3-1 CAUSES OF ACUTE RENAL FAILURE

Prerenal Postrenal Renal

Hypoperfusion secondary to Urinary tract obstruction: Interstitial disease (interstitial

hypovolemia, blood loss, renal ultrasound can quickly nephritis or acute tubular necrosis)*
dehydration diagnose acute obstruction
Maldistribution, as in sepsis or Glomerular disease
liver disease, low cardiac output Renovascular disease
*Interstitial nephritis may be associated with the use of antibiotics or nonsteroidal anti-inflammatory drugs; acute tubular necrosis
may be secondary to myoglobinemia, uric acidemia (large tumor load), cytotoxic chemotherapy, the use of radiocontrast material,
or aminoglycosides.

d. Appropriate therapy for renal disease should be initiated if necessary (see

glomerulonephropathies, II B).
e. Established renal failure requires dialysis until the patient enters the
recovery phase.

B. CHRONIC RENAL INSUFFICIENCY/END-STAGE RENAL DISEASE

1. General characteristics
a. Signs and symptoms of chronic renal insufficiency do not occur until approx-
imately 90% of normal renal function is lost.
b. Chronic renal insufficiency is defined as renal function between 5% and
25% of normal function.
i. This condition usually does not require dialysis and is asymptomatic.
ii. Patients may require erythropoietin, phosphate binders, and vitamin D.
c. End-stage renal disease is defined as
5% of normal renal function; patients
require dialysis, erythropoietin, and vitamin D replacement.
d. Causes of chronic renal insufficiency/end-stage renal disease include chronic
glomerulonephritis, chronic reflux nephropathy, chronic pyelonephritis, diabetes
mellitus, malignant hypertension or bilateral renovascular disease (essential hyper-
tension rarely leads to end-stage renal disease), and polycystic kidney disease.
2. Clinical features
a. If untreated, patients may become edematous and hypertensive.
b. Tachypnea may be present if metabolic acidosis has occurred.
c. Hyperkalemia may lead to a catastrophic cardiac event (i.e., asystole).
d. Osteodystrophy occurs secondary to decreased renal formation of 1,25-
dihydroxyvitamin D and increased levels of parathyroid hormone secondary
to poor phosphate excretion.
e. Uremic toxin-associated signs and symptoms include anorexia, nausea,
vomiting, and malaise, which may progress to obtundation.
f. Conditions associated with uremic toxemia include:
i. Metabolic encephalopathy
ii. Pleuropericarditis
iii. Volume-dependent hypertension and pulmonary edema
iv. Peripheral neuropathy
v. Pruritus
vi. Volume-independent hypertension
vii. Platelet dysfunction
3. Laboratory findings
a. Normochromic, normocytic anemia may be present.
b. Patients are hyperkalemic.
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40 CHAPTER 3

c. Anion-gap acidosis may be present.

d. Serum phosphate levels are elevated, and serum calcium levels are decreased.
e. Serum urea and creatinine levels are elevated.
4. Treatment
a. Treatment for end-stage renal disease involves dialysis until a successful kid-
ney transplantation can be performed.
b. Phosphate binders may decrease intestinal phosphate absorption.
c. Patients should receive erythropoietin therapy and calcium and vitamin D
supplements.

II Abnormal Urinalysis and Glomerulonephropathy

A. ABNORMAL URINALYSIS
1. General characteristics
a. Abnormal urinalysis indicative of renal pathology involves either proteinuria
or some forms of hematuria (discussed in parts 2 and 3 of this section) or
both.
b. Understanding the significance of an active urinary sediment can aid the
diagnosis of glomerulonephropathy.
2. Proteinuria
a. A 24-hour urine collection must be obtained if proteinuria is detected on ini-
tial urinalysis, and the cause is unclear.
b. Proteinuria more than 2.0 g/day is usually due to a glomerulonephropathy
(i.e., glomerular disease).
c. Proteinuria 3.5 g/day is indicative of nephrotic syndrome (see glomeru-
lonephropathies, II B); this degree of proteinuria is not seen in interstitial or
tubular disease.
d. Proteinuria
2.0 g/day is associated with interstitial or tubular disease
(e.g., acute tubular necrosis, interstitial nephritis, pyelonephritis), but does
not exclude glomerulonephropathy.
e. Malignant hypertension may be associated with glomerular range protein-
uria (2.0 g/day), but chronic mild or moderate essential hypertension is
typically associated with proteinuria of
1.0 g/day.
f. Complications of excessive renal protein loss include edema secondary to
decreased oncotic pressure, hyperlipidemia, hypercoagulable state, hypogam-
maglobulinemia, and vitamin D deficiency (vitamin D is bound to filtered protein
and is therefore lost).
3. Hematuria
a. General characteristics
i. Hematuria may arise anywhere along the genitourinary tract from the kid-
neys to the urethra.
ii. Glomerular hematuria occurs when a glomerulonephritis is present (for
which there are several causes).
iii. Nonglomerular hematuria may be the result of trauma, stones, tumors,
or infection involving any part of the genitourinary tract.
b. Glomerular hematuria can be distinguished from nonglomerular hematuria by
the following:
i. Presence of RBC casts is pathognomonic for acute glomerulonephritis;
however, RBC casts are not always present.
ii. Glomerular range proteinuria (2.0 g/day) with hematuria indicates a
glomerular origin.
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RENAL, FLUID, AND ELECTROLYTE DISORDERS 41

iii. Crenated RBCs in the urine are a product of glomerular disease, whereas
normal RBCs arise from nonglomerular hemorrhage.

B. GLOMERULONEPHROPATHIES
1. General characteristics
a. Glomerulonephropathies may be diffuse (involving all glomeruli), focal
(involving only some of the glomeruli), or segmental (involving a portion of
each individual glomerulus).
b. The condition may be primary (disease process is localized to the kidney) or
secondary to an underlying disease.
c. Glomerulonephropathies are divided into two main categories: proliferative
glomerulonephropathies and nonproliferative glomerulonephropathies.
2. Proliferative glomerulonephropathies
a. General characteristics
i. Urinalysis reveals the presence of RBCs (20 RBCs/high-powered field)
and / RBC casts; proteinuria is present in variable amounts.
ii. This condition involves a diffuse or focal proliferation of glomerular cells.
iii. In primary glomerulonephropathy, disease is primary to the kidney; in
secondary glomerulonephropathy, underlying disease produces renal
damage.
iv. Patients may present with acute or chronic symptoms of renal failure (see
renal failure, I A 2).
v. Primary causes are commonly associated with either poststreptococcal
glomerulonephritis or IgA nephropathy (Berger disease).
b. Poststreptococcal glomerulonephritis
i. This condition occurs acutely 10 to 20 days after a pharyngeal or cuta-
neous streptococcal infection.
ii. Signs and symptoms include gross hematuria, proteinuria, edema, and
hypertension.
iii. Serum C3 levels are temporarily reduced (less than 8 weeks’ duration).
c. Immunoglobulin A (IgA) nephropathy
i. This condition is the most common cause of glomerular origin hematuria.
ii. IgA nephropathy is associated with deposits of IgA in the renal mesangium.
iii. Patients are seen with recurrent, gross hematuria immediately following
upper respiratory tract or gastrointestinal tract infection (no lag of 10–20
days, as seen with the poststreptococcal infection).
iv. Urinalysis may be normal between episodes.
v. The presence of hypertension is associated with a poor prognosis (i.e.,
patients develop end-stage renal disease).
vi. Serum C3 levels are normal.
vii. Linear pattern along basement membrane is detected by immunofluo-
rescence study.
d. Goodpasture disease is another primary form of proliferative glomeru-
lonephropathy, which is also associated with pulmonary hemorrhage and
involves antiglomerular basement membrane antibodies.
e. Secondary causes of proliferative glomerulonephropathy include systemic
lupus erythematosus (SLE), Henoch-Schönlein purpura, Wegener granulomatosis,
and polyarteritis nodosa (see Chapter 7 on rheumatic diseases).
3. Nonproliferative glomerulonephropathies
a. Nonproliferative glomerulonephropathies involve disease of the glomerular
basement membrane without proliferation of cells.
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42 CHAPTER 3

TABLE 3-2 CAUSES OF NEPHRITIC VERSUS NEPHROTIC SYNDROMES

Condition Nephritic Nephrotic Associated Etiologies

Acute (postinfectious) X Streptococcal infection

glomerulonephritis
IgA nephropathy (Berger X Viral or flu-like prodrome
disease)
Rapidly progressive X SLE, mixed cryoglobulinemia,
glomerulonephritis endocarditis, Goodpasture,
Wegener
Minimal change disease X Allergy, NSAIDs, Hodgkin
Focal and segmental X Heroin, reflux nephropathy,
glomerulosclerosis HIV
Membranous nephropathy X Non-Hodgkin, SLE, malignancy,
Gold/penicillamine therapy
Membranoproliferative X Upper respiratory infection
glomerulonephropathy
*HIV, human immunodeficiency virus; IgA, immunoglobulin A; NSAIDs, nonsteroidal anti-inflammatory drugs; SLE, systemic lupus
erythematosus.

b. A patient who has this condition may be initially seen with hypertension.
c. Urinalysis reveals glomerular range proteinuria, few RBCs (usually
5 per
high-powered field), and no RBC casts.
d. Nonproliferative glomerulonephropathies may be primary or secondary.
e. Secondary causes include general malignancy, SLE, gold and penicillamine
therapy, heroin use, ureteroreflux, acquired immunodeficiency syndrome,
paraproteinemia secondary to multiple myeloma or amyloid, and diabetes
mellitus.
f. Histologic type known as minimal change disease is common in the pediatric
population, which is usually associated with both normal glomerular filtration
rate and blood pressure, and has a good prognosis after steroid therapy.
g. Pre-eclampsia is associated with nonproliferative glomerulonephropathy.
4. Renal failure may be due to diseases producing nephritic or nephrotic syn-
dromes (Table 3-2).

III Renal Calculi

A. GENERAL CHARACTERISTICS
1. Approximately 1 in 10 persons in the United States has renal calculi.
2. Renal calculi are twice as common in men as compared with women and are
uncommon in children.
3. Renal calculi are commonly composed of calcium (80% of all renal calculi), magne-
sium ammonium sulfate (struvite or infection stones), or, less frequently, uric acid.

B. CLINICAL FEATURES
1. Fever may be present.
2. Patients have severe ipsilateral costovertebral angle and/or lower back pain
and tenderness.
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RENAL, FLUID, AND ELECTROLYTE DISORDERS 43

3. Gross hematuria may be present.

4. Decreased urine output may be noted.

C. LABORATORY FINDINGS
1. Laboratory results vary with stone type.
2. Urine should be sent for culture and sensitivity to rule out struvite stones and
pyelonephritis.
3. Urinalysis should be performed to assess for the presence of stone-specific crystals.
4. A 24-hour urine collection is used to identify the presence of excess levels of
stone-forming substrates such as calcium or uric acid.
5. Serum electrolytes, including calcium, uric acid, and phosphate, should be
measured because elevated levels of these substances may reveal the composition
of the stone.
6. Intravenous pyelogram is often diagnostic of the presence of renal calculi;
however, a renal protocol CT scan is now most commonly used to make the
diagnosis.
7. Plain radiographic studies may reveal the location of the stone if it is radiopaque
(uric acid stones are radiolucent; calcium stones are radiopaque).

D. TREATMENT
1. Patients should be given adequate pain medication over 3 to 5 days, during
which time they are likely to pass the stone.
2. Fluid intake is encouraged, and diuretics (particularly thiazides, which lower uri-
nary calcium) may be of some benefit in preventing recurrence.
3. Allopurinol is useful in treating patients who have uric acid stones.
4. Orthophosphate can be used in patients who have hypercalciuria and calcium
stones to decrease the absorption of dietary calcium.
5. Lithotripsy may be necessary for stones that do not pass spontaneously.
6. Antibiotics such as a fluoroquinolone may be necessary if there is an associated uri-
nary tract infection/pyelonephritis.

IV Renovascular Disease
A. GENERAL CHARACTERISTICS
1. Renal artery stenosis is the most common cause of secondary hypertension
(accounts for 5% of all persons who have hypertensive disease), which is usually
secondary to atherosclerotic narrowing of the renal artery.
2. Secondary hypertension is more common in younger patients, elderly patients
who have new onset of hypertension, and persons who have malignant
hypertension.
3. Secondary hypertension results in stimulation of the renin-angiotensin-aldosterone
system.
4. Renovascular disease may be less commonly due to fibromuscular disease (seen
in young women), localized aneurysms, and space-occupying lesions of the kidney
such as cysts or tumors.

B. CLINICAL FEATURES
1. Patients are hypertensive (hypertension may be in the malignant hypertensive
range, with diastolic 120 mm Hg).
2. Evidence of peripheral vascular disease may be present along with a history of
intermittent claudication.
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44 CHAPTER 3

3. Midabdominal bruit may be present.

4. Patients are resistant to antihypertensive medications.
5. Muscle weakness and tetany may occur secondary to hypokalemia.

C. LABORATORY FINDINGS
1. Hypokalemia may be present.
2. Captopril renography shows less radiolabeled enhancement in the affected kidney
when captopril is given. In renal artery stenosis, the affected kidney relies on
increased angiotensin II-renin activity to maintain perfusion. When captopril
(angiotensin-converting enzyme inhibitor) is given, the affected kidney will be
underperfused relative to the unaffected kidney because it is more sensitive to the
reduced angiotensin-renin axis.
3. Digital subtraction renal arteriography should be performed if the captopril test
is positive to reveal the location of the stenosis; in contrast to bilateral arteriogra-
phy, this test does not require arterial cannulation.
4. If digital subtraction is nondiagnostic, bilateral arteriography should then be
performed.
5. If renal function is poor such that intravenous contrast is contraindicated, mag-
netic resonance angiography can localize the stenotic region.

D. TREATMENT
1. Surgery and angioplasty are superior to medical therapy because the former
therapies relieve the stenosis, thereby eliminating the cause of the hypertension as
well as restoring normal blood flow to the affected kidney.
2. Angioplasty should be attempted in short segments of stenosis (
1 cm) because it
is less invasive and yields similar results to surgery.

V Assessment and Diagnosis of Volume and Electrolyte Disorders

A. GENERAL CONSIDERATIONS
1. Assessment of volume disturbances requires a clinical evaluation of the patient as
well as assessment of the patient’s serum sodium level to determine the most
appropriate course.
2. Dehydration indicates a decrease in the total body sodium level.
3. Serum sodium is a measure of sodium concentration and therefore indicates the
body’s relative need for free water.
a. If the serum sodium level is elevated, the patient needs free water to return the
sodium concentration to normal.
b. If the serum sodium level is decreased, the patient has more free water relative
to sodium.
4. Appropriate treatment of the patient who has sodium and water imbalances
involves an assessment of both the serum sodium level and the patient’s volume status.

B. HYPONATREMIA
1. Hyponatremia may occur:
a. With an increased total body sodium level (the patient is edematous and
hence has an increased total body sodium level; however, total body water also
increases, disproportionately producing a relative hyponatremia)
b. With a decreased total body sodium level (the patient appears dehydrated
and hence has a decreased total body sodium level)
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RENAL, FLUID, AND ELECTROLYTE DISORDERS 45

TABLE 3-3 DIFFERENTIAL DIAGNOSIS FOR INCREASED OSMOLAR GAP

Measured Calculated Cause

Normal Low Pseudohyponatremia secondary to

abnormal lipid protein levels
High Normal Search for abnormal solute levels (e.g., alcohol,
ethylene glycol, methanol)
Low Normal Laboratory error

c. With a normal total body sodium level (the patient appears euvolemic and
hence has a normal total body sodium level but an increase in total body water,
for example, syndrome of inappropriate antidiuretic hormone)
d. Secondary to pseudohyponatremia
2. The following equation determines the osmolar gap.

osmolar gap  calculated osmolarity  measured osmolarity

calculated osmolarity  2 (serum Na)  glucose (mmol/L)/18
 urea (mmol/L)/2.8

a. The osmolar gap should be
10; if it is 10, then one of the following is true
(Table 3-3):
b. The true [Na] level can be determined by adding 3 mmol/L of Na to the serum
[Na] level for every 10-mmol increase in serum glucose.
c. Hypernatremia can be evaluated clinically in a manner similar to that of
hyponatremia (Figures 3-1 and 3-2).

C. HYPERKALEMIA AND HYPOKALEMIA

1. General considerations
a. Chronic changes in potassium levels occur as a result of renal potassium
handling.
b. Acute changes in potassium levels are governed by:
i. Increased sympathetic drive (causing increased cellular uptake of potas-
sium, which leads to hypokalemia)
ii. Insulin (increased cellular uptake also causes hypokalemia)
iii. Acidosis (increased cellular efflux of potassium with influx of hydrogen
ions, which leads to hyperkalemia)
iv. Alkalosis (increased efflux of hydrogen ions and influx of potassium,
which leads to hypokalemia)
2. Assessment of hypokalemia is shown in Figure 3-3.
3. Hyperkalemia can be the result of:
a. False hyperkalemia
i. Hemolyzed blood sample is very common, especially if it is difficult to
obtain a venous blood specimen.
ii. Recheck the potassium level.
b. Massive tissue injury that can occur with hemolysis is associated with
chemotherapy and cell death, or burns; dialysis or diuresis with fluid replace-
ment may be required.
c. Type IV renal tubular acidosis (RTA) (see V D)
d. Acute or end-stage renal failure
 46

Hyponatremia
CHAPTER 3

Assessment: Hypovolemia Euvolemia Edema

Depleted in total body [Na] Total body [Na] normal, Excess total body [Na]
and water, but more but excess water and water, but more
depleted in Na water than Na
5580_Ch03_pp038-052 8/28/06 11:22 AM Page 46

Renal loss Impaired free water excretion Renal

Source: vs. vs. vs.
Non-renal loss Excess free water intake Non-renal

Urine Na Urine osmolarity Urine Na

Labs: >20 mmol/L <10 mmol/L <100 mOsm/kg >150 mOsm/kg >20 mmol/L <10 mmol/L

Renal loss, Non-renal loss, Excess water Impaired renal, Renal cause, Non-renal,
e.g., diuretics, e.g., GI losses intake water excretion e.g., acute or e.g., heart failure,
mineralocorticoid e.g., SIADH chronic renal cirrhosis
deficiency failure

● Figure 3-1. Diagnostic approach to hyponatremia. GI, gastrointestinal; SIADH, syndrome of inappropriate antidiuretic hormone.
 Hypernatremia

Hypovolemia Euvolemia Hypervolemia

5580_Ch03_pp038-052 8/28/06 11:22 AM Page 47

Depleted in total body [Na] Normal total body [Na], Excess total body [Na]
and water, but more depleted in water and water, but more
water loss Na than water

Renal loss Non-renal loss Renal loss Non-renal loss Usually iatrogenic

Urine Na Urine Na Urine osmolality Urine osmolality

> < < >
20 mmol/L, 10 mmol/L, Plasma osmolality, Plasma osmolality,
e.g., diuretics e.g., excessive sweating e.g., diabetes insipidus e.g., insensible losses

● Figure 3-2. Diagnostic approach to hypernatremia.

RENAL, FLUID, AND ELECTROLYTE DISORDERS
47
 48
CHAPTER 3

Check Acid-Base Status

Acidotic Alkalotic Normal

5580_Ch03_pp038-052 8/28/06 11:22 AM Page 48

Non–anion-gap Transcellular shifts,

Anion-gap acidosis Urine chloride e.g., increased sympathetic
acidosis
drive, insulin overdose

GI losses, e.g., diarrhea Check for ketones, Low, i.e., <20 mmol/L High, i.e., >50 mmol/L
or lactate, salicylate, Vomiting, remote Excessive
renal losses, e.g., alcohols, or diuretic use mineralocorticoids
renal tubular acidosis renal failure or diuretics

● Figure 3-3. Diagnostic approach to hypokalemia. GI, gastrointestinal.

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RENAL, FLUID, AND ELECTROLYTE DISORDERS 49

D. ACID–BASE DISORDERS
1. General considerations
a. Acid–base disorders can be either metabolic (changes in serum [bicarbonate]
level) or respiratory (changes in PaCO2 level).
b. 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), meta-
bolic alkalosis (increased serum [bicarbonate] level), respiratory acidosis
(increased PaCO2 level), and respiratory alkalosis (decreased PaCO2 level).
c. 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 hyperven-
tilate 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 aci-
dosis (increased PaCO2 level) will develop a metabolic alkalosis (increased
serum [bicarbonate] level; this response, mediated by the kidneys, may
require 2 to 3 days).
d. 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.
e. 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 [bicar-
bonate] 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 [bicarbon-
ate] level.
f. When calculating the appropriate physiologic response of a patient with an
acid–base disturbance, allow /2 units.
g. 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 respira-
tory 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)
 50
Metabolic acidosis
CHAPTER 3

Anion-gap acidosis Non–anion-gap acidosis

(hyperchloremic)

GI losses RTA
(renal tubular acidosis)
5580_Ch03_pp038-052 8/28/06 11:22 AM Page 50

Ketones [i.e., diabetic

ketoacidosis (DKA)] Diarrhea Type I distal RTA
associated with hypokalemia

Beta-hydroxybutyrate
also seen in DKA Fistula Type II proximal RTA
associated with hypokalemia

Salicylates and other Type IV hyperkalemic

Ureterosigmoidostomy
toxins distal RTA
secondary to decreased
aldosterone or renal
aldosterone resistance
Lactate (often seen in
those with necrotic bowel)

Phosphates (advanced
renal disease)

● Figure 3-4. Diagnostic considerations in a patient who has metabolic acidosis. GI, gastrointestinal.
5580_Ch03_pp038-052 8/28/06 11:22 AM Page 51

RENAL, FLUID, AND ELECTROLYTE DISORDERS 51

Metabolic alkalosis

Chloride responsive* Chloride resistant

Low urine chloride High urine chloride

(usually <10 mmol/L) (usually >20 mmol/L)

Vomiting Primary hyperaldosteronism

(loss of HCl) (also hypokalemic)

Nasogastric Cushing syndrome

suction (excess mineralocorticoids)

Diuretic use in a patient Bartter syndrome

with NaCl restriction

* 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 appropri-
ate 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 dis-
order 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–anion-
gap 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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52 CHAPTER 3

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.
5580_Ch04_pp053-081 8/28/06 11:22 AM Page 53

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. Reflux esophagitis may be associated with a primary defect in lower esophageal
sphincter (LES) tone.
b. Secondary causes include pregnancy, drugs (anticholinergics, β2-agonists, cal-
cium channel blockers), surgical vagotomy, smoking, and alcohol and caffeine
ingestion.
2. Clinical features
a. 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.
b. The disease may lead to the formation of strictures, which may cause dys-
phagia for solid foods.
c. Blood from esophageal erosions may be present in regurgitated material.
d. Signs and symptoms of anemia may be present if bleeding is chronic or severe.
3. Laboratory findings
a. Barium swallow and upper gastrointestinal (GI) series test results are positive
only in patients who have severe disease; therefore, these tests are not very sen-
sitive. They are useful in ruling out other esophageal disorders such as achalasia.
b. Esophageal manometry allows assessment of LES pressures at rest and dur-
ing swallowing.
c. Endoscopy with biopsy is used to rule out associated peptic ulcer disease and
Barrett esophagus (premalignant epithelial changes associated with chronic reflux).
4. Treatment
a. Mild disease responds to simple measures such as elevating the head of the
bed and not eating before bedtime.
b. Patients can try liquid antacids after meals and before bed.
c. H2-receptor blockers (cimetidine, ranitidine) are also effective; however, pro-
ton pump inhibitors (e.g., omeprazole) are now considered the treatment of
choice. As several randomized trials show, they are superior to H2 blockers.
d. 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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54 CHAPTER 4

C. GASTRITIS
1. Acute gastritis
a. 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.
b. 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.
c. Laboratory findings from endoscopic examination are best for diagnosis.
d. 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.
2. Chronic gastritis
a. Chronic gastritis is associated with the use of NSAIDs, ethanol ingestion,
radiation injury, and immunologic factors (pernicious anemia).
b. This disease lacks definite clinical manifestations other than anemia associ-
ated with atrophic gastritis.
c. 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).
d. Patients with chronic gastritis have an increased incidence of gastric ulcer and
gastric carcinoma.
e. 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. 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.
b. Clinical features
i. Patients experience a progressive dysphagia for solids.
ii. Signs and symptoms of advanced disease include pain, weight loss, dys-
phagia for liquids, cough, and hoarseness.
c. 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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GASTROINTESTINAL DISORDERS 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 consider-
ably 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. 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).
b. 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.
c. 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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56 CHAPTER 4

● 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.

ii. A high LES resting pressure that fails to relax during swallowing (detect-
ed with esophageal manometry) is associated with achalasia; the pres-
ence of low-amplitude, coordinated contractions or even the complete
absence of peristalsis distinguishes achalasia from DES.
d. 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 perfo-
ration 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 anti-
cholinergics, nitrates, or calcium channel blockers.
iv. Longitudinal myotomy is reserved for DES patients who are incapacitated
by the disease.
2. 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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GASTROINTESTINAL DISORDERS 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 sur-
gery or in mentally ill patients who consume indigestible substances such
as hair (trichobezoars).
v. Gastroparesis is most commonly associated with longstanding diabetes.
b. Clinical features
i. Signs and symptoms of gastric outlet obstruction predominate, includ-
ing 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.
c. 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.
d. 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.

F. PEPTIC ULCER DISEASE

1. General characteristics
a. Peptic ulcers occur in the stomach or proximal duodenum.
b. Peptic ulcer disease occurs most commonly in middle-aged men.
c. Associated risk factors include smoking, NSAID use, corticosteroid use,
ethanol ingestion, family history, and chronic anxiety.
d. Duodenal ulcers are benign, but gastric ulcers may be malignant.
e. Approximately 75% of duodenal ulcers are associated with H. pylori infection.
2. Clinical features
a. The main symptom is an epigastric burning sensation.
b. 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.
c. Patients may initially be seen with upper GI hemorrhage, that is, hemateme-
sis, melena, and abdominal pain.
d. Signs and symptoms of anemia may be present if chronic and/or significant
upper GI hemorrhage has occurred.
3. 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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58 CHAPTER 4

● 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 dis-
ease. H. pylori gastric biopsy should also be performed in this setting.
c. In patients who are diagnosed with ulcer disease without endoscopy, serolog-
ic 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 (cimeti-
dine 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 com-
bination of two antibiotics, bismuth, and a proton pump inhibitor is necessary
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GASTROINTESTINAL DISORDERS 59

for 10-14 days. Commonly effective antibiotics include amoxicillin, metro-

nidazole, and clarithromycin.
f. Surgery for intractable cases or complicated (perforated, bleeding, obstructed)
peptic ulcer disease is indicated.

II Diseases of the Small Intestine

A. DIARRHEA
1. General characteristics
a. Diarrhea is defined as increased volume and liquidity of stool.
b. 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).
c. Abnormal intestinal motility (from rapid or slow peristalsis) causes diarrhea
and is most often associated with longstanding diabetes.
d. Longstanding diarrhea may be associated with irritable bowel syndrome.
2. Clinical features
a.
Persistent diarrhea in the absence of food intake suggests a secretory diarrhea.
b.
Absence of diarrhea after a 2- to 3-day fast suggests osmotic diarrhea.
c.
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 bac-
terial strain. Campylobacter, Salmonella, and E. coli are most common.
b. Microscopic examination of stool may reveal ova or parasites that can cause diar-
rhea (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 inflam-
matory 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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60 CHAPTER 4

TABLE 4-1 COMMON CAUSES OF INFECTIOUS DIARRHEA

Organism Spread Comments Treatment

Escherichia coli Fecal contamination Most common cause TMP-SMX if severe

of food/water of traveler’s diarrhea
Secretory diarrhea Pepto-Bismol for
symptomatic relief
Self-limited
Campylobacter Contaminated water One of the most common Usually not required
or milk causes of bacterial diarrhea
in United States
Self-limited, short duration Ciprofloxacin if prolonged
Salmonella spp. Contamination Acute, self-limited Usually no treatment
of eggs or milk because can lead to
prolonged carrier state
Crampy, abdominal Severe disease treated with
pain with fever ampicillin or TMP-SMX
Shigella spp. Fecal-oral Most common in day care Ampicillin or TMP-SMX
centers and urban poor
Seen in “gay bowel Amoxicillin cannot be
syndrome” substituted because ineffective
Crampy, abdominal pain
progressing to bloody
diarrhea if untreated
Giardia lamblia Fecal contamination Most common cause of Metronidazole
of water water-borne infectious
diarrhea in United States
Causes mild or severe
symptoms
Norwalk agent/ Person to person Common cause of Not necessary
rotavirus self-limited diarrhea
TMP-SMX, trimethoprim-sulfamethoxazole.

b. Small bowel obstruction can also be secondary to an adynamic (paralytic) ileus

that can occur with trauma, abdominal surgery, hypokalemia, and peritonitis.
2. Clinical features
a. 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.
b. 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.
c. Additional symptoms include vomiting and constipation.
d. Obstruction may lead to intestinal ischemia and gangrene.
3. Laboratory findings
a. 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.
b. If strangulation and ischemia occur, leukocytosis may occur.
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GASTROINTESTINAL DISORDERS 61

Blood or leukocytes in stool

YES NO

Systemic signs and symptoms Nausea and vomiting

Mild NO YES
Moderate/Severe
(>5 days illness, fever,
>8 stools/day)
SIGNS OF BOWEL
OBSTRUCTION

OBSERVE Stool culture

and exam VIRAL, FOOD
for parasites POISONING,
HISTORY OF
LAXATIVES
NO YES

ORGANISM IDENTIFIED DRUG- FECAL

INDUCED? IMPACTION
OR PARTIAL
OBSTRUCTION
NO
YES NO

Stool culture and

exam for parasites

SPECIFIC THERAPY
FOR ORGANISM

NEGATIVE POSITIVE

Radiographs and biopsy SPECIFIC

to rule out inflammatory THERAPY
bowel disease and ischemia FOR
ORGANISM

● Figure 4-3. Workup for acute diarrhea.

4. Treatment
a. Therapy for adynamic ileus includes continuous decompression via naso-
gastric tube and treatment of the primary cause.
b. Therapy for mechanical obstruction includes operative correction if the
obstruction is complete and strangulation is in progress; intravenous (IV)
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62 CHAPTER 4

TABLE 4-2 BACTERIAL FOOD POISONING SYNDROMES

Organism Incubation Period Source of Infection Comment

Staphylococcus 2–6 h Meat and dairy Sudden onset of vomiting,

aureus handlers 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 8–14 h Reheated meats, Profuse diarrhea with severe
perfringens poultry, and legumes 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 1–3 d Food and water Causes traveler’s diarrhea
Escherichia coli Prophylaxis with TMP-SMX
Vibrio cholerae 1–3 d Fecally contaminated Common in southeast Asia
water
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 1–2 d Canned foods Neurologic manifestations
botulinum Ventilatory support required
Requires immediate administration
of antitoxin
Clostridium During or within Antibiotic-associated Produces pseudomembranous colitis
difficile 4 weeks of Treated with vancomycin or
discontinuing metronidazole
antibiotic therapy

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. Malabsorption may be secondary to a large number of clinical entities.
b. The most common of these entities include lactase deficiency, inflammatory
bowel disease (e.g., Crohn disease), small bowel infections, chronic pancreati-
tis (often secondary to alcoholism), obstructive liver disease leading to bile salt
deficiency (e.g., cholangiocarcinoma), celiac disease, and longstanding dia-
betes mellitus.
c. Calcium, folic acid, and iron are absorbed from the proximal small bowel;
bile acids and vitamin B12 are absorbed from the ileum.
d. 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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GASTROINTESTINAL DISORDERS 63

2. Clinical features
a. Features vary with the etiology of the malabsorptive process.
b. Signs and symptoms of malabsorption may include steatorrhea (greasy,
foul-smelling stools that may float in the toilet bowl), weight loss, hypoalbu-
minemia leading to edema and ascites, and anemia.
c. Fractures secondary to poor vitamin D absorption may occur.
d. Paresthesias and tetany may result from hypocalcemia.
e. Coagulation disorder may occur due to decreased vitamin K absorption.
3. Laboratory findings
a. 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 asso-
ciated with pancreatic disease.
b. Decreased absorption seen in the xylose absorption test indicates injury to
intestinal mucosa.
c. 14C-xylose conversion to 14CO is increased in patients who have bacterial
2
overgrowth that can be measured during a breath test.
d. Abdominal radiographic study may reveal a fistula, blind loop, or areas of
stasis, which indicate bacterial overgrowth syndrome.
e. Decreased stool pH suggests unabsorbed carbohydrates; this sign is usually
seen in patients who have lactase deficiency or celiac disease.
f. Schilling test (see I C 2 c)
4. Treatment
a. Treatment is based on the underlying cause of the malabsorption.
b. Pancreatic enzyme replacement is indicated in patients who have chronic
pancreatitis.
c. Ampicillin or tetracycline may be useful in patients who have bacterial over-
growth syndrome.
d. Gluten-free diet should be prescribed for patients who have celiac disease.

E. CROHN DISEASE
1. General characteristics
a. Crohn disease is a chronic granulomatous disease that most often affects
the ileum.
b. The disease is often seen in persons who are in early adulthood or over
age 50.
c. 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.
2. Clinical features
a. Signs and symptoms include fever, weight loss, anorexia, colicky pain, and
diarrhea.
b. A right lower quadrant abdominal mass may be palpable if the ileum is
extensively involved; this sign mimics appendicitis.
c. Fecal occult blood is present.
d. Colon and rectum involvement produce significant diarrhea, perirectal fis-
sures, fistulas, and abscesses.
e. Peripheral arthritis may occur in 10% of patients (see Chapter 7, Rheumatic
Diseases).
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64 CHAPTER 4

● 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. Abdominal radiographic study reveals deep ulcerations and long, strictured
segments alternating with uninvolved areas (Figure 4-4).
b. Endoscopy may reveal inflammatory changes; inflammation can be confirmed
with biopsy of affected areas.
c. Anemia, leukocytosis, and protein loss may be present; however, these find-
ings are nonspecific.
4. Treatment
a. In severe disease, bowel rest with intravenous fluid/total parenteral nutrition
(TPN) and broad-spectrum antibiotics are indicated.
b. In acute disease, sulfasalazine (or other 5-aminosalicylate [5-ASA] agents)
therapy with or without corticosteroids is indicated (corticosteroids for severe
disease).
c. Surgery is often required for fistula formation, abscesses, or obstruction.
d. 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.
e. Vitamin B12 may be required if the ileum is significantly involved.
f. Metronidazole is useful in fistulous perianal disease.
g. Infliximab, an antitumor necrosis factor antibody, has been effective in disease
refractory to 5-ASA and steroids.
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GASTROINTESTINAL DISORDERS 65

III Diseases of the Colon, Rectum, and Anus

A. GENERAL CHARACTERISTICS
1. The main disorders of the colon include constipation, appendicitis, diverticular
disease, ulcerative colitis, and colonic tumors.
2. 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. Maximum incidence occurs in the second and third decades of life, but
appendicitis may occur at any time.
b. The disease begins with obstruction of the appendiceal lumen by a fecalith,
followed by distention of the appendix with mucous secretions from the
mucosa.
c. Bacterial invasion of the appendiceal wall concomitant with venous
engorgement and arterial insufficiency occur as a result of the increasing
intraluminal pressure.
2. 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. Leukocytosis is common.
b. 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 visu-
alized; 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.
4. Differential diagnosis includes mittelschmerz (rupture of graafian follicle), mesen-
teric lymphadenitis, ectopic pregnancy, pelvic inflammatory disease, and Crohn
disease.
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66 CHAPTER 4

5. Treatment
a. Appendicitis is a mechanical disease, and therefore appendectomy is the
treatment of choice.
b. Intravenous fluids should be administered because these patients often have
had little fluid intake during the onset of the disease.
c. Antibiotics effective against enteric organisms such as E. coli and Bacteroides frag-
ilis 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. Diverticular disease is common in persons older than age 60.
b. The disease is most often found in the sigmoid colon.
c. Diverticular disease may be associated with a low-fiber diet.
2. Clinical features
a. Patients who have this disease are usually asymptomatic but may occasion-
ally have alternating diarrhea and constipation or crampy abdominal pain
that is relieved by a bowel movement.
b. Occasionally, significant painless bleeding from a diverticulum occurs.
c. Diverticulitis is a frequent complication.
i. Signs and symptoms of diverticulitis include left lower quadrant abdom-
inal 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.
3. Laboratory findings
a. Plain film abdominal radiographs may suggest the presence of diverticula.
b. Barium enema is often diagnostic but should not be performed during the
acute phase of diverticulitis due to risk of perforation (Figure 4-5).
c. Sigmoidoscopy/colonoscopy is diagnostic but should be performed cautious-
ly in the acute phase.
d. Leukocytosis is often present in diverticulitis.
e. 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.
4. Treatment
a. Increased fiber consumption can relieve some of the uncomfortable symp-
toms of diverticular disease but should be done after resolution of acute
inflammation.
b. Diverticulitis requires bowel rest and broad-spectrum antibiotics.
c. More than two bouts or an episode of diverticulitis with abscess, fistula, or free
perforation are indications for sigmoidectomy.
d. Surgery may be required if bleeding does not respond to medical management.

E. ULCERATIVE COLITIS
1. General characteristics
a. Ulcerative colitis is characterized by diffuse inflammation of the rectum and
colon; unlike Crohn disease, inflamed areas do not alternate with uninflamed
areas.
b. Ulcerative colitis is more common in women than in men.
c. Microabscesses are produced.
2. Clinical features
a. The disease may be limited to the rectum, which leads to ulcerative proctitis.
b. Nocturnal passage of small amounts of blood and mucus may occur.
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GASTROINTESTINAL DISORDERS 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. Severe disease may involve diarrhea, fever, weight loss, abdominal pain, and
rectal bleeding.
d. Severe disease may progress to toxic megacolon (Figure 4-6), colonic perfo-
ration, hypokalemia, and shock.
e. Individuals who have ulcerative colitis are at increased risk of colonic
malignancy.
3. Laboratory findings
a. Bacterial and parasitic infection must be ruled out with appropriate stool
cultures.
b. Malignancy must be ruled out with colonoscopy and biopsy.
c. Analysis of stool sample reveals presence of blood, mucus, and white blood
cells without parasites or bacterial pathogens.
d. 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.
e. Proctoscopy reveals friable, edematous, hyperemic mucosa with ulcerations.
f. Yearly colonoscopic evaluations are required to rule out neoplastic changes.
4. Treatment
a. Acute flare-ups can be treated with bowel rest, IV solutions, and TPN, if
necessary.
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68 CHAPTER 4

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

b. Corticosteroids, sulfasalazine, and 5-ASA have been shown to reduce symp-

toms and induce remission in the acute phase of the disease.
c. Sulfasalazine should be used on a regular basis to prevent recurrence.
d. Total colectomy is required for recurrent, severe disease, or if the patient
shows evidence of neoplastic disease.
e. Toxic megacolon requires immediate hospitalization with broad-spectrum
antibiotics, replacement of blood and electrolytes, and prompt surgical
consultation.

F. COLONIC NEOPLASTIC DISEASE

1. General characteristics
a. Colonic neoplastic disease includes benign tumors and adenocarcinoma.
b. Also included are the familial polyposis syndromes; because these syn-
dromes are relatively uncommon, they are not discussed here.
2. 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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GASTROINTESTINAL DISORDERS 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.
b. Clinical features
i. Patients who have benign tumors may be asymptomatic or may have rec-
tal bleeding that can be significant.
ii. Patients who have large polyps may have signs and symptoms of incom-
plete obstruction.
c. 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.
d. 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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70 CHAPTER 4

3. Adenocarcinoma
a. 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.
b. 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.
c. 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.
d. Treatment involves surgical consultation for removal and appropriate postoper-
ative management. Postoperative chemotherapy has been shown to improve sur-
vival in patients with metastatic nodal disease (e.g., fluorouracil and leukovorin).

G. INFECTIOUS PROCTITIS
1. General characteristics
a. Infectious proctitis is common in men who have sex with men.
b. The disease is caused by syphilis, gonorrhea, chlamydia, and herpes simplex.
2. Clinical features
a. Tenesmus, constipation, anorectal pain, hematochezia, and mucopuru-
lent discharge may be present.
b. The nonspecific signs of fever and leukocytosis may be present.
c. Anoscopy reveals mucosal exudate and friable mucosa.
3. Laboratory findings
a. Culture of sample taken from the anus is often diagnostic.
b. Microscopy of anal sample is also often diagnostic.
4. Treatment
a. Appropriate antibiotic therapy is required, for example, ceftriaxone for gon-
orrhea and doxycycline for chlamydia.
b. Acyclovir is indicated for prolonged, frequently recurrent herpes.

H. PSEUDOMEMBRANOUS COLITIS (ALSO KNOWN AS CLOSTRIDIUM

DIFFICILE COLITIS)
1. General characteristics
a. Associated with antibiotic use leading to C. difficile overgrowth.
b. Symptoms usually begin during or shortly after antibiotic therapy.
c. Ampicillin, clindamycin, and third-generation cephalosporins are most
often the causative agent, but virtually all antibiotics have been implicated.
d. May progress to toxic megacolon in severe cases.
e. Most common cause of diarrhea among hospitalized patients.
2. Clinical features
a. Foul-smelling, watery diarrhea, occasionally bloody (more than three watery
stools per day for more than 2 days)
b. Lower abdominal cramping
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GASTROINTESTINAL DISORDERS 71

c. Fever, mental status changes, dehydration, and hypotension may be present in

more severe cases.
d. Abdominal tenderness, often left-sided or generalized, with mild to moderate
distension and guaiac positive stools
3. Laboratory findings
a. 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.
b. Flexible sigmoidoscopy shows yellow adherent plaques (pseudomembranes),
which should undergo biopsy to show their characteristic fibrin and neu-
trophil exudate.
c. Patients with severe disease may show dilated (
9 cm) colon on plain film or
CT if toxic megacolon is present.
4. Treatment
a. Discontinue offending antibiotic. Do not use antiperistaltic/antidiarrheal
agents because these worsen the disease.
b. Metronidazole is the first-line therapy. Oral administration is best but can be
given IV.
c. Vancomycin (given orally) is used for patients who cannot tolerate metron-
idazole or who do not improve.
d. In severe cases unresponsive to medical treatment, total abdominal colectomy
may be necessary.

IV Pancreatic Disorders
A. ACUTE PANCREATITIS
1. General characteristics
a. Acute pancreatitis is defined as acute inflammation of the pancreas, which
begins with edema but may progress to autodigestion, necrosis, and hemorrhage.
b. Gallstones and alcohol are most commonly associated with pancreatitis.
2. Clinical features
a. Patients experience steady, severe epigastric pain that may radiate to the back.
b. Nausea and vomiting usually are not present unless disease is severe.
c. In severe disease, abdominal distention may result from ileus.
d. Severe disease may lead to fever, tachycardia, and shock.
e. Epigastric mass may be palpable if pseudocyst develops.
f. Hemorrhagic pancreatitis may cause Grey-Turner sign (discoloration of the
flanks) or Cullen sign (periumbilical discoloration).
3. Differential diagnoses include biliary colic, perforated viscus (especially if patient
has had gastroduodenal ulcers), and acute cholecystitis.
4. Laboratory findings
a. CT is diagnostic showing an edematous, inflamed pancreas and may reveal
areas of necrosis and/or peripancreatic fluid.
b. Diagnosis is confirmed when a positive CT scan occurs with a significantly
elevated serum amylase level (often more than three times normal).
c. Hemoconcentration, increased blood urea nitrogen/creatinine, and acidosis are
present when severe disease produces hypovolemia and hypoperfusion.
d. Hypoxia, hyperglycemia, and hypocalcemia are signs of severe disease.
e. In patients with alcohol ingestion, right upper quadrant (RUQ) ultrasound
should be obtained to assess for gallstones as the cause.
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72 CHAPTER 4

5. Treatment
a. IV fluid replacement is required.
b. Pain relief can be achieved with narcotics.
c. Nasogastric suction should be performed in patients with significant nau-
sea/vomiting, but it des not change the course of the pancreatitis.
d. Associated findings should be treated; for example, hypocalcemia requires
calcium, and hyperglycemia requires insulin.
e. 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. Chronic pancreatitis is the progressive destruction and distortion of the
pancreas and its ducts.
b. The disease is associated with alcoholism in adults and cystic fibrosis in
children.
2. Clinical features
a. Patients experience severe, intractable abdominal pain.
b. Eventually, diabetes and malabsorption with steatorrhea may occur, which
lead to weight loss.
c. Obstructive jaundice can occur if fibrous tissue envelops the common bile
duct (CBD).
d. Gastritis is commonly seen secondary to excessive alcohol intake.
e. Fifteen percent of patients with idiopathic chronic pancreatitis have a genetic
basis for the disease.
3. Differential diagnosis
a. Abdominal malignancy must be considered, especially carcinoma of the pancreas.
b. Patients who have peptic ulcer disease may have similar presenting symptoms.
c. Biliary tract disease should also be considered.
4. Laboratory findings
a. Analysis of the serum amylase level is usually not helpful because the amy-
lase level is elevated only in acute pancreatitis, not in chronic disease.
b. Abdominal radiographic study may reveal pancreatic calcification, a cardinal
sign of chronic pancreatitis.
c. CT scan may help determine the presence of pancreatic calcification and may
also reveal the presence of pseudocysts.
d. Endoscopic retrograde cholangiopancreatography (ERCP) is useful in diag-
nosing the distorted ductal anatomy.
e. Pancreatic stimulation tests are usually unnecessary but reveal decreased
secretion of virtually all pancreatic substances.
5. Treatment
a. Patients must reduce alcohol consumption if alcohol is a factor.
b. Pancreatic digestive enzyme supplements can be used to reduce the effects
of malabsorption.
c. Insulin is indicated for diabetes mellitus.
d. 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 73

b. Pancreatic carcinoma has a high mortality rate.

c. The tumor is usually an adenocarcinoma (90%); islet cell tumors constitute
the remaining 10% of pancreatic cancers.
2. Clinical features
a. Epigastric pain and weight loss are the cardinal symptoms.
b. Pain is often noncolicky, dull, and persistent.
c. Additional signs and symptoms include anorexia, nausea, vomiting, and
diarrhea/steatorrhea.
d. Obstructive jaundice is common when carcinoma affects the head of the pan-
creas and may lead to a palpable gallbladder.
e. Paraneoplastic syndromes such as Cushing syndrome or hypercalcemia
can occur.
f. Invasion of the tumor into the GI tract may cause upper GI bleeding.
g. The diagnosis should be considered in older patients who have unexplained
weight loss, abdominal pain, or recent onset of diabetes without obesity.
3. Laboratory findings
a. Presence of tumor markers (CEA, cancer antigen 19-9) suggests the diagno-
sis 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 diag-
nosis 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.
4. Treatment is mostly palliative due to the poor response to therapy.

V Biliary Tract Disease

A. ACUTE CHOLECYSTITIS
1. General characteristics
a. Acute cholecystitis is defined as an inflammation of the gallbladder.
b. It is most commonly due to obstruction of the cystic duct by an impacted
gallstone.
2. Clinical features
a. Patients experience crampy epigastric or RUQ pain; pain is often postpran-
dial 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.
3. Differential diagnoses include choledocholithiasis, choledochal cysts, and gall-
bladder or bile duct carcinoma in elderly individuals.
4. Laboratory findings
a. Because most gallstones are composed of cholesterol and hence are radiolu-
cent, abdominal radiographic study is often of little value.
b. Abdominal ultrasound is useful in detecting gallstones within the gallblad-
der, and may reveal pericholecystic fluid and gallbladder wall thickening.
c. 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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74 CHAPTER 4

d. Serum analysis reveals leukocytosis. Bilirubin level may be mildly elevated

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

B. CHOLEDOCHOLITHIASIS
1. General characteristics
a. Choledocholithiasis is defined as the presence of gallstones in the CBD.
b. This condition is most often caused by stones that have formed in the gall-
bladder.
2. Clinical features
a. Jaundice and RUQ pain are the most common signs and symptoms.
b. Sepsis with cholangitis and shock may occur in severe disease.
3. Laboratory findings
a. Serum analysis reveals elevated alkaline phosphatase (AP) and transaminase
levels.
b. Total serum bilirubin is 85 mol/L.
c. Cholangiography reveals the obstructed CBD.
d. 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.
4. Treatment
a. Patients should receive antibiotics (e.g., piperacillin/tazobactam) until the
obstruction has been alleviated.
b. Stones can be removed surgically or via endoscopic extraction.

C. ASCENDING CHOLANGITIS
1. General characteristics
a. Most often secondary to biliary obstruction due to gallstones (choledo-
cholithiasis) that migrate from the gallbladder.
b. 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.
c. Extrinsic compression of the CBD from metastatic cancer may also occur.
d. If untreated, may result in sepsis, biliary cirrhosis, and hepatic failure.
2. Clinical features
a. Often a previous history of biliary colic—sharp intermittent RUQ pain.
b. Jaundice develops with prolonged obstruction, typically 1–2 days.
c. Charcot’s triad is the classic presentation of cholangitis and includes fever,
RUQ pain, and jaundice.
d. Altered mental status and septic shock with hypotension indicates acute
suppurative cholangitis, which is an emergency.
e. A history of clay stools and tea urine may be present.
3. Laboratory findings
a. Hyperbilirubinemia (predominantly conjugated) (85/L)
b. Elevated alkaline phosphatase is highly suggestive of biliary obstruction.
c. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels
may be transiently increased.
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GASTROINTESTINAL DISORDERS 75

d. Prothrombin time (PT) is often mildly elevated.

e. Leukocytosis develops as the infection progresses.
f. 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.
4. Treatment
a. 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.
b. Patients with coexistent cholelithiasis should have cholecystectomy after ERCP.
c. Vitamin K should be administered prior to procedures if PT is elevated.
d. Antibiotics should be administered until the obstruction is resolved (e.g.,
piperacillin/tazobactam).

D. TUMORS OF THE BILIARY SYSTEM

1. General characteristics
a. Adenocarcinoma of the gallbladder is most common in older women and
is associated with a history of gallstones.
b. Adenocarcinoma of the bile duct (cholangiocarcinoma) is most common in
older men and is associated with a history of ulcerative colitis.
2. Clinical features
a. 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.
b. Signs and symptoms of adenocarcinoma of the bile duct include jaundice
with or without pain and weight loss.
3. Laboratory findings
a. 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.
4. 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.

VI Liver Disease
A. VIRAL HEPATITIS
1. General characteristics
a. Viral hepatitis is defined as a viral inflammatory disease of the liver.
b. 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.
c. All except hepatitis B are RNA viruses; hepatitis B is a DNA virus.
2. Clinical features (Figure 4-8)
a. Signs and symptoms include malaise, anorexia, fatigue, arthritis, urticaria,
and jaundice.
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76 CHAPTER 4

TABLE 4-3 COMPARISON OF VIRAL HEPATITIS AGENTS

Mechanism Incidence With

Agent of Spread Blood Transfusion Prevention Complications

Hepatitis A Fecal-oral Rare Immune serum globulin; Fulminant hepatitis

give to close contacts (very rare)
Hepatitis B Parenteral (e.g., 10%–20% Hepatitis B immune Chronic active hepatitis,
intravenous drug globulin; hepatitis B occasionally causes fulminant
abusers); sexual vaccine; may attain hepatitis; increased risk of
contact symptoms if given hepatocellular carcinoma
7 days after exposure if chronic hepatitis
Hepatitis C Parenteral 60%–70% Immune serum globulin Same as hepatitis B
Delta agent Parenteral Unknown Unknown Often present with
hepatitis B in cases of
fulminant or chronic
active hepatitis

b. Influenza-like syndrome may be present with nausea, vomiting, myalgias,

and headache.
c. Dark urine/light-colored stools are caused by impaired bilirubin conjugation.
d. The liver is enlarged and tender.
e. Splenomegaly may occur.
3. Laboratory findings
a. Serum AST and ALT levels are elevated as much as 20-fold.
b. AP level is usually not significantly elevated (in contrast to biliary disease).
c. Serum and urine bilirubin levels are increased.
d. Serum antibodies and antigens are useful diagnostically.
i. Presence of anti-hepatitis A immunoglobulin M (IgM) antibody indi-
cates 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 chron-
ic 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. 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.
b. Patients should maintain good hydration and dietary intake.
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GASTROINTESTINAL DISORDERS 77

A
Symptomatic Phase

Titer IgM IgG

Fecal
HAV

0 4 8 12 16 20
Wks After
Exposure Exposure

B
Symptomatic Phase

HBeAg
Titer Anti-HBe
IgG Anti-HBc
HBsAg
Anti-HBs

0 4 8 12 16 20 24 28 32 36 40 52
Wks After
Exposure Exposure

C
Symptoms

Anti-HCV

HCV RNA

0 1 2 3 4 5 6 1 2 3
Months 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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78 CHAPTER 4

c. Vitamin K administration may be necessary if coagulation parameters are

abnormal.
d. Hospitalization is indicated for patients who have severe nausea/vomiting,
prolonged prothrombin time, or severe liver dysfunction.
e. Incidence of chronic hepatitis C infection may be reduced if interferon and rib-
avirin is given in acute hepatitis C infection.
f. There is no treatment for hepatitis A; hepatitis D may be treated with inter-
feron.
B. ALCOHOLIC LIVER DISEASE
1. General characteristics
a. Alcoholic liver disease is seen in the acute stage as alcoholic fatty liver dis-
ease or alcoholic hepatitis.
b. Chronic injury results in alcoholic cirrhosis.
2. Alcoholic fatty liver disease and alcoholic hepatitis
a. Clinical features
i. Patients who have alcoholic fatty liver disease usually are asympto-
matic, 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.
b. 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 albu-
min level often indicate alcoholic hepatitis.
iv. Alcohol-induced thrombocytopenia may be present.
v. Liver biopsy confirms the diagnosis of alcoholic hepatitis.
c. Treatment
i. Patients must maintain adequate caloric intake.
ii. Thiamine and folate supplements are required because these patients are
often deficient in these vitamins.
3. Alcoholic cirrhosis
a. Clinical features
i. Fibrosis with nodular formation and destruction of normal liver architec-
ture 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, drowsi-
ness, disorientation, and coma.
vi. Patients who have hepatorenal syndrome demonstrate oliguria and pro-
gressive renal failure.
b. Laboratory findings
i. Ultrasound or CT scan effectively demonstrates the characteristic appear-
ance of the cirrhotic liver.
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GASTROINTESTINAL DISORDERS 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.
c. Treatment
i. Acute deterioration requires hospitalization and management of com-
plications.
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. Hepatic abscess may be due to Entamoeba histolytica (which is seen fre-
quently in homosexual men).
b. Hepatic abscess is also associated with infection by the following anaerobes:
E. coli, Klebsiella spp., Staphylococcus spp., and Streptococcus spp. in conjunc-
tion with cholecystitis and cholangitis.
2. Clinical features
a. Signs and symptoms include fever, chills, night sweats, anorexia, liver ten-
derness, and RUQ pain.
b. Pleuritic pain may also occur.
3. Laboratory findings
a. Blood cultures may be positive for bacteria, which indicates bacteremia.
b. Serum liver enzyme levels are elevated.
c. Serum analysis reveals leukocytosis.
d. 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.
4. Treatment
a. E. histolytica is treated with amebicides (e.g., metronidazole) with aspira-
tion of the abscess.
b. 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. Hepatic tumors consist of both benign and malignant lesions.
b. Benign tumors are usually of little clinical relevance (unless complicated by
hemorrhage).
c. The liver is one of the most common organ sites for metastatic disease.
d. The most common primary malignant tumor is hepatocellular carcinoma
(hepatoma).
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80 CHAPTER 4

2. Hepatoma
a. General characteristics
i. Hepatoma is most common in middle-aged men.
ii. Common associated risks include cirrhosis and prior hepatitis B infection.
b. 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 cir-
rhotic patient are hallmarks of hepatoma.
c. 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.
d. 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.

VII Gastrointestinal Bleeding

1. General characteristics
a. May be upper (site proximal to ligament of Treitz) or lower (distal to ligament
of Treitz)
b. Common causes of upper GI bleeds include peptic ulcer disease (50%),
esophageal varices (10%–20%), Mallory-Weiss tear (5%–10%), and vascular
anomalies (10%).
c. 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.
2. Clinical features
a. Upper GI bleed
i. Hematemesis: bright red or coffee grounds
ii. Melena—black stool
iii. Hematochezia is less common and indicates massive upper GI hemor-
rhage. 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 con-
sumption.
vi. History of NSAIDs or steroids suggests peptic ulcer disease.
vii. Nasogastric tube placement helps confirm upper GI source.
b. 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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GASTROINTESTINAL DISORDERS 81

ii. Maroon stools suggest a right colon or small intestine source.

iii. Hematochezia suggests a colonic source.
iv. Painless bleeding is typical of diverticular or AVM bleeding.
v. Bloody diarrhea suggests IBD or infectious or ischemic colitis.
3. Laboratory findings
a. Decreased hematocrit depending on severity of hemorrhage.
b. Leukocytes may be present in infectious or ischemic etiologies.
c. Liver function test results may be abnormal in those with coexistent liver dis-
ease, suggesting esophageal variceal hemorrhage as the etiology.
d. 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.
e. 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.
f. 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.
g. Nuclear medicine scan detects 0.5 mL/min of bleeding but is less sensitive
in localization of the bleeding site than angiography.
4. Treatment
a. 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.
b. Lower GI bleed with cautery
i. Colonoscopy with cautery is very effective in diverticular and AVM-associ-
ated 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. Meningitis may be bacterial (Table 5-1) or aseptic (viral). Streptococcus pneu-
moniae is the most common cause in adults.
b. Most cases occur in children or young adults.
2. 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.
3. 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).
4. 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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INFECTIOUS DISEASES 83

TABLE 5-1 BACTERIAL CAUSES OF MENINGITIS ACCORDING TO AGE

Organism Group Affected

Haemophilus influenzae Infants

Neisseria meningitidis Adolescents and young adults
Streptococcus pneumoniae Adults
20 years old
Listeria monocytogenes Immunosuppressed and elderly

2. Clinical features
a. Signs and symptoms include fever, headache, behavioral changes, altered lev-
els of consciousness, delirium, and speech difficulty.
b. Seizures (focal or generalized) may occur.
c. A prodrome of upper respiratory tract signs and symptoms may occur.
3. Laboratory findings
a. 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.
b. Electroencephalogram shows a characteristic pattern in HSV infection.
c. Serum analysis that measures antibody titers to various encephalitic viruses
can be helpful.
d. Computed tomography (CT) scan and magnetic resonance imaging can
reveal focal abnormalities after a few days of infection.
4. Treatment
a. Acyclovir is commonly used to treat HSV and VZV encephalitis.
b. Other viral causes are treated supportively.
c. Avoid hypotonic intravenous (IV) fluid to decrease cerebral edema.
d. Anticonvulsants for seizures.

C. INTRACRANIAL ABSCESS
1. General characteristics
a. Intracranial abscesses usually arise from infection of a contiguous site (e.g.,
ear or sinus infection).
b. 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.
2. Clinical features
a. Signs and symptoms include fever with worsening headache, decreased level
of consciousness, and vomiting.
b. Focal neurologic signs are present.
c. Seizures occur.

TABLE 5-2 CSF FINDINGS IN MENINGITIS

Bacterial Aseptic

Cells 1000–10,000/L 10–2,000/µL

Percent neutrophils
50%
50%
Glucose 40 mg/dL Normal
Protein
45 mg/dL 100 mg/dL
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84 CHAPTER 5

3. Laboratory findings
a. CT scan is an important diagnostic tool because lumbar puncture is con-
traindicated in these patients (Figure 5-1) due to the risk of herniation.
b. Serum analysis reveals leukocytosis; blood culture may be positive if sep-
ticemia has occurred.
4. 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 metronida-
zole. 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.

II Head and Neck Infections

A. OTITIS
1. Otitis is an infection that may occur in the inner, middle, or outer ear.
2. 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).
3. 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 pyo-
genes, or H. influenzae; these infections often respond to amoxicillin or
trimethoprim-sulfamethoxazole (TMP-SMX).
4. Inner ear infections are usually viral and are thus often untreatable; signs and
symptoms include tinnitus and vertigo.

B. SINUSITIS
1. 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 second-
ary to S. aureus, Pseudomonas, and other resistant gram-negative organisms.
2. Clinical features
a. Patients often have a prodrome of upper respiratory tract signs and symp-
toms.
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.
3. Laboratory findings are usually unnecessary for diagnosis, although sinus radi-
ography may reveal opacification of the affected sinus.
4. 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.

III 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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INFECTIOUS DISEASES 85

● 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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86 CHAPTER 5

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

B. PHARYNGITIS
1. General characteristics
a. Pharyngitis is caused by viruses (e.g., Epstein-Barr virus [EBV]); Mycoplasma;
or group A streptococci.
b. Persistence of signs and symptoms for longer than 1 week, respiratory
stridor, excess secretions, difficulty swallowing, or the presence of a pal-
pable mass should alert the clinician to a more serious cause, such as malig-
nancy or epiglottitis.
2. Clinical features
a. The main symptom is a sore throat.
b. Exudate may be present in either a bacterial or viral infection.
c. The presence of URTI-like symptoms suggests a viral pharyngitis.
d. Malaise, fever, generalized lymphadenopathy, and splenomegaly associated
with hypertrophied tonsils with a white exudate strongly suggest EBV (infec-
tious mononucleosis).
e. EBV infection is more common in the young adult population.
3. Laboratory findings
a. Because clinical distinction of streptococcal pharyngitis from viral pharyngitis
is difficult, a throat swab and culture for group A streptococcus is recom-
mended for patients who have pharyngitis.
b. Monospot test results for heterophile antibodies are positive in patients who
have EBV infection.
4. Treatment
a. Penicillin therapy for streptococci infections should last for at least 10 days
to prevent rheumatic fever.
b. Viral pharyngitis is usually self-limited.
c. 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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INFECTIOUS DISEASES 87

● Figure 5-2. Chest radiograph of a patient who has a right upper lobe infiltrate that may be consistent with pneu-
monia 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.).

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.
c. 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 reticu-
lonodular pattern in S. pneumoniae and Mycoplasma infection (Figure 5-2).
vii. Cavitating lesions are common in aspiration pneumonia (Figure 5-3).
d. 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.
3. Hospital-acquired pneumonias
a. These pneumonias often involve gram-negative bacilli (e.g., Klebsiella,
Pseudomonas, and Escherichia coli) or MRSA.
b. Clinical features are as previously described.
c. Diagnosis involves chest x-ray and may require bronchoscopy with alveolar
lavage to identify the agent.
d. Treatment involves a penicillinase-resistant penicillin or cephalosporin plus
an aminoglycoside (e.g., gentamicin).
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88 CHAPTER 5

● Figure 5-3. Chest radiograph illustrating right upper lobe pneumonia (anterior segment) with multiple areas of necro-
sis 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. This infection occurs in sexually active individuals (usually males).
b. Urethritis is classified as gonococcal (Neisseria gonorrhoeae) or nongonococ-
cal (usually Chlamydia or Mycoplasma).
c. Infections with both organisms may be present in a single patient.
2. Clinical features
a. Dysuria is the main symptom.
b. Purulent discharge is often present in gonococcal disease.
c. Cloudy discharge may be present in nongonococcal disease.
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INFECTIOUS DISEASES 89

3. Laboratory findings from microscopy and culture of urethral swab are diagnostic,
showing gram-negative intracellular diplococci if gonococcal infection is present.
4. Treatment
a. Gonococcal disease is treated with a single dose of ceftriaxone intramuscu-
larly or a fluoroquinolone.
b. If chlamydial infection is suspected, use azithromycin or doxycycline.

B. PELVIC INFLAMMATORY DISEASE (PID)

1. General characteristics
a. PID is defined as infection of the uterus and other adnexal structures.
b. Infection may be caused by N. gonorrhoeae, Chlamydia, or pelvic anaerobes.
c. Intrauterine device use increases risk of PID.
d. PID may lead to infertility or ectopic pregnancy due to scarring of adnexal
structures.
2. Clinical features
a. PID occurs with increased frequency during menses because menstrual
blood provides a growth medium for bacteria.
b. Patients have lower abdominal pain.
c. Fever may be present.
d. Cervix, uterus, and adnexae are tender, with pain during intercourse.
e. Cervical discharge may be observed during speculum examination of the
pelvis.
3. Laboratory findings
a. Cervical swab for culture is often diagnostic.
b. Levels of serum
-human chorionic gonadotropin should be measured to
rule out ectopic pregnancy.
c. Appendicitis should be ruled out by an abdominal ultrasound.
d. 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.
4. Treatment
a. For severe disease, the patient should be hospitalized and parenteral antibi-
otics should be administered.
b. Clindamycin plus gentamicin are often effective when anaerobes are
suspected.
c. 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. These conditions are more common in males than in females.
b. Genital herpes is the most common cause of genital ulcer disease in the
United States, followed by syphilis.
c. Less common causes include lymphogranuloma venereum, chancroid, and
granuloma inguinale.
d. Gonorrhea does not cause genital ulcers.
2. 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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90 CHAPTER 5

b. 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.
c. Features of lymphogranuloma venereum include:
i. Large inguinal lymph nodes accompany the genital ulcer.
ii. This condition is caused by Chlamydia trachomatis.
d. 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.
e. 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.
3. Laboratory findings
a. For herpes, the Tzanck test and culture are diagnostic.
b. For syphilis, dark-field examination and rapid plasma reagin (RPR) testing
are diagnostic.
c. For lymphogranuloma venereum, culture of expressed pus and serologic
testing for presence of anti-C. trachomatis antibodies are diagnostic.
d. For chancroid, culture of Haemophilus ducreyi from the ulcer or suppurative
nodes is diagnostic.
e. For granuloma inguinale, scrapings of the ulcer edge show Donovan bod-
ies with Giemsa or Wright stain.
4. Treatment
a. Herpes symptoms are self-limited but recur; acyclovir can reduce the sever-
ity of outbreaks but is not curative.
b. Syphilis is treated with penicillin.
c. Lymphogranuloma venereum is treated with tetracycline or erythromycin.
d. Chancroid is treated with azithromycin, ceftriaxone, or ciprofloxacin.
e. Granuloma inguinale is treated with tetracycline or TMP-SMX.

VI 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 peri-
urethral 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 conjunc-
tion 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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INFECTIOUS DISEASES 91

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

VII Osteomyelitis and Joint Infections

A. OSTEOMYELITIS
1. General characteristics
a. 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.
b. Staphylococcus aureus is the most common cause of osteomyelitis.
c. S. aureus and E. coli infections are also common among IV drug abusers.
d. Osteomyelitis commonly affects long bones and vertebral bodies.
e. Individuals with prosthetic joint replacements have an increased inci-
dence of joint infections.
2. Clinical features
a. Local pain and tenderness may be present.
b. Redness overlying the infection may be present.
c. Fever may or may not be present.
d. Draining sinus tracts result from chronic infections or implants.
3. Laboratory findings
a. Diagnosis is confirmed with isolation of S. aureus from the blood and/or bone
in a patient who has symptoms of focal bone involvement.
b. If blood cultures are negative, bone biopsy and culture should be considered
to isolate the organism.
c. Bone scan is effective in localizing the site of infection.
d. 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.
e. CT scan is more sensitive than plain radiographs and can localize abscesses.
f. MRI is very sensitive and is the procedure of choice for vertebral osteomyelitis.
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92 CHAPTER 5

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

B. JOINT INFECTIONS
1. General characteristics
a. Patients who receive intra-articular corticosteroids and patients who have
existing joint disease (e.g., rheumatoid arthritis) are at risk for joint infections.
b. The most common causes are N. gonorrhoeae, streptococci, and S. aureus.
c. Pseudomonas is a common cause of joint infection in IV drug abusers.
d. S. epidermidis is a common pathogen in individuals who have prosthetic joints.
2. Clinical features
a. Patients have acute onset of monoarticular pain that commonly involves
the knee.
b. Signs and symptoms include joint pain, swelling, redness, and a decreased
range of motion.
c. Patients who have a joint prosthesis may experience pain and loosening of
the prosthesis.
d. Disseminated gonococcal infection is suggested by additional tenosynovitis
and a vesicopustular skin rash.
e. Gout or pseudogout must also be considered in the differential diagnosis.
3. Laboratory findings
a. Joint fluid should be aspirated for Gram stain and culture.
b. Crystal disease can be ruled out with a specimen for polarizing microscopy
(see Chapter 7, Rheumatic Diseases).
c. In gonococcal infection, skin lesions and joint cultures may be negative;
however, a cervical culture may reveal the diagnosis.
4. Treatment
a. Treatment involves repeated aspiration of infected joint material or surgical
drainage.
b. Systemic antibiotic therapy is recommended for at least 4–6 weeks if a
staphylococcal infection is present (e.g., vancomycin).
c. Gonococcal arthritis responds well to penicillin within 7–10 days.

VIII Other Infectious Syndromes

A. INFECTIOUS MONONUCLEOSIS
1. General characteristics
a. Infectious mononucleosis is caused by EBV.
b. This disease tends to occur in adolescence and young adulthood.
c. In immunocompromised patients, EBV may be associated with lymphoprolif-
erative diseases (Burkitt lymphoma, Hodgkin disease).
2. Clinical features
a. Patients have a fever and discrete, nonsuppurative, slightly painful enlarged
lymph nodes that often involve the posterior cervical chain.
b. Splenomegaly is present in approximately half of the patients.
c. Sore throat, anorexia, and malaise are often present.
d. Ampicillin may induce a petechial rash in these patients.
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INFECTIOUS DISEASES 93

e. Exudative pharyngitis may be present on physical examination.

f. Occasionally, patients may develop hepatitis.
3. Laboratory findings
a. Complete blood count shows an initial granulocytopenia followed by a lym-
phocytic leukocytosis (leukocytes are large in appearance).
b. Positive Monospot test results indicate presence of heterophile antibodies.
c. False-positive Venereal Disease Research Laboratory and RPR test results
can occur with this disease.
d. If the CNS is involved, the CSF will show increased levels of lymphocytes
and protein.
e. Levels of liver enzymes and bilirubin are often elevated.
4. Treatment
a. No specific treatment is available.
b. Nonsteroidal anti-inflammatory drugs may provide symptomatic relief.
c. Contact sports should be avoided in patients who have splenomegaly to
decrease the incidence of splenic rupture.

B. TUBERCULOSIS (TB)
1. General characteristics
a. Increased incidence is largely caused by human immunodeficiency virus
(HIV) infection.
b. TB is common in immigrant and underprivileged groups.
2. Clinical features
a. Pulmonary-related TB signs and symptoms include increased cough, weight
loss, hemoptysis, and fatigue.
b. Extrapulmonary signs and symptoms affect kidneys, bones, and meninges.
3. Laboratory findings
a. 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.
b. Pulmonary TB is detected with acid-fast stain and appropriate culture of sputum.
c. Bronchial washings may be necessary to obtain an appropriate specimen.
4. Treatment
a. 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.
b. Chemoprophylaxis with isoniazid alone for the following high-risk indi-
viduals 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. Eosinophilia is associated with multicellular parasitic infections (e.g.,
schistosomes, pinworms).
b. Parasitic causes must be differentiated from allergic causes of eosinophilia,
which are commonly associated with drug reactions.
2. Clinical features of pinworm infection
a. Pinworms commonly affect young children.
b. Cecum and adjacent bowel are often inhabited by the organism.
c. Eggs are laid at the anus after infection occurs.
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94 CHAPTER 5

d. Patients have perianal pruritus, irritability, restlessness, and enuresis.

e. Patients have vague abdominal complaints, particularly in the right lower
quadrant.
3. Laboratory findings
a. The presence of eggs on perianal skin is diagnostic.
b. Stool examination may reveal adult worms.
c. Eosinophilia may be present.
4. Treatment
a. Oral mebendazole is highly effective and should be used in symptomatic patients.
b. 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. TSS is caused by toxin formed by certain strains of S. aureus.
b. TSS often involves vaginal colonization by the staphylococci, with
increased incidence in females using tampons.
c. TSS may occur with infection at other sites as well.
2. Clinical features
a. Signs and symptoms include fever, hypotension, desquamative rash on the
hands and feet, vomiting, and diarrhea.
b. Nonpurulent conjunctivitis may occur.
3. Laboratory findings
a. Blood cultures are usually negative because the disease is caused by an
immune reaction to the toxin.
b. The toxin-producing organism may be cultured from wound scrapings or the
vagina if colonization has occurred.
c. Increased liver function tests (LFTs), azotemia, leukocytosis, and thrombocy-
topenia are common.
4. Treatment
a. Patients require rapid IV rehydration.
b. If vaginal colonization is present, the tampon should be removed.
c. Antibiotics such as nafcillin or vancomycin are indicated.

E. LYME DISEASE
1. General characteristics
a. Lyme disease is characterized by multiorgan involvement.
b. The causative organism is Borrelia burgdorferi, which is transmitted to
humans by a biting tick.
2. Clinical features
a. 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.
b. 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.
c. Arthritis (usually a migratory polyarthritis) may develop months after initial
infection as well.
d. Myocarditis may also occur after initial infection.
3. Laboratory findings
a. Diagnosis is established by detection of antibodies against the organism.
b. Joint fluid aspiration for culture is negative.
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INFECTIOUS DISEASES 95

4. Treatment involves tetracycline, erythromycin, or penicillin; these drugs can hasten

recovery and reduce the severity of late manifestations.

F. AIDS
1. General characteristics
a. AIDS patients are HIV positive and show a CD4 lymphocyte count
200
cells/L and/or opportunistic infections (e.g., Mycobacterium, coccidioidomy-
cosis, histoplasmosis, Pneumocystis) and/or unusual neoplasms (lymphoma,
Kaposi sarcoma).
b. Risk factors include sexual contact with an HIV-positive person, IV drug abuse
with needle sharing, and health occupational-related exposure.
c. Risk of transmission from blood transfusion is now about 1:8,000,000.
d. HIV, a retrovirus, predominately infects CD4 cells leading to immuno-
dysfunction.
2. Clinical features
a. Asymptomatic phase is approximately 10 years after exposure. Infectious
complications correlate with CD4 counts (Table 5-3).
b. Constitutional symptoms are common (e.g., fever, night sweats, weight loss).
c. Anorexia, nausea, and vomiting, which may occur in isolation or secondary to
intestinal infection
d. Cough
i. Infectious causes. Cough may indicate pneumonia secondary to community-
acquired bacterial, Mycoplasma, Pseudomonas, cytomegalovirus (CMV),
histoplasmosis, coccidioidomycosis, cryptococcal, or pneumocystis organ-
isms. Hypoxia may occur with severe infections.
ii. Other (noninfectious) causes of pulmonary symptoms include lymphoid
interstitial pneumonitis, lymphoma, and less commonly, Kaposi sarcoma.
e. Chronic sinusitis is common.
f. CNS infections produce encephalopathy, meningitis, or intracerebral space-
occupying 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.

TABLE 5-3 OPPORTUNISTIC INFECTIONS CORRELATED WITH CD4 COUNT

CD4  600 CD4  200 CD4  50

Bacterial infection Pneumocystis Disseminated mycobacterium

Tuberculosis Toxoplasmosis
Herpes simplex/varicella zoster Cryptococcus Histoplasmosis
Vaginal candidiasis Coccidioidomycosis CMV
Hairy leukoplakia Lymphoma
Kaposi sarcoma
CMV, cytomegalovirus.
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96 CHAPTER 5

g. Large-joint arthritis is common.

h. Retinitis may occur due to CMV infection and appears as perivascular hem-
orrhages 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, cryp-
tosporidium, or Entamoeba may occur.
k. Skin manifestations include herpes simplex or zoster, folliculitis, and Kaposi
sarcoma.
3. Laboratory findings
a. HIV serology is positive and is confirmed by Western blot analysis indicating
HIV infection.
b. CD4 lymphocyte counts should be done every 6 months for those with
350 cells/L, which necessitates prophylaxis.
c. 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 antiretrovi-
ral therapy. Measurements should be done every 3–6 months.
d. Anemia, lymphopenia, and thrombocytopenia are common.
e. Purified protein derivative (PPD), Toxoplasma immunoglobulin G serology,
and CMV immunoglobulin G serology should be performed.
f. Radiologic evaluation should be directed toward the presenting symptoms.
4. Treatment
a. 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.
b. 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 pyra-
zinamide
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
c. 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.
d. Malignancy treatment
i. Lymphoma: modified CHOP (cyclophosphamide, doxorubican, vin-
cristine, 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 hypo-
function, and pituitary hyperfunction.
3. Posterior pituitary diseases include diabetes insipidus and syndrome of inappro-
priate antidiuretic hormone secretion (SIADH).

B. PITUITARY TUMORS
1. General characteristics
a. Pituitary tumors account for 10% of intracranial tumors.
b. Pituitary tumors may be nonfunctioning.
c. Functioning tumors are usually chromophobic adenomas that produce adreno-
corticotropic hormone (ACTH), growth hormone (GH), or prolactin (PRL).
d. Secretion of thyroid-stimulating hormone (TSH), follicle-stimulating hor-
mone (FSH), or luteinizing hormone (LH) is rare.
e. May be associated with multiple endocrine neoplasia syndrome (MEN I),
which includes parathyroid adenoma and pancreatic islet cell adenomas.
2. Clinical features
a. Patients who have pituitary tumors may be seen with headache or visual dis-
turbance (bitemporal hemianopia).
b. Patients who have functioning tumors may be seen with endocrinologic man-
ifestations, for example, galactorrhea-amenorrhea (PRL-secreting tumor),
acromegaly (GH-secreting tumor), Cushing syndrome (ACTH-secreting
tumor).
c. Patients who have nonfunctioning tumors may be seen with signs and symp-
toms of anterior pituitary hypofunction (see I C).
3. Laboratory findings
a. Computed tomography (CT) scans with contrast medium are useful in diag-
nosing adenomas
10 mm in diameter (microadenomas).
b. Magnetic resonance imaging (MRI) is the diagnostic procedure of choice, with
adenoma density appearing low on T1-weighted and high on T2-weighted
images.
c. Growth hormone, prolactin, or ACTH (and cortisol) levels are often elevated
even when diagnostic imaging cannot visualize the tumor.
4. 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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98 CHAPTER 6

(
10 mm) asymptomatic microadenomas may be observed and removed

when they enlarge or become functional.
b. Radiotherapy alone or as an adjunct to surgery often reduces tumor size, but
often results in hypopituitarism.
c. Bromocriptine (dopamine agonist) often sufficiently controls small PRL-
secreting adenomas.
d. In nonfunctioning tumors, hormonal replacement is required.

C. ANTERIOR PITUITARY HYPOFUNCTION

1. General characteristics
a. Anterior pituitary hypofunction may occur secondary to destruction of the
pituitary by a nonfunctioning pituitary tumor.
b. The disease may also occur secondary to infarction resulting from hypotension
during childbirth (Sheehan syndrome) or surgical removal of the pituitary gland.
2. Clinical features
a. GH deficiency causes growth failure if disease occurs during childhood, but
adults are not affected by GH deficiency.
b. LH/FSH deficiency causes amenorrhea and breast atrophy in women, genital
atrophy, and loss of potency and libido in men.
c. TSH deficiency causes signs and symptoms associated with hypothyroidism
(see II C).
d. ACTH deficiency causes secondary adrenal insufficiency (which differs clini-
cally 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.
e. PRL deficiency causes no clinical manifestations except in Sheehan syndrome,
in which it results in postpartum failure of lactation.
3. Laboratory findings
a. 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).
b. 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.
c. 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.
4. Treatment
a. An underlying cause for hypopituitarism (e.g., a tumor) must be ruled out.
b. GH replacement is necessary only in affected children.
c. PRL replacement is generally unnecessary.
d. 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).
e. Testosterone is indicated to restore libido and potency in men, and estrogen-
progesterone is indicated to restore menstrual function in women.
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ENDOCRINOLOGIC AND METABOLIC DISORDERS 99

D. PITUITARY HYPERFUNCTION
1. General characteristics
a. Pituitary hyperfunction primarily presents as hyperprolactinemia (most com-
mon hormone produced in pituitary hyperfunction) or acromegaly/gigantism.
b. Because PRL secretion is inhibited by hypothalamic dopamine, damage to the pitu-
itary stalk or inhibition of dopamine will produce hyperprolactinemia (e.g., phe-
nothiazines, which act as dopamine antagonists, will cause hyperprolactinemia).
2. Clinical features
a. In women, hyperprolactinemia produces persistent galactorrhea (unprovoked
by breast stimulation), infertility, and amenorrhea; in men, it may also pro-
duce galactorrhea, but loss of libido and impotence are more common.
b. Before adulthood, gigantism occurs because of increased linear growth of
bones before epiphyseal closure.
c. 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.
d. Impaired glucose tolerance occurs as a result of the glucose-elevating effect
of GH; overt diabetes is uncommon.
e. GH increases renal phosphate reabsorption, which results in hyperphosphatemia.
3. Laboratory findings
a. 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.
b. Gigantism/acromegaly can be confirmed by GH levels 10 ng/mL under basal con-
ditions (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.
4. Treatment
a. 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)
b. 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. Diabetes insipidus is caused by an impaired urinary concentrating mechanism.
b. 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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100 CHAPTER 6

TABLE 6-1 RESULTS OF WATER DEPRIVATION TEST FOR DIABETES INSIPIDUS (DI)

Patient Type Increase in [Urine] With Dehydration Further Response to ADH

Normal Yes None

Nephrogenic DI None None
Central DI None Yes
ADH, antidiuretic hormone.

2. Clinical features
a. Polyuria is a prominent symptom (3–15 L/d is not uncommon).
b. Patients report excessive thirst, which is a physiologic response to water loss.
3. Laboratory findings
a. Urine is dilute with specific gravity
1.010 and osmolality
300 mOsm/kg.
b. 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.
c. 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 depriva-
tion tests.
4. Treatment
a. In acute central DI (e.g., head injuries), DDAVP (desmopressin) acts rapidly.
b. For partial ADH deficiency, chlorpropamide (an oral hypoglycemic agent)
will potentiate the effects of ADH on the renal tubule.
c. Thiazide diuretics are the only treatment for nephrogenic DI.

F. SIADH
1. General characteristics
a. Excess ADH may be produced by malignant tumors (e.g., oat cell carcinoma
of the lung), pulmonary diseases (e.g., pneumonia, tuberculosis), central nerv-
ous system (CNS) disorders (e.g., stroke, head injury), or drugs (e.g., chlor-
propamide, 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 hypona-
tremia.
2. Clinical features of SIADH are those of hyponatremia, such as lethargy, confusion,
headache, focal neurologic abnormalities, convulsions, and coma.
3. Laboratory findings
a. Hyponatremia is indicated by a serum Na+ level
135 mmol/L; hyponatrem-
ia is critical if serum Na+ level falls acutely below 125 mmol/L.
b. Urinary sodium excretion continues despite hyponatremia (>20 mmol/day)
and Uosm (urine osmolality) > Sosm (serum osmolality).
4. Treatment
a. It is necessary to treat the underlying cause of SIADH.
b. Fluid restriction of 500–1,000 mL/day will effectively correct hyponatremia.
c. 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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ENDOCRINOLOGIC AND METABOLIC DISORDERS 101

central pontine myelinolysis; infuse 3% saline at a rate of
0.05 mL/kg/min

and check serum Na frequently.
d. 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.

II 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. Graves disease (diffuse toxic goiter) is the most common form of hyperthy-
roidism.
i. Graves disease is an autoimmune disorder in which TSH receptor antibod-
ies are produced.
ii. Production of TSH receptor antibodies leads to diffuse thyroid enlargement
and thyroid hormone (TH) production.
b. Plummer disease (nodular toxic goiter) affects older individuals.
i. This disease is characterized by discrete areas of autonomously hyper-
functioning thyroid gland.
ii. Normal thyroid tissue functions are suppressed because of negative
feedback on TSH.
c. Subacute thyroiditis is another type of hyperthyroidism (see thyroiditis, II D).
d. Factitious hyperthyroidism is caused by excessive ingestion of TH by patients.
2. 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 ventric-
ular 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 rest-
lessness, 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. Elevated serum levels of T3 and T4 (thyroid hormones) with low TSH indi-
cate hyperthyroidism.
b. 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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102 CHAPTER 6

c. 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.
4. Treatment
a. Thirty percent of patients who have Graves disease will go into spontaneous
remission within 2 years; therefore, cautious medical management is pre-
ferred to total thyroid ablation (which causes hypothyroidism).
b.
-Blockers can be used initially to stabilize the patient’s cardiovascular function.
c. 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 bet-
ter chance of remission.
iii. Side effects of PTU include skin rash in 3%–5% of patients and agranulo-
cytosis in
0.5% of patients.
d. Subtotal thyroidectomy offers rapid therapy with a high cure rate and elimi-
nates 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.
e. 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 dis-
ease 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. Hypothyroidism is most commonly caused by Hashimoto (chronic) thyroidi-
tis (see II D 3).
b. Idiopathic atrophy (often associated with antithyroid antibodies) is also com-
mon.
c. Hypothyroidism frequently develops as a result of treatment for Graves hyper-
thyroidism.
d. Drugs such as lithium, iodide, and amiodarone have been reported to cause
hyperthyroidism as well.
e. Hypothyroidism may be secondary to hypothalamic-pituitary dysfunction.
f. Iodine deficiency is an uncommon cause in developed countries, but may be
more common in other areas of the world.
2. Clinical features
a. Symptoms include weakness, lethargy, slowness of thought and speech, sleepi-
ness, and fatigue.
b. Signs include puffy appearance, nonpitting edema (myxedema), dry skin,
coarse hair, and cold intolerance.
c. Patients report diminished appetite but experience mild weight gain (due to
decreased metabolic rate) and constipation.
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ENDOCRINOLOGIC AND METABOLIC DISORDERS 103

d. Edema of the larynx and middle ear leads to voice changes and hearing loss.
e. Menstrual irregularities may also occur and are associated with anovulatory
cycles.
f. Slow return phase of deep tendon reflexes is observed.
g. 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
3. Laboratory findings
a. Serum levels of T3, T4, and T3-resin uptake are decreased.
b. Radioactive iodine uptake is decreased.
c. In primary hypothyroidism, serum TSH is increased.
d. Thyroid peroxidase antibodies are present in Hashimoto thyroiditis.
4. Treatment
a. L-thyroxine is the agent of choice (maintenance dose is 0.1–0.15 mg/day in
adults; half dose in the elderly).
b. Treatment must be started slowly because patients who have severe disease
have increased sensitivity to TH.
c. Myxedema coma must be treated rapidly despite the risks associated with sud-
den hormone replacement (0.5-mg intravenous bolus).
d. Therapy adequacy is determined by a return of TSH and serum thyroid hor-
mones to normal levels.

D. THYROIDITIS
1. Thyroiditis is a group of disorders consisting predominantly of subacute thy-
roiditis (de Quervain thyroiditis), Hashimoto (chronic) thyroiditis, and painless
thyroiditis.
2. Subacute thyroiditis
a. Subacute thyroiditis has a viral etiology (mumps or coxsackievirus).
b. 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 nor-
mal size.
c. 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 hyper-
function of the gland.
ii. TSH levels are low because of excess thyroid hormone.
d. Treatment
i. Symptomatic treatment is sufficient until disease remits.
ii. Nonsteroidal anti-inflammatory drugs (NSAIDs) relieve pain of inflamma-
tion, whereas β-blocking agents are used to relieve symptoms of hyperthy-
roidism.
iii. If NSAIDs are inadequate, prednisone is effective.
iv. PTU and methimazole are not useful because excess hormone is not pro-
duced.
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104 CHAPTER 6

3. Hashimoto thyroiditis
a. General characteristics
i. Hashimoto thyroiditis is an autoimmune disease in which antithyroid
antibodies are produced.
ii. The disease primarily affects women.
b. 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.
c. 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.
d. 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 enlarge-
ment.
4. Painless thyroiditis (lymphocytic thyroiditis)
a. Clinical features
i. Painless thyroiditis is similar to subacute thyroiditis; that is, it is a self-
limiting hyperthyroidism secondary to inflammatory damage (lympho-
cytic 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.
b. 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.
c. Treatment
i. Symptomatic therapy is given with
-blockers until remission occurs.
ii. Antithyroid drugs are not useful.

E. THYROID CANCER
1. General characteristics
a. Thyroid cancer is associated with previous radiotherapy to the neck.
b. A genetic association has been found to medullary carcinoma of the thyroid.
c. 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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ENDOCRINOLOGIC AND METABOLIC DISORDERS 105

2. Types of thyroid cancer include:

a. 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.
b. 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 nor-
mal thyroid tissue.
iii. This cancer metastasizes to bone, brain, and lung.
iv. Ten-year survival rate is 50%.
c. 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.
d. Medullary carcinoma
i. Medullary carcinoma arises from parafollicular cells.
ii. The tumor can produce calcitonin.
iii. This cancer is associated with MEN type II.
3. Treatment
a. Prognosis is worse if there is distant metastasis, age 50 years, or tumor size
4 cm.
b. Papillary, follicular, and medullary carcinoma are first surgically removed.
c. Because these tumors are TSH sensitive, L-thyroxine is then administered
indefinitely to suppress TSH.
d. Radioactive iodine therapy is used to ablate distant metastases and any remain-
ing thyroid gland tumor after surgery.

F. THYROID NODULES
1. General characteristics
a. Thyroid nodules are present in up to 5% of the population.
b. Ten to twenty percent of nodules are malignant; the remainder may be cys-
tic, colloid, hemorrhagic, or inflammatory.
c. 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.
2. Diagnosis
a. Radioactive iodine scintigraphy determines whether the lesion is more likely
to be malignant (i.e., cold), but this procedure is not diagnostic.
b. Fine-needle aspiration is most diagnostic and is easily performed with little
risk to the patient.
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106 CHAPTER 6

3. Treatment
a. 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.
b. Conservative management and observation are indicated if the nodule is
“warm,” history and physical examination are not suspicious, and cytology is
benign.

III Disorders of the Parathyroid Gland

A. PRIMARY HYPERPARATHYROIDISM AND HYPERCALCEMIA
1. General characteristics
a. Oversecretion of parathyroid hormone (PTH) causes hypercalcemia.
b. Primary hyperparathyroidism affects 1 in 1,000 persons (primarily middle-
aged and elderly women).
c. Most cases are due to parathyroid adenoma.
d. Primary hyperparathyroidism may be associated with MEN syndromes.
e. 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).
2. Clinical features of hypercalcemia
a. In the renal system, increased serum calcium leads to urinary calculi and
nephrocalcinosis, which may progress to renal failure.
b. CNS signs and symptoms include lethargy, stupor, fatigue, proximal myopa-
thy and hypotonia, and coma.
c. GI signs and symptoms include anorexia, nausea, vomiting, constipation,
and abdominal pain.
d. Hypercalcemia causes osteitis fibrosa cystica, which is characterized by
bone pain, fractures, deformities, bone cysts, generalized osteopenia, and sub-
periosteal bone resorption in the phalanges.
3. Laboratory findings
a. 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).
b. Urinalysis may indicate hypercalciuria.
c. 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.
4. Differential diagnosis of hypercalcemia
a. Differential diagnosis of hypercalcemia is based on PTH levels.
b. Disorders in which PTH levels are decreased are secondary causes of hypercal-
cemia and include:
i. Tumors with bone metastases (e.g., breast, myeloma, lymphoma)
ii. Tumors without bone metastases in which a PTH-like substance is pro-
duced 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 granulo-
mas and leads to hypercalcemia
iv. Vitamin D intoxication
v. Familial hypocalciuric hypercalcemia
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ENDOCRINOLOGIC AND METABOLIC DISORDERS 107

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 sub-
sides, producing hypercalcemia (over 2–3 weeks).
viii. Medications (e.g., lithium)
5. Treatment
a. 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 depo-
sition in tissues may occur.
b. Surgical removal of parathyroid adenoma is indicated in patients who have
elevated serum calcium levels (11.0 mg/dL).
c. Medical therapy is indicated for patients who have mildly elevated serum cal-
cium 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 post-
menopausal patients who have mild hypercalcemia.

B. HYPOPARATHYROIDISM AND HYPOCALCEMIA

1. General characteristics
a. Hypoparathyroidism is most commonly caused by surgical removal of the
parathyroid glands during a neck procedure.
b. Idiopathic cases occur less commonly.
2. Clinical features
a. Latent tetany, which occurs with mild hypocalcemia, may manifest as mus-
cular 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).
b. Overt tetany, which occurs with severe hypocalcemia, manifests as muscle
twitching and spasm progressing to laryngeal stridor and seizures.
c. 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.
3. 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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108 CHAPTER 6

TABLE 6-3 LABORATORY FINDINGS IN CALCIUM METABOLISM ABNORMALITIES

_
Condition Ca++ Po 4 PTH

Primary hyperparathyroid ↑ ↓ ↑
Secondary hyperparathyroid (from renal failure∗) ↓ ↑ ↑
Primary hypoparathyroid ↓ ↑ ↓
∗Note: 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.

b. In renal failure, decreased 1,25-dihydroxyvitamin D3 leads to decreased

calcium absorption.
c. Osteoblastic metastasis of lung, prostate, or breast cancers may cause rapid
uptake of calcium by bone.
d. Hypomagnesemia leads to decreased production of PTH and inhibits action of
PTH and vitamin D on bone.
e. In acute pancreatitis, an association with hypocalcemia has been established,
but the cause remains uncertain.
4. Laboratory findings
a. Serum analysis indicates low calcium and high phosphate levels, with a con-
comitantly decreased PTH level (Table 6-3).
b. Radiography indicates no specific changes.
5. Treatment
a. PTH is not available for treatment.
b. Therapy consists of replacement of serum calcium orally or intravenously (if
severe) along with vitamin D.

IV Glucose Homeostasis
A. DIABETES MELLITUS
1. General characteristics
a. 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.
b. 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.
2. Clinical features
a. Symptoms include polyuria, polydipsia, blurred vision, and weight loss and
weakness despite increased food intake.
b. Patients have an increased frequency of skin and urinary tract infections.
c. A complication of diabetes is retinopathy, which is most commonly associated
with soft exudates, microaneurysms, and retinal hemorrhages.
d. 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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ENDOCRINOLOGIC AND METABOLIC DISORDERS 109

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. Persistent fasting blood sugar 126 mg/dL is diagnostic.
b. 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.
c. 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.
d. Urine glucose levels are often variable, and therefore are not useful in diagnosis.
4. Treatment
a. 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% car-
bohydrate, 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 begin-
ning treatment, the morning dose of insulin is increased.
v. If only morning serum glucose levels are high, the prior evening’s inter-
mediate-acting insulin should be increased.
vi. If only evening serum glucose levels are high, the intermediate-acting
morning insulin should be increased.
b. 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], gly-
buride, or glipizide) or insulin is indicated.
c. Exercise lowers serum glucose and raises insulin sensitivity.
d. Pancreas transplant is an option for type I diabetes mellitus.

TABLE 6-4 CLASSIFICATION OF INSULIN TYPES

Insulin Type Classification Onset of Action (h)

Regular Short-acting
1 h
Isophane insulin Intermediate-acting 2–3 h
Zinc (Lente) insulin Intermediate-acting 2–3 h
Ultralente insulin Long-acting 4–6 h
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110 CHAPTER 6

B. DIABETIC KETOACIDOSIS
1. General characteristics
a. 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.
b. Insufficient insulin → increased lipolysis → increased ketones → anion gap
metabolic acidosis (see IV B 3 a) → compensatory respiratory alkalosis
(hyperventilation).
2. Clinical features
a. Patients exhibit a decreased level of consciousness.
b. Deep rapid breathing (Kussmaul respirations) occurs.
c. Acetone breath is detected.
d. Signs of dehydration are apparent, for example, dry mucous membranes and
axillae, tachycardia, and postural hypotension.
3. Laboratory findings
a. 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].
b. Urinalysis indicates elevated glucose and ketone levels; this test allows rapid
diagnosis of the condition.
c. Serum potassium levels are initially increased because of intracellular shifts
secondary to acidosis; later, serum potassium levels decrease as acidosis is cor-
rected.
4. Treatment
a. 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 hypo-
glycemia.
b. 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 hyper-
glycemia and acidosis are corrected.
c. 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. This condition occurs primarily in elderly patients who have type 2.
b. 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 men-
tal status.
c. Ketoacidosis does not occur because type 2 patients have sufficient insulin to
inhibit ketogenesis.
2. Clinical features
a. Signs of dehydration (tachycardia, dry mucous membranes, poor skin turgor,
and postural hypotension) are evident.
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ENDOCRINOLOGIC AND METABOLIC DISORDERS 111

b. Patients exhibit cloudy sensorium that may progress to coma.

c. Seizures can occur.
3. Laboratory findings
a. Serum analysis indicates glucose levels often reaching 1,000 mg/dL, which
produce elevated serum osmolality and increased urea:creatinine ratio (indica-
tive of dehydration).
b. Mild metabolic acidosis secondary to decreased renal excretion of organic
acids as well as from starvation ketosis may be present.
4. Treatment
a. Therapy is similar to that for DKA (fluids, insulin, and electrolyte replacement).
b. Because this complication is often secondary to infection, a septic workup is
indicated for these patients.

D. HYPOGLYCEMIC COMA
1. General characteristics
a. Hypoglycemic coma must be rapidly differentiated from DKA or hyper-
glycemic nonketotic coma.
b. This condition often occurs secondary to excess insulin, delayed ingestion of
meals, or excess physical activity.
c. Less commonly, it may be secondary to an insulinoma.
2. Clinical features
a. Sweating is important to recognize because the DKA patient is dehydrated with
dry skin.
b. Other signs and symptoms include tachycardia, tremulousness, and palpita-
tions secondary to adrenergic stimulation.
c. Symptoms may then progress to somnolence, confusion, and coma.
3. Laboratory findings
a. Fingerstick blood glucose analysis provides a rapid means of hypoglycemia
diagnosis.
b. In the instance of insulinoma, elevated serum insulin levels are found with
hypoglycemia.
c. CT scan is effective in detecting insulinomas.
4. Treatment
a. Fifty milliliters of 50% glucose is given intravenously over 3–5 minutes, fol-
lowed by a constant infusion of 5% or 10% glucose at a rate sufficient to main-
tain serum glucose levels >100 mg/dL.
b. Therapy may be required for several days, depending on the duration of action
of insulin or the oral hypoglycemic agent involved.

V 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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112 CHAPTER 6

b. If not iatrogenic, this syndrome is most commonly caused by increased lev-

els of pituitary ACTH, which leads to adrenal gland hyperplasia and increased
serum cortisol levels (known as Cushing disease).
c. 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.
2. 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. Diurnal variation in serum cortisol is absent.
b. Twenty-four-hour urinary free cortisol excretion is often variable and is there-
fore not a useful screening test, but it may show increased cortisol excretion.
c. Serum glucose levels are elevated, and leukocytosis is present (nonspecific
findings).
d. 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.
e. 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).
f. CT scan of the adrenal glands reveals adrenal hyperplasia but does not dis-
tinguish between ACTH stimulation from a pituitary source or ectopic source;
CT of the head may reveal pituitary adenoma producing ACTH.
4. Treatment
a. Adrenal adenoma
i. Surgical resection of the tumor often results in cure.

TABLE 6-5 STANDARD DEXAMETHASONE SUPPRESSION TEST RESULTS

Patient Type Suppression With Low Dose Suppression With High Dose

Normal  
Adrenal tumor  
Ectopic ACTH production  
Cushing disease  
ACTH, adrenocorticotropic hormone.
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ENDOCRINOLOGIC AND METABOLIC DISORDERS 113

ii. Postoperative cortisol replacement is required for a few months until the
remaining normal adrenal tissue resumes function.
b. Adrenal carcinoma
i. Surgical resection is often not possible; once the diagnosis is made, sur-
gery is associated with a poor outcome.
ii. Symptomatic relief may be achieved through the use of adrenal steroid
production-inhibiting drugs (mitotane, metyrapone, aminoglutethimide).
c. 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.
d. Cushing disease
i. Transsphenoidal pituitary surgery is the treatment of choice, with suc-
cess 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 replace-
ment 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. Addison disease is an adrenocortical insufficiency most commonly caused by
an idiopathic atrophy of the adrenal cortex, which is believed to be autoim-
mune related.
b. Tuberculosis, bilateral adrenalectomy, or adrenal suppression after
steroid therapy are potential causes of Addison disease.
c. A less common cause is hypopituitarism (i.e., secondary adrenal insufficiency).
2. Clinical features
a. 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 melanocyte-
stimulating 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.
b. 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.
c. Adrenal crisis is an acute, potentially fatal exacerbation of adrenal insuffi-
ciency that presents with fever, vomiting, decreased sensorium, abdominal ten-
derness, and vascular collapse.
3. Laboratory findings
a. Serum analysis indicates hyperkalemia, hyponatremia, hypoglycemia, increased
eosinophil count (cortisol lowers peripheral eosinophil count), and decreased
cortisol and aldosterone levels.
b. Chest radiographic studies may reveal a small heart.
c. Definitive diagnosis relies on ACTH testing.
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114 CHAPTER 6

i. A 250-g dose of ACTH fails to induce a significant increase in serum cor-

tisol 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.
d. Electrocardiogram (ECG) shows characteristic changes of hyperkalemia, includ-
ing high-peaked T waves, prolonged PR interval, heart block, and atrial asystole.
4. Treatment
a. 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).
b. Mineralocorticoid replacement (fludrocortisone, 0.05–0.2 mg/d) is required
in patients who have persistent hyponatremia, hyperkalemia, and hypotension.
c. 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 vol-
ume.
ii. Mineralocorticoids may be necessary if hypotension and dehydration persist.

D. PRIMARY ALDOSTERONISM
1. General characteristics
a. Primary aldosteronism is characterized by autonomous production of aldos-
terone by the adrenal gland (Conn syndrome).
b. The disease is most commonly caused by a benign adrenal adenoma but
can also occur secondary to bilateral adrenal hyperplasia.
c. Autonomous aldosterone production by the adrenal gland causes increased
sodium retention in exchange for potassium and hydrogen excretion at the dis-
tal tubule.
2. Clinical features
a. Hypertension occurs as a result of volume expansion secondary to sodium
retention.
b. 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.
c. 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).
d. Metabolic alkalosis occurs secondary to renal hydrogen ion loss.
3. Laboratory findings
a. Hypokalemia may be detected.
b. 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.
c. 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.
d. The biochemical changes are more pronounced if they are caused by an ade-
noma versus adrenal hyperplasia.
e. CT scan may enable visualization of the adenoma.
f. If the diagnosis of primary hyperaldosteronism is made but an obvious adeno-
ma cannot be seen on CT, adrenal vein sampling will reveal which gland is
secreting excess aldosterone.
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ENDOCRINOLOGIC AND METABOLIC DISORDERS 115

4. Treatment
a. For adenoma, patients respond best to surgical removal.
b. 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. CAH is caused by a congenital lack of the enzyme necessary for cortisol syn-
thesis.
b. The enzyme deficiency causes ACTH levels to increase, which in turn stimu-
lates the adrenal gland to produce excess steroids not affected by the enzyme
deficiency (i.e., androgens); this leads to adrenal hyperplasia.
c. Cortisol deficiency is usually minimal, and therefore is not clinically apparent.
d. 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.
2. Clinical features
a. Androgen excess produces ambiguous genitalia in the female fetus (female
pseudohermaphroditism) and macrogenitosomia in the male fetus.
b. Androgen excess may not manifest until later in childhood, resulting in vir-
ilization and amenorrhea in females and precocious puberty in males.
c. Mineralocorticoid deficiency leads to hyperkalemia, hyponatremia, dehydra-
tion, and hypotension.
3. Laboratory findings
a. Urinary 17-ketosteroids and pregnanetriol levels are elevated.
b. Serum testosterone, androstenedione, and 17-hydroxyprogesterone (corti-
sol precursor) levels are elevated.
4. Treatment
a. Cortisol administration suppresses ACTH-mediated adrenal hyperplasia.
b. Mineralocorticoid replacement (fludrocortisone) is prescribed for the salt-
losing form.
c. Surgical reconstruction of external genitalia may be performed.

F. PHEOCHROMOCYTOMA
1. General characteristics
a. Pheochromocytoma is a catecholamine-producing adrenal tumor.
b. This tumor is a rare cause of hypertension.
c. Pheochromocytoma occurs within families, such as part of MEN type II syn-
drome (pheochromocytoma, hyperparathyroidism, and medullary carcinoma
of the thyroid gland); it is also associated with neurofibromatosis.
d. Pheochromocytoma is usually not malignant (
10%); 10% are bilateral and
10% are extra-adrenal.
2. Clinical features
a. Signs and symptoms include episodic hypertension, headache, sweating, pal-
pitations, and nervousness occurring with abdominal palpation or exercise.
b. Weight loss and hyperglycemia may also occur.
3. Laboratory findings
a. Analysis of urinary catecholamine metanephrines and vanillylmandelic
acid levels is most useful in making the diagnosis.
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116 CHAPTER 6

b. 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 extra-
adrenal tumors.
4. 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 con-
trolled, -blockage is initiated (e.g., propranolol) to prevent catecholamine crisis
during surgery.

VI Female Reproductive Disorders

A. Reproductive disorders that have an endocrinologic basis include primary amenor-
rhea, secondary amenorrhea, and androgen excess syndromes.

B. PRIMARY AMENORRHEA
1. General characteristics
a. Primary amenorrhea is defined as the absence of menarche after 16 years of
age (i.e., patient has never had a menstrual period).
b. Gonadal causes include gonadal dysgenesis (Turner syndrome), testicular fem-
inization syndrome (androgen resistance), and resistant ovary syndrome (rare).
c. Extragonadal causes include hypogonadotropic hypogonadism, CAH (see
adrenal gland dysfunction, V), and physical abnormalities.
2. Turner syndrome
a. 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 neg-
ative feedback).
b. 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 sex-
ual characteristics (e.g., breast, pubic, and axillary hair); therefore, these
patients often present in adolescence.
c. 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.
d. 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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ENDOCRINOLOGIC AND METABOLIC DISORDERS 117

iv. Streak gonads associated with the 46XY/45X mosaic chromosomal arrange-
ment must be removed because of the increased incidence of gonadoblas-
toma in this population; karyotyping is therefore necessary.
3. Testicular feminization syndrome (androgen resistance)
a. 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 inhibito-
ry 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 ado-
lescence with the complaint of primary amenorrhea.
b. 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.
c. Laboratory findings. Pelvic ultrasound easily reveals the anatomic abnormalities.
d. 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.
4. Hypogonadotropic hypogonadism
a. General characteristics
i. Hypogonadotropic hypogonadism may be associated with panhypopitu-
itarism 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 diet-
ing, 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).
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 func-
tioning end organs.
c. Treatment
i. Condition may resolve if the stressful event is reversed.
ii. Estrogen therapy induces menses and maintains secondary sexual charac-
teristics.
iii. Cyclic estrogen–progesterone therapy induces menses but suppresses
ovulation.
iv. Gonadotropin hormone can be administered if pregnancy is desired.
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118 CHAPTER 6

5. Physical abnormalities
a. Physical abnormalities that can lead to primary amenorrhea include:
i. Labial agglutination (fusion); this condition, often associated with ambigu-
ous genitalia, may be seen in disorders such as CAH.
ii. Congenital defects of the vagina or imperforate hymen
iii. Transverse vaginal septae
b. These patients are seen with cyclic abdominal pain because menstrual out-
flow 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 dis-
continuation 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. Polycystic ovary disease causes chronic anovulation associated with androgen
excess and obesity.
b. Approximately 5% of reproductive-age women have polycystic ovary disease.
c. Ovary produces excess androstenedione (androgenic steroid), which is con-
verted in the periphery to estrone.
d. Excess androgenic steroids prevent follicular maturation, which leads to
anovulation.
e. Increased levels of circulating estrone have positive feedback on LH secre-
tion and inhibit FSH secretion, which leads to enlarged ovaries with small fol-
licular cysts.
f. Unopposed estrogens (i.e., no ovulation and therefore no progesterone) may
increase the risk of endometrial cancer in this population.
3. Clinical features
a. Chronic anovulation leads to infertility and menstrual irregularities such as
oligomenorrhea or amenorrhea.
b. Oily skin, hirsutism, and acne occur because of androgen excess.
c. Obesity is often present.
4. Laboratory findings
a. LH:FSH ratio is increased (2), LH level is elevated, and FSH level is low to
normal.
b. Serum testosterone and androstenedione levels are elevated.
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ENDOCRINOLOGIC AND METABOLIC DISORDERS 119

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

level is normal.
5. Treatment
a. 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.
b. 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 amenor-
rhea (Premarin [a conjugated estrogen] 1.25 mg for 21 days followed by the pro-
gesterone 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 fur-
ther investigation.
c. Bleeding suggests either ovarian dysfunction or hypothalamic–pituitary dis-
ease, 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. Hypogonadism results in inadequate testosterone and sperm production.
b. Hypogonadotropic hypogonadism indicates that the testes lack stimulation
from a diseased hypothalamic–pituitary axis; this condition may manifest as
delayed puberty.
c. Hypergonadotropic hypogonadism indicates a disorder within the testes them-
selves, and that negative feedback on the hypothalamic–pituitary axis is absent.
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120 CHAPTER 6

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. Depo-Testosterone is necessary for full virilization.
b. 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. Osteoporosis is characterized by decreased bone volume; bone structure is
normal.
b. This disease is familial and predominates in Caucasian postmenopausal
women.
c. Calcium deficiency can increase bone resorption and osteoporosis.
d. Estrogen has a protective effect on bone; therefore, osteoporosis is more com-
mon in postmenopausal women.
e. Osteoporosis may be secondary to malabsorption syndromes, steroid ther-
apy, or multiple myeloma.
2. Clinical features
a. Vertebral compression fractures in the lower thoracic and lumbar vertebrae
occur, the initial symptoms of which may be acute back pain.
b. Femur fractures (at the neck) are also common.
3. Laboratory findings
a. Radiography reveals decreased bone density if bone loss is more than 30%.
b. Wedge-shaped deformities are characteristic of vertebral compression frac-
tures (Figure 6-1).
c. Bone marrow density measurement is now the diagnostic standard used.
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ENDOCRINOLOGIC AND METABOLIC DISORDERS 121

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

4. Treatment
a. Estrogen replacement therapy (ERT) in the postmenopausal woman can pre-
vent 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.
b. Calcium supplementation is essential to maintain bone mass (1,500 mg/day)
and prevent or slow osteoporosis.
c. Weight-bearing exercise and an active lifestyle may help prevent osteoporosis.
d. Recently, selective estrogen response modulators (e.g., tamoxifen) have
increased bone density and may be beneficial for those at risk for breast can-
cer who have osteoporosis.

B. OSTEOMALACIA
1. General characteristics
a. Osteomalacia is a disease of inadequate mineralization of bone matrix.
b. 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.
c. Liver and renal diseases can impair vitamin D metabolism and therefore lead
to decreased bone mineralization.
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122 CHAPTER 6

d. GI disorders that impair absorption interfere with vitamin D absorption and

normal calcium metabolism.
2. Clinical features
a. Pain and tenderness are felt in the spine, ribs, and lower extremities.
b. Proximal muscle weakness results in a waddling gait.
c. Lower extremities are bowed and prone to fractures.
3. Laboratory findings
a. Radiography reveals decreased bone density and a coarsened trabecular pat-
tern.
b. Serum analysis indicates low serum phosphate and calcium levels and an ele-
vated alkaline phosphatase level.
4. Treatment
a. Therapy should treat the primary disorder affecting the abnormal calcium
metabolism.
b. Vitamin D benefits individuals who have a lack of or impairment in metabo-
lism of the vitamin.
c. Supplemental calcium is of little benefit because the disorder is not caused
by calcium deficiency; however, during bone reformation, calcium supple-
ments may be necessary.
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Chapter 7
Rheumatic Diseases

I Osteoarthritis and Rheumatoid Arthritis

A. OSTEOARTHRITIS (OA) (ALSO CALLED DEGENERATIVE JOINT DISEASE)
1. General characteristics
a. OA is the most common rheumatic disease.
b. Incidence increases with age, wear and tear, and obesity.
c. 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.
d. OA may be classified as primary OA or secondary OA, depending on the
absence or presence of an underlying etiologic factor.
e. 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).
2. Clinical features
a. 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 com-
partments 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.
3. Differential diagnosis includes seronegative rheumatoid arthritis, psoriatic arthri-
tis or Reiter syndrome, chronic infective arthritis, and tendonitis and/or bursitis.
Unlike rheumatoid arthritis, OA affects distal interphalangeal joints.
4. Laboratory findings
a. Results of hematologic studies are usually normal, including the erythrocyte
sedimentation rate (ESR).
b. 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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124 CHAPTER 7

c. Radiography indicates joint space narrowing, marginal osteophytes, and

subchondral cysts; erosions are usually not present.
5. Treatment
a. Joint preservation can be achieved through weight reduction, physical ther-
apy, and mechanical devices (canes, braces).
b. Estrogen replacement therapy (ERT) may reduce hip and knee OA in post-
menopausal women, although its use should be balanced with the risks of hor-
monal therapy.
c. Acetaminophen, aspirin, and other nonsteroidal anti-inflammatory drugs
(NSAIDs) are beneficial. COX–2 inhibitors are an alternative if no renal dys-
function exists; however, there is increasing concern regarding cardiovascular
side effects with COX-2 inhibitors.
d. 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.
e. Glucosamine may reduce pain and may be chondroprotective.
f. In severely affected joints, surgery to correct severe deformity or complete
joint replacement may be indicated.

B. RHEUMATOID ARTHRITIS (RA)

1. General characteristics
a. RA is a chronic, systemic, inflammatory disorder that more commonly
begins in women during their childbearing years.
b. RA involves an inflammation and hypertrophy of the synovium, with infil-
tration by lymphocytes; the resulting immune complex formation leads to
an immune reaction.
c. The inflammatory process eventually leads to ulcerations in the cartilage,
surrounding ligaments, and bone.
2. 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 sublux-
ation of the PIPs are common; swan-neck deformities (hyperextension of
PIP and flexion of DIP) or boutonniere deformities (flexion of PIP and exten-
sion 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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RHEUMATIC DISEASES 125

j. 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.
3. Differential diagnosis
a. Systemic lupus erythematosus often involves joints symmetrically but is
usually not deforming.
b. Spondyloarthropathies are distinguished from RA by their sacroiliac and
axial spine involvement.
c. Systemic sclerosis is characterized by short-lived joint inflammation and
characteristic skin changes.
d. Rheumatic fever, uncommon in adults, should be considered if an associated
pharyngitis and migratory arthritis are present.
e. Polymyalgia rheumatica is distinguished from RA by intermittent, nonde-
forming arthritis, which is rheumatoid factor negative.
f. 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).
4. Laboratory findings
a. Hematologic studies indicate normochromic-normocytic or hypochromic-
microcytic anemia, thrombocytosis (500–700  109/L), and elevated ESR; pos-
itive 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.
b. Synovial fluid aspiration reveals 5,000–40,000 cells/mm3 with 50%–70%
polymorphonuclear neutrophils (PMNs), decreased complement, and poor
mucin clot formation.
c. 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.
5. 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) pro-
duce 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 abnor-
malities and renal dysfunction.
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126 CHAPTER 7

● Figure 7-1. A patient with rheumatoid arthritis who has marked protrusion of the acetabula and joint space narrow-
ing. 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 syn-
drome, GI upset, obliterative bronchitis, and alterations in taste perceptions.

II Crystal-Related Joint Diseases

A. GOUT
1. General characteristics
a. Gout occurs secondary to a disorder of purine metabolism that leads to hy-
peruricemia, and therefore to intra-articular and extra-articular urate deposition.
b. Gout commonly affects middle-aged men.
c. 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).
d. 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 disor-
ders, psoriasis, chemotherapy).
2. 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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RHEUMATIC DISEASES 127

b. A mild fever may be present in the acute phase.

c. Attacks may be triggered by trauma, alcohol, stress, or acute medical illness.
d. 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.
3. 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.
4. Laboratory findings
a. Hematologic studies indicate mild leukocytosis and a mildly elevated ESR.
b. 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.
c. Synovial fluid aspiration indicates the presence of monosodium urate crys-
tals (needle-shaped and negatively birefringent in polarized light) in the syn-
ovial fluid; cell count is 10,000–60,000 cells/mm3 (70% PMNs).
d. Aspiration of gouty tophi reveals urate crystals, which differentiate the gouty
tophi from rheumatoid nodules.
e. Radiography is usually of little value during the acute attack because radi-
ographs reveal only soft-tissue swelling.
i. However, radiography may help exclude septic arthritis from the differ-
ential diagnosis because gout is characteristically accompanied by destruc-
tive changes.
ii. In the case of chronic tophaceous gout, radiographs may show punched-
out erosions in the subchondral bone.
5. 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 perfu-
sion (contraindications for the use of NSAIDs).
c. Intra-articular corticosteroids may be effective treatment if the aforemen-
tioned 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 lev-
els 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 cal-
culi (contraindication to the use of uricosuric agents) or patients with
decreased renal function who would therefore gain little benefit from uri-
cosuric agents.
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128 CHAPTER 7

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. CPPD is also known as pseudogout.
b. CPPD may be hereditary (autosomal dominant), idiopathic, or associated with
other metabolic disorders (e.g., hemochromatosis and hyperparathyroidism).
2. Clinical features
a. Attacks are common after surgery, trauma, or medical illness.
b. 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.
3. Differential diagnosis includes septic arthritis, gout, and OA.
4. Laboratory findings
a. Synovial fluid aspiration reveals rhomboid crystals that show weakly positive
results for birefringence in polarized light.
b. 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.
5. Treatment
a. Repeated aspiration of synovial fluid can shorten the duration of attacks.
b. NSAIDs, intra-articular corticosteroids, or a combination of these are use-
ful in alleviating painful symptoms.
c. 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. Hemochromatosis is an inherited disorder of iron metabolism associated
with excessive body iron stores.
b. Hemochromatosis may occur secondary to repeated blood transfusions.
c. Hemosiderin accumulates in the synovial lining and articular cartilage.
2. Clinical features
a. Hemochromatosis primarily affects the second and third MCP joints.
b. Other joints may secondarily become affected in association with CPPD
deposition.
3. Laboratory findings
a. Serum analysis indicates elevated serum iron and ferritin levels.
b. Synovial fluid aspiration indicates
1,000 cells/mm3, good mucin clot for-
mation, and iron levels that reflect those of serum.
c. Radiography reveals chondrocalcinosis in 50% of cases.
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RHEUMATIC DISEASES 129

4. Treatment
a. Phlebotomy to decrease body iron stores does not seem to affect already estab-
lished arthropathy.
b. NSAIDs may provide symptomatic relief.

III 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. Ankylosing spondylitis primarily involves the sacroiliac joints and spine.
b. Human leukocyte antigen (HLA)-B27 is associated with ankylosing spondyli-
tis; therefore, a positive family history is often present.
c. Onset usually occurs in the second and third decades of life.
2. Clinical features
a. 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.
b. Patients experience decreased spinal mobility, loss of lumbar lordosis, and
increased thoracic kyphosis.
c. Peripheral joint involvement and pulmonary fibrosis are features of severe
disease.
d. Transient uveitis (pain, redness, and photophobia) develops in up to 25% of
patients.
3. Differential diagnosis
a. Mechanical low backache usually worsens with activity and is relieved by rest.
b. Other spondyloarthropathies can be distinguished from ankylosing spondyli-
tis on the basis of associated symptoms described later in this chapter.
4. Laboratory findings
a. 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.
b. 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.
5. Treatment
a. Physical therapy is critical to preserve function and prevent further deformity.
b. NSAIDs provide relief of pain so that patients can achieve maximum function.
c. Anti-TNF antibodies are being used more frequently, yielding rapid improve-
ment in disease progression (e.g., infliximab).
d. Bisphosphonates and sulfasalazine in men have modest results.
e. Due to thoracic deformities and the risk of fibrosis, smoking is severely dis-
couraged in this population.
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130 CHAPTER 7

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

C. REACTIVE ARTHRITIS
1. General characteristics
a. Occurs secondary to chlamydial urethritis or gastrointestinal infections by
Shigella, Salmonella, Yersinia, and Campylobacter.
b. Because organisms are not cultured from arthritic joints, this is a reactive
arthritis.
c. The disease often occurs in young adulthood.
d. HLA-B27 is seen in the majority of patients, suggesting a general predispo-
sition.
2. Clinical features
a. Signs and symptoms usually occur 2–4 weeks after the initial infection.
b. Acute onset is characterized by asymmetric arthritis in knees and ankles.
c. 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
d. Forty percent of patients develop mild, noninfectious, transient conjunctivitis,
and 3%–5% develop disabling iritis, uveitis, or corneal ulceration.
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RHEUMATIC DISEASES 131

e. 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.
f. The majority of patients experience recurrent episodes of arthritis, but severe
disability is rare.
3. Laboratory findings
a. Hematologic studies indicate elevated ESR and leukocytosis.
b. Reactive arthritis is HLA-B27–linked.
c. Synovial fluid aspiration indicates 500–75,000 cells/mm3 with a predomi-
nance of PMNs.
d. Radiography reveals erosions and periosteal changes at the ischial tuberosi-
ties, 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).
4. Treatment
a. NSAIDs are the primary line of therapy.
b. No evidence exists showing that antibiotics alter the disease course.
c. Systemic corticosteroids are ineffective, but intra-articular steroids for severe
monoarthritic disease produce relief.
d. Topical corticosteroids may be prescribed for keratoderma blennorrhagicum
and conjunctivitis.
e. Sulfasalazine is the second line of therapy if NSAIDs are inadequate.

D. PSORIATIC ARTHRITIS
1. General characteristics
a. Psoriatic arthritis is an inflammatory arthritis associated with psoriasis.
b. Approximately 7% of patients who have psoriasis have some form of inflam-
matory arthritis.
c. Several HLA types have been associated with this form of arthritis.
2. Clinical features
a. Disease onset occurs in the 30s and 40s, with skin lesions followed by arthritis.
b. The majority of patients have peripheral, asymmetric joint involvement;
spinal involvement is not uncommon.
c. Approximately 25% of patients have a symmetric polyarthritis similar to that
of RA.
d. Patients may develop sausage digits as in reactive arthritis.
e. Psoriatic lesions are commonly found on the extensor surfaces.
f. Nail involvement may include pitting and longitudinal ridges.
g. Conjunctivitis or anterior uveitis may occur in up to 30% of patients.
3. Laboratory findings
a. Serum analysis reveals mildly elevated ESR; hyperuricemia may be present
with cases of severe psoriasis.
b. Synovial fluid aspiration reveals mild inflammation, with 2,000–15,000
cells/mm3 and a predominance of PMNs.
c. Radiography indicates distal interphalangeal erosions progressing to tele-
scoping joints.
i. Asymmetric sacroiliitis progressing to fusion is also common.
ii. Isolated axial syndesmophytes may be seen at any level.
4. Treatment
a. NSAIDs such as indomethacin are effective in relieving joint symptoms.
b. Severe disease may require intra-articular corticosteroid treatment.
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132 CHAPTER 7

c. Methotrexate, penicillamine, gold, and hydroxychloroquine are effective

second-line agents.
d. 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. Enteropathic arthropathies are forms of polyarticular arthritis and are asso-
ciated with ulcerative colitis or Crohn disease.
b. Peripheral (lower extremity) arthritis exists in approximately 20% of
patients, whereas sacroiliitis predominates in another 20%.
c. HLA-B27 is not linked with lower extremity arthritic syndrome, but HLA-B27
linkage is present in the sacroiliitis form.
d. Peripheral arthritis tends to exacerbate with flare-ups of the bowel disease,
whereas sacroiliitis tends to progress independent of the bowel disease.
2. Laboratory findings
a. Synovial fluid aspiration reveals effusions that are mildly to severely inflam-
matory and nonspecific.
b. Radiography indicates that:
i. Sacroiliitis is symmetric, as in ankylosing spondylitis
ii. No destructive changes are present in the peripheral arthritis form
3. Treatment
a. Successful management of the inflammatory bowel disease alleviates the
peripheral arthritis.
b. Therapy for the sacroiliitis form is identical to that for ankylosing spondylitis.
c. Anti-TNF antibodies are being used for treatment more routinely (e.g.,
infliximab).

IV 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 involve-
ment. 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 devel-
op 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, psy-
choses, and mononeuritis multiplex.
4. Cardiac signs and symptoms include pericardial effusions and myocarditis.
5. Pulmonary signs and symptoms include pleuritis, pleural effusions, and pneu-
monitis.
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RHEUMATIC DISEASES 133

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 lymphadenopa-
thy; 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 consid-
ered 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 (normochromic-
normocytic) or Coombs’ positive hemolytic anemia, lymphopenia secondary to
autoantibodies (more common than leukopenia), thrombocytopenia, and an elon-
gated 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 dis-
ease.
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 sys-
temically 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 cyclophos-
phamide (which may cause bone marrow suppression, bladder carcinoma, or
myeloproliferative and lymphoproliferative malignancies) or azathioprine (which
is less toxic).
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134 CHAPTER 7

V 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 phe-
nomenon, 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 hyper-
emia), 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 skin-
folds, 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 sur-
faces, 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 hypo-
motility is not uncommon, producing diarrhea, malabsorption, and occasionally,
bacterial overgrowth syndrome.
5. Pulmonary signs and symptoms include shortness of breath on exertion second-
ary 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 arte-
rioles 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 anti-
centromere 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 asso-
ciated with a worse prognosis.
c. Anti-RNA polymerases are associated with more frequent cardiac and renal
involvement.
2. Radiography
a. Barium esophagrams can effectively show dysmotility and reflux.
b. Osteopenia is usually the only bony abnormality associated with systemic
sclerosis.
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RHEUMATIC DISEASES 135

D. TREATMENT
1. Frequent evaluations are necessary to assess the multiple systems affected by
this disease, for example, barium swallows to assess esophageal motility; pul-
monary function tests, cardiac ultrasound, and Holter monitoring to assess ven-
tricular function and rhythm disturbances; and routine urinalysis to assess renal
function.
2. Penicillamine inhibits collagen cross-linking, which leads to decreased skin
thickening.
3. Captopril is effective in treating renal hypertensive disease.
4. Calcium channel blockers may provide relief of Raynaud phenomenon.
5. Corticosteroids are generally not effective except for the treatment of polymyosi-
tis and pulmonary complications.
6. Sucralfate, ranitidine, or omeprazole may be beneficial for the symptoms of
esophageal reflux, whereas metoclopramide (a smooth muscle stimulant) may
improve intestinal motility.

VI 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. Symmetric proximal muscle weakness occurs after an insidious onset of malaise,
weakness, and weight loss.
2. Neck flexion weakness is also present.
3. Facial or ocular weakness is not present (unlike myasthenia gravis).
4. Affected muscles may be tender on palpation.
5. Dermatomyositis is associated with erythematous smooth or scaly patches over
elbows, knees, and medial malleoli, as well as heliotrope eyelids (violet discol-
oration of the eyelids). There is an increased incidence of ovarian, breast, and colon
cancer; melanoma; and lymphoma.
6. Cardiac involvement may lead to arrhythmias or CHF.
7. Swallowing difficulties (dysphagia) are not uncommon.
8. 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 poten-
tials, fibrillations, and high-frequency action potentials.
4. Muscle biopsy is the only specific test, showing lymphoid inflammatory infil-
trates in both cases.

D. TREATMENT
1. High-dose oral corticosteroids are prescribed for a 3-month trial period.
2. Azathioprine, cyclophosphamide, and methotrexate are second-line agents.
3. Hydroxychloroquine may be beneficial for resistant skin manifestations.
4. In refractory cases, intravenous immunoglobulin promotes short-term improvement.
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136 CHAPTER 7

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

VIII 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. Hypersensitivity angiitis is the most common form of vasculitis.
b. The disease is localized to skin involvement.
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RHEUMATIC DISEASES 137

c. Infiltration of dermal capillaries with PMNs occurs.

d. The disease tends to occur after drug exposure.
2. Clinical features
a. Fever and arthralgias may occur.
b. Palpable purpura is the primary skin feature, usually first seen on the lower
extremities.
3. Laboratory findings
a. Skin biopsy is the only diagnostic test.
b. Serum complement levels may be low or normal.
4. Treatment
a. The causative agent should be discontinued.
b. Corticosteroids are useful in treating widespread disease.

C. HENOCH-SCHÖNLEIN PURPURA
1. General characteristics
a. Henoch-Schönlein purpura is also known as anaphylactoid or allergic pur-
pura, which involves the small vessels.
b. The disease occurs in children or young adults.
c. The disease occurs secondary to streptococcal infections, insect stings, or
administration of drugs.
2. Clinical features
a. First signs of the disease are palpable purpura on the lower extremities, which
may coalesce and ulcerate; purpura subsides in several weeks.
b. Abdominal pain, upper or lower GI bleeding, and lower-extremity arthritis
may occur with the skin lesions or afterward; these signs and symptoms sub-
side spontaneously.
c. Renal involvement occurs in more than half of patients and is self-limiting.
3. Laboratory findings
a. Hematologic studies indicate mild anemia, leukocytosis, and elevated ESR.
Serum immunoglobulin (Ig) A levels are raised in 50% of patients.
b. Urinalysis indicates hematuria, red blood cell casts, and proteinuria, which
indicate renal involvement.
c. The presence of IgA in tissue biopsy confirms the diagnosis in patients who
have appropriate symptomatology.
4. Treatment
a. Therapy is supportive for mild disease.
b. Corticosteroids are prescribed for treating arthralgias and renal disease.

D. CHURG-STRAUSS SYNDROME
1. General characteristics
a. Churg-Strauss syndrome is characterized by the triad of asthma or allergic
rhinitis, peripheral eosinophilia, and systemic vasculitis involving small and
medium arteries.
b. The disease primarily affects men.
2. Clinical features
a. Allergic rhinitis usually precedes asthma.
b. Second phase of the disease involves eosinophilic tissue infiltration.
c. Third phase is characterized by systemic necrotizing vasculitis, weight loss,
and fever.
d. Vasculitis leads to nonprogressive glomerulonephritis, palpable purpura, and a
nondeforming arthritis.
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138 CHAPTER 7

3. Laboratory findings
a. Hematologic studies indicate leukocytosis with  eosinophils, elevated lev-
els of serum IgE, and normochromic anemia.
b. Tissue biopsy reveals small-vessel vasculitis and eosinophilic infiltration.
c. Visceral angiography may reveal tortuous vessels with areas of obliteration or
partial occlusion.
d. Chest radiograph may show nodular opacities.
4. Treatment
a. Systemic corticosteroids are usually sufficient.
b. Azathioprine or cyclophosphamide may be necessary to treat unremitting
disease or to allow for tapering of corticosteroids.

E. POLYARTERITIS NODOSA
1. General characteristics
a. Polyarteritis nodosa involves small and medium-sized muscular arteries that
form aneurysms and areas of occlusion.
b. The disease primarily affects middle-aged men.
c. The disease commonly affects skin, joints, nerves, GI tract, and kidneys.
2. Clinical features
a. Fever, malaise, and weight loss occur frequently.
b. Seventy percent of patients have renal involvement, which may lead to renal
insufficiency and hypertension.
c. Peripheral neuropathy occurs in 50%–70% of patients, beginning with sud-
den radicular pain and paresthesias, followed by motor deficits involving
that peripheral nerve.
d. In the skin, palpable purpura, ulcerations, and digital tip infarcts may occur.
e. In the joints, nondeforming arthritis involving any number of joints may
occur.
f. GI signs and symptoms include generalized abdominal pain and distention
that is suggestive of mesenteric artery involvement and may lead to obstruc-
tion, perforation, and GI bleeds.
g. Rupture of aneurysms may lead to hemorrhagic shock and death.
3. 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 indi-
cate 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. Wegener granulomatosis involves small arteries and veins.
b. The disease is characterized by granulomatous vasculitis of the upper and
lower respiratory tract and a necrotizing glomerulonephritis.
c. The disease primarily affects middle-aged men.
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RHEUMATIC DISEASES 139

2. Clinical features
a. Fever, anorexia, and weight loss are common.
b. Ulcerations of respiratory tract mucosa lead to chronic purulent sinusitis
and saddle-nose deformity, as well as pneumonitis, cavity formation, cough,
and hemoptysis.
c. Progressive renal disease can be fatal.
d. Eye inflammation with episcleritis occurs in over half of patients.
e. GI tract and peripheral nerves are less commonly involved (unlike in poly-
arteritis nodosa).
3. Laboratory findings
a. 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 indi-
cate glomerular disease.
d. Pulmonary biopsy shows a granulomatous vasculitis.
4. Treatment consists of combined corticosteroid and cyclophosphamide therapy,
which has markedly improved outcomes in this disease.

G. GOODPASTURE SYNDROME
1. General characteristics
a. 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.
2. Clinical features include an initial flulike prodrome, followed by renal and lung
manifestations (cough and hemoptysis).
3. Laboratory findings
a. Hematologic studies indicate microcytic, hypochromic anemia and low serum
iron levels.
b. Urinalysis reveals proteinuria, hematuria, and red blood cell casts, which indi-
cate glomerular involvement.
c. Immunohistologic studies of renal biopsy tissue show linear deposits of anti-
bodies along the glomerular basement membrane.
d. Lung biopsy reveals alveolar hemorrhage and hemosiderosis; immunologic
studies show linear deposits of antibodies along the alveolar basement mem-
brane. Renal biopsy shows crescents in the glomeruli.
e. Antiglomerular basement membrane antibodies to type IV collagen is diag-
nostic.
4. Treatment
a. High-dose corticosteroids, cyclophosphamide, and emergent plasmaphere-
sis, if started early, can prevent permanent renal failure.
b. Hemodialysis may be necessary.

H. GIANT CELL ARTERITIS (TEMPORAL ARTERITIS)

1. General characteristics
a. Giant cell arteritis is a granulomatous medium- and large-artery vasculitis that
affects persons older than 50 years of age.
b. The disease may coexist with polymyalgia rheumatica (characterized by aching
extremities, stiffness, fatigue, and headache).
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140 CHAPTER 7

2. Clinical features
a. Symptoms include those of claudication (pain, pallor, paresthesias, pulse-
lessness), headache, visual changes, and scalp tenderness.
b. Common sites of claudication include jaw (indicating temporal arteritis),
tongue, and extremities.
c. Visual changes include blurring, ptosis, diplopia, and partial or complete
blindness (due to ophthalmic vessel arteritis).
d. New onset of headache in an elderly person with fever and anemia suggests
the diagnosis.
e. 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.
3. Laboratory findings
a. Hematologic studies indicate normochromic anemia, leukocytosis, thrombo-
cytosis, 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.
4. Treatment consists of corticosteroids, which should be administered if the diag-
nosis is highly suspected on the basis of clinical symptoms, to avert the complica-
tion of blindness (even if biopsy has not yet been performed).
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Chapter 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 metas-
tasis (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. Signs and symptoms include dysphagia, hoarseness, and swelling in the neck.
2. White plaques may be evident within the oral cavity.
3. Neck swellings must be differentiated from simple lymphadenopathy through
assessment of size, firmness, and adherence to adjacent tissues.
4. Occasionally, patients may present with persistent cervical lymphadenopathy.

C. LABORATORY FINDINGS
1. Biopsy confirms the diagnosis.
2. Computed tomography (CT) scan or magnetic resonance imaging may be help-
ful in delineating the extent of the lesion.
3. In persistent cervical lymphadenopathy with no obvious tumor on physical exam-
ination, lymph node biopsy should be performed. If it reveals squamous cell carci-
noma, 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. Localized lesions (T1 or T2) are treated with surgical removal or radiotherapy.
Radiation for small laryngeal cancer is preferred to preserve voice.
2. 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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142 CHAPTER 8

II 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. Signs and symptoms of renal cancer include flank pain, hematuria, abdominal
mass that may be palpable, fatigue, anemia, and weight loss.
2. 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 differen-
tiate 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. Renal cancer is primarily treated with radical nephrectomy for stage I and II dis-
ease 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.
2. Cystoscopic resection of superficial lesions not invading muscle is possible for blad-
der cancer, but more extensive lesions require cystectomy with urinary diversion.
3. After cystoscopic removal, intravesical treatment with bacillus Calmette-Guérin
(BCG) can prevent recurrence.

III 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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ONCOLOGIC DISEASES 143

5. 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 biop-
sy). 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 meas-
ured 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. Surgery or radiotherapy may result in a cure in early-stage disease.
2. 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 symp-
toms 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 differ-
entiate 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 con-
fined to the testicle without invasion (T1) and markers are reduced, no further
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144 CHAPTER 8

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 resec-
tion is followed by chemotherapy (e.g., etoposide, cisplatin,  bleomycin).
c. If staging shows metastatic disease outside of the abdomen, then chemother-
apy without retroperitoneal lymph node dissection is used.
2. 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 dis-
tant metastatic disease.

V Ovarian Cancer
A. GENERAL CHARACTERISTICS
1. There is a lower risk in patients on oral contraceptives, who have had multiple preg-
nancies, 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 pres-
ence 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 oophorec-
tomy) 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. Gastric cancer is twice as common in men as in women.
4. The tumor is almost always an adenocarcinoma. Other types include primary
gastric lymphoma and gastrointestinal stromal tumors.
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ONCOLOGIC DISEASES 145

5. 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 usu-
ally 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; coffee-
ground 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. 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%).
2. Adjuvant chemotherapy has proved to be of little value.
3. Radiation therapy is only used palliatively and does not improve survival.
4. Combined chemoradiation after surgical resection has a small improvement in survival.
5. 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]).

VII 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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146 CHAPTER 8

B. CLINICAL FEATURES
1. Signs and symptoms include weight loss, obstructive jaundice (if tumor is locat-
ed at the head of the pancreas), and deep-seated abdominal pain.
2. Pain may radiate to the back in 25% of patients and is associated with a worse prog-
nosis; pain may be relieved by sitting up with the spine flexed and is aggravated by
recumbency.
3. Hepatomegaly may be present.
4. An epigastric mass may be palpated and is usually indicative of a nonresectable
lesion.
5. A palpable, nontender gallbladder in a patient who has jaundice suggests neo-
plastic obstruction of the common bile duct (seen in 50% of patients).
6. Jaundice is associated with pruritus.
7. Ascites may be present.

C. LABORATORY FINDINGS
1. Serum bilirubin level (average is 18 mg/dL) is much higher than that found in
benign disease of the biliary tree.
2. Aspartate aminotransferase and alanine aminotransferase are usually not sig-
nificantly elevated.
3. Elevated alkaline phosphatase level occurs when bile duct obstruction is pres-
ent and/or liver metastasis has occurred.
4. 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 automat-
ically denote cancer.
5. 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 pan-
creatic mass.
6. 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
1. Surgical resection is indicated for resectable tumors (only 20%).
2. Jaundice and pruritus are relieved by choledochojejunostomy or placement of
a biliary stent in patients who have unresectable lesions.
3. Although radiotherapy and chemotherapy can provide some palliation, these
therapies are not curative.

VIII Colorectal Carcinoma

A. CANCER OF THE COLON AND RECTUM
1. General characteristics
a. Colorectal cancer is the second leading cause of death due to cancer (after
lung cancer).
b. Incidence increases with age, peaking in the 70s and 80s.
c. Carcinoma of the right colon is more common in women, whereas carci-
noma of the rectum is more common in men.
d. The majority of colorectal tumors are adenocarcinomas.
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ONCOLOGIC DISEASES 147

e. 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.
2. Clinical features
a. 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.
b. 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.
c. 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.
d. Inguinal and supraclavicular nodes should be palpated in all bowel carcino-
ma patients because enlargement of these nodes is evidence of metastasis; an
enlarged node may also provide an accessible site for biopsy.
e. Colorectal cancer patients initially may be seen with symptoms of obstruc-
tion, including nausea; vomiting; severe, cramping abdominal pain; and
absence of flatus and bowel movements. Fever and tachycardia may also occur.
3. Laboratory findings
a. Patients have hypochromic, microcytic anemia.
b. 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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148 CHAPTER 8

j. Radiographic studies are unreliable for diagnosis of rectal cancer; rectal car-
cinomas are best diagnosed with a sigmoidoscopy.
k. CT scans are not essential for diagnosis of colorectal cancer but may assist in
assessment of disease extent.
4. Treatment
a. For colonic cancer, surgical resection of the affected colon is often per-
formed even if metastasis is present, because removal of the lesion can prevent
obstruction and hemorrhage.
b. For rectal cancer, surgical resection is performed with an attempt to pre-
serve anal sphincter function when possible; neoadjuvant chemotherapy and
radiotherapy can significantly reduce the surgical resection necessary for
tumor removal.
c. 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.
d. Patients with nodal metastases should receive chemotherapy (e.g., 5-FU and
leucovorin).

B. COLONIC AND RECTAL POLYPS

1. General characteristics
a. Polyps may be sessile or pedunculated.
b. Polyps may be benign or malignant.
c. Most polyps are adenomatous and are either tubular, tubulovillous, or villous,
and have neoplastic potential; sessile lesions are more likely to become malig-
nant than are pedunculated lesions.
d. At least half of all polyps occur in the sigmoid colon or rectum.
e. Other polyp types include hyperplastic and inflammatory polyps; both are
nonneoplastic.
f. Familial polyposis syndromes are a rare group of diseases summarized in
Table 8-1.
2. Clinical features
a. Most patients who have polyps are asymptomatic; most polyps are dis-
covered by routine sigmoidoscopy.
b. Rectal bleeding is the most common complaint; the bleeding is usually inter-
mittent (rarely profuse).
c. Generally, patients do not report a change in bowel habits unless the polyp is
large.
d. Peristaltic cramps occasionally may be caused by polypoid tumors.
e. 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, Yes
sebaceous cysts
Turcot syndrome Polyposis, medulloblastoma/glioma Yes
Peutz-Jeghers syndrome Multiple hamartomatous polyps, melanotic Small
pigmentation of skin andmucous membranes
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ONCOLOGIC DISEASES 149

3. Laboratory findings
a. Anemia usually is not present because bleeding is typically not extensive
unless the polyp is malignant.
b. Barium enemas may reveal a filling defect associated with the polyp(s); how-
ever, polyps 5 mm are generally difficult to detect.
c. Colonoscopy is the most reliable means of detecting and treating small poly-
poid lesions.
4. Treatment
a. Polyps should be removed because they are either symptomatic (e.g., bleed-
ing) or have malignant potential.
b. 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.

IX 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 sympto-
matic 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, recur-
rent 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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150 CHAPTER 8

2. 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, syn-
drome of inappropriate antidiuretic hormone, neuropathies, clubbing, and
hypertrophic pulmonary osteoarthropathy.
3. Nonspecific signs and symptoms include weight loss, anorexia, weakness, and
malaise.

C. LABORATORY FINDINGS
1. Microscopic analysis of sputum may reveal atypical cells; however, cell yields are
often inconsistent.
2. Some patients may have anemia that is consistent with chronic disease.
3. 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.
4. CT scan of the chest is used to determine resectability potential based on appear-
ance of the tumor and nodal spread.
5. Bronchoscopy with biopsy/brushings establishes the diagnosis in the majority of
patients. CT-guided transthoracic biopsy may be necessary if bronchoscopy is negative.
6. Patients experiencing signs and symptoms of paraneoplastic syndromes should
be evaluated.
7. 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.
8. Ventilation-perfusion scan can be used to preoperatively assess pulmonary reserve.
9. Positron emission tomography (PET) is used for patients who have resectable dis-
ease on CT scan to determine whether there is metastatic disease not visible on CT.

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

X
Multiple Myeloma
A. GENERAL CHARACTERISTICS
1. Multiple myeloma is a malignant proliferation of plasma cells derived from a
single clone.
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ONCOLOGIC DISEASES 151

2. Incidence increases with age (rare in patients 40 years of age).

3. 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, pneu-
monia and pyelonephritis; Streptococcus pneumoniae, Staphylococcus aureus, and
Klebsiella species commonly cause pneumonia, whereas Escherichia coli is pre-
dominant 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. Radiotherapy to solitary bone plasmacytomas often is curative; radiotherapy may
be used palliatively as well.
2. Chemotherapy is also useful, for example, cyclophosphamide and prednisone.
3. Corticosteroids, hydration, and natriuresis are indicated for hypercalcemia.
4. Uric acid nephropathy may occur during chemotherapy (from lysis of tumor bur-
den) and cause renal failure; nephropathy can be treated with allopurinol.
5. Pneumococcal vaccines are of little use in preventing infection.

XI
The Lymphomas
A. HODGKIN LYMPHOMA
1. General characteristics
a. In the United States, Hodgkin lymphoma has a bimodal incidence that peaks
at ages 15–35 and also over age 50.
b. The disease is more common in men, especially within the younger age group.
c. Incidence increases in patients who have immunodeficiencies as well as
patients who have autoimmune diseases. The B-lymphocyte is the cell that
predominates.
d. Table 8-2 lists the four histologic subtypes.
2. Clinical features
a. Patients are usually first seen with a mass or group of lymph nodes that are
firm, nonfixed, and nontender.
b. Adenopathy is common in the neck and/or supraclavicular area.
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152 CHAPTER 8

TABLE 8-2 REY CLASSIFICATION OF HODGKIN LYMPHOMA

Subtype Proportion Pathology Prognosis

Lymphocyte-predominant 5–10 Predominantly normal- Very good

appearing lymphocytes
Lymphocyte-depleted 10–15 Few lymphocytes, Poor
pleomorphic cells, fibrosis
Mixed cellularity 25–40 Pleomorphic cells Good
Nodular sclerosis 50–80 Lymphoid nodules, Good
collagen bands

c. Approximately 50%–60% of patients have mediastinal lymphadenopathy.

d. 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. Patients who have lymph nodes
1 cm for more than 4–6 weeks should
undergo biopsy.
b. Presence of Reed-Sternberg cells confirms the diagnosis.
c. Hematologic analysis reveals normochromic-normocytic anemia, with ele-
vated iron stores and low iron-binding capacity consistent with anemia of
chronic disease.
d. A marked leukemoid reaction is evident.
e. Staging is done with CT of the chest/abdomen/pelvis, and PET scan is fre-
quently being used after treatment to document remission.
4. Treatment
a. Radiotherapy (localized disease: stages I and II) and chemotherapy (dis-
seminated 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. Peak incidence occurs in individuals between ages 20 and 40.
b. This disease may be associated with viral infection and immunosuppres-
sion (e.g., iatrogenic or acquired immunodeficiency syndrome).
c. The majority of subtypes are of B-cell lineage (except for the high-grade lym-
phoblastic subtype, which has a T-cell origin).
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ONCOLOGIC DISEASES 153

2. Clinical features
a. Persistent, painless, peripheral lymphadenopathy is common.
b. Epitrochlear and mesenteric node involvement are more suggestive of non-
Hodgkin than Hodgkin lymphoma.
c. Patients are less likely to have constitutional signs and symptoms (com-
pared with Hodgkin lymphoma).
d. Site-specific signs and symptoms associated with lymphadenopathy may
occur.
e. Hepatosplenomegaly may be present.
3. Laboratory findings
a. Biopsy of suspicious nodes is required for diagnosis.
b. 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.
c. Hypergammaglobulinemia is not present because the overproduced B cell is
typically in a resting state (unlike in multiple myeloma).
4. Treatment
a. Treatment is based on histologic subtype (low-, intermediate-, or high-grade
lymphoma).
b. Radiotherapy has a limited role.
c. Chemotherapy is the most common treatment modality. Most involve some
form of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone).
d. Bone marrow transplantation is of some benefit for patients whose condi-
tions are refractory to standard chemotherapy.

XII 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 cer-
tain chemotherapeutic agents (alkylating agents).
3. The four main subtypes are acute lymphocytic leukemia (ALL), acute mye-
logenous 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 rela-
tively 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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154 CHAPTER 8

4. Clinical features
a. Signs and symptoms of ALL and AML are similar.
b. 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 bruis-
ing).
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 organ-
isms, and Candida species.
ii. Mucosal breakdown leads to infection of the skin, gingiva, perirectal tis-
sue, 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. Signs typical of pancytopenia (normochromic-normocytic anemia) are pres-
ent, with the exception of large numbers of lymphoblasts (ALL) or myeloblasts
(AML).
b. 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.
c. Serum lactate dehydrogenase and uric acid levels may be increased due to
increased cell turnover.
d. Cerebrospinal fluid may reveal leukemic blast cells, increased protein levels,
and decreased glucose levels in leukemic meningitis.
e. Bone marrow biopsy confirms the diagnosis.
f. CT scan may be useful in delineating extramedullary sites that are impinging
on other structures.
6. Treatment
a. Patients should receive transfusion with the appropriate blood products;
platelet count should be maintained above 20  109/L.
b. 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.
c. Because fungal infections may also exist, a patient whose condition is unre-
sponsive 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.
d. The use of granulocyte transfusions remains controversial.
e. Fifty percent of children who have ALL are cured with chemotherapy
(cytarabine, anthracycline).
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ONCOLOGIC DISEASES 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. CLL is characterized by accumulation of mature-appearing lymphocytes
in the peripheral blood and infiltration of these lymphocytes into the mar-
row, spleen, and lymph nodes.
b. This disease usually occurs in individuals over age 50.
c. The disease is more common in men and is the most common form of
chronic leukemia in the United States.
d. CLL is most often caused by a clonal expansion of B cells.
2. Clinical features
a. CLL may be discovered incidentally.
b. Patients may initially be seen with signs and symptoms of anemia such as
fatigue, pallor, and dyspnea on exertion.
c. Lymphadenopathy may be present.
d. Intercurrent infection (decreased levels of mature PMNs) may be present.
e. Patients who have advanced disease may have easy bruising and gingival
bleeding (thrombocytopenia).
f. Hepatosplenomegaly may be noted.
3. Laboratory findings
a. Normochromic-normocytic anemia is present.
b. WBC count ranges between 15 and 200  109/L, with a predominance of
mature-appearing lymphocytes.
c. Lymph node biopsy may be necessary to distinguish a normal reactive lym-
phocytosis from CLL.
d. An M spike shown on protein electrophoresis similar to that seen in multi-
ple myeloma may be present.
4. Treatment
a. Cure is usually not achieved despite chemotherapy.
b. The goal of treatment is palliative.
c. 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.
d. Patients may live 10–15 years after diagnosis of the disease.

D. CHRONIC MYELOGENOUS LEUKEMIA

1. General characteristics
a. CML is characterized by increased numbers of granulocytes (neutrophils).
b. The disease generally runs a mild course (chronic phase) until the develop-
ment of the blastic phase.
c. CML can occur at any age, but peak incidence occurs between the third
and fourth decades of life.
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156 CHAPTER 8

2. Clinical features
a. Patients may initially be seen with upper left quadrant abdominal discom-
fort associated with splenomegaly (often palpable on physical examination).
b. Patients have signs and symptoms of anemia, such as pallor, fatigue, and
dyspnea on exertion.
c. Lymphadenopathy is typically not present during the chronic phase of the
disease.
d. Weight loss and fever may be present.
e. Meningeal leukemia is rare.
f. Blastic phase is associated with marked anemia, thrombocytopenia (easy
bruising), and predominance of blasts.
3. Laboratory findings
a. Normochromic-normocytic anemia is present.
b. 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 distin-
guishes 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. Allogenic stem cell transplant is curative and reasonable in patients with good
end-organ function.
b. Imatinib induces apoptosis in leukemic cells and can induce remission in 60%
of patients.
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Chapter 9
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: hypochromic-
microcytic 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, faint-
ness, 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. These anemias are caused by an abnormality in heme or globin synthesis
(Figure 9-1).
b. The most common cause is iron deficiency secondary to chronic blood loss
or low dietary intake (seen mainly in children or pregnant women).
c. 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.
2. Iron deficiency
a. General characteristics
i. Iron deficiency is most often secondary to chronic bleeding of the gas-
trointestinal (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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158 CHAPTER 9

TABLE 9-1 NORMAL BLOOD MEASUREMENTS

Important Values Male Female

Hemoglobin 13.7–17.5 g/dL 11.5–15.5 g/dL

Red blood cells 4.5–6.5  1012/L 3.9–5.6  1012/L
Hematocrit 40%–52% 35%–47%

b. 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.
c. 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.
3. Anemia of chronic disease
a. 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.
b. Laboratory findings
i. Serum iron is decreased.
ii. Unlike iron deficiency, serum ferritin level is elevated, and TIBC is decreased.
c. Treatment
i. Usually, the anemia is mild and requires no treatment.
ii. Anemia resolves when the underlying disease is treated.
4. 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 27–34 pg

Mean corpuscular volume 80–100 fL
Mean corpuscular Hgb concentration 30–35 g/dL
Hgb, hemoglobin
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HEMATOLOGIC DISEASES 159

Peripheral smear

Red blood cell indices

MACROCYTIC NORMOCYTIC MICROCYTIC

Are reticulocytes Are reticulocytes Is iron low?

increased? increased?

yes no yes no

HEMORRHAGE Megaloblastic IRON ANEMIA OF

marrow? DEFICIENCY CHRONIC
DISEASE
HEMOLYSIS
POST-
yes no HEMORRHAGIC
THALASSEMIA
ANEMIA

B12 OR FOLATE HYPOPLASTIC

DEFICIENCY MARROW SIDEROBLASTIC
ANEMIA

yes no HEMOGLOBINOPATHIES

PRIOR HEMOLYSIS
Bone marrow
aspiration
and biopsy
PRIOR HEMORRHAGE

Abnormal marrow Normal marrow

MYELOMA HYPOTHYROID
METASTASES
MYELOFIBROSIS
LEUKEMIA LIVER DISEASE
RENAL FAILURE
(hypoplastic marrow)
ANEMIA OF CHRONIC
DISEASE

● Figure 9-1. Diagnostic approach to anemias.

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160 CHAPTER 9

TABLE 9-3 NORMAL CONCENTRATIONS OF BLOOD COMPONENTS

Other Parameters Values

Platelets 150–440 109/L

Reticulocyte count 0.5%–2.0% (of normal RBCs)
Segmented neutrophils 2.5–7.5  109/L (50%–70%)
Bands 0.1–0.6  109/L (2%–6%)
Lymphocytes 1.0–5.0  109/L (20%–45%)
Monocytes 0.1–1.0  109/L (2%–9%)
Eosinophils 0.0–0.4  109/L (0%–4%)
Basophils 0.0–0.2  109/L (0%–2%)
RBC, red blood cells.

b. 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.
c. Treatment
i. The offending agents should be discontinued.
ii. Transfusions may be necessary if the degree of anemia is significant.
5. Sickle-cell disease
a. 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.
b. Clinical features
i. Signs and symptoms begin in infancy when fetal hemoglobin (Hgb F) lev-
els 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 organ-
isms (e.g., Streptococcus pneumoniae).
c. 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.
d. Treatment
i. Treatment is largely symptomatic.
ii. Painful crises are managed with oxygen therapy, fluids, correction of aci-
dosis, and analgesics.
iii. Because sickle-cell crisis itself does not cause fever, infection must be sus-
pected in a patient who has fever, because the infection can precipitate a crisis.
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HEMATOLOGIC DISEASES 161

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. General characteristics
i. Two types of thalassemias exist: -thalassemia and -thalassemia; both
are congenital.
ii. Each type may occur homozygously (more severe disease) or heterozy-
gously (minor disease).
iii. The minor forms are typically benign and require no therapy.
b. -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 destruc-
tion.
c. -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 with-
in 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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162 CHAPTER 9

D. NORMOCHROMIC-NORMOCYTIC ANEMIAS
1. General characteristics
a. These disorders can be classified as anemias in which bone marrow production
is impaired and anemias in which red blood cell production is normal.
b. Anemias in which bone marrow production is impaired include aplastic
anemia, myelophthisic syndromes, and red blood cell aplasia.
c. Normochromic-normocytic anemias may also occur as a result of anemia of
chronic disease (see hypochromic-microcytic anemias, I C).
d. Anemias in which erythropoietic response is normal include anemia of
hemorrhage and hemolytic anemias (may be macrocytic due to the predomi-
nance of reticulocytes; see macrocytic anemias, I E).
2. Aplastic anemia
a. 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).
b. 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.
c. 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.
d. Treatment
i. Blood transfusions should be given as required.
ii. Bone marrow transplantation may also be effective if the appropriate
donor is found.
3. Myelophthisic syndromes (myelofibrosis)
a. 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.
b. Clinical features
i. Patients experience an insidious onset of weight loss, weakness, and pallor.
ii. Splenomegaly → platelet trapping → bleeding and petechiae.
c. 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 abnor-
mal tissue.
iii. Bone marrow biopsy must therefore be performed to reveal the abnormal
marrow architecture.
d. Treatment
i. The primary pathologic process must be treated.
ii. Blood transfusions may be necessary.
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HEMATOLOGIC DISEASES 163

4. Red blood cell aplasia

a. Red blood cell aplasia is characterized by anemia with no evidence of retic-
ulocytosis.
b. Platelet and WBC counts are normal; bone marrow is also normal, except
for the absence of erythroid precursors.
c. Red blood cell aplasia is associated with immunologic deficiency states
(including thymoma).
d. It may also be drug-induced (chlorpropamide, gold, isoniazid).
e. Clinical features are similar to those of anemia.
f. 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. An acute hemorrhage is characterized by a clinically apparent site of bleed-
ing (trauma, GI tract).
b. Patients develop compensatory reticulocytosis.
c. Patients have signs and symptoms of acute blood loss, that is, tachycardia,
hypotension, sweating, pallor, and cold and clammy extremities.
d. Rapid replacement of blood products may be required if hemorrhage is sig-
nificant.
3. Hemolytic anemias
a. Intravascular hemolytic anemia
i. General characteristics
(a) This type of anemia is caused by acute transfusion reactions (anti-
body-mediated), prosthetic heart valve dysfunction, cold agglu-
tinin disease, or clostridial infection.
(b) RBC destruction → free hemoglobin binding to haptoglobin, hemo-
pexin, 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 hemo-
siderin 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 transfu-
sion 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 dehydro-
genase (LDH) level is elevated, and total and indirect (unconju-
gated) 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 pos-
itive 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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164 CHAPTER 9

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.
b. 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 intravas-
cular 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.
c. 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 con-
sidered 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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HEMATOLOGIC DISEASES 165

(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 per-
sons of Mediterranean descent.
(iii) This X-linked disorder causes a buildup of intracellular methe-
moglobin, which precipitates in the RBC → these precipitates
are cleared in the spleen via microcytosis of red blood cell mem-
brane → microspherocytes.
(iv) Lack of this enzyme also leads to a buildup of intracellular oxi-
dants that causes cell lysis (intravascular hemolysis).
(v) Exacerbations are brought on by infection, certain drugs (anti-
malarials, 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, hemoglo-
binemia, 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. 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 ery-
thropoiesis.
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.
b. 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 demyeli-
nation, which causes paresthesias, weakness, diminished position,
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166 CHAPTER 9

and vibration sense and ataxia; effects on the cerebrum may lead to
dementia.
iii. Signs and symptoms of anemia are seen in both deficiencies.
c. 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, fol-
lowed 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.
d. Treatment
i. Administration of the appropriate vitamin leads to bone marrow
changes within 24–48 hours, reticulocytosis within 3–4 days, normal-
ization of leukopenia and thrombocytopenia within 10 days, decreased
bilirubin and LDH levels within 1–3 weeks, correction of anemia with-
in 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 intramus-
cular 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 cor-
rect the neuronal damage caused by a lack of vitamin B12.

II 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. Stress erythrocytosis typically affects obese, hypertensive, tense men.
b. This condition is not a true erythrocytosis because red blood cell mass is nor-
mal (plasma volume is contracted).
2. Clinical features
a. Signs and symptoms include dizziness, headache, epistaxis, and a character-
istic “ruddy” cyanosis.
b. Splenomegaly is absent (unlike polycythemia vera).
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HEMATOLOGIC DISEASES 167

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

C. ABSOLUTE ERYTHROCYTOSIS
1. General characteristics
a. This condition is characterized by a definite increase in RBC mass.
b. Causes include chronic hypoxia (lung disease, heart failure), erythropoietin-
secreting tumors (renal tumors), and polycythemia vera (which is caused by
autonomous bone marrow).
2. Polycythemia vera
a. 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.
b. 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; leuko-
cytosis and thrombocytosis are also present.
iii. Erythropoietin is nearly absent.
c. Treatment
i. Repeated phlebotomies are necessary to bring the hematocrit to
50%.
ii. Chemotherapy (hydroxyurea) may be necessary for resistant cases.

III Leukocyte Disorders

A. LYMPHOPENIA
1. General characteristics
a. Lymphopenia may be secondary to another condition (acute infection, ele-
vated cortisol level), but antibody production is not affected.
b. Lymphopenia that causes immunodeficiency is most likely secondary to
human immunodeficiency virus infection or a congenital disease (if signs
and symptoms appear in infancy).
c. Lymphopenia is usually caused by a lack of T cells (thymic hypoplasia).
d. B cells may also be deficient (Bruton agammaglobulinemia).
2. Clinical features
a. T-cell deficiency may be associated with rashes, eczema, and mucocutaneous
candidiasis.
b. In acquired immunodeficiency syndrome, opportunistic viral, fungal, and
protozoal infections predominate (Pneumocystis carinii pneumonia,
Mycobacterium avium-intracellulare pneumonia or disseminated disease, hepa-
titis, cytomegalovirus, herpes).
c. B-cell deficiency is associated with repeated infections by encapsulated organ-
isms (S. pneumoniae).
3. Laboratory findings
a. Lymphocyte count
1.5  109/L (or
10%).
b. Bone marrow is usually normocellular (5%–20% of bone marrow cells are
lymphocytes).
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168 CHAPTER 9

c. T-cell count is decreased.

d. Quantitation of immunoglobulins is useful in detecting B-lymphocyte
deficiencies.
4. Treatment
a. Thymic transplantation for thymic hypoplasia has some benefit.
b. Therapy is supportive with appropriate antibiotics.

B. LYMPHOCYTOSIS
1. General characteristics
a. Lymphocytosis may be caused by infection, that is, a reactive lymphocytosis
caused by EBV, hepatitis, or cytomegalovirus.
b. Lymphocytosis can also be caused by leukemias and lymphomas.
2. Clinical features
a. Malaise, fever, exanthem, and pharyngitis are common.
b. If the cause is reactive, duration is
6 weeks.
c. Lymphadenopathy, usually cervical, may be present.
3. Laboratory findings
a. Peripheral smear that reveals anisocytotic, atypical lymphocytes indicates
a reactive process; morphologic monotony suggests neoplastic disease.
b. Serologic testing for viral causes can help differentiate between reactive and
neoplastic disease.
c. T- and B-cell immunocytochemistry may identify malignant markers present
on lymphocytes.
4. Treatment
a. For reactive lymphocytosis, treatment is supportive, because the disease
resolves spontaneously.
b. Chemotherapy for neoplasms may be required (see Chapter 8, Oncologic
Diseases).

C. NEUTROPHILIA
1. General characteristics
a. Neutrophilia is usually secondary to infection (neutrophil count is usually
20  109/L).
b. Neutrophilia may also be present in inflammatory diseases.
c. The most common malignancy associated with neutrophilia is chronic mye-
logenous leukemia (CML).
d. Neutrophilia can also be drug-induced (e.g., heparin, digitalis).
2. Clinical features
a. If the cause is infectious, patients have signs and symptoms of infection,
that is, fever, localized pain, swelling, and purulent exudates.
b. Splenomegaly is present in CML.
3. Laboratory findings
a. WBC count is elevated in CML.
b. Serum alkaline phosphatase level is decreased in CML.
c. Bone marrow aspiration is indicated if WBC 20  109/L or increased intra-
cellular 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.
d. Karyotyping should be performed to look for the Philadelphia chromosome
(marker for CML).
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HEMATOLOGIC DISEASES 169

e. Peripheral WBC count 100  109/L occurs with CML, as does thrombo-
cytosis.
4. Treatment
a. Infection is treated with appropriate antibiotic therapy.
b. CML should be treated appropriately (see Chapter 8, Oncologic Diseases).

D. NEUTROPENIA
1. General characteristics
a. Neutropenia is most commonly secondary to exogenous factors such as
infections (hepatitis, influenza) or certain drugs (phenothiazines, antithy-
roid drugs, chemotherapeutic agents).
b. Neutropenia is often a feature of collagen vascular diseases (e.g., systemic
lupus erythematosus).
c. Neutropenia is also a feature of leukemias, lymphomas, or myelofibrosis.
2. Clinical features
a. Neutropenia is apparent in agranulocytosis (neutrophil count
0.5  109/L).
b. Signs and symptoms include high fever, necrotic pharyngitis, regional lym-
phadenopathy, and proctitis.
c. Cellulitis, pneumonia, and urinary tract infections ensue.
d. Mortality is high without treatment.
3. Laboratory findings
a. Peripheral neutrophil count is
1.5  109/L.
b. Hypocellular marrow revealed after bone marrow aspiration and biopsy sug-
gests chemical-induced toxicity; evidence of neoplastic disease or myelofi-
brosis may be apparent.
c. Presence of antinuclear antibodies indicates that collagen vascular dis-
eases may be present.
4. Treatment
a. Patients should discontinue possible toxic agents.
b. Infection is treated with broad-spectrum antibiotics (ampicillin and gentam-
icin are common choices).
c. Granulocyte transfusions are usually of little benefit.

E. DYSFUNCTIONAL NEUTROPHILS
1. General characteristics
a. Although these conditions are rare, they have serious clinical effects.
b. These conditions include chronic granulomatous disease (CGD) and
myeloperoxidase deficiency.
c. CGD is X-linked recessive; in this disease, PMNs lack superoxide, which caus-
es increased susceptibility to Staphylococcus, gram-negative organisms, and fungi.
d. Myeloperoxidase deficiency is autosomal recessive; in this disease, patients
have an increased susceptibility to catalase-positive organisms (e.g.,
Staphylococcus aureus).
2. Clinical features
a. Clinical features are secondary to infection.
b. Patients may have fever, regional lymphadenopathy, and eczematoid skin
eruptions.
3. Laboratory findings
a. Granulocytosis indicates infection.
b. Bone marrow aspiration reveals granulomas in CGD and hyperplasia in
infection.
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170 CHAPTER 9

c. 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.
4. Treatment with penicillin, vancomycin, or trimethoprim-sulfamethoxazole can
decrease duration and frequency of recurrent infections.

IV 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 thrombo-
cytopenia and may be immune-mediated (or idiopathic) or due to throm-
bocytopenic purpura (discussed next), sepsis, platelet transfusions, or cer-
tain 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 mucocu-
taneous bleeding.
(b) Laboratory findings
(i) Peripheral smear reveals thrombocytopenia with large
platelets; other cell lines are normal.
(ii) Bone marrow aspiration/biopsy reveals increased megakary-
ocytes.
(iii) Platelet-associated immunoglobulin G indicates immune-
mediated disease.
(c) Treatment
(i) Patients should avoid drugs that act as platelet antagonists
(e.g., aspirin).
(ii) Corticosteroids are recommended for severe thrombocytope-
nia.
(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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HEMATOLOGIC DISEASES 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).
b. 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 thrombocy-
topenia 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.
c. Impaired platelet production
i. General characteristics
(a) Impaired platelet production commonly occurs secondary to adminis-
tration of certain drugs (e.g., ethanol, thiazide diuretics, chemotherapy).
(b) The condition is also associated with vitamin B12 and folate defi-
ciency or may be secondary to bone marrow disease (e.g., myelofi-
brosis or bone marrow aplasia), therefore affecting other cell lines.
ii. Laboratory findings
(a) Bone marrow biopsy is necessary if no obvious drug or vitamin defi-
ciency 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 treat-
ment 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. Platelet dysfunction is most commonly caused by certain drugs (e.g., acetyl-
salicylic acid and other nonsteroidal anti-inflammatory drugs [NSAIDs]).
b. This condition is also seen in uremia and is therefore not uncommon in
chronic renal failure.
2. Laboratory findings
a. Peripheral smear is normal (normal number of platelets).
b. Platelet function study results are abnormal.
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172 CHAPTER 9

3. Treatment
a. The offending agent should be discontinued.
b. Dialysis may benefit patients who have uremia.

C. PLATELET CONSUMPTION SYNDROMES

1. Thrombotic thrombocytopenic purpura (TTP)
a. General characteristics
i. TTP usually affects young women.
ii. A viral prodrome is common.
iii. Presence of hyaline thrombi in arterioles without vessel wall inflamma-
tion (i.e., not a vasculitis) → microvascular disease.
iv. Extensive activation of the coagulation system does not occur.
b. Clinical features include a pentad of symptoms and signs: thrombocytopenia,
microangiopathic hemolytic anemia, neurologic abnormalities, renal dysfunc-
tion, and fever.
c. Laboratory findings
i. Peripheral smear reveals severe thrombocytopenia, schistocytes, frag-
mented 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 character-
istic of the disease.
d. Treatment involves exchange transfusion or plasmapheresis coupled with
fresh frozen plasma; this therapy has improved outcome.
2. Hemolytic uremic syndrome (HUS)
a. HUS is similar to TTP.
b. HUS occurs in children.
c. Because this disease is localized to the kidney, no neurologic abnormalities
occur; otherwise, HUS has the same clinical picture as TTP.
3. Disseminated intravascular coagulation
a. General characteristics
i. In DIC, an activated coagulation system leads to abnormal formation
of excessive thrombin within the circulation → consumption of coagu-
lation 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).
b. 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 clot-
ting and peripheral acrocyanosis.
c. 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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HEMATOLOGIC DISEASES 173

TABLE 9-4 DIAGNOSTIC SUMMARY OF BLEEDING PARAMETERS

Platelet Count Bleeding Time PTT PT Likely Diagnosis

Decreased Increased Normal Normal Thrombocytopenia

Normal Increased Normal Normal Thrombocytopathia
Normal Normal Increased Normal Hemophilia A
Normal Increased Increased Normal VWD
Normal Normal Increased Increased 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. 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 mol-
ecule) is deficient, whereas VIIIag (the antigenic portion of the factor VIII
molecule) is present in normal amounts.
b. 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.
c. Laboratory findings
i. Bleeding parameters: PTT is prolonged (reflects function of the intrinsic
coagulation pathway), PT is normal (reflects function of extrinsic and com-
mon pathways), and bleeding times are normal (reflects platelet function).
ii. Levels of VIIIpro are decreased, and VIIIag levels are normal.
d. 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.
2. 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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174 CHAPTER 9

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

E. ACQUIRED COAGULOPATHIES
1. General characteristics
a. Acquired coagulopathies usually involve multiple coagulation factor defi-
ciencies.
b. The common deficiencies are the vitamin K–dependent factor deficiencies.
c. Other causes include DIC (see IV C 3), presence of lupus inhibitor, and
antifactor VIII antibody–mediated coagulopathy.
2. Vitamin K–dependent factor deficiencies
a. 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).
b. Clinical features
i. Features of the primary disorder typically predominate.
ii. Soft-tissue bleeding with hemarthrosis may occur if deficiencies are
severe.
c. 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.
d. 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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Chapter 10
Neurologic Diseases

I Cerebrovascular Disease
A. STROKE
1. General characteristics
a. May be ischemic (arterial thrombosis, venous thrombosis, and arterial embolism)
or hemorrhagic (intracerebral hemorrhage or subarachnoid hemorrhage)
(Figure 10-1).
b. 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).
c. Stroke incidence increases with age.
d. Risk factors are divided into major and minor contributors (Table 10-1).
e. Lacunar strokes are caused by occlusion of small, penetrating intracerebral
arteries and are most commonly associated with hypertension or diabetes
mellitus.
2. Clinical features
a. 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 contralat-
eral motor and/or sensory deficits.
b. Signs and symptoms associated with the brain stem or cerebellum include
dysarthria, dysphagia, ataxia, diplopia, vertigo, nausea, nystagmus, ipsilateral
numbness, and contralateral motor deficits.
c. 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.
d. Infarcts involving the anterior cerebral artery distribution typically cause more
significant weakness in the contralateral leg than in the contralateral arm and face.
e. Infarcts involving the contralateral posterior cerebral artery distribution
typically cause an isolated homonymous hemianopia.
f. 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.
g. 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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176 CHAPTER 10

Stroke

Primary ischemic Primary hemorrhagic

(80%) (20%)

Cerebral Cerebral Intracerebral Subarachnoid

thrombosis (50%) embolus (30%) hemorrhage (15%) hemorrhage (5%)

Large artery Lacunar infarct

thrombosis (30%) (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 vom-
iting, 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 cere-
bral embolus (multiple emboli).

TABLE 10-1 RISK FACTORS FOR STROKE

Major Minor

Age Hypercholesterolemia
Male gender Obesity
Race (African American) Physical inactivity
Family history Oral contraceptive use
Diabetes Alcohol consumption
Smoking
Hypertension
Prior stroke
TIAs
Cardiac disease (e.g., atrial fibrillation with thrombus)
Asymptomatic bruit
TIA, transient ischemic attack.
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NEUROLOGIC DISEASES 177

3. Laboratory findings
a. Complete blood count (CBC), prothrombin time/partial thromboplastin
time, and platelet count should be performed to look for evidence of coagu-
lation 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 sub-
cortical 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 effec-
tive 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. 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.
b. Early, vigorous treatment of hypertension immediately after a nonhemor-
rhagic 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.
c. 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 pro-
gressing should be heparinized once hemorrhage is excluded.
d. Anticoagulation therapy (e.g., sodium warfarin) is indicated for a cardio-
genic source of emboli if the stroke is nonhemorrhagic.
e. 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.
f. 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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178 CHAPTER 10

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. The most common nontraumatic causes of subarachnoid hemorrhage
include ruptured intracranial aneurysm and bleeding of an arteriovenous mal-
formation (AVM).
b. AVMs usually occur in persons under the age of 40; AVMs are congenital
and twice as common in men.
c. 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.
2. Clinical features
a. Patients experience acute onset of severe, localized headache.
b. Meningismus may be present.
c. Focal neurologic deficits may or may not be present.
d. Seizure may be the first sign of an AVM.
e. Cerebral vagoplasm occurs in 30% of patients about 1–2 weeks after the
bleed, producing clinical symptoms of stroke depending on the vessels involved.
3. Laboratory findings
a. CBC and coagulation studies should be performed to assess the patient’s
coagulation ability because surgical intervention is often immediately nec-
essary. Serum Na must be monitored because cerebral salt wasting leading to
increased Na excretion can cause profound hyponatremia.
b. Cerebral angiography remains diagnostic for both AVM and cerebral
aneurysm; cerebral artery vasospasm may become evident 2–3 days after a
bleed.
c. 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.
4. Treatment
a. Neurosurgical consultation is necessary. The aneurysm should be clipped
surgically or coiled angiographically by interventional radiology.
b. Appropriate antiseizure therapy should be administered if the patient has
seizure; therapy includes phenytoin and ventilatory support, if needed.
c. Increased intracranial pressure should be managed, for example, with ele-
vation of the head of the bed, mannitol, intubation, and hyperventilation.
d. Airway protection may be necessary if the patient is obtunded.
e. Raised intracranial pressure may be due to hydrocephalus from blood
obstructing normal CSF flow and will require ventricular drainage.
f. Vasospasm is treated with calcium channel blockers (e.g., nimodipine), vol-
ume expansion, and increasing blood pressure.
g. Hyponatremia should be treated with hypertonic saline.
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NEUROLOGIC DISEASES 179

II 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. Frontal lobe contusions often result from head injury.
b. These lesions may be infarcted by anterior communicating artery aneurysm
rupture or compressed by a meningioma arising from the olfactory groove.
c. Patients exhibit lack of social appropriateness and inhibitions, which may
lead to urination or masturbation in public.
d. Perseveration is present.
e. Stroking the hand from lateral to medial aspect leads to the sustained grasp-
ing reflex.
f. 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. Temporal lobe lesions often produce seizures.
b. Aphasia may occur if the lesion progresses posteriorly on the dominant hemi-
sphere.
c. Superior quadrantic hemianopia occurs when Meyer loop is involved.
2. Clinical features
a. Patients exhibit brief, repetitive behaviors (e.g., lip smacking, eye twitching,
chewing).
b. Seizures are preceded by an aura that may be olfactory or gustatory.
c. Patients may experience an intense feeling of unfamiliarity or familiarity
with their surroundings.
d. 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-
lary response (which involves brain stem nuclei only) is maintained, but vision is lost.
2. A single affected occipital lobe leads to a crossed homonymous hemianopia.
3. 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 visu-
al fields are moved.
2. Patients exhibit contralateral astereognosis (inability to recognize objects by feel-
ing 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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180 CHAPTER 10

F. APHASIA
1. Expressive aphasia (Broca aphasia)
a. Spontaneous language production is slow.
b. Patients often overuse and repeat nouns.
c. Little intonation is present in speech.
d. Comprehension of language is good.
e. Proximity of the lesion to the facial motor strip may lead to associated con-
tralateral facial palsy.
f. Patients often appear distressed about the inability to clearly express
themselves because they comprehend their disability.
2. Receptive aphasia (Wernicke aphasia)
a. Patients can generate speech, but it contains few nouns and lacks meaning.
b. Patients may use unknown meaningless words (neologisms).
c. Comprehension is impaired.
d. Patients often have poor insight into their deficit.
3. Conduction aphasia
a. Patients’ speech contains semantic confusions.
b. Patients exhibit little dysphasia and good comprehension.
c. Patients have poor ability to repeat heard words.

III 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 hyper-
tension.
a. Drugs that commonly cause dementia include sedatives, ranitidine and cimet-
idine, 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. Forgetfulness in the absence of depression
b. Loss of computational ability
c. Word-finding and concentration problems (e.g., inability to read a paragraph)
d. Difficulties with daily activities, such as dressing or balancing a checkbook
e. Progression to severe memory loss, disorientation, and social withdrawal.
2. Patients who have Alzheimer disease experience an insidious onset and steady
progression of signs and symptoms.
3. Patients who have multi-infarct dementia exhibit a stepwise deterioration.
4. Rapid onset and short duration of dementia suggest a treatable cause such as
infection or drug-associated dementia.
5. Normal-pressure hydrocephalus is associated with the triad of dementia, urinary
incontinence, and gait instability.
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NEUROLOGIC DISEASES 181

6. Depression can be mistaken for dementia.

a. These patients also perform poorly on mental status examinations, may be
irritable, and exhibit short attention spans.
b. 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 asso-
ciated with Alzheimer disease.

D. TREATMENT
1. Reversible causes should be treated; for example, discontinue any suspected med-
ications known to have a side effect of dementia; correct any electrolyte, mineral,
and/or vitamin deficiencies; and treat any apparent infections.
2. 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.
3. Cessation of smoking and treatment of hypertension may alter the natural
course of multi-infarct dementia.
4. Treatment of depression (psychiatric referral) should be initiated if the diagnosis
is established.

IV 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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182 CHAPTER 10

seizure involving the left leg indicates seizure activity originating in the right
cortical motor strip associated with leg function).
b. Complex partial seizures resemble simple partial seizures except that an
associated disturbance or loss of consciousness occurs.
c. 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).
d. 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. No relationship typically exists between postural changes and the onset of
seizures (compared with vasovagal syncope).
2. The neurologic examination is often normal in patients who have seizures; the
exception is the patient who has sustained developmental delay from recur-
rent seizures during infancy.
3. Lateralizing signs may be seen immediately after focal seizures that may point
out the affected area.
4. Temporal lobe seizures are often preceded by an aura (often of an odor or a feel-
ing of strange, intense familiarity with the surroundings).
5. Petit mal seizures typically last
15 seconds.
6. 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).
7. Pseudoseizures are seizure-like episodes of psychogenic origin.
a. Pseudoseizures can be distinguished from true seizure disorders by varia-
tions in the seizure types described by the patient and by the clinician’s obser-
vation of a tight association between seizures and stressors or significant per-
sonal events.
b. Patients who have pseudoseizures may report an awareness of their sur-
roundings 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
Petit mal Ethosuximide
Valproic acid
Myoclonic Valproic acid

3. 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 improve-
ment 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 dos-
ing 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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184 CHAPTER 10

c. Headache typically lasts for a day or longer.

d. Both types of migraines tend to begin in adolescence or early adulthood
and may be associated with vomiting.
3. Tension headache is characterized by a feeling of tightness, pressure, and con-
striction.
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.
4. 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.
5. 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).
6. Giant cell (temporal) arteritis (see Chapter 7 VIII H) is another type of headache.

C. LABORATORY FINDINGS
1. If a patient has neurologic findings, behavioral changes, or a chronic persis-
tent 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.
2. In a young patient who has trigeminal neuralgia, multiple sclerosis must be
suspected; cerebrospinal fluid (CSF) and nerve conduction studies may corrob-
orate this suspicion (see multiple sclerosis, XI).
3. CT scan may be necessary to rule out posterior fossa tumor.

D. TREATMENT
1. Migraine treatment consists of:
a. Resting in a quiet, dark room
b. Initial treatment with aspirin
c. Ergotamine and caffeine combination
d. 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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NEUROLOGIC DISEASES 185

e. Prophylactic treatment if patients experience migraines more than 2–3 times

per month (e.g., amitriptyline)
f. Calcium channel blockers (e.g., nifedipine)
2. 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
3. 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.
4. Tension headache treatment consists of:
a. Stress relief exercises
b. Aspirin or acetaminophen
c. Antimigrainous agents if patient is refractory to simple analgesics
5. For treatment of giant cell arteritis, see Chapter 7, Rheumatic Diseases, VIII H 4.

VI Movement Disorders
A. BENIGN ESSENTIAL TREMOR
1. General characteristics
a. Benign essential tremors commonly occur after age 40; incidence increases
with age.
b. These tremors may be familial related.
c. Diagnosis should be distinguished from Parkinson disease (see VI B).
2. Clinical features
a. Postural tremor is often seen in the hands.
b. Tremor attenuates with movement but becomes more obvious when the tar-
get is reached (e.g., when a patient attempts to grab a glass, the tremor is ini-
tially 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).
3. Laboratory findings are typically not used in the diagnosis, which is most often
made by history and physical examination.
4. Treatment
a. One or two ounces of alcohol may improve the tremor.
b. If tremor is disabling, propranolol or primidone may be effective in reducing
the severity.
c. Thalamotomy or deep brain stimulator implantation is used for patients refrac-
tory to medical therapy.

B. PARKINSON DISEASE
1. General characteristics
a. Parkinson disease is the most frequently encountered extrapyramidal
movement disorder.
b. This neurodegenerative disease begins most often in the fifth and sixth
decades of life.
c. Parkinson disease is characterized by low dopamine levels in the corpus
striatum.
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186 CHAPTER 10

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. Diagnosis is based on history and physical examination.
b. CT scan of the head may be used to rule out other diagnostic possibilities
such as normal pressure hydrocephalus.
c. Apomorphine (a short-acting dopamine agonist) can be used as a therapeutic
challenge; if symptoms improve, Parkinson disease is confirmed.
4. Treatment
a. No cure exists.
b. Amantadine is often used for patients who have mild symptoms.
c. Anticholinergic drugs (e.g., benztropine) tend to alleviate tremor and rigidi-
ty rather than bradykinesia; these drugs are contraindicated in patients who
have narrow-angle glaucoma.
d. 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.
e. Bromocriptine acts on dopamine receptors and can be used synergistically
with levodopa/carbidopa.
f. 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. Huntington disease is characterized by chorea and dementia.
b. The disease is autosomal dominant.
c. Onset is delayed until after age 30 (usually after the patient has had children).
d. The disease is caused by decreased
-aminobutyric acid and cholinergic activi-
ty relative to dopamine activity.
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NEUROLOGIC DISEASES 187

2. Clinical features
a. Huntington disease is progressive, with a fatal outcome within 15–20 years.
b. Early changes include irritability, moodiness, and antisocial behavior.
c. Subsequent dementia occurs.
d. Dyskinesia may begin as restlessness and progress to choreiform movements.
e. Patients exhibit irregular, involuntary hand and facial movements.
f. Reflexes are typically brisk.
g. Smooth eye pursuit movements are absent.
h. Stance is wide with variable cadence.
i. Patients are unable to maintain tongue protrusion.
3. Laboratory findings
a. Diagnosis is based on history and physical examination.
b. Recombinant deoxyribonucleic acid testing is used to diagnose family mem-
bers of patients with Huntington disease (particularly children of affected indi-
viduals); test is 99% accurate.
4. Treatment
a. No cure exists.
b. Dopamine-blocking agents such as phenothiazines or haloperidol may con-
trol dyskinesia and behavioral problems.
c. Reserpine, which blocks neurotransmitter reuptake and therefore depletes
stores of dopamine, has provided some benefit.
d. Genetic counseling is recommended for children of patients.

D. TOURETTE SYNDROME
1. General characteristics
a. Signs and symptoms begin before age 15.
b. Tourette syndrome is a chronic, lifelong disorder with relapses and remissions.
2. Clinical features
a. 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.
3. Laboratory findings are usually unnecessary because the diagnosis is based on
history and physical examination.
4. Treatment
a. Clonazepam and clonidine are used as first-line drug therapy.
b. Haloperidol is effective but has extrapyramidal side effects.
c. Reserpine appears to be effective and better tolerated than the typical antipsy-
chotics.

E. WILSON DISEASE
1. General characteristics
a. Wilson disease is characterized by hepatolenticular degeneration.
b. The disease is rare autosomal recessive.
c. Onset occurs between the first and third decades of life.
d. Excessive deposition of copper in the liver and brain is an important fea-
ture 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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188 CHAPTER 10

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

hepatic dysfunction.
2. Clinical features
a. Patients may exhibit rigidity and parkinsonian tremor.
b. Dysarthria is a consistent finding.
c. Neurologic symptoms progress slowly over years.
d. Psychiatric disorders may be present and vary from adjustment disorder to
depression to schizophrenia.
e. Kayser-Fleischer rings (fine, pigmented, brownish deposits in the cornea)
may be present.
f. Hepatitis is often the earliest sign of the disease (occurring before the neuro-
logic signs and symptoms).
i. Patients with hepatitis have jaundice, malaise, and anorexia, which
usually spontaneously resolve.
ii. Cirrhosis may be detected.
3. Laboratory findings
a. Urine copper level is 100 g/24 h.
b. Ceruloplasmin level is decreased (
20 g/dL).
4. Treatment
a. Early treatment is necessary to prevent permanent hepatic and neurologic
damage.
b. Penicillamine enhances urinary excretion of chelated copper.
c. Pyridoxine is given in conjunction with penicillamine treatment because
penicillamine is a pyridoxine antimetabolite.
d. Patients should restrict their intake of dietary copper (shellfish, legumes).
e. Oral zinc decreases gastrointestinal absorption of copper and may be used as
maintenance therapy.
f. Screening tests for family members of affected individuals are recommended.

VII Spinal Cord Syndromes

A. TRAUMATIC INJURY TO THE SPINAL CORD
1. General characteristics
a. Traumatic spinal cord injuries usually occur in the prime of life.
b. These injuries are commonly associated with motor vehicle accidents, diving
accidents, and falls.
2. Clinical features
a. If conscious, the patient reports a lack of feeling and paralysis below the
level of the injury.
b. 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.
c. The cervical, thoracic, and/or lumbar spines are often tender to palpation
when a vertebra is fractured.
d. Reflexes may be brisk below the level of the lesion.
3. Laboratory findings
a. 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.
b. 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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NEUROLOGIC DISEASES 189

c. If clinical suspicion is high for a spinal cord injury, but radiographs are unre-
vealing, immobilization must be continued until the presence or absence of
neurologic injury can be confirmed clinically.
4. Treatment
a. Spinal immobilization must be maintained.
b. Neurosurgical consultation is necessary.
c. Methylprednisolone may be of benefit if given within 8 hours of the injury.
d. 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. Whiplash injury is a common cause of these syndromes.
b. Spondylotic degenerative cervical spine changes are another common cause.
2. Clinical features
a. Whiplash usually occurs during a motor vehicle accident commonly involv-
ing 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 degen-
erative disease, may produce cervical radicular syndromes (see next).
b. Spondylotic degenerative changes most commonly affect C6–C7.
c. 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).
d. 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.
3. Laboratory findings
a. In patients who have spondylotic degenerative changes, radiographic study
may reveal osteophyte formation and narrowing of the intervertebral disk space.
b. MRI is particularly effective in detecting disk propulsion into the spinal cord.
c. Whiplash injury typically does not appear in radiographic studies because
it typically involves the ligaments.
4. Treatment
a. A soft collar may provide some comfort.
b. Analgesics such as NSAIDs may be of benefit.
c. Continued pain and weakness may necessitate a neurosurgical decompres-
sion of the affected nerve root.

C. LUMBAR SPINAL AND RADICULAR SYNDROMES

1. General characteristics
a. These syndromes are most often due to prolapsed intervertebral lumbar disks.
b. Patients may have a history of awkward lifting or straining.
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190 CHAPTER 10

c. Injury most commonly arises at the L5–S1 level (70%), which causes com-
pression of the first sacral root, followed by injury at L4–L5 (25%), which
causes compression of the fifth lumbar root.
2. Clinical features
a. Patients experience sciatica, or pain in the buttock and down the back of the
thigh and leg.
b. 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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NEUROLOGIC DISEASES 191

c. 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.
3. Laboratory findings
a. Radiographs may reveal narrowing of lumbar disk spaces.
b. MRI may show herniated disk material and a compressed nerve root.
c. These studies are necessary if the patient requires surgery (i.e., the patient does
not respond to conservative management).
4. Treatment
a. Conservative management includes bed rest and NSAIDs.
b. Steroid injections are not beneficial.
c. 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. Lesions occur outside the dura but cause signs and symptoms due to spinal
cord compression.
b. 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 anticoagu-
lant therapy).
c. Primary tumors such as meningiomas and neurofibromas (more common
than intramedullary tumors) may also cause cord compression.
2. Clinical features
a. Presence of fever suggests infectious etiology.
b. History of prostatic, breast, or lung cancer should prompt a search for bony
metastasis.
c. Radicular pain is felt at the dermatomal level of the lesion.
d. Ipsilateral extremity weakness and sensory deficits eventually progress to
the contralateral extremity as the lesion expands.
e. Patients may experience urgency of micturition and impotency.
f. 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.
3. Laboratory findings
a. Radiographs may reveal calcification associated with a tumor mass.
b. CT scan and MRI are often more revealing of the nature and extent of the
lesion.
c. Bone scans are often performed on patients who have prostatic or breast car-
cinoma to rule out bony metastases.
4. Treatment
a. 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).
b. Neurosurgical consultation is necessary.
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192 CHAPTER 10

E. INTRAMEDULLARY LESIONS
1. General characteristics
a. These lesions occur within the spinal cord.
b. Types of intramedullary lesions include astrocytomas, ependymomas,
syringomyelia, vascular infarcts, or plaque demyelination in association with
multiple sclerosis.
2. Clinical features
a. Syringomyelia or a centrally located ependymoma impairs pain and tem-
perature sensation and spares pinprick sensation and proprioception (dissoci-
ated sensory loss); sacral sparing is typical (this sign differentiates an
intramedullary lesion from an extramedullary lesion).
b. A lesion involving the left portion of the spinal cord causes ipsilateral
weakness and contralateral lack of pain and temperature sensation below
the lesion.
3. Laboratory findings
a. CT scan and MRI are required for delineation of the lesion.
b. CSF may reveal the presence of malignant cells.
4. Treatment requires a neurosurgical consultation regarding surgical resectability
versus chemotherapy/radiotherapy.

VIII Neurocutaneous Syndromes

A. TUBEROUS SCLEROSIS
1. General characteristics
a. This disease may be sporadic or autosomal dominant with variable pene-
trance.
b. Tuberous sclerosis is a multiple intracerebral hamartoma.
2. Clinical features
a. Patients are initially seen in early childhood to have seizures and psychomo-
tor retardation.
b. Reddened nodules on the face appear between ages 5 and 10.
c. CT scan/MRI reveals the intracranial lesions.
3. Treatment
a. No specific treatment is available.
b. Anticonvulsant drugs may control the seizures.

B. NEUROFIBROMATOSIS
1. General characteristics
a. The disease may be sporadic or autosomal dominant with variable pene-
trance.
b. Two types exist:
i. Type I (Recklinghausen disease) is characterized by multiple hyperpig-
mented macules and neurofibromas.
ii. Type II is characterized by intraspinal, intracranial tumors and a high inci-
dence of multiple, bilateral, acoustic neuromas.
2. Clinical features
a. Café au lait spots (patches of cutaneous pigmentation) appear.
b. CT scan/MRI is used for diagnosis and to follow up on the growth of
lesions.
3. Treatment involves surgical resection of symptomatic tumors.
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NEUROLOGIC DISEASES 193

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

IX Peripheral Neural Disorders

A. POLYNEUROPATHIES
1. General characteristics
a. Subacute polyneuropathy may occur secondary to a primary process, such as
diabetes mellitus, chronic renal failure, deficiency in vitamin B12, or alcoholism.
b. Polyneuropathy may occur as a primary process (e.g., Guillain-Barré syndrome).
2. Clinical features
a. Patients have unpleasant paresthesias (prickling or burning sensations) in
the tips of the toes or on the soles of feet.
b. Paresthesias may then spread to fingertips.
c. Muscle weakness is usually not prominent if the onset of the disease is slow.
d. Ankle and knee jerks are decreased.
e. Patients lose vibration sensation before losing light-touch sensation.
f. Positive Romberg sign and ataxia may be present.
g. 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.
3. Laboratory findings
a. Evaluation is primarily based on patient history and physical examination
to narrow the diagnostic possibilities.
b. Elevated blood sugar level suggests a diabetic etiology.
c. Elevated blood alcohol level and decreased serum vitamin B12 level often
coexist in alcoholics.
d. Elevated serum creatinine and blood urea nitrogen levels exist in individuals
who have chronic renal failure.
e. CSF analysis reveals an elevated protein level and often a normal or increased
lymphocyte count in Guillain-Barré syndrome.
4. Treatment
a. Treatment is based on etiology.
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194 CHAPTER 10

b. Progression of diabetic neuropathy can be decreased with strict diabetic con-

trol; pain often spontaneously resolves after a period of 1 year.
c. Vitamin B12 deficiency is treated with replacement of the vitamin through
regular injections or oral supplements.
d. 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. 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).
b. 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 sec-
ond and third fingers distal to the middle interphalangeal joint (Figure 10-3).
ii. Pain may radiate into the forearm and is exacerbated by manual activi-
ty, 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.
c. 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.
2. Radial nerve injury
a. 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.
b. The injured nerve causes weakness or paralysis of the arm extension at the
elbow, wrist extension, metacarpophalangeal joint extension, and thumb extension.
c. A secondary sensory deficit may occur at the dorsolateral aspect of the hand
(see Figure 10-3).
3. Ulnar nerve injury
a. Trauma or pressure typically occurs behind the medial epicondyle (may be
seen in persons undergoing surgery who have been improperly positioned).
b. Sensory changes occur in the medial 1.5 fingers and along the medial border
of the hand (see Figure 10-3).
c. Wrist inversion (flexor carpi ulnaris function), palmar abduction, and
thumb adduction may be weak.
4. 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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NEUROLOGIC DISEASES 195

● 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. Weakness of dorsiflexion and eversion of the foot are present.

c. Sensory deficit occurs along the anterolateral aspect of the calf and dorsum of
the foot.
5. Bell facial palsy
a. 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.
b. 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.
c. 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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196 CHAPTER 10

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. ALS is a degeneration of anterior horn cells (lower motoneurons) and pyram-
idal neurons (upper motoneurons).
b. Most cases occur sporadically.
c. The cause of ALS remains unknown.
2. Clinical features
a. Patients experience asymmetric weakness and atrophy.
b. Footdrop and/or clawhand deformity are common.
c. Fasciculations and/or spasticity may be seen.
d. Hyperreflexia in an atrophic fasciculating extremity strongly suggests the
diagnosis.
e. Spread to virtually all muscle groups may occur over weeks to months.
f. Facial and eye movements tend to be spared.
g. Most patients succumb to respiratory insufficiency or infection within 2–3
years.
3. Laboratory findings
a. EMG is most diagnostic because it reveals abnormal spontaneous activity in
resting muscles.
b. Sensory conduction studies are normal.
c. CSF is normal.
d. Serum creatine kinase level may be slightly elevated but not to the degree
seen in muscular dystrophies.
4. Treatment
a. Treatment is symptomatic.
b. Stretching exercises prevent contractures.
c. Adaptive equipment and bracing are required.
d. Swallowing dysfunction may lead to aspiration or choking; the patient must
be closely watched.
e. Diazepam may relieve a degree of spasticity.
f. Riluzole appears to increase survival.

B. MYASTHENIA GRAVIS
1. General characteristics
a. Myasthenia gravis may occur at any age.
b. This disease can be associated with thymic tumors or thyrotoxicosis.
c. Disease occurs most commonly in young women with human leukocyte
antigen-DR3.
d. Onset is usually insidious, but may be unmasked by a coincidental infection
that exacerbates symptoms.
e. The disease has an autoimmune etiology.
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NEUROLOGIC DISEASES 197

2. Clinical features
a. Signs and symptoms include ptosis, diplopia, difficulty chewing or swallow-
ing, respiratory difficulties, and limb weakness.
b. Weakness may be localized to only a few muscle groups, especially the
extraocular muscles, or may be generalized.
c. Weakness improves after rest.
d. Sensation and reflexes are normal.
3. Laboratory findings
a. Diagnosis is confirmed by marked improvement in muscle strength that
lasts approximately 5–10 minutes after a therapeutic challenge with edropho-
nium (an anticholinesterase inhibitor).
b. Posteroanterior and lateral films of the chest (or CT scan) should be
obtained to rule out a possible thymoma.
c. Serum acetylcholine receptor antibody titer is elevated.
d. Decremental muscle response to repetitive stimulation of motor nerves occurs.
4. Treatment
a. Patients should avoid aminoglycosides, which exacerbate signs and symptoms.
b. Anticholinesterase drugs (neostigmine and/or pyridostigmine) provide
symptomatic relief.
c. Corticosteroids may benefit patients who are refractory to anticholinesterase
drugs.
d. Patients who have severe signs and symptoms may benefit from plasmapheresis.
e. Thymectomy usually leads to symptomatic relief or remission and should be
considered in patients under age 60.

C. BOTULISM
1. General characteristics
a. Botulism is caused by ingesting Clostridium botulinum toxin or infection
with the bacterium.
b. The toxin prevents the release of acetylcholine at the neuromuscular junction.
c. Botulism often results from ingestion of contaminated home-canned food.
2. 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 contami-
nated 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. EMG shows normal nerve conduction velocities.
b. Repetitive stimulation of a motor nerve may show a posttetanic increase in
amplitude of the evoked muscle response.
4. Treatment
a. Patients must be hospitalized if ventilatory support is required.
b. Polyvalent antitoxin should be administered.
c. Antibiotic therapy is not used because it may produce large quantities of
toxin release as a result of bacterial death.
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198 CHAPTER 10

D. DUCHENNE-TYPE MUSCULAR DYSTROPHY

1. General characteristics
a. Duchenne muscular dystrophy is an inherited disease.
b. Because it is an X-linked recessive disorder, the disease typically affects boys.
2. Clinical features
a. Affected toddlers have a waddling, clumsy gait.
b. The abdomen protrudes due to increased lumbar lordosis.
c. Pseudohypertrophy of the calves is present.
d. 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. Creatine kinase level (20–100 times normal) is elevated before the disease is
clinically evident.
b. Muscle biopsy is diagnostic.
4. Treatment
a. No cure exists.
b. Early rehabilitation prevents the progression of contractures, and strength
maintenance exercises can improve the quality of life.
c. Parents should receive genetic counseling.

XI 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 diag-
nosis, 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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NEUROLOGIC DISEASES 199

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. Progression of the disorder cannot be prevented.
2. Corticosteroids may hasten recovery from relapses.
3. 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 lung, 34, 149, 150

pancreatic, 73
Abdominal pain ADH. See Antidiuretic hormone (ADH)
in aortic aneurysm, 15 Adrenal cortex diseases, 111–115
in appendicitis, 65 Adrenal crisis, 113, 114
in cholangitis, 74 Adrenal gland dysfunction
in cholecystitis, 73 Addison disease, 113–114
in pancreatic carcinoma, 73 congenital adrenal hyperplasia, 115
in pancreatitis, 72 Cushing syndrome, 111–113, 112t
in pelvic inflammatory disease (PID), 89 pheochromocytoma, 115–116
in peptic ulcer disease, 57 primary aldosteronism, 114–115
Abdominal radiography. See Radiography Adrenal hyperplasia, congenital, 115
ABG. See Arterial blood gas Adrenal medulla diseases, 115–116
Abscess Adrenalectomy, 113
hepatic, 79 Adrenergic agonists
intracranial, 83–84, 85 for asthma, 20t
supratentorial brain, 181 for COPD, 21
Acalculia, 179 Adrenocortical insufficiency, 113–114
ACE inhibitors. See Angiotensin-converting enzyme (ACE) Adrenocorticotropic hormone (ACTH)
inhibitors deficiency, 98
Acetaminophen excess and Cushing syndrome, 112, 113
for headache, 185 increase in congenital adrenal hyperplasia, 115
for osteoarthritis, 124 secretion by pituitary tumors, 97
Acetone breath, in ketoacidosis, 110 testing for Addison disease, 113–114
Acetylcholine receptor antibody titer, 197 Adult respiratory distress syndrome (ARDS), 27–28
Acetylsalicylic acid (ASA) AFP (
-fetoprotein), 80, 143
gastritis from, 54 AIDS. See Acquired immunodeficiency syndrome (AIDS)
for gout, 127 Alanine aminotransferase (ALT)
for ischemic heart disease, 4 in alcoholic liver disease, 78
for ulcerative colitis, 68 in viral hepatitis, 76
Achalasia, 55–56, 56 Albuterol, for asthma, 20
Acid-base disorders, 49, 50, 51, 51–52 Alcohol abuse
Acid phosphatase, in prostatic carcinoma, 143 dementia from, 180
Acidosis pancreatitis associated with, 72
anion-gap acidosis in chronic renal disease, 40 Alcoholic liver disease, 78–79
ketoacidosis, 110 Aldosterone deficiency, 113
metabolic, 49, 50, 110, 111 Aldosteronism, primary, 114–115
respiratory, 49 Alkaline phosphatase
Acquired immunodeficiency syndrome (AIDS) in alcoholic liver disease, 78
clinical features, 95–96, 95t in biliary obstruction, 74
general characteristics, 95 in choledocholithiasis, 74
laboratory findings, 96 in chronic myelogenous leukemia (CML), 156, 168
lymphopenia in, 167 in colorectal cancer, 147
treatment, 96 in hepatoma, 80
Acromegaly, 99 in lung carcinoma, 150
ACTH. See Adrenocorticotropic hormone (ACTH) in pancreatic carcinoma, 146
Acute lymphocytic leukemia (ALL), 153–155 Alkalosis
Acute myelogenous leukemia (AML), 153–155 metabolic, 49, 51, 114
Acute promyelocytic leukemia, 155 respiratory, 49
Acute renal failure (ARF), 38–39, 39t ALL (acute lymphocytic leukemia), 153–155
Acyclovir Allergic purpura, 137
for genital herpes, 90 Allergic rhinitis, in Churg-Strauss syndrome, 137
for herpes simplex virus (HSV), 70, 96 Allopurinol
for HSV encephalitis, 83 for gout, 127–128
Addison disease, 113–114 for nephropathy, 151
Adenocarcinoma for renal calculi, 43
biliary, 75 toxicity, 128
colonic, 70
-blockers, for hypertension, 17

200
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INDEX 201

-fetoprotein (AFP), 80, 143 Aneurysms

-thalassemia, 161 aortic, 15–16
ALS (amyotrophic lateral sclerosis), 196 intracranial, 178
ALT. See Alanine aminotransferase (ALT) in polyarteritis nodosa, 138
Alzheimer disease, dementia in, 180–181 Angiitis, hypersensitivity, 136–137
Amantadine, for Parkinson disease, 186 Angina, 3–4
Amebicides, for hepatic abscess, 79 in aortic stenosis, 6
Amenorrhea in hypertrophic obstructive cardiomyopathy, 10
diagnostic evaluation of patients, 119 Angiography
hypothalamic (functional), 118 in aortic aneurysms, 16
in pituitary hyperfunction, 99 cerebral, 178
primary in choledocholithiasis, 74
general characteristics, 116 in Churg-Strauss syndrome, 138
hypogonadotropic hypogonadism, 117 in gastrointestinal bleeding, 81
physical abnormalities, 118 in polyarteritis nodosa, 138
testicular feminization syndrome, 117 in pulmonary embolus, 14
Turner syndrome, 116–117 in subarachnoid hemorrhage, 178
secondary, 118 Angiomatosis, leptomeningeal, in Sturge-Weber
Aminoglutethimide, for Cushing syndrome, 113 syndrome, 193
Aminoglycosides Angioplasty
for cystic fibrosis, 24 for hypertension, 18
for pneumonia, 87 for renovascular disease, 44
Amiodarone, for atrial fibrillation, 5 Angiotensin-converting enzyme (ACE) inhibitors
Amitriptyline, for headache, 185 for heart failure, 2
AML (acute myelogenous leukemia), 153–155 for hypertension, 17, 18
Amoxicillin for ischemic heart disease, 4
for otitis, 84 Anion-gap acidosis, in chronic renal disease, 40
for peptic ulcer disease, 59 Ankylosing spondylitis, 129, 130
for sinusitis, 84 Anorexia, in appendicitis, 65
Ampicillin Anorexia nervosa, amenorrhea and, 117, 118
for bacterial overgrowth syndrome, 63 Antacids
for hepatic abscess, 79 for gastritis, 54
for meningitis, 82 for peptic ulcer disease, 58
petechial rash from, 92 for reflux esophagitis, 53
pseudomembranous colitis from, 70 Anthracycline, for acute leukemia, 154
for urinary tract infection, 91 Anti-dsDNA, in systemic lupus erythematosus, 133
Ampicillin/sulbactam, for appendicitis, 66 Anti-nucleoprotein antibodies, in Sjögren syndrome, 136
Amylase level Anti-RNA polymerases, 134
in pancreatitis, 72 Anti-scleroderma antibody (SCL-70), 134
in pleural effusion, 29 Anti-Sm, in systemic lupus erythematosus, 133
Amyotrophic lateral sclerosis (ALS), 196 Anti-tumor necrosis factor (TNF) agents
Anaphylactoid purpura, 137 for ankylosing spondylitis, 129
Anaplastic carcinoma, thyroid, 105 for enteropathic arthropathies, 132
ANAs. See Antinuclear antibodies (ANAs) for psoriatic arthritis, 132
Androgen excess for rheumatoid arthritis, 125
in congenital adrenal hyperplasia, 115 Antibiotic therapy
syndromes, 118–119 for acute leukemia, 154
Androstenedione, excess production of, 118 for adult respiratory distress syndrome (ARDS), 28
Anemia for appendicitis, 66
from acute hemorrhage, 163 for bronchiectasis, 23
aplastic, 162 for cholangitis, 75
of chronic disease, 158 for choledocholithiasis, 74
in chronic lymphocytic leukemia, 155 for chronic myelogenous leukemia (CML), 169
in chronic myelogenous leukemia, 156 for cystic fibrosis, 24
in chronic renal disease, 39 for diverticular disease, 66
clinical features, 157 for endocarditis, 7
in colorectal polyps, 149 for hepatic abscess, 79
in Crohn disease, 64 for intracellular abscess, 84
diagnostic approach to, 157–158, 159 for joint infections, 92
in gastric cancer, 145 for Lyme disease, 95
general characteristics, 157, 158t for lymphopenia, 168
hemolytic, 163–165 for mediastinitis, 31
hypochromic-microcytic, 157–161 for meningitis, 82
iron deficiency, 70, 157–158 for osteomyelitis, 92
in lung carcinoma, 150 for otitis, 84
macrocytic, 163–166 for pancreatitis, 72
in malabsorption, 63 for pelvic inflammatory disease (PID), 89
megaloblastic, 165–166 for peptic ulcer disease, 58–59
in multiple myeloma, 151 for pharyngitis, 86
myelophthisic syndromes, 162 for pneumonia, 87
normochromic-normocytic, 162–163 pseudomembranous colitis from, 70
in peptic ulcer disease, 57 for renal calculi, 43
pernicious, 54 for sinusitis, 84
red blood cell aplasia, 163 for toxic shock syndrome (TSS), 94
sickle-cell disease, 160–161 for urethritis, 89
sideroblastic, 158, 160 for urinary tract infection, 91
thalassemias, 161 Anticentromere antibodies, in systemic sclerosis, 134
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202 INDEX

Anticholinergic drugs Aspartate aminotransferase (AST)

for esophageal dysmotility, 56 in alcoholic liver disease, 78
for Parkinson disease, 186 in viral hepatitis, 76
Anticholinesterase drugs, for myasthenia gravis, 197 Aspiration pneumonia, 86–87, 88
Anticoagulant therapy Aspirin
for aortic regurgitation, 7 for headache, 184, 185
for atrial fibrillation, 5 for osteoarthritis, 124
for deep venous thrombosis, 13–14 for stroke, 177
for DIC, 173 for thromboembolism prevention, 5
for ischemic heart disease, 4 AST. See Aspartate aminotransferase (AST)
for mitral regurgitation, 8 Astereognosis, 179
for mitral stenosis, 7 Asthma, 19–20, 20t
for pulmonary embolus, 15 Atherosclerotic disease
for stroke, 177 aortic aneurysms from, 15
Anticonvulsants, 183, 183t ischemic heart disease from, 3
Antidiuretic hormone (ADH) renovascular hypertension from, 17
in diabetes insipidus, 99–100, 100t Atrial fibrillation, 5
in SIADH, 100–101 Atropine, for ischemic heart disease, 4
Antiglomerular basement membrane antibodies, 36, 139 Auer bodies, in acute myelogenous leukemia, 153
Antinuclear antibodies (ANAs) Aura, seizure, 182
in polymyositis, 135 AVM (arteriovenous malformation), 178
in Sjögren syndrome, 136 Azathioprine
in systemic lupus erythematosus, 133 for Churg-Strauss syndrome, 138
in systemic sclerosis, 134 for polymyositis, 135
Antiphospholipid antibodies, in systemic lupus erythematosus, 133 for pulmonary fibrosis, 25
Antiretroviral therapy, in AIDS, 96 for systemic lupus erythematosus, 133
Antithyroid antibodies (thyroid peroxidase antibodies), 104 for thrombocytopenia, 170
Anuria, in acute renal failure, 38 Azithromycin
Aortic aneurysms, 15–16 for chancroid, 90
Aortic regurgitation, 6–7 for urethritis, 89
Aortic stenosis, 5–6 Azotemia, in Goodpasture syndrome, 36
AP. See Alkaline phosphatase
Aphasia, 179, 180
Aplastic anemia, 162
B
Apomorphine, for Parkinson disease, 186 B-cell deficiency, 167
Appendicitis, 65–66 Back pain
ARDS (adult respiratory distress syndrome), 27–28 in aortic aneurysm, 15
ARF (acute renal failure), 38–39, 39t in pancreatic carcinoma, 73
Arrhythmias in renal calculi, 42
atrial fibrillation, 5 Bacterial food poisoning syndromes, 62t
in ischemic heart disease, 3–4 Bacterial overgrowth syndrome, 63
in polymyositis, 135 Barium enema
in sarcoidosis, 26 in colonic neoplastic disease, 69, 69, 70
Arterial blood gas in colorectal cancer, 147
in adult respiratory distress syndrome (ARDS), 27 in colorectal polyps, 149
in asthma, 20 diverticular disease, 66, 67
in dementia, 181 for ulcerative colitis, 67, 68
in pulmonary embolus, 14 Barium swallow
Arteriography in esophageal neoplasms, 54
in giant cell arteritis, 140 in reflux esophagitis, 53
in renovascular disease, 44 Barrett esophagus, 54, 55
Arteriovenous malformation (AVM), 178 Bart Hgb, 161
Arteritis, giant cell arteritis, 139–140, 184, 185 Basophilia, in chronic myelogenous leukemia, 156
Arthritis Bell facial palsy, 195–196
acute gouty, 126 Bence-Jones (M-chain) proteins, in multiple myeloma, 151
in AIDS, 96 Benign essential tremor, 185
gonococcal, 92 Benztropine, for Parkinson disease, 186
in Henoch-Schönlein purpura, 137 Beta-adrenergic agonists
in Lyme disease, 94 for asthma, 20t
osteoarthritis, 123–124 for COPD, 21
peripheral, 63, 132 -blockers
in polyarteritis nodosa, 138 for atrial fibrillation, 5
rheumatoid, 124–126, 126 for heart failure, 3
in sarcoidosis, 26 for hypertension, 17
spondyloarthropathies, 129–132 for hyperthyroidism, 102
ankylosing spondylitis, 129, 130 for hypertrophic obstructive cardiomyopathy, 10
enteropathic arthropathies, 132 for ischemic heart disease, 4
general characteristics, 129 for pheochromocytoma, 18
psoriatic arthritis, 131–132 for thyroiditis, 103, 104
reactive arthritis, 130–131 -thalassemia major, 161
Artificial tears, for xerophthalmia, 136 Bezoars, gastric, 57
ASA. See Acetylsalicylic acid (ASA) Bile duct adenocarcinoma, 75
Asbestos exposure, 25 Biliary tract disease
Ascites acute cholecystitis, 73–74
in alcoholic liver disease, 78 ascending cholangitis, 74–75
in hepatoma, 80 choledocholithiasis, 74
in pancreatic carcinoma, 146 tumors, 75
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INDEX 203

Bilirubin Bowel obstruction, 59–62

in biliary tumors, 75 in cystic fibrosis, 23
in cholangitis, 74 Bradykinesia, in Parkinson disease, 186
in choledocholithiasis, 74 Brain lesions
in pancreatic carcinoma, 146 aphasia from, 181
in viral hepatitis, 76 frontal lobe, 180
Biopsy occipital lobe, 180
in alcoholic liver disease, 78 parietal lobe, 180
in bladder carcinoma, 142 temporal lobe, 180
in chronic lymphocytic leukemia, 155 Breath sounds
in Churg-Strauss syndrome, 138 in pleural effusion, 28
in colonic neoplastic disease, 70 in pneumothorax, 30
in giant cell arteritis, 140 Broca aphasia, 180
in head and neck carcinoma, 141 Bromocriptine
in Henoch-Schönlein purpura, 137 for Parkinson disease, 186
in mediastinal masses, 32 for pituitary hyperfunction, 99
in non-Hodgkin lymphoma, 153 for pituitary tumors, 98
in pancreatic carcinoma, 73 Bronchial washings, in pneumonia, 87
in peptic ulcer disease, 58 Bronchiectasis, 22–23, 23
in pneumothorax, 31 Bronchitis, 21
in polyarteritis nodosa, 138 Bronchodilators, for cystic fibrosis, 24
in prostatic carcinoma, 143 Bronchogram, 23
in pseudomonas colitis, 71 Bronchoscopy
in reflux esophagitis, 53 in bronchiectasis, 22
in renal carcinoma, 142 in lung neoplasia, 35, 150
in sarcoidosis, 26 Brucella cereus food poisoning, 62t
in Sjögren syndrome, 136
in Wegener granulomatosis, 37, 139
Bisphosphonates C
for ankylosing spondylitis, 129
for hypercalcemia, 107 Cabergoline, for pituitary hyperfunction, 99
Bladder carcinoma, 142 Café au lait spots, in neurofibromatosis, 192
Bleeding. See also Hemorrhage Caffeine, for headache, 184
gastrointestinal, 80–81 CAH (congenital adrenal hyperplasia), 115
rectal, 148 Calcinosis, subcutaneous, in systemic sclerosis, 134
in reflux esophagitis, 53 Calcitonin, for hypercalcemia, 107
variceal, 78, 79 Calcium
Bleeding disorders, 170–174, 173t for chronic renal disease, 40
Bleeding time, 172, 173t metabolism disorders
Bleomycin hypercalcemia, 106–107
for Hodgkin lymphoma, 152 hypocalcemia, 107–108
for testicular cancer, 144 laboratory findings, 108t
Blindness in multiple myeloma, 151
in giant cell arteritis, 140 renal calculi, 42
monocular, in stroke, 175 supplementation for osteoporosis, 121
Blood components, normal concentrations of, 160t Calcium channel blockers
Blood gases. See Arterial blood gas for esophageal dysmotility, 56
Blood measurements, normal, 158t for headache, 185
Blood pressure. See Hypertension for hypertrophic obstructive cardiomyopathy, 10
Blood urea nitrogen, in multiple myeloma, 151 for Raynaud phenomenon, 135
Blue bloaters, 21 Calcium pyrophosphate dihydrate deposition disease (CPPD), 128
Bone marrow aspiration/biopsy Calculi, renal, 42–43
in acute leukemia, 154 Calymmatobacterium granulomatis, 90
in aplastic anemia, 162 Campylobacter, diarrhea from, 60t
in chronic myelogenous leukemia (CML), 156, Cancer, 141–156. See also specific cancers
168 biliary, 75
in dysfunctional neutrophil disorders, 169 colorectal, 68–70, 69, 146–149
in lymphopenia, 167 esophagus, 54–55
in myelophthisic syndromes, 162 gastric, 55, 144–145
in neutropenia, 169 head and neck carcinoma, 141
in thrombocytopenia, 170, 171 hepatic, 79–80
Bone marrow transplantation leukemia, 153–156
for aplastic anemia, 162 lung, 33–36, 34, 36, 149–150
for non-Hodgkin lymphoma, 153 lymphoma, 151–153
Bone metabolism disorders multiple myeloma, 150–151
osteomalacia, 121–122 ovarian cancer, 144
osteoporosis, 120–121 pancreatic, 72–73, 145–146
Bone pain pleural, 31
in leukemia, 154 prostatic carcinoma, 142–143
in multiple myeloma, 151 renal and bladder carcinoma, 142
Bone scan testicular cancer, 143–144
in osteomyelitis, 91 thyroid, 104–105
in spinal extramedullary lesions, 191 TNM staging, 141
Borrelia burgdorferi, 94 Candidiasis, in AIDS, 96
Botulism, 197 Captopril
Bouchard nodes, in osteoarthritis, 123 for renal hypertension, 135
Boutonniere deformities, in rheumatoid arthritis, 124 renography in renovascular disease, 44
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204 INDEX

Carbamazepine Chemotherapy
for headache, 185 for absolute erythrocytosis, 167
for seizure, 183t for acute leukemia, 154
Carbidopa, for Parkinson disease, 186 for colorectal cancer, 148
Carcinoembryonic antigen (CEA) for gastric neoplasms, 55, 145
in colonic neoplastic disease, 70 for head and neck carcinoma, 141
in gastric cancer, 145 for Hodgkin lymphoma, 152
in gastric neoplasms, 55 for lung carcinoma, 150
in pancreatic carcinoma, 73 for multiple myeloma, 151
Cardiac catheterization for non-Hodgkin lymphoma, 153
in congestive cardiomyopathy, 9 platinum-based, 144
in constrictive pericarditis, 13 for testicular cancer, 144
in heart failure, 1 Chest pain
in hypertrophic obstructive cardiomyopathy, 10 in pericarditis, 11
in mitral stenosis, 7 in pleural effusion, 28
in restrictive cardiomyopathy, 10 in pleural neoplasia, 31
Cardiac tamponade, 11 in pneumothorax, 30
Cardiomyopathy Chest physiotherapy, for cystic fibrosis, 24
congestive (dilated), 9 Chest radiography. See Radiography
hypertrophic obstructive, 10 Chest wall disorders, 32–33, 33
restrictive, 10–11 Chlamydia, 88, 89, 91
Cardiovascular disease, 1–18 Chloroma, 154
aortic aneurysms, 15–16 Chloroquine, for systemic lupus erythematosus, 133
atrial fibrillation, 5 Chlorpropamide
cardiomyopathy, 9–11 for diabetes insipidus, 100
congestive heart failure, 1–3 for diabetes mellitus, 109
deep venous thrombosis, 13–14 Cholangiocarcinoma, 75
hypertension, 16–18 Cholangiography, in choledocholithiasis, 74
ischemic heart disease, 3–4 Cholangitis, ascending, 74–75
pericardial disease, 11–13 Cholecystitis, acute, 73–74
pulmonary embolus, 14–15 Choledocholithiasis, 74
valvular heart disease, 5–9 Cholelithiasis, in glucose-6-phosphate dehydrogenase (G6PD)
Cardioversion, for atrial fibrillation, 5 deficiency, 165
Carotid bruit, in stroke, 176 Cholesterol level
Carpal tunnel syndrome, 194 in dementia, 181
in rheumatoid arthritis, 124 in stroke, 177
Cauda equina syndrome, 191 Chorea, in Huntington disease, 186
with osteoarthritis, 123 Chronic disease, anemia of, 158
CEA. See Carcinoembryonic antigen (CEA) Chronic granulomatous disease (CGD), neutrophil dysfunction in, 169
Cefotaxime, for meningitis, 82 Chronic lymphocytic leukemia (CLL), 155
Cefoxitin, for pelvic inflammatory disease (PID), 89 Chronic myelogenous leukemia (CML), 155–156, 168
Ceftriaxone Chronic obstructive pulmonary disease (COPD), 20, 21–22
for chancroid, 90 Chronic renal insufficiency, 39–40
for gonorrhea, 70 Churg-Strauss syndrome, 137–138
for meningitis, 82 Chvostek sign, 107
for urethritis, 89 Cimetidine, for reflux esophagitis, 53
Celiac disease, 63 Ciprofloxacin, for chancroid, 90
Central nervous system infections, 82–84 Cirrhosis, alcoholic, 78–79
in AIDS, 95 Cisplatin
encephalitis, 82–83 for head and neck carcinoma, 141
intracranial abscess, 83–84, 85 for lung neoplasia, 35
meningitis, 82, 83t for mediastinal masses, 32
Cephalosporin for testicular cancer, 144
for cystic fibrosis, 24 Clarithromycin, for peptic ulcer disease, 59
for intracellular abscess, 84 Claudication
for pneumonia, 87 in giant cell arteritis, 140
pseudomembranous colitis from, 70 intermittent, in renovascular disease, 43
Cerebellar hematoma, 178 Clindamycin
Cerebral angiography, 178 for pelvic inflammatory disease (PID), 89
Cerebral artery vasospasm, 178 pseudomembranous colitis from, 70
Cerebrospinal fluid (CSF) analysis CLL (chronic lymphocytic leukemia), 155
in acute leukemia, 154 Clomiphene, for androgen excess syndrome, 119
in amyotrophic lateral sclerosis, 196 Clonazepam, for Tourette syndrome, 187
in encephalitis, 83, 83t Clonidine
in Guillain-Barré syndrome, 193 for hypertension, 17
in headache, 184 for Tourette syndrome, 187
in meningitis, 82 Clopidogrel, for ischemic heart disease, 4
in multiple sclerosis, 199 Clostridium botulinum, 197
in spinal intramedullary lesions, 192 food poisoning, 62t
Cerebrovascular disease Clostridium difficile, 70–71
stroke, 175–178 food poisoning, 62t
subarachnoid hemorrhage, 178 Clostridium perfringens, food poisoning from, 62t
Ceruloplasmin level, in Wilson disease, 188 Clubbing
Cervical spinal syndromes, 189 in bronchiectasis, 22
Chancroid, 89–90 in lung neoplasia, 34
Charcot triad, in cholangitis, 74 Cluster headaches, 184, 185
Chemoembolization, for hepatoma, 80 CML (chronic myelogenous leukemia), 155–156, 168
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Coagulation Conn syndrome, 114

disorders, 170–174, 173t Constipation, 65
disseminated intravascular, 172–173 Coombs test, in hemolytic anemia, 133, 163
Coagulopathies COPD (chronic obstructive pulmonary disease),
acquired, 174 20, 21–22
hereditary, 173–174 Copper deposition, in Wilson disease, 187–188
Cognitive disorders, 180–181 Coprolalia, in Tourette syndrome, 187
Cogwheel rigidity, in Parkinson disease, 186 Cor pulmonale
Colchicine, for gout, 127 in bronchiectasis, 22
Cold-air challenge test, in asthma, 19 in COPD, 21
Colectomy, for ulcerative colitis, 68 in cystic fibrosis, 23
Colitis Corticosteroids
pseudomembranous, 70–71 for asthma, 20
ulcerative, 66–68, 68 for calcium pyrophosphate dihydrate deposition
Collagen vascular disease, 11 disease, 128
Colonic and rectal polyps, 148–149, 148t for Churg-Strauss syndrome, 138
Colonic neoplastic disease, 68–70, 69 for COPD, 21
Colonoscopy for Crohn disease, 64
in colorectal cancer, 147, 148 for giant cell arteritis, 140
in colorectal polyps, 149 for Goodpasture syndrome, 37, 139
in diverticular disease, 66 for gout, 127
in gastrointestinal bleeding, 81 for Henoch-Schönlein purpura, 137
in ulcerative colitis, 67 for hypersensitivity angiitis, 137
Colorectal cancer, 68–70, 69, 146–148 for hypersensitivity pneumonitis, 26
Colorectal polyps, 68–69, 148–149 for multiple myeloma, 151
Coma for multiple sclerosis, 199
hyperosmolar nonketotic, 110–111 for myasthenia gravis, 197
hypoglycemic, 111 for polyarteritis nodosa, 138
myxedema, 103 for polymyositis, 135
Community-acquired pneumonia, 86–87 for psoriatic arthritis, 131
Complement deficiency, in systemic lupus erythematosus, 133 for pulmonary fibrosis, 25
Computed tomography (CT) for reactive arthritis, 131
in acute leukemia, 154 for rheumatoid arthritis, 125
in alcoholic liver disease, 78 for sarcoidosis, 27
in aldosteronism, 114 for Sjögren syndrome, 136
in appendicitis, 65 for systemic lupus erythematosus, 133
in bronchiectasis, 22 for thrombocytopenia, 170
in Cushing syndrome, 112 for ulcerative colitis, 68
in dementia, 181 for Wegener granulomatosis, 37, 139
in encephalitis, 83 Cortisol
in esophageal neoplasms, 55 for congenital adrenal hyperplasia, 115
in head and neck carcinoma, 141 in Cushing syndrome, 112
in headache, 184 deficiency in congenital adrenal hyperplasia, 115
in hepatic abscess, 79 Cough
in hepatoma, 80 in achalasia, 55
in insulinoma, 111 in asthma, 19
in intracellular abscess, 84 in bronchiectasis, 22
in lung carcinoma, 150 in COPD, 21
in lung neoplasia, 35 in Goodpasture syndrome, 139
in mediastinal masses, 32 in hypersensitivity pneumonitis, 26
in neurofibromatosis, 192 in pneumoconiosis, 25
in osteomyelitis, 91 in pulmonary fibrosis, 25
in ovarian cancer, 144 CPPD (calcium pyrophosphate dihydrate deposition
in pancreatic carcinoma, 73, 146 disease), 128
in pancreatitis, 71, 72 Crackles
in Parkinson disease, 186 in bronchiectasis, 22
in pheochromocytoma, 18, 116 in heart failure, 1
in pituitary tumors, 97 in hypersensitivity pneumonitis, 26
in pleural effusions, 29 Creatine kinase
in primary hyperparathyroidism, 106 in amyotrophic lateral sclerosis, 196
in pulmonary embolus, 14 in Duchenne muscular dystrophy, 198
in renal calculi, 43 in ischemic heart disease, 4
in renal carcinoma, 142 Creatinine
in seizure, 182 in acute renal failure, 38
in spinal cord injury, 188 in chronic renal disease, 40
in spinal extramedullary lesions, 191 in multiple myeloma, 151
in spinal intramedullary lesions, 192 CREST syndrome, 134
in stroke, 177 Crohn disease, 63–64, 64
in subarachnoid hemorrhage, 178 Cromolyn sodium, for asthma, 20
in tuberous sclerosis, 192 Cryoprecipitate therapy
Conduction aphasia, 180 for hemophilia A, 173
Congenital adrenal hyperplasia (CAH), 115 for von Willebrand disease, 174
Congestive (dilated) cardiomyopathy, 9 Cryptococcal meningitis, 95
Congestive heart failure (CHF). See Heart failure Crystal-related joint disease, 92
Conjunctivitis CSF. See Cerebrospinal fluid (CSF) analysis
in psoriatic arthritis, 131 CT. See Computed tomography (CT)
in reactive arthritis, 130 Cullen sign, in pancreatitis, 71
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206 INDEX

Cushing syndrome, 111–113, 112t for mitral regurgitation, 8

Cutaneous innervation of the hand, 195 for restrictive cardiomyopathy, 11
Cyclophosphamide Digoxin
for Churg-Strauss syndrome, 138 for atrial fibrillation, 5
for Goodpasture syndrome, 139 for heart failure, 2
for polyarteritis nodosa, 138 Disseminated intravascular coagulation (DIC), 172–173
for polymyositis, 135 Diuresis, for hypercalcemia, 107
for pulmonary fibrosis, 25 Diuretic drugs
for Sjögren syndrome, 136 for aortic regurgitation, 7
for systemic lupus erythematosus, 133 for congestive cardiomyopathy, 9
for thrombocytopenia, 170 for heart failure, 2
for Wegener granulomatosis, 37, 139 for hemolytic anemia, 164
Cystic fibrosis (CF), 23–24, 24 for hypertension, 17
pancreatitis associated with, 72 for mitral regurgitation, 8
Cytarabine, for acute leukemia, 154 for mitral stenosis, 7
Cytoscopy, in bladder carcinoma, 142 for renal calculi, 43
for restrictive cardiomyopathy, 11
Diverticular disease, 66, 67
D DNA testing, in Huntington disease, 187
Donepezil, for Alzheimer disease, 181
Dacarbazine, for Hodgkin lymphoma, 152 Dopamine, for Parkinson disease, 186
DDAVP (desmopressin), for diabetes insipidus, 100 Dopamine-blocking agents, for Huntington disease, 187
Deep venous thrombosis (DVT), 13–14 Doppler studies
Degenerative joint disease, 123–124 in deep venous thrombosis, 13
Dehydration, 44 in stroke, 177
Demeclocycline, for syndrome of inappropriate antidiuretic Doxorubicin, for Hodgkin lymphoma, 152
hormone, 101 Doxycycline
Dementia for chlamydia, 70
in AIDS, 95 for pelvic inflammatory disease (PID), 89
clinical features, 180–181 for urethritis, 89
general characteristics, 180 Duchenne-type muscular dystrophy, 198
in Huntington disease, 186, 187 DVT (deep venous thrombosis), 13–14
laboratory findings, 181 Dyskinesia, in Huntington disease, 187
treatment, 181 Dysphagia
Depo-Testosterone, for hypogonadotropic hypogonadism, 120 in esophageal neoplasms, 54
Depression, dementia confused with, 181 in polymyositis, 135
Dermatomes of the leg, 190 Dyspnea
Dermatomyositis, 135 in asthma, 19
Desferrioxamine, for thalassemias, 161 in bronchiectasis, 22
Desmopressin, for diabetes insipidus, 100 in constrictive pericarditis, 13
Dexamethasone suppression test, 112, 112t in COPD, 21
Dextrose, for hypoglycemia, 183 in Goodpasture syndrome, 36
Diabetes insipidus, 99–100, 100t in hypersensitivity pneumonitis, 26
Diabetes mellitus in hypertension, 16
clinical features, 108–109 in hypertrophic obstructive cardiomyopathy, 10
diarrhea in, 59 in kyphoscoliosis, 32
general characteristics, 108 in mitral regurgitation, 8
hyperosmolar nonketotic coma, 110–111 in mitral stenosis, 7
ketoacidosis, 110 in pleural effusions, 28
laboratory findings, 109 in pneumoconiosis, 25
pancreatitis associated with, 72 in pneumothorax, 30, 31
treatment, 109, 109t in pulmonary embolus, 14
Diabetic neuropathy, 194 in pulmonary fibrosis, 24
Dialysis
for acute renal failure, 39
for chronic renal disease, 40 E
for Goodpasture syndrome, 37
for platelet dysfunction, 172 Ear infection, 84
Diaphragmatic paralysis, in lung cancer, 149 EBV. See Epstein-Barr virus (EBV)
Diarrhea ECG. See Electrocardiogram (ECG)
in AIDS, 96 Echocardiography
clinical features, 59 in acute pericarditis, 11
general characteristics, 59 in aortic regurgitation, 7
infectious, 60t in aortic stenosis, 6
laboratory findings, 59 in congestive cardiomyopathy, 9
osmotic, 59 in constrictive pericarditis, 13
secretory, 59 in heart failure, 1
workup for acute, 61 in hypertrophic obstructive cardiomyopathy, 10
Diazepam, for amyotrophic lateral sclerosis, 196 in mitral regurgitation, 8
Dicloxacillin, for osteomyelitis, 92 in mitral stenosis, 7
Diffuse esophageal spasm, 55–56 in pericardial effusion, 11
Diffuse interstitial lung disease, 24–27 in restrictive cardiomyopathy, 10
Digital subtraction renal arteriography, in renovascular in tricuspid regurgitation, 9
disease, 44 Echolalia, in Tourette syndrome, 187
Digitalis Ectopic pregnancy, 89
for aortic regurgitation, 7 Edrophonium challenge, for myasthenia gravis, 197
for congestive cardiomyopathy, 9 EEG. See Electroencephalogram (EEG)
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Electrocardiogram (ECG) Erythrocytosis

in acute pericarditis, 11 absolute, 167
in Addison disease, 114 stress, 166–167
in aortic regurgitation, 6 Erythromycin
in aortic stenosis, 6 for Lyme disease, 95
in atrial fibrillation, 5 for lymphogranuloma venereum, 90
in congestive cardiomyopathy, 9 for pharyngitis, 86
in constrictive pericarditis, 13 Erythropoietin therapy, for chronic renal disease, 40
in heart failure, 1 Escherichia coli
in hypertrophic obstructive cardiomyopathy, 10 diarrhea from, 60t
in ischemic heart disease, 4 food poisoning, 62t
in mitral regurgitation, 8 osteomyelitis, 91
in mitral stenosis, 7 Esophageal dysmotility, 55–56, 56
in pericardial effusion, 11, 12 Esophageal manometry
in pulmonary embolus, 14 in esophageal dysmotility, 56
in restrictive cardiomyopathy, 10 in reflux esophagitis, 53
in stroke, 177 Esophageal neoplasms, 54–55
in tricuspid regurgitation, 9 Esophageal perforation, 31
Electroencephalogram (EEG) Esophagram, in esophageal dysmotility, 55, 56
in encephalitis, 83 Estrogen
in headache, 184 deficiency in Turner syndrome, 116
in seizure, 182 for hypercalcemia, 107
Electrolyte disorders for hypogonadotropic hypogonadism, 117
acid-base disorders, 49, 50, 51, 51–52 for prostatic carcinoma, 143
hyperkalemia, 45 for testicular feminization syndrome, 117
hypernatremia, 45, 47 for Turner syndrome, 116
hypokalemia, 45, 48 Estrogen-progesterone withdrawal test, for amenorrhea diagnosis,
hyponatremia, 44–45, 46 119
osmolar gap, 45, 45t Estrogen-progestin combinations, for androgen excess syndrome,
Electromyography (EMG) 119
in amyotrophic lateral sclerosis, 196 Estrogen replacement therapy (ERT)
in botulism, 197 for osteoarthritis, 124
in carpal tunnel syndrome, 194 for osteoporosis, 121
in polymyositis, 135 Estrone, increase in androgen excess syndrome, 118, 119
Embolization, for gastrointestinal bleeding, 81 Etanercept, for rheumatoid arthritis, 125
EMG. See Electromyography (EMG) Ethambutol, for tuberculosis, 93
Emphysema, 21 Ethanol, gastritis from, 54
Emphysematous bullous disease, pneumothorax secondary Ethosuximide, for seizure, 183t
to, 21 Etoposide, for testicular cancer, 144
Encephalitis, 82–83 Exophthalmos, in Graves disease, 101
Encephalopathy, hepatic, 78 Expressive aphasia, 180
End-stage renal disease, 39–40 Exudative fluid, 28t
Endocrinologic and metabolic disorders
adrenal gland, 111–116
bone metabolism disorders, 120–122
female reproductive disorders, 116–119 F
glucose homeostasis, 108–111
male reproductive disorders, 119–120 Facial palsy, 195–196
parathyroid gland, 106–108 Familial polyposis syndromes, 68, 148, 148t
pituitary gland, 97–101 Fanconi anemia, 162
thyroid gland, 101–106 Farmer’s lung, 25
Endoscopic retrograde cholangiopancreatography (ERCP) Fasciculations, in amyotrophic lateral sclerosis, 196
in cholangitis, 75 Fat malabsorption, 63
in pancreatic carcinoma, 73, 146 Febrile seizures, 182
in pancreatitis, 72 Fecal fat analysis, in malabsorption, 63
Endoscopy Fecal occult blood, in Crohn disease, 63
in colonic neoplastic disease, 69, 70 Female reproductive disorders, 116–119
in Crohn disease, 64 amenorrhea, primary, 116–118
in esophageal neoplasms, 54 amenorrhea, secondary, 118
in gastric emptying disorders, 57 androgen excess syndrome, 118–119
in gastric neoplasms, 55 diagnostic evaluation, 119
in gastritis, 54 Fever
in gastrointestinal bleeding, 81 in alcoholic liver disease, 78
in peptic ulcer disease, 57–58 in chronic myelogenous leukemia, 156
in reflux esophagitis, 53 in CPPD, 128
Entamoeba histolytica, 79 in dysfunctional neutrophil disorders, 169
Enteropathic arthropathies, 132 in gastric emptying disorders, 57
Eosinophilia-associated infections, 93–94 in gout, 127
Ependymoma, 192 in hypersensitivity angiitis, 137
Epigastric pain. See Abdominal pain in hypersensitivity pneumonitis, 26
Episcleritis, in Wegener granulomatosis, 139 in leukemia, 154
Epstein-Barr virus (EBV) in polyarteritis nodosa, 138
infectious mononucleosis, 92–93 in pulmonary fibrosis, 24
pharyngitis, 86 in renal calculi, 42
Ergotamine, for headache, 184, 185 in Wegener granulomatosis, 139
ERT. See Estrogen replacement therapy (ERT) 5-ASA. See Acetylsalicylic acid (ASA)
Erythema chronicum migrans, in Lyme disease, 94 Fluconazole, for candidiasis, 96
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208 INDEX

Fludrocortisone nonproliferative, 41–42

for Addison disease, 114 proliferative, 41
for congenital adrenal hyperplasia, 115 proteinuria in, 40
Fluoroquinolone Glucocorticoids
for pneumonia, 87 for Addison disease, 114
for renal calculi, 43 for androgen excess syndrome, 119
for urethritis, 89 for hypercalcemia, 107
Fluorouracil, for head and neck carcinoma, 141 for rheumatoid arthritis, 125
Folate Glucosamine, for osteoarthritis, 124
for alcoholic liver disease, 78 Glucose
deficiency, 165–166, 171 for diabetic ketoacidosis, 110
Follicular carcinoma, thyroid, 105 homeostasis
Food poisoning, bacterial, 62t diabetes mellitus, 108–109
Footdrop, in amyotrophic lateral sclerosis, 196 diabetic ketoacidosis, 110
Fremitus, vocal, in pleural effusion, 28 hyperosmolar nonketotic coma, 110–111
Friction rub, pericardial, 11 hypoglycemic coma, 111
Frontal lobe lesions, 179 insulin types, 109t
FSH/LH levels for hypoglycemia, 111
in androgen excess syndrome, 118–119 Glucose-6-phosphate dehydrogenase (G6PD) deficiency, 165
in hypogonadotropic hypogonadism, 117 Glucose tolerance
in Turner syndrome, 116 in Cushing syndrome, 112
Furosemide impaired, 112
for heart failure, 2 in pituitary hyperfunction, 99
for hypercalcemia, 107 Glucose tolerance test, 109
Glyburide, for diabetes mellitus, 109
Glycoprotein IIb/IIIa inhibitors, for ischemic heart disease, 4
G Glycosylated hemoglobin levels, 109
Goiter
Galactorrhea, 99 diffuse toxic, 101
Gallbladder. See also Biliary tract disease nodular toxic, 101
adenocarcinoma, 75 Gold therapy
cholecystitis, 73–74 for psoriatic arthritis, 132
perforation, 73 for rheumatoid arthritis, 125
surgical removal, 74 side effects, 126
Gallstones, 73, 74 Gonadotropin releasing hormone (Gn-RH), for hypogonadotropic
in hereditary spherocytosis, 164 hypogonadism, 120
pancreatitis from, 71 Gonadotropin releasing hormone (Gn-RH) deficiency, in
-glutamyltransferase, in alcoholic liver disease, 78 hypogonadotropic hypogonadism, 117
Gastric bezoars, 57 Gonococcal infection, 88
Gastric carcinoma, 144–145 Goodpasture syndrome, 36–37, 139
Gastric emptying disorders, 56–57 Gout, 126–128
Gastric manometry, in gastric emptying disorders, 57 Granuloma inguinale, 89–90
Gastric neoplasms, 55 Graves disease, 101–102
Gastric volvulus, 57 Grey-Turner sign, in pancreatitis, 71
Gastritis Group A streptococci, 86
acute, 54 Growth hormone
chronic, 54 assessing secretion of, 98
Gastroesophageal reflux disease (GERD), 53 deficiency, 98
Gastrointestinal disorders secretion by pituitary tumors, 97
biliary tract disease, 73–75 Guaiac test, in diarrhea, 59
bleeding, 80–81 Guillain-Barré syndrome, 193, 194
colon, rectum, and anus, 65–71, 67–69 Gynecomastia, 120
esophagus and stomach, 53–59, 56, 58
infections, 88
liver diseases, 75–80, 76t, 77 H
pancreatic disorders, 71–73
small intestine, 59–64, 60t, 61, 62t H2-receptor blockers
Gastroparesis, 57 for gastritis, 54
Genital infections, 88–90 for peptic ulcer disease, 58
Genital ulcer and lymphadenopathy syndromes, 89–90 for reflux esophagitis, 53
Gentamicin Haemophilus ducreyi, 90
for hepatic abscess, 79 Haemophilus influenzae, 82, 83t, 84, 86
for otitis, 84 Haloperidol
for pelvic inflammatory disease (PID), 89 for Huntington disease, 187
for pneumonia, 87 for Tourette syndrome, 187
for urinary tract infection, 91 Hashimoto thyroiditis, 102, 104
GERD (gastroesophageal reflux disease), 53 Head
Giant cell arteritis, 139–140, 184, 185 carcinoma, 141
Giardia lamblia, diarrhea from, 60t infections, 84
Gigantism, 99 Headache
Glipizide, for diabetes mellitus, 109 clinical features, 183–184
Glomerulonephritis cluster, 184, 185
in Goodpasture syndrome, 36 general characteristics, 183
poststreptococcal, 41, 42t in giant cell arteritis, 184, 185
Glomerulonephropathy laboratory findings, 184
general characteristics, 41 migraine, 183–185
nephritic versus nephrotic syndromes, 42t in pituitary tumors, 97
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Headache (continued) Heparin-induced thrombocytopenia, 171

tension, 184, 185 Hepatitis
treatment, 184–185 alcoholic, 78–79
in trigeminal neuralgia, 184, 185 viral, 75–76, 76t, 77
Heart failure in Wilson disease, 188
clinical features, 1 Hepatoma, 80
general characteristics, 1 Hepatomegaly
laboratory findings, 1, 2 in alcoholic liver disease, 78
treatment, 2–3 in pancreatic carcinoma, 146
Heart murmur Hepatosplenomegaly
aortic regurgitation, 6 in acute leukemia, 154
in hypertrophic obstructive cardiomyopathy, 10 in chronic lymphocytic leukemia, 155
in ischemic heart disease, 3 in Hodgkin lymphoma, 152
in mitral regurgitation, 8 in multiple myeloma, 151
in stroke, 176 in non-Hodgkin lymphoma, 153
in tricuspid regurgitation, 8 in systemic lupus erythematosus, 133
Heartburn, 53 Herpes simplex virus (HSV)
Heberden nodes, in osteoarthritis, 123 encephalitis, 82
Helicobacter pylori genital, 89–90
gastric neoplasia and, 55, 145 Hgb H disease, 161
peptic ulcer disease and, 58 Histoplasmosis, 31
Heliotrope eyelids, 135 HIV, 95–96
Heller myotomy, 56 HLA-B27 testing, 129
Hematemesis Hodgkin lymphoma, 151–152, 152t
clinical features, 80 Horner syndrome
in gastritis, 54 in lung cancer, 149
Hematochezia from Pancoast tumor, 34
clinical features, 80 Hospital-acquired pneumonia, 87
in colorectal cancer, 70, 147 HSV. See Herpes simplex virus (HSV)
in infectious proctitis, 70 Human immunodeficiency virus (HIV), 95–96
Hematocrit disorders, 166–167 Huntington disease, 186–187
Hematologic diseases, 157–174 HUS (hemolytic uremic syndrome), 172
anemias, 157–166 Hyaluronan injection, for osteoarthritis, 124
hematocrit disorders, 166–167 Hydralazine
hemostasis and coagulation disorders, 170–174 for hypertension, 17
leukocyte disorders, 167–170 SLE induced by, 132
Hematoma Hydrocephalus, normal-pressure, 180
in aneurysm, 16 21-hydroxylase deficiency, 115
extradural, 191 Hydroxychloroquine
Hematuria, 40–41 for polymyositis, 135
in bladder cancer, 142 for psoriatic arthritis, 132
in prostatic carcinoma, 142 for systemic lupus erythematosus, 133
in renal calculi, 43 Hydroxyurea, for absolute erythrocytosis, 167
Hemianopia, 179 Hypercalcemia, 106–107, 108t
Hemochromatosis, 128–129 in multiple myeloma, 151
Hemodialysis, for Goodpasture syndrome, 139 Hypergammaglobulinemia, in non-Hodgkin lymphoma, 153
Hemoglobin electrophoresis, 160 Hyperglycemia
Hemoglobin H disease, 161 in diabetes mellitus, 109
Hemolytic anemias, 163–165 in hyperosmolar nonketotic coma, 110
extravascular hemolysis, 164 in ketoacidosis, 110
glucose-6-phosphate dehydrogenase (G6PD) deficiency, 165 Hypergonadotropic hypogonadism, 119
hereditary spherocytosis, 164–165 Hyperkalemia, 45
intracorpuscular abnormalities, 164–165 in Addison disease, 113
intravascular, 163–164 in chronic renal disease, 39
Hemolytic uremic syndrome (HUS), 172 Hyperosmolar nonketotic coma, 110
Hemophilia A, 173 Hyperparathyroidism
Hemoptysis primary, 106–107, 108t
in Goodpasture syndrome, 36, 139 secondary, 106, 108t
in mitral stenosis, 7 Hyperpigmentation, in Addison disease, 113
Hemorrhage. See also Bleeding Hyperprolactinemia, 99
in acquired coagulopathies, 174 Hyperreflexia, in ALS, 196
anemia from acute, 163 Hyperresonance, in pneumothorax, 30
in gastritis, 54 Hypersensitivity angiitis, 136–137
intra-alveolar in Goodpasture syndrome, 36 Hypersensitivity pneumonitis, 25–26
intracerebral, in stroke, 175, 176 Hypertension
in peptic ulcer disease, 57 in aldosteronism, 114
subarachnoid, 178 essential (primary), 16–17
Hemorrhagic stroke, 175–177 from pheochromocytoma, 18
Hemosiderosis, idiopathic pulmonary, 37 renovascular, 17–18
Hemostasis disorders, 170–174, 173t in renovascular disease, 43
Henoch-Schönlein purpura, 137 secondary, 17–18, 43
Heparin Hyperthyroidism, 101–102
for acute promyelocytic leukemia, 155 diarrhea in, 59
for deep venous thrombosis, 13 hypercalcemia in, 107
for DIC, 173 Hypertonic saline, for SIADH, 100–101
for ischemic heart disease, 4 Hypertrophic obstructive cardiomyopathy, 10
for pulmonary embolus, 14–15 Hyperuricemia, 126
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Hypoalbuminemia, hypocalcemia in, 107 Inner ear infection, 84

Hypocalcemia, 107–108, 108t Insulin, 109–110, 109t
Hypochromic-microcytic anemia, 157–161 Insulin-induced hypoglycemia test, 98
Hypochromic-microcytic anemias, 157–161 Insulinoma, 111
Hypocomplementemia, in systemic lupus erythematosus, 133 Interferon therapy
Hypoglycemia, in Addison disease, 113 for Kaposi sarcoma, 96
Hypoglycemic agents, for diabetes mellitus, 109 for multiple sclerosis, 199
Hypoglycemic coma, 111 Intermittent claudication, 43
Hypogonadism Interstitial lung disease, 24–27
gynecomastia with, 120 Intervertebral disks, prolapse of, 189–191
hypogonadotropic, 117 Intracranial abscess, 83–84, 85
in males, 119–120 Intracranial pressure, increased
Hypogonadotropic hypogonadism, 117, 119–120 in stroke, 177–178
Hypokalemia, 45, 48 in subarachnoid hemorrhage, 178
in aldosteronism, 114 Intravenous immunoglobulin, for polymyositis, 135
in renovascular disease, 44 Intravenous pyelography, in renal carcinoma, 142
Hypomagnesemia, 108 Intravenous urography, in urinary tract infections, 91
Hyponatremia, 44–45, 46 Intrinsic factor, 54
in Addison disease, 113 Iodine deficiency, 102
in SIADH, 100 Ion gap, in diarrhea, 59
Hypoparathyroidism, 107–108, 108t Ipratropium bromide, for COPD, 21
Hypopituitarism Iron deficiency anemia, 157–158
in Addison disease, 113 in Goodpasture syndrome, 37
in hypogonadotropic hypogonadism, 117 Irritable bowel syndrome, 59
Hypotension, orthostatic Ischemia
in acute renal failure, 38 heart disease, 3–4
in Addison disease, 113 in small bowel obstruction, 60
in pheochromocytoma, 18 in stroke, 175–177
Hypothyroidism, 102–103 Isoniazid, for tuberculosis (TB), 93
Hypovolemia, in acute renal failure, 38 ITP (idiopathic thrombocytopenic purpura), 170
Hypoxemia, in dementia, 181
Hypoxia, in COPD, 21

J
I Jaundice
ICD (implantable cardioverter defibrillator), 3 in alcoholic liver disease, 78
Idiopathic pulmonary hemosiderosis, 37 in cholangitis, 74
Idiopathic thrombocytopenic purpura (ITP), 170 in cholecystitis, 73
Ileus, adynamic, in small bowel obstruction, 60, 61 in choledocholithiasis, 74
Imatinib, for chronic myelogenous leukemia, 156 in pancreatic carcinoma, 73, 146
Imipenem, for pancreatitis, 72 in pancreatitis, 72
Immunoglobulin A (IgA) nephropathy, 41 Joint disease. See also Arthritis
Immunosuppressive therapy crystal related, 126–129
for Goodpasture syndrome, 37 calcium pyrophosphate dihydrate deposition disease
for polyarteritis nodosa, 138 (CPPD), 128
for systemic lupus erythematosus, 133 gout, 126–128
Implantable cardioverter defibrillator (ICD), 3 hemochromatosis, 128–129
Impotency, in spinal cord syndromes, 191 degenerative, 123–124
Indomethacin, for gout, 127 infections, 92
Infarction
in dementia, 180–181
in frontal lobe lesions, 179
stroke, 175, 176 K
Infection, 82–96. See also specific diseases Kaposi sarcoma, 95, 96
AIDS, 95–96 Karyotyping, in Turner syndrome, 117
central nervous system (CNS), 82–84 Kayser-Fleischer rings, in Wilson disease, 188
eosinophilia-associated, 93–94 Ketoacidosis, diabetic, 110
gastrointestinal, 88 Klinefelter syndrome, 120
genital and sexually transmitted, 88–90 Kussmaul respirations, in ketoacidosis, 110
head and neck, 84 Kussmaul sign, in restrictive cardiomyopathy, 10
infectious mononucleosis, 92–93 Kyphoscoliosis, 32–33, 33, 198
joint, 92
Lyme disease, 94–95
osteomyelitis, 91–92
respiratory tract, 84–88 L
seizures from, 181
toxic shock syndrome, 94 L-thyroxine
tuberculosis, 93 for hypothyroidism, 103
urinary tract, 90–91 for thyroid cancer, 105
Infectious mononucleosis, 92–93 for thyroiditis, 104
Infliximab Lactase deficiency, 63
for ankylosing spondylitis, 129 Lactate dehydrogenase (LDH)
for Crohn disease, 64 in acute leukemia, 154
for enteropathic arthropathies, 132 in ischemic heart disease, 4
for psoriatic arthritis, 132 in pericardial effusion, 12
for rheumatoid arthritis, 125 in pleural effusions, 29
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Lactulose, 79 Lymphoma
Lacunar strokes, 175, 177 Hodgkin, 151–152, 152t
Lateral sclerosis, amyotrophic, 196 non-Hodgkin lymphoma, 152–153
LDH. See Lactate dehydrogenase (LDH) Sjögren syndrome association with, 136
Leptomeningeal angiomatosis, in Sturge-Weber Lymphopenia, 167–168
syndrome, 193
Leukemia
acute, 153–155
chronic lymphocytic, 155
M
chronic myelogenous, 155–156, 168–169 Macrocytic anemia, 163–166
general characteristics, 153 Magnesium ammonium sulfate, renal calculi, 42
lymphocytosis in, 168 Magnetic resonance imaging (MRI)
neutropenia in, 169 in cervical spinal syndromes, 189
Leukocytic disorders in dementia, 181
dysfunctional neutrophils, 169–170 in encephalitis, 83
lymphocytosis, 168 in head and neck carcinoma, 141
lymphopenia, 167–168 in lumbar spinal syndromes, 191
neutropenia, 169 in multiple sclerosis, 199
neutrophilia, 168–169 in neurofibromatosis, 192
Leukocytosis in osteomyelitis, 91
in asthma, 19 in pituitary tumors, 97
in chronic myelogenous leukemia, 156 in seizure, 182
Levodopa, for Parkinson disease, 186 in spinal cord injury, 188
LH/FSH levels in spinal extramedullary lesions, 191
in androgen excess syndrome, 118–119 in spinal intramedullary lesions, 192
deficiency, 98 in stroke, 177
in hypogonadotropic hypogonadism, 117 in tuberous sclerosis, 192
in Turner syndrome, 116 Malabsorption, 62–63
Listeria monocytogenes, 83t Male reproductive disorders, 119–120
Lithotripsy, for renal calculi, 43 gynecomastia, 120
Liver biopsy hypogonadism, 119–120
in alcoholic liver disease, 78 Malignant hypertension, proteinuria in, 40
in hepatoma, 80 Mannitol, for stroke, 177
Liver diseases, 75–80 Mast cell stabilizer, for asthma, 20
abscess, 79 Mebendazole, for pinworm, 94
alcoholic, 78–79 Meconium ileus, in cystic fibrosis, 23
tumors, 79–80 Mediastinal masses, 31–32
viral hepatitis, 75–76, 76t, 77, 78 Mediastinal shift, in pneumothorax, 30
Lobectomy, for cystic fibrosis, 24 Mediastinitis, 31
Lumbar puncture Medullary carcinoma, thyroid, 105
in intracellular abscess, 84 Megacolon, toxic, 67, 68, 68
in meningitis, 82 Megaloblastic anemia, 165–166
in stroke, 177 Melena, 80
Lumbar spinal syndromes, 189–191 MEN syndromes, 97, 106, 115
Lung Meningitis, 82, 83t
biopsy leukemic, 154
in Goodpasture syndrome, 139 in Lyme disease, 94
in hypersensitivity pneumonitis, 26 Metabolic acidosis, 49, 50
in lung neoplasia, 35 in hyperosmolar nonketotic coma, 111
in pulmonary fibrosis, 25 in ketoacidosis, 110
cancer Metabolic alkalosis, 49, 51
clinical features, 149–150 in aldosteronism, 114
general characteristics, 149 Metaproterenol, for asthma, 20
laboratory findings, 150 Methacholine, in asthma, 19
treatment, 150 Methimazole, for hyperthyroidism, 102
neoplasms, 33–36, 34, 36 Methotrexate
Lung disease. See Pulmonary diseases for polymyositis, 135
Lupus, 132–133 for psoriatic arthritis, 132
Lyme disease, 94–95 for rheumatoid arthritis, 125
Lymph node biopsy Methyldopa, for hypertension, 17
in chronic lymphocytic leukemia, 155 Methylene blue staining, of stools, 59
in lung neoplasia, 35 Methylprednisolone, for spinal cord injury, 189
Lymphadenopathy Metoclopramide
in acute leukemia, 154 for gastric emptying disorders, 57
in chronic lymphocytic leukemia, 155 for intestinal motility, 135
in chronic myelogenous leukemia, 156 Metronidazole
in dysfunctional neutrophil disorders, 169 for Crohn disease, 64
in head and neck carcinoma, 141 for hepatic abscess, 79
in Hodgkin lymphoma, 152 for intracellular abscess, 84
in lymphocytosis, 168 for peptic ulcer disease, 59
in non-Hodgkin lymphoma, 153 for pseudomonas colitis, 71
in systemic lupus erythematosus, 133 Metyrapone, for Cushing syndrome, 113
Lymphocytic leukemia Metyrapone test, 98
acute, 153–155 Microscopy, polarizing, 92
chronic, 155 Midabdominal bruit, in renovascular disease,
Lymphocytosis, 168 44
Lymphogranuloma venereum, 89–90 Middle ear infection, 84
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Migraine, 183–185 ovarian cancer, 144

Milwaukee brace, for kyphoscoliosis, 33 pancreatic, 72–73, 145–146
Mineralocorticoid pleural, 31
deficiency in congenital adrenal hyperplasia, 115 prostatic carcinoma, 142–143
replacement renal and bladder carcinoma, 142
for Addison disease, 114 testicular cancer, 143–144
for congenital adrenal hyperplasia, 115 thyroid, 104–105
Minoxidil, for hypertension, 17 TNM staging, 141
Mitotane, for Cushing syndrome, 113 Neostigmine, for myasthenia gravis, 197
Mitral regurgitation, 8 Nephrectomy, for renal cancer, 142
Mononeuropathies, 194–196 Nephritic versus nephrotic syndromes, 42t
Morphine, for heart failure, 2 Nephropathy, diabetic, 108
Motor stroke, 175 Nephrotic syndrome, proteinuria in, 40
Movement disorders Nerve conduction studies
benign essential tremor, 185 in headache, 184
Huntington disease, 186–187 in polymyositis, 135
Parkinson disease, 185–186 Neurocutaneous syndromes
Tourette syndrome, 187 neurofibromatosis, 192
Wilson disease, 187–188 Sturge-Weber syndrome, 193
MRI. See Magnetic resonance imaging (MRI) tuberous sclerosis, 192
MS. See Multiple sclerosis (MS) Neurofibromatosis, 192
Mucolytics, for COPD, 21 Neurological diseases, 175–199
Multiple endocrine neoplasm (MEN), 97, 106, amyotrophic lateral sclerosis (ALS), 196
115 aphasia, 180
Multiple myeloma, 150–151 benign essential tremor, 185
Multiple sclerosis (MS) botulism, 197
clinical features, 198–199 cerebrovascular disease, 175–178
general characteristics, 198 dementia, 180–181
laboratory findings, 199 disorders of higher cognitive function, 179–180
treatment, 199 headaches, 183–185
Mumps orchitis, 120 Huntington disease, 186–187
Muscle biopsy movement disorders, 185–188
in Duchenne muscular dystrophy, 198 multiple sclerosis, 198–199
in polymyositis, 135 muscular dystrophy, Duchenne-type, 198
Muscular dystrophy, Duchenne, 198 myasthenia gravis, 196–197
Myasthenia gravis, 196–197 neurocutaneous syndromes, 192–193
mediastinal mass in, 31 neurofibromatosis, 192
Mycoplasma, 86–87, 88 neuromuscular disorders, 196–198
Myelogenous leukemia Parkinson disease, 185–186
acute, 153–155 peripheral neural disorders, 192–196
chronic, 155–156, 168 seizures, 181–183
Myeloperoxidase deficiency, 169–170 spinal cord syndromes, 188–192
Myelophthisic syndromes (myelofibrosis), 162 stroke, 175–178
Myocardial infarction, 1 Sturge-Weber syndrome, 192
Myocardial ischemia, 3–4 subarachnoid hemorrhage, 178
Myocarditis, in Lyme disease, 94 Tourette syndrome, 187
Myotomy tuberous sclerosis, 192
for esophageal dysmotility, 56 Wilson disease, 187–188
for gastric emptying disorders, 57 Neuromuscular disorders
Myxedema coma, 103 amyotrophic lateral sclerosis (ALS), 196
botulism, 197
muscular dystrophy, Duchenne-type, 198
N myasthenia gravis, 196–197
Neuropathy, in diabetes mellitus, 109
N-acetylcysteine, for COPD, 21 Neutropenia, 169
Nafcillin Neutrophilia, 168–169
for osteomyelitis, 92 Neutrophils, dysfunctional, 169–170
for toxic shock syndrome (TSS), 94 Nissen fundoplication, for reflux esophagitis,
Narcotics, for pancreatitis, 72 53
Natriuresis, in SIADH, 100 Nitrates, for esophageal dysmotility, 56
Nausea, in appendicitis, 65 Nitroblue tetrazolium dye test, 170
Neck carcinoma, 141 Nitroglycerin
Neck infections, 84 for angina, 2
Neisseria gonorrhoeae, 88, 89, 92 for ischemic heart disease, 4
Neisseria meningitidis, 82, 83t Nocturia, in heart failure, 1
Neoplasia, 141–156. See also specific cancers Non-Hodgkin lymphoma, 152–153
biliary, 75 in AIDS, 95
colonic, 68–70, 69 Nonsteroidal anti-inflammatory drugs (NSAIDs)
colorectal cancer, 146–149 for acute pericarditis, 11
esophagus, 54–55 for ankylosing spondylitis, 129
gastric, 55, 144–145 for calcium pyrophosphate dihydrate deposition
head and neck carcinoma, 141 disease, 128
hepatic, 79–80 gastritis from, 54
leukemia, 153–156 for gout, 127
lung, 33–36, 34, 36, 149–150 for hemochromatosis, 129
lymphoma, 151–153 for infectious mononucleosis, 93
multiple myeloma, 150–151 for osteoarthritis, 124
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Nonsteroidal anti-inflammatory drugs (NSAIDs) (continued) P

for psoriatic arthritis, 131
for reactive arthritis, 131 Pain
for rheumatoid arthritis, 125 in aortic aneurysm, 15
for spinal syndromes, 189, 191 in appendicitis, 65
for systemic lupus erythematosus, 133 in cholangitis, 74
for thyroiditis, 103 in cholecystitis, 73
Normochromic-normocytic anemia, 162–163 in leukemia, 154
Norwalk agent, diarrhea from, 60t in multiple myeloma, 151
NSAIDs. See Nonsteroidal anti-inflammatory drugs in pancreatic carcinoma, 73
(NSAIDs) in pancreatitis, 72
Nuclear medicine scan, in gastrointestinal bleeding, 81 in pelvic inflammatory disease (PID), 89
Nystagmus, in multiple sclerosis, 198 in peptic ulcer disease, 57
in pericarditis, 11
in pleural effusion, 28
O in pleural neoplasia, 31
in pneumothorax, 30
Obstruction in renal calculi, 42
colonic, 70 Palsy
small bowel, 59–62 Bell facial, 195–196
Obstructive lung disease, 19–24 sciatic nerve, 194–195
Obturator sign, in appendicitis, 65 Pancoast syndrome, 149
Occipital lobe lesions, 179 Pancoast tumor, 34, 34
Oliguria, in acute renal failure, 38 Pancreatic carcinoma, 72–73, 145–146
Omeprazole Pancreatic enzyme
for esophageal reflux, 135 for bacterial overgrowth syndrome, 63
for reflux esophagitis, 53 for cystic fibrosis, 24
Oncologic diseases, 141–156 for pancreatitis, 72
colorectal cancer, 146–149 Pancreatic stimulation tests, 72
gastric cancer, 144–145 Pancreatitis
head and neck carcinoma, 141 acute, 71–72
leukemia, 153–156 chronic, 72
lung carcinoma, 149–150 Pancytopenia
lymphoma, 151–153 in acute leukemia, 154
multiple myeloma, 150–151 in aplastic anemia, 162
ovarian cancer, 144 Papillary carcinoma, thyroid, 105
pancreatic cancer, 145–146 Paraneoplastic syndromes
prostatic carcinoma, 142–143 in lung carcinoma, 150
renal and bladder carcinoma, 142 in pancreatic carcinoma, 73
testicular cancer, 143–144 Parathyroid gland disorders
TNM staging, 141 hypoparathyroidism, 107–108
Opportunistic infections, in AIDS, 95–96, 95t primary hyperparathyroidism, 106–107
Orthophosphate, for renal calculi, 43 Paresthesias, in polyneuropathies, 193
Orthopnea Parietal lobe lesions, 179
in constrictive pericarditis, 13 Parkinson disease, 185–186
in heart failure, 1 Parkinsonian tremor, in Wilson disease, 188
in mitral regurgitation, 8 Partial thromboplastin (PTT) time, 172, 173t
in mitral stenosis, 7 Pelvic inflammatory disease (PID), 89
Orthostatic hypotension Penicillamine
in acute renal failure, 38 for psoriatic arthritis, 132
in Addison disease, 113 for rheumatoid arthritis, 125
in pheochromocytoma, 18 side effects, 126
Osmolality, in diabetes insipidus, 100 for systemic sclerosis, 135
Osmolar gap, 45, 45t for Wilson disease, 188
Osmotic fragility test, in hereditary spherocytosis, 164 Penicillin
Osteitis fibrosa cystica, 107 for cystic fibrosis, 24
Osteoarthritis, 123–124 for dysfunctional neutrophil disorders, 170
Osteoblastic metastasis, 108 for joint infections, 92
Osteodystrophy, in chronic renal disease, 39 for Lyme disease, 95
Osteomalacia, 121–122 for pharyngitis, 86
Osteomyelitis, 91–92 for pneumonia, 87
Osteoporosis, 120–121, 121 for sinusitis, 84
Otitis, 84 for syphilis, 90
Ovary Peptic ulcer disease, 57–59, 58
cancer, 144 Percutaneous needle aspiration, in lung neoplasia, 35
failure to develop in Turner syndrome, 116 Pericardial effusion, 11–12
granulosa-theca tumor, 118 Pericardiocentesis, 12
ovarian failure, primary, 118 Pericarditis
polycystic, 118–119 acute, 11, 12
Oxacillin, for osteomyelitis, 92 constrictive, 12–13
Oxygen therapy Peripheral neural disorders
for adult respiratory distress syndrome (ARDS), 28 mononeuropathies, 194–196
for cystic fibrosis, 24 polyneuropathies, 193–194
for headache, 185 Peripheral neuropathy, in polyarteritis nodosa, 138
for heart failure, 3 Peritonitis, in appendicitis, 65
for pneumoconiosis, 25 Pernicious anemia, 54
for pulmonary embolus, 14 PET (positron emission tomography), in lung carcinoma, 150
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Pharyngitis, 86 Procainamide
Phenothiazines, for Huntington disease, 187 for atrial fibrillation, 5
Phenoxybenzamine, for hypertension, 17 SLE induced by, 132
Phenytoin, for seizure, 178, 183, 183t Proctitis
Pheochromocytoma, 18, 115–116 infectious, 70
Philadelphia chromosome, 156, 168 ulcerative, 66
Phlebotomy, for hemochromatosis, 129 Progesterone withdrawal test
Phosphate, for hypercalcemia, 107 for amenorrhea diagnosis, 119
Phosphate binders, for chronic renal disease, 40 in hypogonadotropic hypogonadism, 117
Pica, iron deficiency anemia and, 157 Prolactin
PID (pelvic inflammatory disease), 89 deficiency, 98
Pigeon-breeder’s lung, 25 secretion by pituitary tumors, 97
Pink puffers, 21 Prolactinoma, 117
Pinworm infection, 93–94 Propranolol
Piperacillin for benign essential tremor, 185
for cholangitis, 75 for hypertension, 17
for pneumonia, 87 for hypertrophic obstructive cardiomyopathy, 10
Pituitary gland disorders Propylthiouracil, for hyperthyroidism, 102
diabetes insipidus, 99–100, 100t Prostate-specific antigen (PSA), 143
general characteristics, 97 Prostatic carcinoma, 142–143
hyperfunction, 99 Protein electrophoresis
hypofunction, 98 in chronic lymphocytic leukemia, 155
SIADH (syndrome of inappropriate antidiuretic hormone in multiple myeloma, 151
secretion), 100–101 Proteinuria, 40
tumors, 97–98 Prothrombin (PT) time, 172, 173t
Plasmapheresis Proton pump inhibitors
for Goodpasture syndrome, 37, 139 for peptic ulcer disease, 58
for Guillain-Barré syndrome, 194 for reflux esophagitis, 53
for myasthenia gravis, 197 Proctoscopy, 67
Platelets Pruritus, in Hodgkin lymphoma, 152
consumption syndromes, 172–173 PSA (prostate-specific antigen), 143
dysfunction, 171–172 Pseudogout, 128
thrombocytopenia, 170–171 Pseudomembranous colitis, 70–71
Pleural diseases Pseudomonas, 84, 92
pleural effusions, 28–29, 28t, 29t Pseudoseizures, 182
pleural neoplasia, 31 Psoas sign, in appendicitis, 65
pneumothorax, 29–31, 30 Psoriatic arthritis, 131–132
Pleural effusions, 28–29, 28t, 29t PT (prothrombin) time, 172, 173t
Pleural neoplasia, 31 PTT (partial thromboplastin) time, 172, 173t
Pleurodesis, chemical Pulmonary angiography, in pulmonary embolus, 14
for pleural effusion, 29 Pulmonary diseases
for pneumothorax, 30 adult respiratory distress syndrome (ARDS), 27–28
Plummer disease, 101 chest wall disorders, 32–33
Pneumatic dilatation, for achalasia, 56 diffuse interstitial lung disease, 24–27
Pneumoconiosis, 25–26 mediastinal diseases, 31–32
Pneumomediastinum, 31 neoplasms, 33–36
Pneumonia obstructive lung disease, 19–24
community-acquired, 86–87 pleural disease, 28–31
hospital-acquired, 87 of unknown etiology, 36–37
radiography, 87, 87, 88 Pulmonary edema, secondary to heart failure, 2
Pneumonitis Pulmonary embolus, 14–15, 15
hypersensitivity, 25–26 Pulmonary fibrosis, 24–25
in lung carcinoma, 150 in ankylosing spondylitis, 129
Pneumothorax, 29–31, 30 Pulmonary function tests
in emphysematous bullous disease, 21 in asthma, 19
Polyarteritis nodosa, 138 in bronchiectasis, 22
Polycystic ovary disease, 118–119 in COPD, 21
Polymyalgia rheumatica, 139 in cystic fibrosis, 23
Polymyositis, 135 in Goodpasture syndrome, 37
Polyneuropathies, 193–194 in hypersensitivity pneumonitis, 26
Polyposis syndromes, familial, 68, 148, 148t in pneumoconiosis, 25
Polyps, colonic and rectal, 68–69, 148–149, 148t in pulmonary fibrosis, 25
Polyuria, in diabetes insipidus, 100 in sarcoidosis, 26, 27
Positron emission tomography (PET), in lung carcinoma, 150 Pulsus paradoxus, in asthma, 19
Poststreptococcal glomerulonephritis, 41, 42t Purpura
Potassium anaphylactoid (allergic), 137
hyperkalemia, 45 Henoch-Schönlein, 137
hypokalemia, 45, 48 in hypersensitivity angiitis, 137
in ketoacidosis, 110 idiopathic thrombocytopenic, 170
loss in aldosteronism, 114 palpable, 82
Prazosin, for hypertension, 17 thrombotic thrombocytopenic, 172
Prednisone Pyelogram, intravenous, in renal calculi, 43
for Bell facial palsy, 196 Pyelonephritis, 90, 91
for thyroiditis, 103 Pyloric stenosis, 57
Pregnancy test, 119 Pyrazinamide, for tuberculosis, 93
Primidone, for benign essential tremor, 185 Pyridostigmine, for myasthenia gravis, 197
Probenecid, for gout, 127 Pyridoxine, for Wilson disease, 188
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Q in small bowel obstruction, 60

in spinal cord injury, 188
Quinolone, for urinary tract infection, 91 in spinal extramedullary lesions, 191
in Sturge-Weber syndrome, 193
in systemic sclerosis, 134
R in tricuspid regurgitation, 9
in ulcerative colitis, 67, 68
Radial nerve injury, 194 in urinary tract infections, 91
Radicular syndromes in Wegener granulomatosis, 37
cervical, 189 Radionuclide biliary scan, in cholecystitis, 73
lumbar, 189–191 Radiotherapy
Radioactive iodine scintigraphy, in thyroid nodule disease, for colorectal cancer, 148
105 for Cushing syndrome, 113
Radioactive iodine therapy for esophageal neoplasms, 55
for hyperthyroidism, 102 for gastric neoplasms, 55
for thyroid cancer, 105 for head and neck carcinoma, 141
Radioactive iodine uptake test, 101 for Hodgkin lymphoma, 152
Radiography for hyperthyroidism, 102
in Addison disease, 113 for lung carcinoma, 150
in adult respiratory distress syndrome (ARDS), 27 for multiple myeloma, 151
in AIDS, 96 for non-Hodgkin lymphoma, 153
in ankylosing spondylitis, 129, 130 for pituitary hyperfunction, 99
in aortic regurgitation, 6 for pituitary tumors, 98
in appendicitis, 65 for prostatic carcinoma, 143
in asthma, 19 Ranitidine
in bronchiectasis, 22, 23 for peptic ulcer disease, 58
in cervical spinal syndromes, 189 for reflux esophagitis, 53, 135
in cholecystitis, 73 Raynaud phenomenon, 134, 135
in colonic neoplastic disease, 69, 69, 70 RBC casts, 40
in colorectal cancer, 147–148 Reactive arthritis, 130–131
in congestive cardiomyopathy, 9 Receptive aphasia, 180
in constrictive pericarditis, 13 Recklinghausen disease, 192
in COPD, 21, 22 Red blood cell aplasia, 163
in CPPD, 128 Red blood cell indices, 157, 158t
in Crohn disease, 64, 64 Reed-Sternberg cells, in Hodgkin lymphoma, 152
in cystic fibrosis, 23, 24 Reflux esophagitis, 53
in enteropathic arthropathies, 132 Reiter syndrome, 131
in esophageal dysmotility, 55, 56 Renal artery stenosis, 43
in gastric cancer, 145 Renal biopsy, in acute renal failure, 38
in gastric emptying disorders, 57 Renal calculi, 42–43
in gastric neoplasms, 55 Renal carcinoma, 142
in Goodpasture syndrome, 37 Renal failure
in gout, 127 acute, 38–39, 39t
in heart failure, 1, 2 chronic, 39–40
in hemochromatosis, 128 Renovascular disease, 43–44
in hypersensitivity pneumonitis, 26 Renovascular hypertension, 17–18
in kyphoscoliosis, 33 Reproductive disorders
in lumbar spinal syndromes, 191 female, 116–119
in lung carcinoma, 150 amenorrhea, primary, 116–118
in malabsorption, 63 amenorrhea, secondary, 118
in mediastinal masses, 32 androgen excess syndrome, 118–119
in mediastinitis, 31 diagnostic evaluation, 119
in mitral regurgitation, 8 male, 119–120
in mitral stenosis, 7 gynecomastia, 120
in multiple myeloma, 151 hypogonadism, 119–120
in myasthenia gravis, 197 Reserpine
in osteoarthritis, 124 for Huntington disease, 187
in osteomalacia, 122 for Tourette syndrome, 187
in osteomyelitis, 91 Respiratory acidosis, 49
in osteoporosis, 120, 121 Respiratory alkalosis, 49
in pancreatitis, 72 Respiratory tract infections, 84–88
in peptic ulcer disease, 57–58, 58 pharyngitis, 86
in pericardial effusion, 11 pneumonia, 86–87, 87, 88
in pleural effusions, 28 upper respiratory tract infections (URTIs), 84, 86
in pneumoconiosis, 25 Restrictive cardiomyopathy, 10–11
in pneumonia, 87, 87, 88 Reticulocytosis, anemia from, 163
in pneumothorax, 30, 30, 31 Retinitis, in AIDS, 96
in psoriatic arthritis, 131 Reversible ischemic neurologic deficit (RIND),
in pulmonary embolus, 14, 15 175
in pulmonary fibrosis, 25 Rhabdomyolysis, hypercalcemia in, 107
in reactive arthritis, 131 Rheumatic diseases, 123–140
in reflux esophagitis, 53 crystal-related joint diseases, 126–129
in renal calculi, 43 osteoarthritis, 123–124
in restrictive cardiomyopathy, 10 polymyositis and dermatomyositis, 135
in rheumatoid arthritis, 125, 126 rheumatoid arthritis, 124–126, 126
in sarcoidosis, 26, 27, 27 Sjögren syndrome, 136
in sinusitis, 84 spondyloarthropathies, 129–132
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Rheumatic diseases (continued) Crohn disease, 63–64, 64

systemic lupus erythematosus, 132–133 diarrhea, 59, 60t, 61
systemic sclerosis (scleroderma), 134–135 malabsorption, 62–63
vasculitic syndromes, 136–140 obstruction, 59–62
Rheumatic fever Sodium
mitral regurgitation from, 8 hypernatremia, 45, 47
mitral stenosis from, 7 hyponatremia, 44–45, 46
tricuspid regurgitation from, 8 Sodium restriction
Rheumatoid arthritis, 124–126, 126 for congestive cardiomyopathy, 9
Rhinitis, allergic in Churg-Strauss syndrome, 137 for hypertension, 17
Rifampin Somatostatin analogues, for pituitary hyperfunction, 99
for meningitis, 82 Spasticity, in amyotrophic lateral sclerosis, 196
for tuberculosis, 93 Spherocytosis, hereditary, 164–165
Riluzole, for amyotrophic lateral sclerosis, 196 Spinal cord
RIND (reversible ischemic neurologic deficit), 175 cervical and radicular syndromes, 189
Rotavirus, diarrhea from, 60t extramedullary lesions, 191
Rovsing sign, in appendicitis, 65 intramedullary lesions, 192
lumber and radicular syndromes, 189–191
traumatic injury, 188–189
S Spirometry, in COPD, 21
Spironolactone
Sacroiliitis, 131, 132 for aldosteronism, 115
Saddle-nose deformity, in Wegener granulomatosis, 139 for androgen excess syndrome, 119
Salicylates, side effects of, 125 for heart failure, 3
Saline, intravenous Splenectomy
for Addison disease, 114 for hereditary spherocytosis, 165
for hypercalcemia, 107 for thalassemias, 161
Salmonella spp. in thrombocytopenia, 171
diarrhea from, 60t Splenic infarction, in sickle-cell disease, 160
food poisoning, 62t Splenomegaly
Sarcoidosis, 26–27, 27 in chronic myelogenous leukemia (CML), 156, 168
hypercalcemia in, 106 in glucose-6-phosphate dehydrogenase (G6PD) deficiency,
mediastinal disease, 31 165
Schilling test, 54, 63, 166 in hereditary spherocytosis, 164
Sciatic nerve palsy, 194–195 in thrombocytopenia, 171
Sciatica, 90 in viral hepatitis, 76
Scleroderma, 134–135 Spondyloarthropathies, 129–132
Sclerosis, tuberous, 192 ankylosing spondylitis, 129, 130
Seizure enteropathic arthropathies, 132
in arteriovenous malformation, 178 general characteristics, 129
clinical features, 182 psoriatic arthritis, 131–132
in encephalitis, 83 reactive arthritis, 130–131
febrile, 182 Spondylotic degeneration, cervical spine, 189
general characteristics, 181–182 Sputum
generalized, 182 in asthma, 19
in hyperosmolar nonketotic coma, 111 in bronchiectasis, 22
in intracranial abscess, 83 in lung carcinoma, 150
laboratory findings, 182–183 in lung neoplasia, 35
partial in sarcoidosis, 26
complex, 182 Squamous cell carcinoma, lung, 34, 34, 149
simple, 181–182 Staphylococcus aureus
pseudoseizures, 182 food poisoning, 62t
status epilepticus, 182, 183 MRSA, 84, 87
in Sturge-Weber syndrome, 193 osteomyelitis, 91, 92
in temporal lobe lesions, 179 toxic shock syndrome, 94
treatment, 183, 183t Staphylococcus epidermidis, 92
in tuberous sclerosis, 192 Status asthmaticus, 19
Seminoma, 143–144 Steatorrhea
Sensory conduction studies, in amyotrophic lateral sclerosis, 196 in cystic fibrosis, 23
Sexually transmitted infectious diseases, 88–90 in malabsorption, 63
Sheehan syndrome, 98 in pancreatitis, 72
Shigella spp. Stem cell transplant, for chronic myelogenous leukemia, 156
diarrhea from, 60t Stent therapy, for esophageal neoplasms, 55
food poisoning, 62t Steroids. See also Corticosteroids
Shock, in gastritis, 54 for acute pericarditis, 11
Sickle-cell disease, 160–161 Stomach disorders
Sideroblastic anemia, 158, 160 emptying disorders, 56–57
Sigmoidoscopy, for pseudomonas colitis, 71 gastritis, 54
Silicosis, 25 neoplasia, 55
Sinusitis, 84 peptic ulcer disease, 57–59, 58
in Wegener granulomatosis, 139 Stool analysis
Sjögren syndrome, 136 in colonic neoplastic disease, 70
Skin biopsy, in hypersensitivity angiitis, 137 in diarrhea, 59
SLE (systemic lupus erythematosus), 132–133 fecal fat analysis, in malabsorption, 63
Small-cell carcinoma, lung, 34, 35, 149 fecal occult blood, in Crohn disease, 63
Small intestine diseases in pseudomonas colitis, 71
bacterial food poisoning, 62t in ulcerative colitis, 67
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Streak gonads, 117 Tetany

Streptococci, 83, 92 in hypokalemia, 44
Streptococcus pneumoniae, 82, 83t, 86–87, 87 latent, 107
Streptococcus pyogenes, 84 overt, 107
Streptokinase Tetracycline
for deep venous thrombosis, 13–14 for bacterial overgrowth syndrome, 63
for pulmonary embolus, 15 for chemical pleurodesis, 29, 30
Stroke for granuloma inguinale, 90
clinical features, 175–176 for Lyme disease, 95
general characteristics, 175, 176 for lymphogranuloma venereum, 90
hemorrhage, 175–177 for pharyngitis, 86
ischemic, 175–177 Thalassemias, 161
laboratory findings, 177 Thiamine, for alcoholic liver disease, 78
motor, 175 Thiazides
risk factors, 175, 176t for diabetes insipidus, 100
treatment, 177–178 for hypertension, 17
Sturge-Weber syndrome, 193 for renal calculi, 43
Subarachnoid hemorrhage, 178 Thoracocentesis
Subcutaneous calcinosis, in systemic sclerosis, 134 in pleural effusions, 29
Sucralfate in pneumothorax, 31
for esophageal reflux, 135 Thrombocytopenia, 170
for gastritis, 54 in acute leukemia, 154
for peptic ulcer disease, 58 alcohol-induced, 78
Sulfasalazine Thrombocytosis, in chronic myelogenous leukemia (CML), 169
for ankylosing spondylitis, 129 Thromboembolic stroke. See Stroke
for Crohn disease, 64 Thrombolytic agents
for reactive arthritis, 131 for deep venous thrombosis, 13–14
for ulcerative colitis, 68 for pulmonary embolus, 15
Sulfinpyrazone, for gout, 127 Thrombotic thrombocytopenic purpura (TTP), 172
Sumatriptan, for headache, 184 Thymectomy, for myasthenia gravis, 197
Swallowing dysfunction, in amyotrophic lateral sclerosis, 196 Thyroid cancer, 104–105
Swan-neck deformities, in rheumatoid arthritis, 124 Thyroid gland disorders, 101–106, 104t
Sweat test, in cystic fibrosis, 23 cancer, 104–105
Sympathomimetics, for asthma, 20 hyperthyroidism, 101–102
Syncope hypothyroidism, 102–103
in aortic regurgitation, 6 nodules, 105–106
in aortic stenosis, 6 thyroiditis, 103–104
in pulmonary embolus, 14 Thyroid nodules, 105–106
seizure compared, 182 Thyroid storm, 101
Syndesmophytes, in reactive arthritis, 131 Thyroidectomy, subtotal, 102
Syndrome of inappropriate antidiuretic hormone secretion Thyroiditis
(SIADH), 100–101 Hashimoto, 102, 104
Synovial fluid analysis lymphocytic, 104
in CPPD, 128 painless, 104
in enteropathic arthropathies, 132 subacute, 101, 103
in gout, 127 Thyroxine
in hemochromatosis, 128 for hypothyroidism, 103
in osteoarthritis, 123 for thyroid cancer, 105
in psoriatic arthritis, 131 for thyroiditis, 104
in reactive arthritis, 131 TIA (transient ischemic attack), 175, 177
in rheumatoid arthritis, 125 Ticlopidine, for ischemic heart disease, 4
Syphilis, 89–90 Tics, in Tourette syndrome, 187
Syringomyelia, 192 Tissue plasminogen activator (t-PA)
Systemic hypertension. See Hypertension for deep venous thrombosis, 13–14
Systemic lupus erythematosus (SLE), 132–133 for ischemic heart disease, 4
Systemic sclerosis, 134–135 for pulmonary embolus, 15
for stroke, 177
Tourette syndrome, 187
T Toxic megacolon, 67, 68, 68
Toxic shock syndrome (TSS), 94
T-cell deficiency, 167 Toxoplasmosis, in AIDS, 95, 96
T3 resin uptake test, 102 Transfusion
Tachycardia, in heart failure, 1 for acute leukemia, 154
Tachypnea, in chronic renal disease, 39 for aplastic anemia, 162
Tazobactam for glucose-6-phosphate dehydrogenase (G6PD) deficiency,
for cholangitis, 75 165
for pneumonia, 87 for hereditary spherocytosis, 165
Telangiectasias, in systemic sclerosis, 134 for myelophthisic syndromes, 162
Temporal arteritis, 139–140 platelet, 170, 171
Temporal lobe lesions, 179 for red blood cell aplasia, 163
Tension headache, 184, 185 for sickle-cell disease, 161
Tension pneumothorax, 30, 30–31 for sideroblastic anemia, 160
Terminal deoxynucleotidyl transferase, 153 for thalassemias, 161
Testicular agenesis, 120 for thrombocytopenia, 170
Testicular cancer, 143–144 Transfusion reaction, hemolytic anemia from, 163
Testicular choriocarcinoma, 120 Transient ischemic attack (TIA), 175, 177
Testicular feminization syndrome (androgen resistance), 117 Transudative fluid, 28t
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218 INDEX

Tremor in acute renal failure, 38

benign essential, 185 in colorectal cancer, 147
in multiple sclerosis, 198 in dementia, 181
in Parkinson disease, 186 in Goodpasture syndrome, 37, 139
in Wilson disease, 188 in Henoch-Schönlein purpura, 137
Tricuspid regurgitation, 8–9 in ketoacidosis, 110
Trigeminal neuralgia, headache in, 184, 185 in multiple myeloma, 151
Trimethoprim-sulfamethoxazole (TMP-SMX) in nonproliferative glomerulonephropathy, 42
for dysfunctional neutrophil disorders, 170 in pheochromocytoma, 18
for granuloma inguinale, 90 in polyarteritis nodosa, 138
for otitis, 84 in primary hyperparathyroidism, 106
for toxoplasmosis, 96 in proliferative glomerulonephropathy, 41
for urinary tract infection, 91 in renal calculi, 43
Troponin, in ischemic heart disease, 4 in urinary tract infections, 91
Trousseau sign, 107 in Wegener granulomatosis, 139
TSH deficiency, 98 Urinary sodium excretion, in SIADH, 100
TSS (toxic shock syndrome), 94 Urinary tract infections (UTIs), 90–91
TTP (thrombotic thrombocytopenic purpura), 172 Urine collection, 24-hour, in renal calculi, 43
Tube thoracostomy, 30 Urine culture, 91
Tuberculosis, 93 Uropathy, acute obstructive, 127
Tuberous sclerosis, 192 Uveitis
Tumor in ankylosing spondylitis, 129
biliary, 75 in psoriatic arthritis, 131
hepatic, 79–80 in sarcoidosis, 26
mediastinal masses, 31–32
pheochromocytoma, 115–116
pituitary, 97–98 V
spinal cord, 191, 192
testicular, 120 Valproic acid, for seizure, 183t
Tumor necrosis factor. See Anti-tumor necrosis factor (TNF) Valvular heart disease
agents aortic regurgitation, 6–7
Turner syndrome, 116–117 aortic stenosis, 5–6
21-hydroxylase deficiency, 115 mitral regurgitation, 8
Tzanck test, 90 mitral stenosis, 7
tricuspid regurgitation, 8–9
Valvuloplasty, balloon, for aortic stenosis, 6
U Valvuloplasty, mitral, 7
Vancomycin
Ulcer for dysfunctional neutrophil disorders, 170
genital, 89–90 for joint infections, 92
peptic, 57–59, 58 for meningitis, 82
Ulcerative colitis, 66–68, 68 for osteomyelitis, 92
Ulnar nerve injury, 194 for pseudomonas colitis, 71
Ultrasound for toxic shock syndrome (TSS), 94
in alcoholic liver disease, 78 Vasculitic syndromes, 136–140
in aortic aneurysms, 16 Churg-Strauss syndrome, 137–138
in appendicitis, 65 general characteristics, 136
in cholangitis, 75 giant cell arteritis, 139–140
in cholecystitis, 73 Goodpasture syndrome, 139
in choledocholithiasis, 74 Henoch-Schönlein purpura, 137
in hepatic abscess, 79 hypersensitivity angiitis, 136–137
in ovarian cancer, 144 polyarteritis nodosa, 138
in pancreatitis, 71 Wegener granulomatosis, 138–139
in pelvic inflammatory disease (PID), 89 Vasculitis, in Wegener granulomatosis, 37
in primary hyperparathyroidism, 106 Vasodilators
in prostatic carcinoma, 143 for aortic regurgitation, 7
in renal carcinoma, 142 for hypertension, 17
in testicular cancer, 143 for mitral regurgitation, 8
Upper GI series Vasopressin, for gastrointestinal bleeding, 81
in gastric neoplasms, 55 Venography, contrast, in deep venous thrombosis, 13
in peptic ulcer disease, 57–58, 58 Ventilation-perfusion scan
in reflux esophagitis, 53 in lung carcinoma, 150
Urea in pulmonary embolus, 14
in acute renal failure, 38 Verapamil, for hypertrophic obstructive cardiomyopathy, 10
in chronic renal disease, 40 Vertebral wedge-shaped deformity, in osteoporosis, 120, 121
Ureaplasma, 91 Vibrio cholerae, food poisoning, 62t
Uremic toxemia, in chronic renal disease, 39 Vinblastine, for Hodgkin lymphoma, 152
Urethritis, 88–89 Virchow node, 55, 145
Uric acid Visceral angiography
in acute leukemia, 154 in Churg-Strauss syndrome, 138
in gout, 126–127 in polyarteritis nodosa, 138
nephropathy in multiple myeloma, 151 Visual and auditory evoked responses, in multiple sclerosis, 199
renal calculi, 42 Visual disturbance, in pituitary tumors, 97
Urinalysis Vitamin B12
abnormal for Crohn disease, 64
hematuria, 40–41 deficiency, 165–166, 171
proteinuria, 40 polyneuropathy from, 194
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Vitamin C, for Alzheimer disease, 181 Water deprivation test, for diabetes insipidus, 100, 100t
Vitamin D Wegener granulomatosis, 138–139
for chronic renal disease, 40 Wernicke aphasia, 180
deficiency, osteomalacia from, 121 Whiplash injury, 189
intoxication, 106 Wilson disease, 187–188
for osteomalacia, 122 Wright staining, of stools, 59
Vitamin K, for viral hepatitis, 78
Vitamin K-dependent factor deficiencies, 174
Vocal fremitus, in pleural effusion, 28 X
Volume and electrolyte disorders, 44–52
Vomiting, in appendicitis, 65 Xerophthalmia, 136
Von Willebrand disease, 173–174 Xerostomia, 136
Xylose absorption test, in malabsorption, 63

W
Z
Warfarin
for atrial fibrillation, 5 Zinc, for Wilson disease, 188
for mitral stenosis, 7 Zoledronate, for hypercalcemia, 107