Saint-Frances Guide To Inpatient Medicine

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SAINT-FRANCES
GUIDE TO :---
INPATIENT
MEDICINE
Sanjay Saint, M.D.
Chief Medical Resident, 1995-96
University of Califoria, San Francisco
San Francisco. California
Craig Frances, M.D.
San Francisco, Califoria
Williams & Wilkins
A WAVRY COMPA
BALTIMORE' PHILADELPHIA' LOJDON PARIS' BANGKOK
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Copyright L 1997 Williams & Wilkins
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Printed in the United States of Ameri ca
First Edition,
Library of Congress Catatogtng-in-Publicatlon Data
Saint, Sanjay.
Saint-Frances guide to inpatient medicine I Sanjay
Saint, Craig Frances.
p. e.
ISBN 0-683-{7547-{
1. Internal medicine-Outlines, syllabi, etc. 2. Mnemonics.
I. Frances. Craig. II. TItle.
[DNLM: 1. Internal Medicine-outlines. 2. Diagnosis,
Differential-outlines. WB 18.2S152h]
RC59.S25 1997
616-dc20
DNLM/DLC 96-29151
for Library of Congress CIP
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97 9899
1 2 3 4567 89 10
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Dedication
To Veronica, Sean, and Kirin Saint
Sanjay Saint
To Vera Frances and Stacie Mayoras
Craig Frances
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GUIDE TO
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MEDICINE
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Contents
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Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Xlii
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: Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xv
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Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . XVll
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PART I: GENERAL APPROACH TO MEDICAL

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PROBLEMS
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l. APPROACH TO DIFFERENTIAL DIAGNOSIS 3
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2. ApPROACH TO MEDICAL DECISION MAKING 5
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PART II: CARDIOLOGY
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3. CARDIAC EXINATION 13
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4. ELECTROARDIOGRA INTERPREATION 21
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5. SYNCOPE 30
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6. ARRYHMIAS 34
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7. ATRIAL FIBRILLDON 50

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8. CHEST PAIN
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9. ANGINA 64
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10. MYOCARDIAL INFARCTION 73

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1l. CONGESTIVE HEART FAILURE 85
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12. SHOCK 91
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viii
Contents
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Contents
ix
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PART III: PULONARY AND CRITICAL CARE
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PART V: RENAL/ACID-BASE
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13. AcU DYSPNEA 101
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34. OERVIE OF NEPHROLOGY
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203
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14. MASSIVE HEOPTYSIS 105
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35. ACUTE RENAL FAILURE
205
15. ApPROACH TO THE CHEST RADIOGRAPH 109
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I 36. NEPHROTIC SYNDROME 217
113
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16. HYPOXEMIA
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37. NEPHRITIC SYNDROME
220
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17. PULONARY FUNCTION TESTS 117

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38. RENAL TUBULR DEFECTS 224
18. OBSTRUCTIVE LUNG DISEAE 120
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39. URINARY TRACT INFECTIONS 227 0.
19. RESTRlcnVE LUNG DISEASE 123
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40. APPROACH TO ACID-BASE DISORDERS :
233
20. COMMUNITY-ACQUIRED PNEUMONIA 129
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41. HYPONATREMIA
242
21. PULONARY HYPERENSION 132
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42. HYPERTENSION
246
22. PULONARY EMBOLISM 138

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23. RESPIRATORY FAILURE 144
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PART VI: INFECTIOUS DISEASE
24. MECHANICAL VENTILTION 147
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43. APPROACH TO FEVER 253 C
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44. APPROACH TO MICROBIOLOGY 259
PART IV: GASTROENTEROLOGY
V
45.
25. ABDOMINAL PAIN 155
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FEVER AND RASH
264
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26. LIVER TESTS 162
46. FEVER OF UNKNOWN ORIGIN 270
27. ACUTE DIARRHEA 166
I 47. ACUTE RHEUMATIC FEVER 275
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28. ACUTE GASTROINESTINAL BLEEDING 169
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48. INFEcnVE ENDARDITIS
278
29. SPLENOMEGALY 175
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49. CD4 COUNTS AND COMPLICATIONS OF HI
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INFEcnON
284
30. ASCITES 179
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50. PULONARY DISEASE IN HIV-INFECTED
31. ACUTE PANCREATITIS 185
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PATIENTS
t: 287
32. ALCOHOLIC LIVER DISEASE 189
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O 51. GASTROINTESTINAL MANIFESTATIONS OF
33. LIVER FAILURE 192
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HIV DISEASE
291
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x Contents
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Contents xi
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52. NEUROLOIC MANIFESTATIONS OF
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PART IX: ENDOCRINOLOGY
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HIV DISEASE 295
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71. HYPERCALCEMIA 0
405
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PART VII: HEMATOLOGY/ONCOLOGY
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72. HYPOCALCEMIA 408
53. PANCYTOPENIA 303
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73. DIABETIC KETOACIDOSIS 411
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54. THROMBOCYTOPENIA 309
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74. THYROID DISEASE 418 .
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55. THROMBOCYTOSIS 315

75. ADRENOCORTICAL INSUFFICIENCY 424
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56. ANEMIA 317
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PART X: NEUROLOGY
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76. ALTERED MENTAL STATUS
57. POLYCYHEMIA 323
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431
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77. PERIPHERAL NEUROPATHY
58. LEUKOCYTOSIS 327
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435
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78. VERTIGO
59. EOSINOPHILIA 330
&
440

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79. SINGULTUS
60. BLEEDING DISORDERS 333
444
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80. STROKE 446
61. HYPERCOAGULBLE STATES 345
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62. LYMPHADENOPATHY 349
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82. SPINAL CORD COMPRESSION 0 461
63. LYMPHOMA 353
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PART XI: DERMATOLOGY
64. MYELOPROLIFERATIVE VERSUS MYELODYSPLSTIC
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SYNDROMES 361
83. EXANHEMS 467
65. ACUTE LEUKEMIA 369
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84. PRURITUS 471
66. PLSMA CELL DYSCRASIAS
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85. CLUBBING
375
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67. METASTATIC NEOPLSMS 381
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PART XII: TOXICOLOGY

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PART VIII: RHEUMATOLOGY
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86. ALCOHOL INOXICATION AND WITHDRAWAL 479 0
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87. TOXICOLOIC EMERGENCIES 482
68. MONOARTICULR ARTHRms 387
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Summary of Mnemonics . . . . . . . . . . . . . . . . . . . . . . . 489
69. POLYARTICULR ARTHRITIS 392
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Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 509
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70. VASCULITIS 396
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Contributrs
Joshua S. Adler, M.D.
University of California, San Francisco
Chapter 13, Acute Dyspnea
Steve Bent, M.D.
Medical Resident, 1993-96
Chapter 5, Syncope
Chapter 7, Atrial Fibrillation
Chapter 18, Obstructive Lung Disease
Kent Dauterman. M.D.
Chapter 86, Alcohol Intoxication and Withdrawal
Mark D. Eisner, M.D.
Chapter 22, Pulmonary Embolism
Daniel Feikin, M.D.
Chapter 27. Acute Diarrhea
Scott A. Flanders, M.D.
University of California. San Francisco
Chapter 19, Restrictive Lung Disease
Chapter 2n, Liver Tests
Daniel J. Friedland, M.D.
Medical Resident, 1 992-95
Chapter 76, Altered Mental Status
xiii
xiv
Pushkal P. Garg, M.D.
Chapter 61, Hypercoagulable Stales
Alan S. Go, M.D.
Chapter 20, Community-Acquired Pneumonia
Chris Goss, M.D.
Chapler 2, Re.piratory Failure
S. Claiborne Johnston, M.D.
Chief Resident in Neurology, 1995-96
Chapler 80, Stroke
M. Andrew Mirhej, M.D.
Chapter 28, Acute Gastrointestinal Bleeding
Somnath Saha, M.D.
Chapter 14, Massive Hemoptysis
Peter Salzmann, M.D.
University of Califora, San Francisco
Chapler 2, Approach Medical Decision Making
E. Rand Sutherland, M.D.
Chapter 87, Toxicologic Emergencies
Mary Whooley, M.D.
Chapter 24, Mechanical Ventilation
Contributors
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Preface
"There is too much to know in medicine." So said one of our
medical students after being asked a series of increasingly detailed
questions by the attending. The feld of internal medicine is indeed
overwhelming. As you progress in your education and your respon
sibilities increase, your anxiety level may also rise. As an inter
and resident, you will often care for patients with complex and
life-threatening medical disorders, but you may not have an ap
proach to help you deal with the problems you encounter. Text
books may not reduce your anxiety, because long lists of informa
tion are usually presented in a way that may not make sense or is
too diffcult to remember. Furthermore, patients usually do not
present with easiy defned diseases; rather, they present with symp
toms or signs. By primarily addressing individual diseases, many
texts work backward from what happens in real life.
Our book is meant to be very practical. We have found simple
and straightforward approaches to common medical problems that
are easy to learn and equally easy to remember. Broad topics
like anemia, renal failure, and vasculitis are broken down into
manageable pieces. Mnemonics that have been successfully used
by many clinicians are presented to help you organize and remem
ber large amounts of information. We use mnemonics primarily
as a means of creating extensive differential diagnoses. We then
teach you what to do next in a step-by-step fashion. To help visually
categorize the information, algorithms, fgures, and tables are pro
vided. In addition to providing you with ways to work forward
from clinical presentation to diagnosis, some chapters discuss the
diagnoses you will make in more depth. So, while you learn how
to approach all patients with chest pain, you also learn the salient
features of some of the causes of chest pain (e.g., myocardial
infarction, pulmonary embolism).
In many ways, the practice of medicine is like a maze. The
clinician is faced with a long row of doors, each of which may be
opened. leading to another series of doors. Saint-Frances Guide
to Inpatient Medicine is meant to help you consider the possible
doors from the stan so that you don't wander off in the wrong
direction. We hope to guide you through the maze by helping you
open the doors that lead to correct diagnoses. While this book
provides you with a concise interal medicine board review and
a means of memorizing enough information to impress your friends
and colleagues, our ultimate goal is to help you take excellent
care of your patients. In the process, we hope to make medicine
manageable and fun.
xv
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Acknowledgments
We would like to acknowledge Alan Go, M.D., for his quick mind
and even quicker pen. We would like to thank the faculty, house
staff, and students at University of California. San Francisco, for
making teaching so fulflling. A special thanks goes to Lawrence
Tierney, M.D., William Seaman, M.D., Deborah Grady, M.D
:
,
Terrie Mendelson, M.D., and Warren Browner, M.D., for theIr
mentorship and guidance. Finally, we would like to als
?
than
our editor, Melanie Cann, whose tireless and talented mput IS
greatly appreciated.
xvii
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PART I
General Approach to
Medical Problems
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1. Approach to
Diferential Diagnosis
...............................................................................................................
a
II
INTRODUCTION. Often, patients present with a constella
tion of symptoms, signs, and data that readily indicate the
likely diagosis. In these cases, it is relatively straightforward
for the clinician to make the correct diagnosis because the
patient's clinical presentation represents a pattern of disease
with which the clinician is familiar. For example, when a
patient presents with fever, cough productive of rusty spu
tum, pleuritic chest pain, and a lobar infltrate, the clinician
quickly diagnoses the patient as having a pneumonia, proba
bly pneumococcal in origin. Occasionally, a patient presents
with an illness that does not easily ft a pattern. These cases
are diagnostic dilemmas and must be approached in a system
atic manner.
SYSTMTIC ApPROACH
A. Generate a list of the patient's medical problems (e.g.,
chest pain, altered mental status, anemia, hypercalcemia,
hyponatremia). The history, physical, and routine labora
tory data are the basis for this list.
B. Generate a list of potential causes-a diferential diag
nosis-for each problem. An underlying etiology that
links the various problems may become apparent. Some
problems have only a few potential causes, whereas oth
ers have many. It is often refeshing to confont a case
where the answer is not readily apparent, as refeshing
as eating chopped mints. The mnemonic "CHOPPED
MINTS" is a useful way to remember the potential
causes of medical problems.
3
4 Chapter 1
Potential Etiologies ("CHOPPED MINTS")
Congenital
Hematologic or vascular
Organ disease
Psychiatric or Psychogenic
Pregnancy-related
Environmental
Drugs (prescription, over-the-counter, herbal, il
licit)
Metabolic or endocrine
Infectious, Inflammatory, Iatrogenic, or Idio
pothic
Neoplasm-related (and paraneoplastic syn
dromes)
Trauma
Surgical or procedure-related
C. Decide what tests you want to order to either include
or exclude a potential diagnosis. Chapter 2 discusses how
to use diagnostic tests in an appropriate manner.
D. Unifying diagnoses. It is often hard to recogize a single
disease that accounts for all of the problems in a complex
case. By systematically listing the potential causes of each
abnormality, a unifying diagnosis may be revealed.
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2. Approach to Medical
Decision Making
a
INT
ODUCTION. Diagnoses tend to exist on the following

contmuum:
II
II
0%
Disease
absent
Probability of Disease
1 00%
Disease
present
A. Most diseases listed on an initial differential diagnosis
will fall somewhere in the middle of this continuum.
B. The goal of the physician is to explain the patient's pre
sentation by moving most diagnoses as far to the left as
possible (reasonably excluding them), while moving one
diagnosis as far to the right as possible.
C. The inappropriate use of diagnostic tests will leave many
diagnoses frustratingly close to the midpoint of the con
tinuum.
QUALITATIVE ASESSMENT. The degree of certainty re
quired to qualify a diagnosis as "reasonable" depends on:
A. The severity of the condition under consideration
B. The extent to which the condition is treatable
C. The risks associated with diagnostic testing
D. The risks associated with the treatment
QUANTTATIVE AsESSENT
A. The pretest probability is the probability of disease prior
to testing.
1. Consider the following three examples:
M A 45-year-old man presents to urgent care
clinic with a history of paroxysmal, sharp, left
sided chest pain occurring both at rest and with
exercise. He denies chest pressure occurring with
exercise. The symptoms have been present for 2
months. A literature search reveals that 50% of
45-year-old men with atypical chest pain have
5
Ifll 1 . . 1. A" UI:AITU efIClfC IIRCAa
6 Chapter 2
coronary artery disease. Therefore, the pretest
probability of coronary artery disease i this pa
tient is 50%.
b. If the patient is a 30-year-old woman with atypi
cal chest pain, the pretest probability of coronary
artery disease would be 5%.
c. If the patient is a 60-year-old man with exertional
chest tightness (typical angina), the pretest prob
ability of coronary artery disease would be 95%.
2. Suppose all three of these patients undergo an exer
cise treadmill test. Is coronary artery disease ruled
in if the tests are positive? Is it ruled out if the tests
are negative? In order to answer these questions,
it is necessary to consider the likelihood ratio as
well.
B. The likelihood ratio is the strength of the diagnostic
test result.
1. Sensitivity and specifcity are the characteristics used
most often to defne diagnostic tests.
a. Sensitivity answers the question, " Among pa
tients with the disease, how likely is a positive
test?"
b. Specifcity answers the question, "Among pa
tients without the disease. how likely is a nega
tive test?"
c. The likelihood ratio helps answer the clinically
more important questions:
(1) Given a positive test result, how likely is it
that the disease i truly present?
(2) Given a negative test result, how likely is it
that the disease is truly absent?
2. Mathematically, likelihood ratios are the odds of hav
ing disease given a test result versus not having a
disease given a test result.
a. For example:
Approach to Medical Decision Making 7
If the circle represents all patients with a positive
test and the shaded portion represents the por
tion who actually have disease, then the likeli
hood ratio is 3.
The chance of a
p
ositive test and disease 3
The chance of a positive test and no disease
b. Consider another example. The likelihood ratio
of a positive treadmill test is 3.5. In a large, het
erogeneous population of patients, all of whom
have had positive treadmill tests, 7 patients will
actually have coronary artery disease for every
2 patients who do not. Therefore, if your patient
has a positive treadmill test, the odds of that
person having coronary artery disease are 7 to
2, or 3.5 to 1. That is, given a positive treadmill
test. it is 3.5 times M likely that coronary artery
disease is present.
3. Likelihood ratios can be found in epidemiology text
books or calculated using the following formulas:
. . True
p
ositive rate
likelihood ratio of a positive test
=
FI T t a se POSI Ive ra e
(Sensitivit)
(1 - Specificit)
. False ne
g
ative rate
likelihood ratio of a negative test =
T r t rue neg a Ive ra e
_ (1 - Sensitivit)
-
(Specificit)
a. Most diagnostic tests have likelihood ratios in
the 2-5 range for positive results and in the 0.5-
0.2 range for negative results. These types of tests
are only very useful if the pretest probability of
disease is in the middle of the scale (e.g . . 30%-
70%). At either end of the probability scale, diag
nostic tests with small likelihood ratios do not
change the probability of disease much.
b. Good tests have positive likelihood ratios of 10
or more. These powerful diagnostic tests help
rule in a diagosis across a broader range of
pretest probabilities. Unfortunately, these types
of tests are often expensive or dangerous.
L- In order for a test to truly rule in disease across
8 Chapter 2
the full range of pretest probabilities, it must
have a likelihood ratio of 100 or more. Very few
tests (e.g., some biopsies, exploratory laparot
omy, cardiac catheterization) have likelihood ra
tios this high.
C. Calculating the posttest probability. Posttest probability
is the probability that a specifc disease is present after
a diagnostic test. Once we have determined the pretest
probability of disease (using clinical information and dis
ease prevalence data) and the likelihood ratio of the
diagnostic test result, we are ready to calculate the post
test probability. First, however, the pretest probability
must be converted to odds (the likelihood ratio is already
expressed in odds).
1. Steps
a. Pretest probability must be converted to pre
test odds:
Odd
=
(Probabili
t)
s
(l Probability)
(For example, a probability of 75% equals odds
of 3 : 1.)
b. Pretest odds are multiplied by the likelihood ra
tio to give posttest odds
c. Posttest odds must then be converted back to
posttest probability:
2. Examples
P b b'I' -
(Odds)
ro a I It y -
(Odds 1)
a. [n the 45-year-old man with the atypical chest
pain and a positive treadmill test, the posttest
probability of disease would be 78%:
(1) The 50% pretest probability is converted to
pretest odds: (0.5)/(1 - 0.5) = (0.5)/(0.5) =
1:1
(2) The 1 : 1 pretest odds are multiplied by the
likelihood ratio (3.5) to yield posttest odds
of 3.5 : 1 .
(3) The posttest odds are converted t o a posttest
probability: (3.5)/(3.5 + 1) = (3.5)/(4.5) =
.78, or 78%. These steps can also be pre
sented schematically:
Approach to Medical Decision Making 9
Pretest
probabilit
likelihood
ratio
Posttest
probabilit
b. In the 30-year-Old woman with atypical chest
pain and a positive treadmill test, the posttest
probability would be 16%:
Pretest likelihood Posttest
probabilit ratio probabilit
5%
1
3.
5 3.
5
'19
x-
l -
=
19
,1
6
%
$ In the 60-year-old man with atypical chest pain
and a positive treadmill test. the posttest proba
bility would be 98.5%:
SUMMARY
Pretest
probabilit
likelihood
ratio
Posttest
probabilit
95
0
/
0
19
3.
5
66.
5
985
1
~ 1
x
-1
-
=
1
- .
A. In order to gain diagnostic strength, several tests may
be combined-as long as they are independent tests. The
posttest probability after the frst test then becomes the
pretest probability for the next test.
B. In order to really lear this approach, you must use it.
Try it on your next patient and you'll be familiar with
odds before you know it!
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PART II
Cardiology
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3. Cardiac Examination
a
NECK VEIN EXINATION. Examination of the neck
veins is an underutilized part of the cardiac examination.
With practice, an accurate evaluation of central venous pres
sure and waveforms can be obtained.
A. Patient positioning. The patient should be sitting at ap
proximately a 30- to 40-degree angle. (The angle of the
bed may need to be increased or decreased until the
crests of the veins are in view.) The patient's head should
be kept close to midline; turning the head in the opposite
direction is a common mistake that results in contraction
of the sterocleidomastoid muscles and an obscured
view. A penlight is helpful in illuminating the veins tan
gentially (i.e., from front to back).
B. Anatomy
L Internal jugular veins. The right internal jugular vein
best displays the various waveforms because it is a
"straight shot" to the right atrium. The left internal
jugular vein can also be used, but may be less ac
curate.
2. External jugular veins may be used if internal veins
are not appreciated, but it is important to ensure that
the vein is flling from below and not above. This
may be accomplished by emptying the vein from the
superior to inferior direction (using a forefnger), and
placing the middle fnger on the superior portion of
the vein.
a. If releasing the vein inferiorly results in flling,
the external jugular is presumably refecting right
atrial pressures.
b. If repeating the procedure and releasing the vein
superiorly results in flling, the external jugular
will not accurately refect right atrial pressures.
3. Carotid arteries. Clinicians sometimes have diffculty
distinguishing the carotid arteries from the jugular
veins.
M Carotid waves have two phases (i.e., in and out),
whereas jugular waves usually have four phases
and appear to undulate.
b. Carotid arteries predominantly move out,
whereas the jugular veins predominantly move
in (i.e., descents are more obvious than crests).
1
3
1 4 Chapter 3
c. The carotid artery usually produces palpable pul
sations.
d. Placing the side of the hand against the base
of the neck may obstruct jugular pulsations, but
carotid impulses are usually unchanged.
C. Findings
1. Central venous pressure (CVP). To estimate the
CVP, hold a straight edge fom the crest of the jugu
lar vein, horizontally across to a point above the
sternal angle (i.e., the palpable ridge). Measure the
vertical distance fom the straight edge to the sternal
angle, and add 5 centimeters.
a. A CVP < 10 cm H20 is considered normal.
b. A CVP > 10 cm H20 may be found with right
ventricular failure, tricuspid stenosis, cardiac
tamponade, and constrictive pericarditis.
2. Waveforms. The letters O J U and y denote atrial
contraction, atrial relaxation, atrial flling, and atrial
emptying, respectively.
IIPRECORDIAL PALPATION
A. Technique. The point of maximal impulse (PMI) is usu
ally appreciated in the fourth or ffh interspaces of the
midclavicular line.
B. Findings. Normally, the examiner feels the impulse hit
and leave the fngers of her right hand before the carotid
impulse is felt with her left hand. A sustained left ventric
ular impulse (i.e., left ventricular heave) is diagnosed
when there is overlap with the carotid impulse, and it
indicates left ventricular hypertrophy or dilatation (i.e.,
failure). The following assessments can be used to distin
guish between hypertrophy and dilatation.
1. Location. Displacement of the PMI inferolaterally is
more indicative of dilatation.
2. Size. A large PMI (i.e., greater than 3 cm or present
in more than one interspace) usually indicates dila
tation.
3. Kinetics. Dilatation usually causes a hypokinetic
PMI, whereas hypertrophy results in a hyperki
netic PMI.
4. Gallops. A third heart sound (S3) is associated with
dilatation, whereas a fourth heart sound (S4) is
thought to be more indicative of hypertrophy.
Cardiac Examination 15
II
AUSCULTATION
A. Techniqne
1. The areas where each valve i best heard are listed
in Table 3-1.
2. A frequently used pattern of auscultation i s to start
with the bell of the stethoscope at the apex and
left sternal border, change to the diaphragm of the
stethoscope, and continue the examination upward
to the pulmonic and then aortic areas.
a. Generally, the bell of the stethoscope is used at
the apex and left lower sternal border to detect
low-pitched sounds (i.e., gallops).
b. The diaphragm of the stethoscope is used to eval
uate murmurs, normal heart sounds, and clicks,
and is often used at the left sternal border and
above.
B. Findings. Rather than trying to appreciate all normal and
abnormal sounds simultaneously, direct your attention to
the first heart sound (St), then the second heart sound
(S2), and fnally to murmurs. There is a differential diag
nosis for each fnding.
1. "Split" St. If you hear two components of the S.,
differential diagnoses include systolic ejection
sounds (i.e., a click), a fourth heart sound (S4)' and
a split St. The following features can help distinguish
among these possibilities.
a. SystoHc ejection sounds often occur with aortic
or pulmonic stenosis, and are the least common
of the three possibilities. They are often high
pitched and are best heard with the diaphragm
over the aortic or pulmonic regions.
b. S4 versus a split St. This is the more common
and diffcult diagnostic question.
TABLE 3-1 : Auscultation
Portion of
Valve Stethoscope Positioning
Aortic
Pulmonic
Tricuspid
Mitral
Diaphragm
Diaphragm
Bell
Bell
Right sternal border, 2nd interspace
Left sternal border, 2nd interspace
Left lower sternal border
Apex and left lower sternal border
16 Chapter 3
(1) Location. The tricuspid valve is usually quiet
because it is closed by a low-pressure system.
Hearing two sounds only over the tricuspid
area favors a split S}, whereas hearing two
sounds over the apex favors an S4 followed
by an S].
(2) Pitch. An S4 is low pitched and best heard
with the bell, whereas tricuspid closure re
sults in a high-pitched sound that is best
heard with the diaphragm.
(3) Volume. Closing of the mitral valve is usually
louder than an S4 or closing of the tricuspid
valve. If the frst of the to split" sounds
is louder. mitral valve closure followed by
tricuspid valve closure is more likely. A
louder second sound favors an S4 followed
by closure of the mitral valve.
2. "Split" Sz. [f you hear to components of the Sz,
differential diagnoses include an S3 and a split Sz. The
pericardial knock of constrictive pericarditis, which is
virtually indistinguishable from an S3, is another,
much less common, possibility.
a. Location. The S3 is usually best heard over the
apex or the lower left sternal border, depending
on whether the sound is emanating from the left
or right ventricle. A split Sz is best appreciated
over the pulmonic area.
b. Pitch. An S3 is very low pitched and heard only
with the bell, whereas pUlmonic closure causes
a higher pitched sound that is best heard with
the diaphragm.
c. Changes during respiration. In a patient with a
split Sz, respiratory variation may cause the inter
mittent appearance and disappearance of one of
the sounds. An S3 is less likely to change with
the respiratory cycle.
3. Murmurs are either systolic (between S] and Sz), dia
stolic (after Sz), or continuous (beginning in systole
and continuing into diastole without interruption).
Simultaneously palpating the carotid artery can help
you decide whether the murmur is systolic, diastolic,
or continuous.
a. Systolic murmurs can be classied as holosystolic,
early systolic, midsystolic, or late systolic.
(1) Holosystolic murmurs begin at S] and end at
Sz and are caused by a continuous pressure
gradient throughout systole. Holosystolic
murmurs are often associated with the fol
lowing disorders.
(a) Mitral regurgitation. The murmur is best
heard at the apex, usually radiates to the
axilla, and is unchanged or decreased
by inspiration.
(b) Tricuspid regurgitation. The murmur is
best heard over the tricuspid area, often
increases with inspiration, and may be
associated with prominent v waves.
(c) Ventricular septal defect. The murmur is
best heard at the left lower sternal bor
der, often radiates to the right sternal
border. and does not increase with inspi
ration.
(d) Patent ductus arteriosis usually results in
a continuous murmur, but when pulmo
nary hypertension develops, the aorto
pulmonary gradient may be diminished
in diastole.
(2) Early systolic murmurs begin at S] and end
prior to Sz . These murmurs occur when the
pressure between chambers equalizes later
in systole. Early systolic murmurs are caused
by basically the same processes that result in
holosystolic murmurs:
(a) Severe, acute mitral regurgitation into a
nondistensible left atrium
(b) Tricuspid regurgitation from infective
endocarditis where right ventricular pres
sures are not increased
(c) Small ventricular septal defects or those
that lead to elevated right ventricular
pressures
(3) Midsystolic murmurs begin after S] and end
prior to S.
(8) High-output states (e.g., anemia, thyro
toxicosis, sepsis) may precipitate fow
murmurs that are usually heard best at
the lower left steral border.
(b) Aortic stenosis produces a harsh, cre
scendo-decrescendo mid systolic mur
mur that is usually best heard at the aortic
area and radiates to the carotid arteries.
(c) Aortic sclerosis is very common in the
r
18
HOT
KEY
Chapter 3
elderly. The munnur is similar to that of
aortic stenosis but tends not to radiate to
the carotid arteries.
(d) Hypertrophic cardiomyopathy may re
sult in outfow obstruction, producing a
murmur that can be distinguished from
that of aortic stenosis by the fact that it
increases with inspiration and on chang
ing position from squatting to standing.
(e) Mitml regurgitation. Some forms of mi
tral regurgitation (usually associated with
left ventricular wall motion abnormali
ties) may result in a midsystolic murmur.
"Finger squeeze" can help distinguish mitral regurgito
tion from aortic murmurs. When the patient squeezes
your fingers, the murmur from mitral regurgitation usu
ally increases, whereas aortic murmurs decrease or
remain the same.
(f Pulmonic stenosis, which is rare in adults,
produces a murmur that is best heard
over the pulmonic area.
(4) Late systolic murmurs begin after S] and end
at S, and usually imply mitral valve prolapse.
A click may precede the murmur. Decreasing
the left ventricular volume (e.g., by having
the patient inhale, perform the Valsalva ma
neuver, or stand up from a squatting position)
will cause the click to occur earlier and
lengthen the murmur.
b. Diastolic murmurs are similarly classified.
(1) Early diastolic murmurs are associated with
the following disorders.
(a) Aortic insufciency results in a decre
scendo murmur over the aortic area or
left steral border. It is best heard when
the patient is sitting upright, leaning for
ward, and holding his breath after a full
expiration. A long and loud murmur im
plies chronic aortic insuffciency, whereas
the murmur of acute aortic insuffciency
is usually shorter and softer because the
ventricle is nondistensible (i.e., there is
less of a pressure gradient).
(b) Pulmonic insuffciency produces a Gra
ham-Steell murmur that is best heard
over the pUlmonic area, and may be dif
fcult to distinguish from the murmur of
aortic insufciency. Pulmonic insuffi
ciency usually occurs in the setting of pul
monary hypertension.
(2) Mid-diastolic murmurs are associated with
the following conditions:
(a) Mitral stenosis often causes an opening
snap followed by a subtle murmur. Listen
with the bell at the apex with the patient
in the left lateral decubitus position.
(b) Tricuspid stenosis. The murmur is best
heard over the tricuspid area, and may
increase with inspiration.
(c) Increased volume across a nonobstructed
valve may also result in similar murmurs.
Mitral regurgitation and ventricular sep
tal defects increase fow across the mitral
valve, and tricuspid regurgitation and
atrial septal defect increase fow across
the tricuspid valve. The condition that
produces the increased volume is usu
ally apparent.
(d) Coronar arter obstruction (especially
obstruction of the proximal left anterior
descending artery) can produce a
Docks murmur.
(3) Late diastoHc murmurs are similar to mid
diastolic murmurs and usually represent mi
tml or tricuspid stenosis. Presystolic augmen
tation of the murmur may result from atrial
contraction, increased valve closure from
ventricular flling, or both.
c. Continuous murmurs are relatively uncommon
in adults. The venous hum of childhood is com
mon and normal. It is best heard over the right
supraclavicular fossa in an upright patient, and
can be abolished by compressing the internal jug
ular vein. Pathologc conditions that cause con
tinuous murmurs include the following.
20
Chopter 3
t. Patent ductus arteriosus results in the classic "ma
chinery" murmur.
2. Coarctation of the aorta may produce a continuous
murmur that is best heard over the back.
3. Arteriovenous fstulae (systemic and coronary) and
many other congenital disorders may result in contin
uous murmurs.
4. Electrocardiogram (EKG)
Interpretation
a
INTRODUCTION. There is no absolute right order for inter
preting EKGs, but it is important to choose a method and
interpret each EKG in precisely the same way. One common
approach is to evaluate EKG fndings in the following order:
rhythm, rate, axis, intervals, hypertrophy, Q waves, and STIT
wave changes.
IIRHYHM
A. Normal sinus rhythm. If each normal P wave (atrial depo
larization) is followed by a QRS complex (ventricular
depolarization) and the heart rate is between 60 and 100
beats/min, then the patient is in normal sinus rhythm.
B. Tachycardia is a heart rate greater than 100 beats/min
(see Chapter 6).
C. Bradycardia is a heart rate less than 60 beats/min.
1. Sinus bradycardia. Each QRS complex is preceded
by a P wave.
2. Other forms of bradycardia [e.g., atrioventricular
(A V) nodal block] are discussed in V A 2.
II
Rt
A. Regular rhythm. If the patient is in sinus rhythm, the
easiest way to calculate the heart rate is to divide 300
by the number of large boxes between two successive
QRS complexes. (Each large box is composed of fve
small boxes, each of which represents 0.04 second.)
B. Irregular rhythm. If the patient has an irregular rhythm,
divide a few consecutive beats (e.g., 4-6) by the number
of large boxes between them to get an average of the
time between beats. Divide 300 by this average to get
the heart rate.
C. Bradycardia. If the patient's heart rate is very slow, it is
easy to see how many beats occurred over a lO-second
period. Multiply the number by 6 to obtain the number
of beats per minute. (Ten-second periods are usually
marked on the EKG and are equivalent to 50 large
boxes.)
21
22
I
Chapter 4
TABLE 4- 1 : Using the EKG to Determine Heart Rate for Patients in
Sinus Rhythm'
Number of Boxes Corresponding Heart Rate
1
2
3
4
300 beats/min
150 beats/min
100 beats/min
75 beats/min
* Divide 300 by the number of large boxes between two successive QRS
complexes.
I AIS_ The QRS axis is the net vector generated by all ven
tricular depolarization. The exact degree of the vector (axis)
is not clinically useful-it is only necessary to determine
whether the axis is normal, shifted left, or shifted right. Left
and right axis shifts suggest disease of the ventricular myo
cardium.
A. Normal axis. A normal axis is between -30 and +90
when plotted using a hexaxial reference system. Any
thing more negative than -30 is called a leftward or
superior axis (because the axis is moving left toward the
12 o'clock position) and anything more positive than
+90 is a rightward axis.
B. Determining axis (Figure 4-1). By inspecting the QRS
complex in each limb lead, you can narrow down where
the net vector (QRS axis) is pointing.
To evaluate axis, it is only necessary to look at limb leads
I and II.
1. Normal axis. Both lead I and lead II are positive.
2. Leftward axis. Lead I is positive and lead Il is neg
ative.
3. Rightward axis. Lead I i negative and lead II is pos
itive.
4. Indeterminate axis. Both lead I and lead II are neg
ative.
C. Causes of axis deviation
1. Left axis deviation (LAD). Left anterior fascicular
block and inferior wall myocardial infarction account
for most cases of LAD.
a. Left anterior fascicular block
(1) Pathogenesis. The left bundle splits into ante-
Electrocardiogram (EKG) Interpretation
A
B
(-) --
III
NLrHal
d I
LII 1
+90
0
aVF
RAD
r
II
(+)
LAD
1
r
-30
aVL
23
FiGURE 4-1 . (A) Determining axis. I f the QRS complex of lead I i s net
p
ositive (i.e., the area above the horizontal is greater than the area be
l
ow), the axis must lie somewhere in the gray shaded region. If lead I I is
net positive, then the axis must lie in the crss-hatched region. The area
of overlap denotes the range for a normal axis. (8) Appearance of the
QRS complex in leads I and II in left axis deviation (LAD), right axis devi
ation (RAD), and normal axis.
24
Chapter 4
rior and psterior fascicles. The anterior fas
cicle runs superiorly; therefore. when the a
terior fasccle is blocked, the muscle that It

serves must be depolarized from inferior
forces. These "extra" inferior to superior
forces rotate the axis leftward (i.e., supe-
riorly).
.
(2) Criteria for diagnosis include an aXIs between
-45 and -90, a OR pattern in lead aVL,
an R peak time (from the beginning of 0 to
the peak of R) in lead aVL greater than or
equal to 45 msec, and a ORS complex usually
less than 0.12 second in duration.
(a) An axis of -30 to -45 may rep
esent
the left anterior fascicular block If the
other criteria are present.
(b) Because lead a VL is located near the left
anterior fasccle (at approximately -30),
a block in the left anterior fascicle causes
initial forces to move away from lead
a VL, producing the OR pattern and de
lay in peak time.
b. Inferior wall myocardial infarction
(1) Pathogenesis. Dead tissue at the inferior as
pect of the lef ventricle does not conduct;
therefore, more net forces move superiorly
(or leftward).
.
(2) Criteria for diagnosis. Look for 0 waves M
the inferior leads (i.e., leads II, III, and a VF)
to make the diagnosis.
c. Posteroseptal accessory pathway. Look for nega
tive delta waves in the inferior leads. a short PR
interval (less than 0.12 second in duration), and
a tall R wave in lead V2.
d. Chronic obstructive pulmonary disease (COPD).
A lower diaphragm can move the right ventricle
below the larger left ventricle and cause more
superor forces. However, when acompanied by
pulmonary hypertension, COPD often produces
right axis deviation (RAD).
e. Congenital heart disease (e.g., atrial septal de
fect, ventricular septal defect)
f. Hyperkalemia (usually severe)
g. Pulmonary embolus can produce LAD but more
often produces RAD.
h. Normal variant
V
I
I
I
I
1
V
I
I
Electrocardioram (EKG) Interpretation
25
2. Right axis deviation (RAD)
a. Right ventricular hypertrophy. RAD is caused
by right ventricular hypertrophy until proven
otherwise. (Criteria for right ventrcular hyper
trophy are discussed in VI B).
b. Acute cor pulmonale (e.g., pulmonary embolus,
acute bronchospasm). Look for a shift of axis to
the right of more than 30 when compared with
a prior EKG.
c. Extensive left free waD myocardial infarction.
Look for 0 waves in leads I and a VL.
d. Lateral left free wall accessory pathway. Look
for a short PR interval.
e. Left posterior fascicular block should be consid
ered a diagnosis of exclusion.
f. Lead reversal. Look for an inverted P wave in
lead I.
g. Pneumothorax
h. Tricyclic antidepressant overdose. Look for frst
degree A V nodal block and increased ORS and
OT intervals.
i. Normal variant (in young people)
INTERVA
A. PR interval. The PR interval is normally between 0.12
second and 0.20 second in duration. The appropriate
measurement is actually from the beginning of the P
wave to the beginning of the 0 wave, not the R wave.
1. A short PR interval is often caused by a high cate
cholamine state that makes the A V node conduct
faster: however, you should look for delta waves to
rule out an accessory pathway.
2. A prolonged PR interval is associated with increased
vagal tone or more permanent disease to the conduc
tion system.
a. First-degree A V nodal block. If each P wave i
followed by a ORS complex at a longer than
normal interval, a frst-degree A V nodal block
is diagnosed.
b. Second-degre A V nodal block. In second-de
gree A V nodal block, some P waves are not fol
lowed by a ORS complex. producing varying de
grees of bradycardia.
c. Third-degree A V nodal block. P waves and ORS
complexes are completely unrelated.
26 Chapter 4
B. QRS interval. The QRS interval is normally less than
0. 1 second in duration. Measurement is from the begin
ning of the Q wave to the end of the S wave.
1. Interventricular conduction delay or incomplete
bundle branch block is diagnosed when the QRS
complex i 0.1-0.12 second in duration.
2. Bundle branch block is diagnosed when the QRS
complex is greater than 0.12 second in duration
(,widened").
a. Pathogenesi. If the right bundle is blocked. de
polarization must proceed down the left bundle
and then slowly to the right from muscle fber to
muscle fber. Muscle conducts slowly compared
with the specialized bundles; therefore, the QRS
complex will be wider than normal, and the late
electrical forces will move to the right. Similarly,
a left bundle branch block will also have a wide
QRS complex, and the late forces will move to
the left.
b. Diagnosis
(1) Determining the dirction of the late forces
(Figure 4-2). Draw a line down the middle
of the QRS complex in lead VI (a rightward
lead) and lead V6 (a leftward lead). The half
of the QRS complex to the right of the line
represents the "late" forces. Check if these
are positive (above the horizontal) or nega
tive (below the horizontal).
(2) Interpretation
(a) Right bundle branch block. If the late
forces of VI are positive and those of
V6 are negative, then the late forces are
moving toward the right from the left,
signifying a right bundle branch block.
(b) Left bundle branch block. If the late
forces of V6 are positive and those of
VI are negatve, then the late forces are
moving toward the left from the right,
indicating a left bundle branch block.
(c) Nonspecifc interventricular bundle
branch block is often diagnosed when the
V1 and V6 are either both negative or
both positive.
C. QT interval. The QT interval varies according to the
heart rate. Measurement is from the beginning of the Q
wave to the end of the T wave. A QT interval greater
Electroardiogram (EKG) Interpretation
A. Right bundle branch block
B. Lef bundle branch block
t
|
|
V1
t
t
|
VI
T
27
V6 +
t
A
V6
FiGURE 4-2. Determining the direction of the late forces. (A) Right bun
dle branch block. The late frces are positive in lead VI and negative in
lead V6. (8) left bundle branch block. The late forces are negative in
lead VI and positive in lead V6.
than 0.48 second in duration is almost always abnormal.
Drugs (e.g., trcyclic antidepressants, amiodarone, type
Ia antiarrhythmics), and electrolyte abnormalities (hypo
kalemia, hypomagnesemia, hypocalcemia) are common
causes of a prolonged QT interval.
I HYPERTROPHY
A. Left ventricular hypertrophy. All EKG criteria for the
diagnosis of left ventricular hypertrophy are poorly sensi
tive but highly specifc. One approach i to proceed
through the following criteria in the order given. If a
criterion is met, you diagnose left ventricular hypertro
phy (high specifcity); i not, you move to the next cri
terion.
1. R wave in lead aVL > 11 mm (> 13 mm if left
anterior fascicular block is present)
2. R wave in lead a VL + S wave in lead V3 > 20 mm
in a woman or 28 mm in a man
3. S wave in lead VI + R wave in leads VS or V6
(whichever is larger) > 35 mm
28 Chapter 4
B. Right ventricular hypertrophy. Criteria for the diagnosis
of right ventricular hypertrophy are also highly specifc
but insensitive.
1. R: S wave ratio in lead VI greater than or equal to 1
2 R wave in lead VI greater than 7 mm
3. R: S wave ratio in lead VS or V6 less than I
C. Left atrial abnonnality was formerly called left atrial
enlargement, but the name was changed because the
EKG fndings may actually represent dilatation, in
creased atrial pressure, or hypertrophy.
1. Lead II. Notched P waves greater than 0.04 second
apart (1 small box) indicate left atrial abnormality.
2. Lead VI. If the P terminal force (the negative defec
tion that represents left atrial depolarization) is equal
to or greater than one small box by one small box
(0.04 sec by 1 mm), left atrial abnormality is diagnosed.
D. Right atrial eulargement
1. Lead I. A P wave greater than 2.5 mm high indicates
right atrial enlargement.
2. Lead VI or V2. A P wave greater than 1.5 mm high
indicates right atrial enlargement.
Q WAVES simply indicate that forces are moving away
from their respective leads.
A. Normal Q waves. Sometimes Q waves are normal and
expected. For example. the interventricular septum is
depolarized left to right, and so a Q wave is expected in
lead V6 (refecting forces moving away from this left
ward lead).
B. Pathologic Q waves signify that forces are moving away
from the area more than would normally be expected.
A pathologic Q wave indicates an old myocardial in
farction, and is only diagnosed when the Q wave is at
least 30 msec (close to one small box) in duration and
one third the height of the ensuing R wave.
1. Inferior wall myocardial infarction. Leads II, III. and
a VF evaluate the inferior surface of the left ventricle.
Therefore, Q waves in these leads denote an inferior
wall myocardial infarction.
2. Posterior wall myocardial infarction. Sometimes an
inferior wall infarction is accompanied by a posterior
wall infarction, producing a large R wave in lead
VI (i.e., forces move away from the posterior wall
anteriorly). Differential diagnoses for a large R wave
in VI include:
, .
Electrocardioram (EKG) Interpretation 29
a. Posterior wall myocardial infarction
b. Posteroseptal accessory pathway
c. Right ventricular hypertrophy
d. Right interventricular conduction delay
e. Right bundle branch block
f. Duchenne's muscular dystrophy
g. Limb lead reversal
h Dextrocardia
i. Normal variant
3. Anterior myocardial infarction. Q waves in the pre
cordial leads (Vl-V6) imply an old anterior myocar
dial infarction.
m 5T /T WAVE CHANGES
A. Canses The most common causes of STfT wave changes are:
1. Myocardial ischemia, injury, or infarction
2. Ventricular enlargement
3. Abnormal ventricular depolarization (e.g., with bun
dle branch block)
4. Electrolyte disturbances
B. Findings
1. T wave inversions often indicate myocardial ischemia.
2. ST elevations or depressions often indicate myocar
dial injury.
3. ST elevations with the appearance of Q waves usually
indicate myocardial infarction.
C. Tenninology. Clinicians often refer to ST depressions
and elevations as ischemia and infarct, respectively,
rather than simply "injury." This is because ST depres
sion is caused by injury to the subendocardial (inner)
region that is often the result of a supply/demand mis
match caused by ischemia. ST elevation implies transmu
ral injury that usually occurs as a result of complete
coronary occlusion during an infarction.
5. Syncope
a
INTRODUCTION
II
A. Defnition. Syncope is a transient loss of consciousness
and postural tone that is caused by inadequate cerebral
blood fow.
B. Epidemiology. Syncope is extremely common, account
ing for approximately 5% of medical admissions and 3%
of emergency room visits. The lifetime incidence ap
proaches 50% in some groups.
CAUSES OF SYNCOPE. There are many causes of syncope,
but the most important can easily be remembered using the
mnemonic, "SYNCOPE."
Causes of Syncope ("SYNCOPE")
Situational
Vasovagal (the V looks like a Y)
Neuroenic
Cardiac
Orthostatic hypotension
Psychiatric
Everything else
1. Situational causes include mictuntlOn, defecation,
swallowing, coughing, subclavian steal, and carotid
sinus sensitivity.
2. Vasovagal syncope, also known as the "common
faint," is the most common cause of syncope in young
patients and is ofen preceded by a painful or emo
tional stimulus.
3. Neurogenic causes inclUde autonomic insufciency
and transient ischemic attacks (TIAs).
a. Transient ischemic attacks (TIAs) are extremely
rare causes of syncope. For syncope to occur, the
vertebrobasilar circulation must be involved.
b. Autonomic insufciency is common in elderly
patients and patients with diabetes.
4. Cardiac causes
30
1
Syncope 31
II
a. Obstructive disorders. Aortic, mitral, or pul
monic stenosis, idiopathic hypertrophic subaortic
stenosis. atrial myxoma, and pulmonary embo
lism interfere with cardiac output and can precip
itate a syncopal attack.
b. Arrhythmias. Disorders that lead to bradycardia
[e.g., sick sinus syndrome, second- and third-de
gree atrioventricular CAY) block] or tachycardia
[e.g., ventricular fbrillation, ventricular tachycar
dia, torsades de pointes, supraventricular tachy
cardia] also interfere with cardiac output.
c. Ischemic disorders can precipitate an episode
of syncope.
5. Orthostatic hypotension can cause syncope.
6. Psychogenic syncope is a diagnosis of exclusion.
7. Everything else
a. Medications (e.g., vasodilators, hypnotics, seda
tives, nitrates, diuretics, O blockers)
b. Drugs (e.g., cocaine, hypnotics, sedatives, al-
cohol)
ApPROACH TO THE PATIENT. The evaluation of a patient
with syncope must be approached in a rigorous. stepwise
fashion to avoid missing life-threatening disease.
A. History and physical examination. A thorough history
and physical examination is a very imprtant aspect of
the evaluation and may establish the diagnosis in
many patients.
1. Situational. Was the episode preceded by urination,
defecation, swallowing, coughing, exertion of arm
muscles (subclavian steal), or manipulation of the
neck (carotid sinus hypersensitivity)?
2. Vasovagal. Did a painful or emotional stimulus pre
cede the event?
3. Neurogenic. Did anyone witness convulsions, bowel
or bladder incontinence, or signs suggestive of a post
ictal state? A seizure is not syncope but could result
in a loss of cnsciousness and therefore must be
considered in the differential diagnosis.
4. Cardiac. A cardiac cause is more likely if the patient
has any history suggestive of cardiac disease. Has
the patient complained of feeling lightheaded during
exercise (suggestive of an obstructive cause)? Has
the patient complained of "palpitations" (suggestive
of an arrhythmic cause)? Patients may also cmplain
of symptoms suggestive of cardiac ischemia.
32 Chapter 5
5. Orthostatic hypotension. Does the patient report
that he "got up too quickly"? Always check or
thostatic vital signs in patients admitted with
syncope.
6. Psychogenic. A psychogenic cause for the syncope
(e.g., hyperventilation) should be considered after
all other causes have been excluded.
7. Everything else. What prescripton, over-the
counter, or illicit drugs might the patient have ac
cess to?
B. Electrocardiogram (EKG). All patients should have an
EKG, although fewer than 10% of the causes of syncope
can be identifed by this test. Look for evidence of acute
or remote myocardial infarction, preexcitation syn
dromes, arrhythmias, and conduction system disease.
C. Rk assessment. Patients should be separated into two
groups: those without evidence of heart disease, and
those who may have heart disease.
1. No evidence of heart disease. Patients who meet all
of the following criteria after a thorough history,
physical examination, and EKG are at low risk for
a cardiac cause, and additional cardiac testing may
not be indicated. However, some patients may re
quire additional evaluation and treatment. The crite
ria are:
a. Y onnger than 60 years of age
b. No history or evidence of coronary artery disease
or congestive heart failnre
c. Normal EKG
2. Evidence of heart disease. Anyone who does not
meet all of the criteria in III C 1 is included in this
group. If there is suspicion of an ischemic or arrhyth
mic cause, admission and EKG monitoring are indi
cated. Additional diagnostic tests to be considered in
clude:
a. Ambulatory EKG monitorng. This test is widely
used, but it establishes a diagnosis in only a small
percentage of patients. Event or loop recorders
may improve the diagnostic yield.
b. Exercise treadmill testing can rule out exercise
or ischemia-induced syncope.
c. Echocardiography allows assessment of valvular
disease, as well as left ventricular size and
function.
d. Electrophysiologic testing is especially useful in
patients at high risk for arrhythmia (i.e., those
l
Syncope 33
with poor left ventricular function) when a diag
nosis cannot be established using noninvasive
methods.
e. Tilt table test. This test can be useful in docu
menting vasovagal syncope, but it has poor speci
fcity.
f. Signal-averaged EKG (SAEKG). The utility of
this test in patients with syncope is controversial.
TREATMENT is cause-specifc.
A. The treatment of any correctable cardiac abnormality
should be the frst consideration.
B. Patients with frequent vasovagal syncope may beneft
from a trial of f blockers.
PREVENTION
A. Medications and the use of alcohol or illicit drugs should
be carefully reviewed.
B. Education about likely precipitants can help prevent re
currences.
6. Arrhyhmias
a INTRODUCTION
A. Bradyarrhythmias usually do not pose a diagnostic di
lemma and have relatively few treatment options (e.g.,
atropine, pacer device).
B. Tachyarrhythmias may pose a signifcant challenge in
diagnosis and often are treated very differently. All
tachyarrhythmias can be classifed according to whether
they are regular (same distance between successive R
waves) or irregular, and whether their QRS complex
is narrow 0.12 second) or wide (> 0.12 second).
Making these two determinations and consulting Table
6-1 can signifcantly narrow the diagnostic possibili
ties:
II NARROW, REl TACHYARRHAS
A. Diferential diagnosis
L Sinus tachycardia
a. Etiologies. Sinus tachycardia is usually a physio
logic response to stress. Important etiologies in
clude:
(1) Low stroke volume states (e.g., from intra
vascular volume depletion or myocardial dys
function)
(2) Hypoxia (e.g., from pulmonary embolus)
(3) Hypercatecholamine states (e.g., from pheo
chromocytoma, pain, anxiety)
(4) Drugs (e.g., inhaled f agonists, theophyl
line, caffeine)
(5) Systemic causes (e.g., fever, anemia, hyper
thyroidism)
(6) Myocarditis and pericarditis
b. Electrocardiogram (EKG) appearance. Upright
P waves in leads II, III, and a VF are always
followed by a QRS complex.
34
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()
:
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Arrhythmias
TABLE 6-1: Classification of Tachyarrhythmias'
Regular Rhythm Irregular Rhythm
Narrow QRS Sinus tachycardia
AVNRT
AVRT
AT
Atrial flutter
Wide Q Ventricular tachycardia
Supraventricular tachy
cardia with aber
rancy
Atrial fibrillation
Atrial flutter with vari
able blok
Multifocal atrial tachy
cardia
Frequent premature
atrial contractions
Atrial fibrillatio with
aberrancy*
Ventricular tachycardia
(monomorphic or
polymorphic)
35
AT = atrial tachycardia; AVNRT = atrioventricular nodal reentrant tachycar
dia; AVRT = atrioventricular reentrant tachycardia.
* Because all arrhythmias characterized by an irregular rhythm and a narrow
QRS camplex can become irre
g
ular with a wide QRS complex in the presence
of aberrant conduction, atrial futter with variable block and multifoeal atrial
tachycardia must also be considered here, although they are much less
common than atrial fibrillation.
HOT
KEY
The maximum heart rate in sinus tachycardia = 220
minus the patient's age.
2. Atrioventricular nodal reentrant tachycardia
(A VRT) accounts for more than 50% of all supra
ventricular tachyarrhythmias. [All narrow, regular
tachyarrhythmias are supraventricular, but the term
supraventricular tachycardia is classically used for
A VNRT, atrioventricular reentrant tachycardia
(A VRT). and atrial tachycardia (AT).]
a. Characteristics include:
36 Chapter 6
(1) A heart rate of 180 beats/min (::10%)
(2) Isolated R waves, pseudo S waves. or in
verted P waves on the EKG
b. Mechanism. Many people have a dual atrioven
tricular (A V) node that contains a fast pathway
with a long refractory period and a slow pathway
with a short refractory period.
(1) Sinus rhythm. During sinus rhythm, the im
pulse i conducted down the fast pathway
to the ventricles. Conduction down the fast
pathway is also able to traverse the A V node
retrograde and block impulses on the slow
pathway (Figure 6-1).
(2) Excitation loop. The incidence of premature
atrial contractions (P ACs) increases with
age. A PAC may be blocked at the fast path
way secondary to its long refractory period;
the impulse is then conducted down the slow
pathway, which has a short refractory period.
The impulse may then enter the fast pathway,
which is no longer refractory, and activate the
atria by retrograde conduction (Figure 6-2).
c. EKG appearance
Slow pathway
(short refractory
period)
SA node
AV
node
Fast pathway
(long refractory
period)
His-Purkinje fibers
FiGURE 6-1. Dual atrioventricular node. sinus rhythm. AV = atrioventric
ular; SA = sinoatrial.

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0
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Arrhythmias 37
PAC
Slow pathway
(short refractory
period)
AV
node
Fast pathway
(long refractory
period)
His-Purkinje fibers
FIGURE 6-2. Atrioventricular nodal reentrant tachycardia (AVNRT) from
premature atrial contractions (PACs). Following conduction down the slow
pathwa
y
, the fast pathway is no longer refractor and may conduct retro
grade, forming an excitation loop. AV = atrioventricular.
(1) In typical AVNRT (90% of cases), a PAC
begins the loop of excitation. The P wave is
inverted and occurs simultaneously with the
QRS complex; only R waves are seen on
the EKG.
(2) In atypical A VNRT (10% of cases), a prema
ture ventricular contraction (PVC) initiates
the conduction of an impUlse up the slow
pathway and down the fast one (Figure 6-3).
Because the retrograde P waves are formed
from the slower pathway, they occur slightly
later and can be seen as pseudo S waves in
the inferior leads (II, III, avF) or as inverted
P waves following the QRS complex.
3. A VRT accounts for more than 30% of all supraven
tricular tachyarrhythmias.
a. Characteristics. A VRT is characterized by a
short RP interval on the EKG.
b. Mechanism. A VRT involves an accessory path
way, an abnormal tract of fast conducting tissue
between the atria and ventricles that bypasses
38
Slow pathway
(short refractory
period)
AV
node
PVC
Chapter 6
Fast pathway
(long refractory
period)
FIGURE 6-3. Atypical atrioventricular nodal reentrant tachycardia
(AVNRT). AV = atrioventricular; PVC = premature ventricular con
traction.
the A V node. Accessory pathways often conduct
in both an anterograde and retrograde direction.
c. EKG appearance
(1) Siu rhythm
(a) During sinus rhythm. anterograde con
duction results in ventricular preexcita
tion, manifested as a short PR interval
and a delta wave on the EKG.
(b) If only retrograde conduction is possible
(as is the case in approximately 25% of
patients), no abnormality is seen during
sinus rhythm (concealed bypass tract).
(2) Excitation loop
(a) Orthodromic conduction occurs when an
impulse is conducted through the A V
node and then up the accessory pathway
in a retrograde direction (Figure 6-4). Be
cause the loop is longer than that of
AVNRT, the retrograde P wave is easily
seen (i.e., it is not buried in the R wave).
The interval from the R wave to the ensu
ing retrograde P wave will be less than
that from the P wave to the next R wave
(short RP or RP < PR tachycardia). This
characteristic helps distinguish A VRT
V
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Arrhythmias
/
/
/

I
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Bypass tract \
I
,
'-
/
-,'"
AV
node
39
fiGURE 6. Orthoromic conduction leading t atrioventricular reen
trant tachycardia (AVRT). A V = atrioventricular.
from AT. The QRS complex remains nar
row because the ventricle is depolarized
normally (i.e., via the His-Purkinje
system).
(b) Antidromic conduction occurs when the
impulse is conducted ante grade down the
bypass tract. Antidromic conduction pro
duces a wide QRS complex because the
tract terminates on ventricular muscle
fbers. (Conduction from fber to fber
is slow.)
4. AT accounts for 15% of all supraventricular tachy
cardias.
a. Characteristics
(1) The atrial rate (as refected by the P waves
on the EKG) is usually less than 250 beatsl
min. (In atrial futter, the atrial rate is approx
imately 300 beats/min.)
(2) A long RP interval is noted on the EKG.
b. Mechanism. Enhanced automaticity of atrial tis
sue or atrial reentry with a focus usually located
in the lower portion of the atrium is thought to
be the mechanism.
(1) Patients often have structural heart disease.
(2) Because digitalis increases atrial and ventric-
ular automaticity and depresses conduction
tissue, AT with variable degrees of A V nodal
block is a common presentation of digitalis
toxicity.
c. EKG appearance. A retrograde P wave, pro
duced by depolarization of the atria from below,
is followed by a narrow QRS complex (produced
40 Chapter 6
HOT
KEY
by conduction of the impulse down the A V
node). The preceding P wave is linked to the R
wave, and the PR interval is shorter than the RP
interval (long RP or short PR tachycardia).
The supraventricular tachycardias can be classified
according to the RP interval:
Short RP = AVRT and, occasionally, AVNRT
long RP = AT
No RP = AVNRT
5. Atrial futter
HOT
KEY
a. Characteristics
(1) The atrial rate is often 300 beats!min, and the
ventricular rate is approximately 150 beats!
min. (In other words. a 2 : 1 A V block is com
monly seen.)
Whenever the ventricular rate is 150 beats/min (::5),
think of atrial flutter.
(2) Atrial futter i frequently transient and may
degenerate to atrial fbrillation or return to
sinus rhythm. In general, the causes of atrial
futter are similar to those of atrial fbril
lation.
b. Mechanism. Waves of organized depolarization
move through the atria.
c. EKG appearance. Because the waves often move
in a superior-inferior direction, futter waves are
best seen in the inferior leads (i.e., leads II, III,
and avF).
Arrhythmias 41
B. Treatment
1. Acute treatment depends on the patient's hemody
namic stability.
a. Hemodynamically unstable (or ischemic) pa
tient. Determine if the patient is in sinus rhythm.
(1) If the patient is not in sinus rhythm, initiate
electrical cardioversion immediately.
(2) If the patient is in sinus rhythm, tre
a
tment is
aimed at the underlying cause.
b. Hemodynamically stable patient
(1) Carotid sinus massage may increase vagal
tone and block impulses at the level of the
A V node. Carotid sinus massage is contrain
dicated in the presence of a carotid bruit and
should be performed with continuous EKG
monitoring and a crash cart available.
(a) A VNRT and A VRT, tachycardias that
involve reentrant loops through the A V
node, may terminate.
(b) AT is usually unaffected by carotid sinus
massage, but may terminate abruptly.
(c) Sinus tachycardia. Carotid sinus massage
may slow the atrial rate.
(d) Atrial futter usually becomes more obvi
ous as the A V block increases and futter
waves appear; the tachycardia will not
terminate.
(2) Administer adenosine in incremental doses
of 6 and 12 mg if carotid sinus massage is
ineffective. (Halve the dose if administration
is via a central line.) Adenosine is contraindi
cated in patients with acute bronchospasm,
and heart transplant patients and patients on
dipyridamole have an increased sensitivity.
The effects of adenosine occur within 15-30
seconds of administration and last for 10-20
seconds. Adenosine has effects similar to
those of carotid sinus massage. but they are
more pronounced.
(a) A VNRT and A VRT. More than 90% of
these tachycardias will be terminated
with a 12-mg dose.
(b) AT rarely terminates. Intravenous ad
ministration of verapamil or diltiazem is
preferable for arresting atrial tachycardia
Z
HOT
KEY
Chapter 6
and may decrease the ventricular re
sponse, even if the tachycardia persists.
(c) Sinus tachycardia transiently slows. Ad
ditional treatment should be aimed at the
underlying cause.
(d) Atrial futter. AV block increases and
futter waves are more evident. The heart
rate returns to its previous accelerated
rate as the efects of the adenosine wane.
Additional treatment may involve A V
nodal blockade with digitalis, { blockers,
or calcium channel blockers, followed by
either chemical (e.g .. procainamide) or
electrical cardioversion.
(i) Often, A V nodal blocking agents
will be unsuccessful at controlling
the heart rate and doses are limited
by their toxicity.
In atrial flutter, la agents should not be given prior to
the administration of AV nodal blocking agents be
cause type la agents may slow atrial conduction suffi
cienrly to permit . conduction through the AV node,
thereby increasing the ventricular response.
(i) Electrical cardioversion starting at
25 J is a reasonable alterative to
A V nodal blocking agents.
2. Chronic treahuent
a. A VNRT. I the patient experiences sporadic epi
sodes, control may be possible using vagal ma
neuvers. For patients who experience frequent or
symptomatic episodes, A V nodal blocking agents
or radiofrequency may be used.
b. A VRT. Symptomatic patients with evidence of
preexcitation on a baseline EKG should proba
bly receive radiofrequency ablation. Patients
with symptoms but no evidence of anterograde
conduction (i.e., concealed bypass tract) can be
treated with ablation or an initial trial of an A V
nodal blocking agent.
0
3
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Arrhythmias o
II
c. Atrial tachycardia. Calcium channel blockers or
{ blockers are often the drugs of frst choice. If
pharmacologic therapy fails, ablation may be in
dicated.
d. Atrial futter usually degenerates to atrial fbril
lation or reverts to sinus rhythm.
NARROW, IRREGULR TACHYARRHYHMIAS
A. Diferential diagnosis. In general, the members of this
category are able to be differentiated easily on the basis
of a 12-lead EKG. It is most diffcult to distinguish atrial
fbrillation from atrial futter with variable block.
1. Atrial fbrillation is discussed in detail in Chapter 7.
This arrhythmia is characterized by irregular atrial
fbrilla tory waves at a rate of 350-600 beats/min and
a ventricular rate of usually 120-160 beats/min.
2. Atrial futter with variable block. To help diferenti
ate atrial futter with variable block from atrial fbril
lation:
a Look at the inferior leads (II, III, avF). With
atrial futter, futter waves can often be "marched
out" at a rate of approxmately 300 beats/min.
Variable block will produce a ventricular rate in
proportion to the atrial rate (i.e .. the ventricular
response to 2 : 1, 3: 1, and 4: 1 A V block will
be 150 beats/min, 100 beats/min, and 75 beats/
min. respectively).
b. Increase A V block by massaging the carotid sinus
or administering adenosine. Flutter waves that
may have been hidden will often become ob
VIOUS.
3. Multifocal atrial tachycardia
a. Mechanism. In approximately 60% of patients,
multifocal atrial tachycardia is associated with
pulmonary disease. For example, cor pulmonale
causes right atrial stretch, producing different
foci of atrial contractions. Multifocal atrial tachy
cardia may also be caused by hypokalemia or
hypomagnesemia.
b. EKG appearance. Diagnosis requires the pres
ence of three distinct P wave morphologies in
the same lead and three separate PR intervals.
As a result, the RR interval varies (i.e., it is irreg
ularly irregular).
Chapter 6
4. Frequent PACs. When frequent, P ACs may give the
appearance of an irregular rhythm.
B. Treatment
1. Hemodynamically unstable (or ischemic) patients
with atrial fbrillation, atrial futter with variable
block, or multifocal atrial tachycardia should un
dergo immediate electrical cardioversion.
2. Hemodynamically stable
a. Atrial fbrillation. Treatment is discussed in
Chapter 7 VI.
b. Atrial futter with variable block. Treatment is
the same as that for atrial futter without variable
block [see II B Ib].
c. Multifocal atrial tachycardia. The underlying
condition (usually related to bronchospasm, hyp
oxia, or metabolic derangements) should be
treated. Intravenous verapamil is often tried, but
this is a diffcult arrhythmia to treat.
I WIDE, REGULR TACHYARRHYHMIAS
A. Mechanism. Normally, the impulse is conducted from
the sinoatrial (SA) node to the A V node, through the
bundle of His, and through the left and right bundle
branches (the Purkinje fbers). The bundles conduct rap
idly and ventricular depolarization is effcient, producing
a narrow QRS complex 100 msec in duration).
1. If one bundle is blocked, conduction will spread
down the remaining budle and then from muscle
fber to muscle fber. This is a slow process that pro
duces a wide QRS complex (> 120 msec in duration).
A QRS complex between 100 and 120 msec in dura
tion represents an incomplete bundle branch block
and is often termed an interventricular conduction
delay.
2. The QRS complex will be wide if the impulse starts
in the ventricle and spreads fber to fber (as is the
case with ventricular tachycardia) or if it starts above
the ventricle but eventually spreads fber to fber (as
is the case with supraventricular tachycardia with
aberrancy). There are three mechanisms of aber
rant conduction:
a. A preexisting underlying bundle branch block
b. A rate-related bundle branch block. As the heart
rate increases, one bundle (usually the right bun
die) is unable to keep up with the other. The
Arrhythmias
impulse is conducted down the faster bundle and

then from fher to fber, producing a wide QRS.
c. An accesr patway. These tracts terminate on
ventricular muscle, necessitatig fber-to-fber con
duction.
B. Diferential diagnosis. The differential is ventricular
tachycardia versus supraventricular tachycardia with ab
errancy.
HOT
KEY
Patients with cardiac disease should be assumed 1
have ventricular tachycardia until proven otherwise.
The Bmgada criteria can help you distinguish between
ventricular tachycardia and supraventricular tachycardia
with aberrancy.! The precordial leads (Vl-V6) are exam
ined on a 12-lead EKG. Each criteria is extremely spe
cifc, but not particularly sensitive, for ventricular tachy
cardia; therefore, if a criterion is met. you should initiate
treatment for ventricular tachycardia, and if the criterion
is not met, you continue to the next.
1. Absence of a true RS pattern in all of the precordial
leads. An S wave is a discrete negative defection. A
broad negative defection is an inverted T wave (as
opposed to an S wave). If there is a monomorphic
pattern (no RS), the arrhythmia is ventricular tachy
cardia.
2. RS complex (from start of R to nadir of S) is greater
than 100 msec. Ventricular depolarization takes
more time if it starts in the ventricle, rather than if
it begins supraventricularly and is conducted aber
rantly. If the RS complex is greater than 100 msec.
then the arrhythmia is ventricular tachycardia.
3. Evidence of A V dissociation includes P waves
1 Brugada P, Brugada J, Mont L, Sweets J, Andreis EW: A new approach
to the differential diagnosis of a regular tachycardia with a wide QRS
complex. Cre 83(5): 1649-59, 1991.
Chapter
marching through at different points of the wide
complexes and fusion or capture beats. Although
these clues are difficult to discern, they are diag
nostic of ventricular tachycardia. If a diagnosis
has still not been reached. morphologic criteria
(given in several texts) can be used to arrive at
a diagnosis.
C. Treatment
L Hemodynamically unstable (or ischemic) patients
should undergo cardioversion, starting with 200 J.
2. Hemodynamically stable patients
a. Ventricular tachycardia
(1) Lidocaine. The initial dose is 1-1.5 mg/kg
administered intravenously. followed by a
second dose of 0.5-0.75 mg/kg after 5-10
minutes.
(2) Procainamide should be considered in pa
tients who do not respond to lidocaine.
Procainamide is probably more effective at
terminating ventricular tachycardia. but hy
potension is common.
b. Supraventricular arrhythmias with aberrancy.
Carotid sinus massage and adenosine should be
employed as described in II B Ib.
c. Undiagnosed
(1) Lidocaine. The patient should be given a lido
cain e trial.
(2) Adenosine. If there is no response, adenosine
trials in 6- and 12-mg increments (half doses
if administered centrally) should be tried. If
the patient has a history of cardiac disease,
ventricular tachycardia is likely and needs to
be treated expediently.
(3) Procainamide. If the patient still fails to
respond, a procainamide trial may be indi
cated.
I WIDE, IRREGULR TACHYARRHYHMIAS
A. Diferential diagnosis. The differential diagnosis is atrial
fbrillation with aberrancy versus ventricular tachycardia
(monomorphic or polymorphic).
I
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Arrhythmias
HOT
KEY
All members of the irregular, narrow categary will
appear irregular and wide with aberrant conduction.
AZ
1. Atrial fbrillation with aberrancy. There are three
possible mechanisms of aberrant conduction.
HOT
KEY
a. Preexisting underlying bundle branch block. If,
upon comparing a previous 12-lead EKG with a
current one, there is evidence of an old bundle
branch block that has the same morphology as
the present one. this diagnosis is extremely likely.
b. Rate-related bundle branch block will usually
have a right bundle branch block pattern on the
EKG because the right bundle is usually slower
than the left bundle.
c. Accessor pathway. If there is evidence of preex
citation during sinus rhythm (i.e., a short PR in
terval, delta waves) on a prior 12-lead EKG, this
diagnosis is extremely likely. Another clue to
an accessory pathway is bizarre conduction (e.g.,
lead VI suggests a left bundle but the nearby
V2 lead suggests a right bundle). An accessory
pathway is a dangerous situation because fbril
latory waves occur at rates of approximately 600
beats/min and the accessory pathway allows
much faster conduction than does the A V node.
Very fast ventricular rates (i.e., 200-300 beats/
min) can be generated; this arrhythmia can
quickly degenerate to ventricular fbrillation.
Whenever you see a patient with a wide, irregular
tachyarrhythmia with a rate greater than Z beats/
min, consider atrial Fibrillation with an accessory
pathway.
Chapler 6
2. Ventricular tachycaria
a. Monomorphic ventricular tachycardia. In ven
tricular tachycardia. the rhythm may be irregular
for the frst 50 beats. A persistently irregular
rhythm after 50 beats essentially rules out mono
morphic ventricular tachycardia.
b. Polymorphic ventricular tachycardia. Because
the impulse is originating from diferent foci
in the ventricle, the rhythm is irregular. Torsades
de pointes is a type of polymorphic ventricular
tachycardia that undulates around the isoelec
tric point.
B. Treatment
1. Hemodynamically unstable (or ischemic) patients
should undergo cardioversion starting at 200 J.
2. Hemodynamically stable patients
a. Procainamide is the drug of choice.
(1) If the rhythm is atrial fbrillation with aber
rancy, procainamide may convert the patient
to sinus rhythm. If the cause of the patient's
aberrant conduction is an accessory path
way, procainamide will slow conduction
through the pathway, decreasing the ventric
ular rate, even though conversion may
not occur.
(2) Procainamide also treats ventricular tachy
cardia. However:
(a) Procainamide is contraindicated in the
setting of torsades de pointes. If a mor
phology consistent with torsades de
pointes is present or there are strong epi
demiologic factors suggestive of torsades
de pointes (e.g., an increased baseline QT
interval, use of quinidine or tricyclic anti
depressants, or electrolyte disturbances
such as hypokalemia or hypomagnese
mia), procainamide is contraindicated
because it will increase prolongation of
the QT interval and promote further tor
sades. Torsades should be treated with
intravenous magnesium or overdrive car
diac pacing.
(b) Procainamide frequently leads to hypo
tension, so patients with borderline blood
pressures (i.e., 90-100 mm Hg) and fast
Arrhythmias
(
J
V
heart rates may be better served with car
dioversion.
b. A V nodal blocking agents ({ blockers, calcium
channel blockers, or digitalis) should only be con
sidered when the patient shows strong evidence
of atrial fbrillation with a underlying bundle
branch block (i.e., a prior EKG shows the same
bundle branch block during sinus rhythm). Oth
erwise, A V nodal blocking agents should not be
administered to patients with wide, irregular
tachycardias because if the patient has an acces
sory pathway, A V nodal blocking agents will pro
mote conduction down the tract, thereby increas
ing the heart rate.
7. Atrial Fibrillation
...............................................................................................................
a
INTRODUCTION
A. Epidemiology
1. Atrial fbrillation is the most common chronic ar
rhythmia, occurring in 2% of the general population.
Of all patients admitted to the hospital, 7% will have
atrial fbrillation.
2. The incidence varies with age:
a. Rare in people younger than 50 years
b. One out of 20 people older than 60 years of age
c. One out of 10 people 80-89 years of age
B. Terminology. There are a number of terms used in associ
ation with atrial fbrillation.
L "Valvular" refers to atrial fbrillation that is second
ary to valve disease, most commonly rheumatic mi
tral valve disease. In the past, rheumatic heart disease
accounted for the majority of cases of atrial fbrilla
tion, but currently accounts for fewer than one-third
of cases. Atrial fbrillation unaccompanied by rheu
matic or other valve disease is termed "nonvalvular."
2. "Isolated" refers to atrial fbrillation that is second
ary to another illness (e.g., hyperthyroidism, pneu
monia, pulmonary embolism) and resolves when the
illness is treated.
3. "Paroxysmal" refers to intermittent episodes of
atrial fibrillation unrelated to an acute illness.
4. "Chronic" refers to atrial fbrillaton when it is the
predominant rhythm.
S. "Lone" refers to atrial fbrillation in the absence of
structural heart disease [e.g .. left ventricular hyper
trophy, congestive heart failure (CHF), valve disease,
cardiomyopathy].
II
CUNICAL MANIFESATIONS OF ATRIAL FIBRILLTION
A. Symptoms are due to loss of the atrial kick and an in
creased heart rate, which results in decreased ventricular
flling, decreased cardiac output, and an increase in car
diac demand. The most common symptoms refect
these processes.
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. Dyspnea
2. Chest pain
3. Palpitations
4. Dizziness or syncope
S. Fatigue
B. Physical examination fnding
1. Irregularly irregular pulse. An irregularly irregular
pulse is the hallmark of atrial fbrillation.
2. Pulse of varing intensity and pulse defcit. Because
diastolic flling varies in length and is often reduced,
pulses are of varying intensity and not all audible
ventricular beats are palpable peripherally.
3. Absent a waves in the jugular venous pulse
4. Variation in the intensity of the frst heart sound (SI)
HOT
Patients in atrial fibrillation never have an 54.
KEY
II
C. Electrocardiography
L The electrocardiogram (EKG) may show f waves
(fne fbrillation of the atria at a rate of 350-600
beats/min) that are best visualized in lead VI.
2. P waves are absent.
3. The ventricular response will be irregulary irregular,
although this may be diffcult to appreciate at higher
heart rates.
CAUSES OF ATRIAL FIBRILLTION. Because many of the
causes of atrial fbrillation are correctable, an effort should
be made to pinpoint the cause of the arrhythmia.
A. Idiopathic. In approximately 10% of patients, no etiology
can be found; these patients are said to have "lone"
atrial fbrillation.
B. Cardiovascular disorders, including sick sinus syndrome,
Wolff-Parkinson-White syndrome. coronary artery dis
ease, congestive heart failure, cardiomyopathy (hyper
trophic and dilated), myocarditis, hypertension, and con
genital heart disease
Z Chapter Z
C. Pulmonary disorders, including pulmonary embolism
D. Pericardial disease
E. Metabolic disturbances, including hyperthyroidism
F. Infltrative diseases, including amyloidosis. sarcoidosis,
and hemochromatosis
G. Intoxication (e.g., alcohol, theophylline, ( agonists)
H. Infection (e.g., endocarditis)
I. Stress-induced (e.g., post-surgery)
Causes of Atrial Fibrillation ("SWAMP
CHILD")
Sick sinus syndrome, Stress
WoIff-Parkinson-White syndrome
Alcohol (intoxication, withdrawal, "holiday
heart")
Myocarditis, Metabolic abnormality
Pericardial disease, Pulmonary disease
CHF, Coronary artery disease, Congenital
heart disease
Hypertension, Hyperthyroidism, Hypertrophic
cardiomyopathy
Infiltrative disease, Infection
Lone (idiopathic)
Dilated cardiomyopathy, Drugs
APPROACH TO THE PATIENT. A knowledge of the differ
ential will help direct diagnostic tests. All patients should
undergo an EKG, a chest radiograph (to rule out pneumonia
and other intrathoracic processes), a complete blood count
(C8C), electrolyte studies, and thyroid function testing. An
echocardiogram is usually obtained to examine cardiac func
tion and atrial size, and to rule out valve disease.
COMPUCATIONS. The risk of stroke in all patients with
atrial fbrillation is approximately 5% per year, fve times
the risk in those without atrial fbrillation. It is important to
"CHASE" after fve important factors that can allow you
to further defne your patient's risk for stroke:
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Risk Factors for Stroke in Patients with Atrial
Fibrillation ("CHASE")
CHF (Within o months)
Hypertension
Atrial size> cm
Stroke in past
Ejection fraction reduced
A. In patients with no risk factors, the risk of stroke is
approximately the same as the risk in the general popu
lation.
B. If the patient has one or two risk factors, the risk of
stroke is approximately 5% per year.
C. If the patient has three or more risk factors, the risk
increases to roughly 20% per year.
TREATMENT
A. Acute treatment. The goal of the acute treatment of a
patient with atrial fbrillation is rate control.
1. Cardioversion
a Indications. Cardioversion is indicated for any
patient with rapid atrial fbrillation ad life
threatening problems (e.g., ischemia, severe hy
potension, or severe pulmonary edema). You
may begin with 100 J in the synchronized mode,
but 360 J may be necessary.
b. Contraindications. Unless there is an emergent
indication. no patient with atrial fbrillation
should be cardioverted until anticoagulation
therapy has been initiated or until atrial throm
bus has been excluded using transesophageal
echocardiography. This usually includes patients
who are thought to have "new onset" atrial f
brillation because it is diffcult to estimate the
length of time the patient has been in atrial fbril
lation from the patient history. Patients who are
cardioverted without undergoing anticoagula
tion therapy have a 3%-5% risk of stroke within
30 days.
4 Chapter Z
2. Pharmacologc therapy
a. Atrioventricular (A V) node blocking agents. There
are several options for controlling heart rate:
(1) Digoxin (0.5 mg intravenously followed by
0.25 mg intravenously every 6 hours to a total
dose of 1 mg)
(2) Diltiazem [15-20 mg (U.25 mg/kg) intrave
nously over 2 minutes; repeat in 15 minutes
at 20-25 mg if necessary; maintenance infu
sion is 5-20 mg/hr intravenously]
(3) Verapamil (2.5-5.0 mg administered as an
intravenous bolus over 1-2 minutes' if
needed, repeat with a dose of 5-10 mg in
15-30 minutes; maximum dose is 30 mg)
(4) Esmolol (500 /Lg/kg intravenously over 1
minute. followed by an intravenous mainte
nance infusion of 50-200 /Lglkglmin)
b. A V node blocking agents are contraindicated in
patients with irregular, wide complex tachycardia
until atrial fbrillation with conduction down an
accessory pathway (e.g .. Wolff-Parkinson-White
syndrome) has been excluded. If Wolff-Parkin
son-White syndrome is present, these agents can
precipitate fatal ventricular fbrillaton.
B. Chronic treatment. The goals of the chronic treatment
of atrial fbrillation are minimization of symptoms and
reduction of the risk for stroke.
L Rate control. The goal is a resting heart rate lower
than Y beats/min. Treatment should be selected
after considering the patient's other medical prob
lems. For example:
a. I patients with hypertension or coronary artery
dIsease, a { blocker is a good choice because it
addresses these problems as well as the atrial
fibrillation. However, in patients with asthma or
chronic obstructive pulmonary disease (COPD),
a { blocker may not be a good choice because
it induces bronchoconstriction.
b. In patients with CHF, digoxin can control the
heart rate as well as improve symptoms of CHF.
However, in patients with chronic renal insuff
ciency, digoxin levels should be monitored
very closely.
2. Rhythm control. Theoretically, conversion to normal
sinus rhythm returns the risk of stroke to baseline
and relieves all rate-related symptoms.
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a Cardioversion should be undertaken only after

atrial thrombus has been excluded, unless there
is an emergent indication.
b. Pharmacologic therapy. Rate must be controlled
prior to the initiation of any antiarrhythmic medi
cation.
(1) Procainamide and quinidine increase the
time to relapse in treated patients, but both
agents are proarrhythmic and have been as
sociated with increased mortality rates. Most
patients should not be treated with these
agents.
(2) Amiodarone appears to be as effective as
procainamide and quinidine for maintaining
sinus rhythm without causing proarrhythmic
effects. Amiodarone is likely to become the
drug of choice. although there are signifcant
side effects.
c. A V node ablation with pacemaker implantation
is used only under special circumstances.
3. Clot control. Stroke is the major cause of morbidity
and mortality in patients with atrial fbrillation. Anti
coagulation therapy is time consuming and bother
some to patients, and the risks and benefts must be
assessed on an individual basis.
a. Wadarin treatment reduces the risk of stroke by
40%-90%. The target international normalized
ratio should be 2.0-3.0. There is a small increase
in the risk of major bleeding.
b. Aspirin alone is a consideration for patients at
low risk for stroke.
c. Lower dose anticoagulation [i.e., a target interna
tional normalized ratio (INR) of 1.0-2.0] and
combination therapy (e.g., aspirin plus wadarin)
is currently being studied.
8. Chest Pain
a
II
II
INTRODUCTION. Because chest pain (including "dis
comfort") is common and its etiologies range from a life
threatening myocardial infarction to benign musculoskeletal
pain, a simple and reliable approach to the patient is nec
essary.
CAUSES OF CHEST PAIN. One way to remember the
causes of chest pain is to use an "outside-in" approach.
A. Skin. Varicella-zoster virus infection (shingles) often
causes pain before vesicular lesions are noted. The pain
usually occurs in a dermatomal distribution.
B. Chest wall. Musculoskeletal pain may result from shoul
der arthritis or bursitis, intercostal injury, metastatic dis
ease to the bones or chest wall, or costochondritis. Breast
pathology (e.g., tumors, fbrocystic disease) and nerve
root compression (from cervical disk herniation) may
also lead to chest pain.
C. Lungs. Infamed pleura from spontaneous pneumothora
ces, pulmonary emboli, infections, malignancies, and
connective tissue disorders can all cause chest pain, which
is usually pleuritic (i.e., it worsens with inspiration or
coughing).
D. Heart and great vessels. Pericarditis. myocardial isch
emia and infarction, and aortic dissection can all cause
chest pain.
E. Gastrointestinal tract. Esophageal disorders (including
esophagitis, spasm, and rupture) are common causes of
chest pain. Other gastrointestinal causes of chest pain
include gastric and duodenal ulcers, pancreatitis, and
biliary disease.
APROACH TO THE PATIENT. Although the outside-in
approach is useful for remembering the differential diagno
ses for chest pain, it fails to highlight the four acutely life
threatening causes:
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HOT
KEY
4 Killer Chest Pins
Myocardial infarction or ischemia
Pulmonary embolism
Aortic dissection
Spontaneous pneumothorax
Because chest pain may represent one of these emergences,
the usual order of evaluation (e.g., history, physical examina
tion, diagnostic tests) may hinder critical early intervention.
The frst step should be a quick screen for the four killer
chest pains, followed by a more in-depth evaluation if the
etiology of the chest pain is still unclear.
A. Screen for the killer chest pains.
1. "Eyeball" the patient. A patient who is clutching his
chest, diaphoretic, and ashen can be presumptively
diagnosed as suffering from myocardial infarction
from across the room. Even if the presentation is not
so classic, you can often decide on who looks "sick,"
and may need a more rapid evaluation in a more
monitored setting.
2 EstabHsh intravenous access and cardiac rhythm
monitoring immediately in patients who appear ill
or who have cardiac risk factors.
3. Evaluate the patient's vital signs
HOT
KEY
Any abnormality of the vital signs should alert you to
the possibility that the chest poin has a potentially
serious cause.
a. Check the blood pressure in both arms. Although
a difference in pressure of 10 mm Hg or more
may be seen in patients with aortic dissection,
Chapter
local atherosclerosis can also produce pressure
diferences. Therefore, the blood pressure read
ing is neither sensitive nor specifc for aortic dis
section.
b. Check the respiratory rate and oxygen satura
tion. A low oxygen saturation may accompany
spontaneous pneumothorax, pulmonary embo
lism, and myocardial infarction (with pulmo
nary edema).
(1) A low oxygen saturation (e.g., < 92%) is of
ten an indication that an arterial blood gas
should be ordered immediately.
(2) A normal oxygen saturation may still be ac
companied by a signifcant alveolar-to-arte
rial (A-a) oxygen gradient during hyperventi
lation. Therefore, arterial blood gas testing
to evaluate the possibility of pulmonary em
bolism may still be necessary if the rest of
the evaluation is unrevealing.
4. Look at the electrocardiogram (EKG). The EKG
leads are often placed while the vitals are obtained.
HOT
KEY
a EKG abnormalities that suggest myocardial in
farction or ischemia are always grounds for ad
mission. Make sure the patient has intravenous
access, a cardiac rhythm monitor, supplemental
oxygen, and has been administered an aspirin
(usually 325 mg) orally. (The emergent treatment
of myocardial infarction and ischemia is dis
cussed in more detail in Chapter 10.)
b. Normal EKG. Because a normal EKG does not
rule out myocardial infarction or ischemia, nitro
glycerin (0.3-0.6 mg sub lingually or via aerosol)
may be administered and the dose repeated every
3-5 minutes as both a diagnostic challenge and
as potential therapy.
In patients with a history of coronary artery disease
or cardiac risk factors and no alternative explanation
for the chest pain after careful evaluation, an admission
to rule out myocardial infarction (ROMI) is usually ap
propriate.
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b. Take a preliminary histor.
a. Cardiac history and risk factors. First, ask about
any prior cardiovascular problems.
(1) If there is a history of coronary artery disease,
the patient has ischemia until proven other
wise.
(2) With a negative cardiac history, you can
quickly establish the pretest probability of
myocardial infarction by assessing cardiac
risk factors (i.e., age, male sex, smoking, dia
betes, hypertension, high cholesterol, and
positive family history).
h. Other risk factors. The preliminary history can
also help elucidate any predisposing factors to
the other killer chest pains. For example, a his
tory of cancer or inactivity may contribute to
pulmonary embolism, and uncontrolled hyper
tension may increase the likelihood of aortic dis
section or myocardial infarction.
6. Perform a preliminar physical examination. Fre
quently, you will have a few brief moments between
tests where you can look at the neck veins, listen to
the heart and lungs, palpate the upper abdomen for
tenderness, and evaluate the pulses in the arms
and legs.
7. Evaluate the chest radiographs. Always compare the
new flms to old flms, if they are available.
a. Spontaneous pneumothorax can be subtle and
you need to look carefully, especially in the
apices.
b. Esophageal rupture may lead to air in the medi
astinum (pneumomediastinum).
c. Myocardial infarction or aortic dissection may
be accompanied by enlargement of the heart or
mediastinum, respectively; however, these struc
tures are often exaggerated on anteroposterior
flms. The presence of pulmonary edema may
also be suggestive of myocardial infarction.
8. Order an arterial blood gas. If not performed earlier,
an arterial blood gas analysis with the patient breath
ing room air is usually necessary.
Further defne the cause of the chest pain.
L Take a more detailed patient histor.
a Type of chest pain. Pulmonary embolism fre
quently presents with pleuritic chest pain, myo
cardial infarction may present with "crushing"
60 Chapter
chest pain or only a mild "discomfort," and aortic
dissection often is characterized by a ripping pain
that radiates to the back.
b. Radiation of chest pain. Pain that radiates to the
neck or left arm should be considered cardiac
until proven otherwise.
(1) Atypical patterns may still indicate ischemia
and include pain, tingling, or numbness in
the left fingertips unaccompanied by arm
pain and pain in the outer left shoulder.
(2) It is wise to consider any neck, upper abdomi
nal, or upper back pain as cardiac in origin
until proven otherwise.
c. Onset of chest pain. Spontaneous pneumothorax,
aortic dissection, and pulmonary embolism usu
ally present with abrupt pain, whereas pain from
myocardial infarction or ischemia may build
more gradually. Spontaneous pneumothorax and
pulmonary embolism often occur while the pa
tient is at rest, whereas aortic dissection and myo
cardial infarction may occur with rest or exertion.
d. Duration of chest pain. Pain that only lasts sec
onds or that has been constant for more than 2
hours is usually not caused by one of the four
killer chest pains. A myocardial infarction is
almost always associated with more than 20
minutes of chest pain.
e. Associated symptoms. Dyspnea, diaphoresis, or
lightheadedness should alert you to a probable
serious cause of chest pain.
f. Aggravating and mitigating factors
(1) Deep inspiration often aggravates pain from
the pleura or pericardium (e.g., pleurisy from
a pulmonary embolism or pericarditis).
(2) Exertion may worsen the pain from myocar
dial infarction or aortic dissection. Rest may
ease the pain from cardiac ischemia, usu
ally gradually.
(3) Position. Patients with pericarditis often feel
worse when supine, and better sitting up. Pa
tients with musculoskeletal pain may feel
worse in certain positions. The pain of myo
cardial infarction is usually unaffected by
changes in position, but this is not always
the case.
(4) Food intake. Pain on swallowing localizes the
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61
problem to the gastroi
.
nt
tinal tract.
.
Ch
t
pain after a meal may mdIcate gastrOJnte
tI
nal pathology, but it also may occur WIth
myocardial infarction.
.
(5) Nitroglycerin. If chest pain decreases WIth
nitrates, (e.g., sublingual nitroglycerin), a car
diac etiology should be presumed; howeve
,
esophageal spasm may also respond to thIS
therapy.
Perform a complete physical examination. Pay extra
attention to the following parts of the exam.
a Jugular venous pressure. An elevated jugular ve
nous pressure should alert you to t?e
p
ossiblity
of a serious disorder (e.g., myocardIal mfarctIOn,
pulmonary embolism, or tension pneumothorax),
but a normal jugular venous pressure does not
exclude these disorders.
b. Cardiac examination (see Chapter 3)
(1) Heart sounds. Listen carefully for a third
heart sound (83) or fourth heart sound (S4)
gallop. which may indicate mpaired venic
ular contractility or ventncular relaxation,
respectively. Both impaired ventricular con
tractility and impaired relaxation can accom-
pany cardiac ischemia.
. .
(2) Murmurs may also increase th

hkelIh
.
ood
of a cardiac etiology of chest pam. A mItral
regurgitant murmur may accompany a
yo
cardial infarction with papillary muscle Isch
emia whereas an ejection murmur may
indicte aortic stenosis or hypertrophic
cardiomyopathy (both of these conditions
may predispose the patient to ischemia).
c. Lung examination. Listen carefully for rales
(e.g., from myocardial infarction with pulmonary
edema) and pleural friction rubs (e.g .. from pul
monary embolism, infection, or other pleural
processes).
d. Chest wall examination. Minimal tenderness to
palpation is nonspecifc, but if the che
t pai

is
exactly and reliably reproduced (especiall
.
y m a
well-localized area), a musculoskeletal etiology
is likely. Briefy inspect the skin for lesions.
e. Abdominal examination. Palpate for any upper
abdominal tenderness that may indicate a gastro
intestinal cause of the chest pain.
Z Chapter
f. Pulses. Check pulses in the arms and legs bilat
eraly.
3. Pearls
a. Myocardial infarction
(1) Because coronary artery disease is such a
common disease, it is always better to admit
patients for ROMI if there is any doubt as
to the diagnosis, even in young patients.
(2) More than 20 minutes of unexplained chest
pain may represent a myocardial infarction,
whereas chest pain that lasts less than 20
minutes but increases in frequency, duration,
or occurs with minimal exertion often repre
sents unstable angina; both patterns are indi
cations for admission.
(3) Frequently, patients with chest pain are given
an antacid and lidocaine swish and swallow
("01 coktail") to evaluate possible refux
esophagitis. Many patients who "beneft"
from this "diagnostic test" may actually have
ischemic pain that is improving sponta
neously or from bed rest and oxygen
therapy.
b. Pulmonary embolism. Clinical suspicion is criti
cal. There is often no evidence of deep vein
thrombosis, and subtle symptoms and signs may
be inappropriately rationalized away. If you have
a high clinical index of suspicion, administer hep
arin before sending the patient for diagnostic
tests.
c. Aortic dissection
(1) The greater curvature of the aorta is the site
for most dissections; the right coronary artery
is the one most frequently "picked of." If
the patient has pain that radiates to the back,
unequal blood pressures, or other suspicious
fndings accompanied by evidence of right
coronary ischemia (i.e., inferior or right ven
tricular ischemia), aortic dissection should
be considered.
(2) Both computed tomography (CT) and trans
esophageal echocardiography are used in the
evaluation of aortic dissection. The choice of
diagnostic modality depends on the patient
(e.g., por renal function may weigh against
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a CT scan) and institutional preferences. If
clinical suspicion is high, the surgeon should
be consulted immediately for his or her input
regarding subsequent evaluation. Transtho
racic echocardiography is not sensitive
enough to rule out aortic dissection.
9. Angina
a
INTRODUCTION
II
A. Defnition. Angna is the symptom of chest pain that
results when the oxygen supply is inadequate to meet
the oxygen demands of the cardiac muscle. Although
other diseases may reduce the oxygen supply (e.g., coro
nary artery spasm, hypoxia, anemia) or increase the oxy
gen demand (e.g., tachycardia as a result of infection,
thyrotoxicosis), angina rarely occurs without underlying
coronary artery disease.
M. Risk factors for coronary artery disease include:
1. Age greater than 45 years (men) or 55 years (women)
2. Male sex
3. Diabetes mellitus
4. Smoking habit
5. Hypercholesterolemia
6. Family history (frst degree male or female relative
with premature coronary artery disease)
C. Classifcation. Angina may be stable or unstable.
1. Stable angina usually results from a fxed atheroscle
rotic plaque that limits oxygen delivery to the cardiac
tissue. When there is an increase in oxygen demand
(e.g., from physical exertion), the oxygen supply can
not be increased to compensate. The oxygen mis
match that results causes a predictable and stable
patter of chest pain during exertion.
2. Unstable angina usually results when an atheroscle
rotic plaque ruptures or becomes thrombosed. As a
result, the oxygen supply is inadequate at lower activ
ity levels, and sometimes even at rest.
CLINICAL MANIFESTATONS OF CORONARY ARTERY
DISEASE
A. Symptoms
1. Angina is usually experienced beneath or left of mid
sternum, increases with physical exertion or stress,
often lasts from a few minutes up to 20 minutes, and
subsides gadually with rest or nitroglycerin.
a If chest pain radiates to the neck or left arm
A
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II
or is accompanied by dyspnea, diaphoresis, or
lightheadedness. the likelihood of coronary ar
tery disease is increased, but these features need
not be present.
b. Symptoms of stable angina occur predictably,
whereas symptoms of unstable angina are in
creasing in frequency or duration or occur with
less exertion (even at rest).
2. "Anginal equivalents." Other symptoms unaccom
panied by chest pain (e.g., dyspnea) may actually
represent "anginal equivalents;" some patients with
coronary artery disease may not have any symptoms
at all.
M. Physical examination fndings. Because patients often
have no discernible signs of illness, a normal physical
examination does not rule out the possibility of coronary
artery disease. Transient signs may occur during ischemic
episodes, including hypertension or, less commonly, hy
potension; ventricular or supraventricular arrhythmias;
a third or fourth heart sound (S3 or S4); or a holosystolic
murmur over the apex (representative of mitral regurgi
tation as a result of papillary muscle ischemia). The pres
ence of elevated jugular venous pressure, pulmonary
edema, a gallop rhythm, pathologic murmurs, or signs of
the cardiac risk factors (e.g., peripheral vascular disease
from diabetes) should all increase your suspicion of coro
nary artery disease.
ApPROACH TO THE PATIENT. Stable and unstable angina
need to be diferentiated from the many other causes of
chest pain (see Chapter 8).
A. Patient history. In patients with classic symptoms, the
diagnosis of stable or unstable angna can be made on
the basis of history alone.
M. Resting electrocardiography. Unstable angina can also
be diagnosed in asymptomatic patients by fnding evi
dence of active ischemia on a resting electrocardiogram
(EKG) [e.g., ST segment depressions and T wave inver
sions].
C. Stress tests may be helpful both diagnostically in patients
with atypical chest pain and prognostically in patients
with typical angina.
1. Types
a Exercise electrocardiography. The presence of 1
mm of down-sloping or horizontal ST-segment
Chapter V
depression is considered a positive test for
ischemia.
b. Myocardial perfusion scintigaphy is often per
formed in conjunction with exercise electrocardi
ography and involves the injection of thallium
201 eOIT) into the peripheral venous blood. Car
diac muscle cells that are ischemic or infarcted
do not take up thallium well.
(1) With time, the thallium spreads fom cell to
cell into regions that are ischemic, but not
into areas of infarction. Reversible defects,
areas that lack thallium on the initial exercise
images but "fll in" on later images (i.e., afer
3-4 hours), indicate ischemia. Fixed defects
do not change on subsequent imaging and
usually denote prior infarction.
(2) In patients who are unable to exercise vigor
ously, dipyridamole, which produces vasodi
latation in normal coronary arteries out of
proportion to that produced in atheroscle
rotic vessels, can be used to shunt thallium
away from cardiac regions served by diseased
vessels. Dypyridamole is contraindicated in
patients with signifcant reversible airway dis
ease because it may facilitate bronchospasm.
c. Exercise radio nuclide angography or echocardi
ography. If exercise results in a decrease in ejec
tion fraction or segmental wall motion abnormal
ities, cardiac ischemia is presumed. Intravenous
dobutamine increases oxygen demand by in
creasing heart rate and contractility and may be
used as an alterative to exercise.
2. Choosing a test. Although one stress test cannot be
universally recommended over the others certain
caveats apply:
'
a. Echocardiography is more likely to be inade
quate in obese patients.
b. Elderly patients or those with other heart disease
may have a higher false-positive rate on exercise
radionuclide angiography or echocardiography.
c. Patients with EKG abnormalities may not be
evaluated appropriately with standard exercise
electrocardiogaphy alone. Scintigraphy is fre
quently added to increase sensitivity and speci
fcity.
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Z
. Coronary catheterization is necessary to defnitively di
agnose coronary artery disease.
1. Unstable angina. Because these patients often have
high-grade coronary occlusions, a cardiac catheter
ization is often indicated to plan future therapy. Usu
ally, catheterization is performed after 1-3 days of
therapy because the incidence of adverse events, in
cluding myocardial infarction. increases with early
catheterization.
2. Stable angina. Because stable angina can usually be
diagnosed on the basis of the patient history or nonin
vasive studies, catheterization is not usually needed
for diagnosis; rather, it is usually performed to help
determine subsequent therapy. If catheterization
demonstrates severe coronary artery disease in a pa
tient with stable angina. revascularization with by
pass surgery or angioplasty may be indicated.
1 TREATMENT
A. General measures. Because angina represents coronary
artery disease, an indispensable part of the treatment is
aimed at identifying and treating cardiac risk factors.
M.
1. Smoking prevention
2. Regular exercise (e.g., brisk walking for 30 minutes
4 times weekly)
3. Weight loss
4. Control of hypercholesterolemia [low-density lipo
proteins (LDL) < 100 mg/dl]; HMG-CoA reductase
inhibitors may be the drugs of choice
5. Control of hypertension (systolic < 140 mm Hg, dia
stolic < 90 mm Hg)
6. Control of diabetes
7. Treatment of other factors that may aggravate angina
(e.g., anemia, hypoxia, thyrotoxicosis)
Specifc measures for the relief of angna
1. Stable angina
a. Pharmacologic therapy is generally aimed at in
creasing the myocardial oxygen supply (by coro
nary vasodilation) or decreasing the oxygen de
mand (by decreasing heart rate, contractility,
preload, or afterload). Most patients are started
on aspirin, a f blocker, and short-acting nitrates
unless there are contraindications. Gradually, the
dose of the f blocker may be increased until
Chapter V
the symptoms are controlled, side efects develop
(e.g., postural lightheadedness), the blood pres
sure falls below approximately 100/60 mm Hg,
the heart rate falls below approximately 6 beats/
min, or the maximal dose is reached. If symptoms
are still not controlled, long-acting nitrates may
be added and increased as needed with attention
to the patient's symptoms, side effects, and
blood pressure.
(1) Aspirin (usually 325 mg/day) inhibits platelet
aggregation and coronary thrombosis, and
may therefore prevent progession to myo
cardial infarction or unstable angina.
(2) Nitrates increase oxygen supply by vasodilat
ing the coronary arteries and decrease oxy
gen demand by decreasing preload and
afterload.
(a) Short-acting nitrates. Nitroglycerin 0.3-
0.6 mg sublingually or by aerosol may be
used for angina prophylaxis (the dose is
taken 5 minutes before an activity known
to result in angina) or immediate therapy
(the dose is administered every 3-5 mi
nutes until the pain is relieved; if pain is
not relieved in 20 minutes, the patient
should get to a hospital immediately).
(b) Long-acting nitrates (e.g., isosorbide din
itrate, isosorbide mononitrate, transder
mal nitroglycerin patChes). An interval
of approximately 8-10 hours per day
without nitrate therapy is needed to pre
vent tachyphylaxis, so the last dose is of
ten given after dinner and patches are
removed overight. Headaches may oc
cur with the initiation of nitrate therapy;
if they can be managed conservatively,
they frequently resolve after 1-2 weeks.
(3) f Blockers can decrease heart rate and myo
cardial contractility, resulting in symptomatic
control of angina. In addition, unlike other
antianginals, they have been shown to have
a mortality beneft in patients with coronary
artery disease who have already experienced
myocardial infarction.
(a) Frequently used f blockers include pro
pranolol (40-80 mg orally 2-4 times
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Angina V
daily), metoprolol (50-100 mg orally 2
times daily), and atenolol (50-100 mg
orally once daily).
(b) f Blockers are contraindicated in pa
tients with bradyarrhythmias or overt
heart failure. In patients with chronic ob
structive pulmonary disease (COPD), a
frselective agent (e.g., metoprolol or
atenolo!) should be used; often, all f
blockers are avoided in patients with se
vere COPD. Patients with impaired left
ventricular function may actually beneft
the most from f blockers; however, can
didates must be "tuned up" prior to the
initiation of therapy (e.g., no evidence of
pulmonary edema should be pres
ent).The patient should be started with
a low dose (e.g., 2.5-5 mg of metoprolo!),
which is gradually increased with fre
quent patient monitoring.
(4) Calcium channel blocers lower oxygen de
mand (by decreasing heart rate, contractility,
and afterload) and may increase oxygen sup
ply (by inducing vasodilation of the coro
nary arteries).
(a) Agents include verapamil, diltiazem, and
nifedipine, in order of increased effect on
lowering systemic vascular resistance and
decreased effect on myocardial inotropy
and chronotropy. Verapamil and diltia
zem are usually preferred.
() Calcium channel blockers have not been
associated with improved survival post
myocardial infarction, and may lead to a
worse outcome; therefore, they are not
the initial drugs of choice for most pa
tients with known or suspected coronary
artery disease.
b. Revascularization. The indications for coronary
artery bypass surgery or angioplasty are contro
versial. Studies are underway to address the rela
tive advantages and disadvantages of coronary
artery bypass surgery compared with angio
plasty.
(1) Coronary artery bypass surgery is generally
considered the treatment of choice for pa-
Z Chapter V
tients with left main artery disease (over 50%
occlusion) or three-vessel disease (over 70%
occlusion) associated with decreased left ven
tricular function (less than 50%).
(2) Bypass surgery may also beneft patients with
three-vessel disease and severe angina (class
III or IV) and patients with proximal left
anterior descending occlusion associated
with two-vessel disease, but there is less of a
consensus on whether bypass surgery, angi
oplasty, or medical therapy is appropriate.
(3) Patients with angina refractory to medical
therapy and patients with a recent myocardial
infarction or unstable angina and continuing
symptoms or signs of ischemia are also candi
dates for revascularization.
2. Unstable angina. Patients with unstable angina re
quire admission and should undergo serial cardiac
enzyme studies and EKGs to rule out myocardial
infarction. Patients with active chest pain or EKG
evidence of ischemia are always managed in the coro
nary care unit (CCU). Patients who have no current
chest pain or EKG evidence of ischemia are some
times treated and monitored in a telemetry unit; how
ever, because a recurrence of chest pain will require
a transfer, it is often easier to simply admit these
patients to the CCU.
a. Pharmacologic therapy is aimed at improving the
oxygen mismatch and inhibiting progession of
the presumed intracoronary thrombus.
(1) Nitmtes are generally given transdermally or
intravenously so that the dose can be care
fully titrated to prevent ischemia and control
blood pressure.
(a) Transdermal nitrates are often used for
patients in telemetry units. Table 9-1 out
lines a sliding scale that could be used.
(b) Intravenous nitrates are often used for
patients in the CCo. The initial dose is
10 p,g/min, which may be titrated upward
to keep the patient symptom-free and the
blood pressure at approximately 100-
120/60-80 mm Hg. Doses may be as high
as 100-300 p,g/min.
(c) Long-acting nitrates may be substituted
for other forms of therapy after the pa-
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Angina Z
TABLE 9- 1 : Sliding Scale f ar Use of Nitropaste
Systolic Blod Pressure
(mm Hg) Dosage
>
-
Z-
- Z
<
Z every hours
."every hours
" every hours
OS' every hours
Wipe off nitropaste
tient has stabilized (often after 24-48
hours). Approximately 20 mg of isosor
bide dinitrate administered orally every
8 hours may be substituted for each inch
of nitropaste the patient required during
sliding scale therapy.
(2) f Blockers should be administered to pa
tients without contraindications, and are es
pecially useful in patients with tachycardia,
hypertension, or both.
(a) Although oral therapy is often suffcient,
intravenous administration of metoprolol
(5 mg every 5 minutes, up to 15 mg) may
provide faster therapy for patients with
active ischemia.
(b) Patients with hemodynamic instability
and those with a higher risk of adverse
efects from f blockers (e.g., a history of
bronchospasm or depressed left ventricu
lar function) may beneft from an esmolol
continuous intravenous drip that allows
rapid discontinuation of therapy.
(3) Calcium channel blockers. Because these
agents are of unproved beneft (and may be
deleterious) and there are other effective
modes of managng unstable angina, they are
rarely used to treat unstable angina. If a pa
tient is already taking calcium channel block
ers, the decision to continue this therapy de
pends on the patient's presentation, whether
f blockers are contraindicated, and the eff-
ZZ Chapter V
cacy of nitrates and other therapies in con
trolling the patient's symptoms.
(4) Aspirin and heparin. The decision to use
aspirin, heparin, or both for unstable angina
is controversial.
(a) Heparin should be used in patients with
active symptoms or EKG evidence of
ischemia, unless there are contraindica
tions. The routine use of heparin in pa
tients without active symptoms or EKG
evidence of ischemia may also be appro
priate.
(b) Aspirin is also usually administered be
cause some patients with presumed un
stable angina may later be diagosed with
infarction. Aspirin decreases mortality
associated with myocardial infarction and
is useful in preventing myocardial in
farction in patients with unstable angina.
b. Revascularization. After symptoms subside, pa
tients with unstable angina are often catheterized
to evaluate their candidacy for revascularization.
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1 0. Myocardial Infarction (MI)
a
II
II
INTRODUcON. Myocardial infarction (MI) is a leading
cause of death in the United States. The failure to recognize
MI in the emergency room has led to inappropriate patient
discharges, resulting in an abundance of malpractice claims.
Many therapies have a proved mortality beneft in the treat
ment of MI; however, studies show that patients frequently
receive suboptimal therapy.
PATHOPHYSIOLOGY OF MI. MI usually results from cor
onary artery disease. The rupture or thrombosis of athero
sclerotic plaques leads to inadequate blood fow and oxygen
delivery, which in turn leads to myocardial cell death. Rarer
causes of MI include vasospasm (usually associated with
coronary artery disease), severe hypotension, emboli (e.g.,
from mitral valve disease), aortic dissection (usually with
right coronary artery involvement), vasculitis, and cocaine
use (vasospasm and platelet aggregation are presumed etio
logies).
CLINICAL MANIFESTATIONS OF MI. Typical symptoms
and signs associated with cardiac ischemia are discussed in
Chapter 8 III B. The chest pain associated with MI may
differ from that of stable angina in that it frequently begins
while the patient is at rest, lasts more than 20 minutes, is
more severe, and is umelieved with nitroglycerin; however,
these fndings are variable and pain that lasts for more than
20 minutes should be considered due to MI until proved oth
erwise.
DIAGNOSIS. Because MI and unstable angina share similar
pathophysiology, it is not surprising that they frequently
cannot be distinguished by clinical criteria alone. Patients are
often admitted for "unstable angna/rule out MI (ROMI)";
serial electrocardiograms (EKGs) and cardiac enzyme stud
ies are required for a defnitive diagnosis.
Zo
Z
HOT
KEY
Chapter
The diagnosis of MI is made by the presence of typical
symptams and signs, EKG changes, or elevated car
diac enzymes. If the patient meets two of these three
criteria, MI is diagnosed.
A. Patient history and physical examination. Chest pain is
the most common symptom of MI, but other signs and
symptoms may also signal MI (e.g., fash pulmonary
edema, hypotension, dyspnea).
M. Electrocardiography. Following admission of the patient,
serial EKGs are usually obtained on a frequent basis until
resolution of symptoms occurs and the EKG changes
stabilize; a daily EKG and an EKG following reports
of any symptoms are usually obtained thereafter. MI is
usually associated with hyperacute (peaked) T waves,
ST elevations, ST depressions, Q waves. or inverted T
waves; occasionally, no EKG changes are noted.
1. ST segment depressions and elevations both refect
myocardial injury.
a. The subendocardial region is the most suscepti
ble to ischemia because it is perfused "last" (i.e.,
the coronary arteries course from the outer epi
cardial surface inward). Because the subendocar
dium is on the inner surface of the heart, away
from the EKG leads on the chest wall, subendo
cardial injury is fequently seen as ST segment
depression. Similarly, the epicardial surface is
near the EKG leads, so epicardial injury results
in ST segment elevation.
b. ST segment depressions are often called "isch
emia." whereas ST segment elevations are called
"infarct." This terminology is an oversimplifca
tion resulting from the observation that de
creases in blood fow frequently cause isolated
subendocardial injury, whereas complete coro
nary occlusion is usually needed for epicardial
injury. Because ST depressions may occur with
subendocardial infarction, and STsegment eleva
tions may occur with transient epicardial isch
emia (e.g., fom vasospasm), STsegment changes
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Myocardial Infarction (MI) Z
are more accurately thought of as representing
myocardial "injury."
2. Q waves signify electrical activity moving away from
the area of the heart where they are seen; they there
fore indicate dead muscle (previous MI) in that
region.
a. Non-Q wave MIs represent approximately 30%-
50% of all MIs and presumably occur because
there is still enough "alive" muscle generating
electrical activity in the given area.
b. Q wave MIs are usually larg<r and associated
with a higher initial mortality rate than non-Q
wave infarctions; however, the remaining viable
myocardium in non-Q wave MIs results in a
higher recurrent infarction rate.
3. A right-sided EKG (leads VI and V2 reversed, with
the other leads placed in corresponding positions on
the right side of the chest) should be obtained in all
patients with an acute inferior wall MI. Because right
ventricular infarction may complicate an inferior wall
MI. a right-sided EKG should always be obtained.
ST segment elevation in leads RV4 or RV3 is a sign
of right ventricular infarction.
C. Cardiac enzyme studies
1. MI is usually associated with an elevation in serum
creatine kinase (CK) levels. Detection of the CK
MB isoenzyme has increased specifcity for cardiac
muscle and maintains a high sensitivity. CK with
isoenzyme studies are usually ordered every 8 hours
for 24 hours or until a peak level is reached (usually
16-18 hours).
2. More recently, troponin levels have been introduced
as a more useful means of diagnosing acute ML
ApPOACH TO TE PATENT. The acute treatment of MI
requires both precision and speed. The following stepwise
approach will allow you to make critical treatment decisions
immediately, followed by those that are less urgent. When
ever a patient is admitted with an acute MI, it is helpful to
answer three questions: What is the patient's hemodynamic
status? Is thrombolysis or percutaneous transluminal coro
nary angioplasty (PTCA) indicated? What other treatments
may beneft the patient?
A. What is the patient's hemodynamic status?
1. Assessment. Hemodynamic status can be approxi
mated by examination of the lungs and extremities.
Z Chapter
a. Low-risk patients have clear lungs and warm ex
tremities associated with normal peripheral
pulses. The presence of clear lungs usually indi
cates normal left ventricular flling pressures
[i.e., a normal pulmonary capillary wedge pres
sure (PCWP)], and normal fndings on examina
tion of the extremities imply adequate cardiac
output.
b. Intermediate-risk patients have a normal extrem
ity exam, but rales are found on pulmonary exam.
In these patients, an elevated left ventricular
pressure (i.e., a PCWP > 18 mm Hg) is suspected.
c. High-risk patients have rales as well as cool ex
tremities with diminished peripheral pulses.
These patients are in cardiogenic shock. The
presence of pulmonary edema suggests that the
PCWP, an estimate of end-diastolic volume, is
elevated. Normally, according to the Starling
curve, a high end-diastolic volume ensures that
the stroke volume will be maximized. If the heart
is unable to adequately perfuse the end organs
despite adequate flling (i.e., a high PCWP), car
diogenic shok is diagnosed.
2. Management
a. Low-risk patients are hemodynamically stable
and have a low mortality rate. Management of
these patients entails deciding whether thrombol
ysis or PTCA is indicated, and what other forms
of therapy might beneft the patient (see V B, C).
b. Intermediate-risk patients have evidence of pul
monary edema, which may decrease oxygenation
while increasing oxygen demand (increased sym
pathetic tone increases the heart rate and myo
cardial contractility).
(1) Agents frequently used in the treatment of
MI (e.g., nitrates, morphine) may also treat
pulmonary edema by decreasing preload.
(2) Intravenous diuretics should be given as
needed.
c. High-risk patients have cardiogenic shock.
(1) Pulmonary artery (P A) line placment is in
dicated for monitoring cardiac output, sys
temic vascular resistance, and PCWP. In pa
tients with MI, only those with evidence of
cardiogenic shock generally require hemody
namic monitoring with a P A line.
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Myocardial Infarction (MI) 77
HOT
KEY
(2) Pharmacologic therapy is dictated by the pa
tient's blood pressure. Although cardiogenic
shock is often accompanied by hypotension,
the blood pressure may still be normal with
low fow states due to a marked increase in
systemic resistance.
Do nat assume that a normal blood pressure indicates
adequate end-organ now.
(a) Systolic blood pressure > 90-100 mm Hg
(i) Dobutamine is often started intrave
nously at a dose of 2. 5 p,g/kg/min.
The dose may be increased gradually
(up to 15-20 p,g/kg/min) until the
cardiac output rises and the PCWP
falls. Dobutamine raises the cardiac
output by increasing myocardial
contractility and by decreasing the
systemic vascular resistance. Be
cause blood pressure is the product
of cardiac output and systemic vas
cular resistance, it may remain sta
ble, increase, or decrease depending
on how much the cardiac output in
creases in comparison with the de
crease in systemic vascular resis
tance. A decrease in blood pressure
commonly occurs with dobutamine
therapy, s the systolic blood pres
sure should be geater than 90 mm
Hg (and preferably geater than 100
mm Hg) before the initiation of
therapy.
(ii) Sodium nitroprusside is an alter
native to dobutamine. but often
requires a higher starting blood pres
sure or the concomitant administra
tion of an inotrope.
Z Chapter
(b) Systolic blood pressure < 90 mm "g. In
travenous dopamine is usually given. Do
pamine usually causes renal artery dilata
tion at doses of 1-2 p,g/kg/min. ("renal
dose" dopamine), increased inotropy
from /
!
- receptor stimulation at doses of
5-10 p,g/kg/min, and vasoconstriction
from a-receptor stimulation at higher
doses; but signifcant overlap and vari
ability exist. Once the systolic blood pres
sure is greater than 90-100 mm Hg, dobu
tamine is often added and the dopamine
is titrated down (preferably to "renal
doses") as tolerated by the blood pres
sure. Because arrhythmias may compli
cate dobutamine or dopamine therapy,
patients require careful rhythm monitor
ing, and electrolytes should be main
tained in the normal range (especially the
potassium and magnesium levels).
(3) Emergent PTCA is the only therapy that has
been shown to decrease mortality in patients
with cardiogenic shock, and is clearly the
treatment of choice.
M. Is thrombolysis or PTCA indicated? Patients with chest
pain of 6 hours or less duration (and possibly up to 12
hours or longer) associated with ST elevations of at least
1 mm in two consecutive EKG leads (or evidence of a
new left bundle branch block) derive a mortality beneft
from coronary reperfusion, and should therefore un
dergo thrombolysis or angoplasty unless there are con
traindications.
L Primary PTCA may be favored when there are con
traindications to thrombolytic therapy, and in centers
that can perform the procedure quickly and with ex
pertise.
2. Thrombolysis
a. Contraindications
(1) Absolute contraindications generally include
the presence of:
(a) Central nervous system (CNS) disease.
Recent trauma or surgery, aneurysms,
arteriovenous malformations, tumors, or
a history of hemorrhagic stroke at any
time or nonhemorrhagic stroke within 3
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Myacardial Infarction (MI) ZV
months are usually considered contrain
dications.
(b) Active gastrointestinal or genitourinary
bleeding
(c) Pregnancy
(2) Relative contraindications generally include:
(a) Traumatic or prolonged cardiopulmo
nary resuscitation
(b) Recent trauma or surgery (within 2
weeks)
(c) Diabetic retinopathy
(d) Sustained hypertension (e.g., blood pres
sure > 180/130 mm Hg)
(e) Coagulopathy, thrombocytopenia, or
current oral anticoagulation therapy
(f ) Noncompressible arterial or venous
puncture sites
b. Other considerations. Patients who have had
prior coronary artery bypass grafting do not ben
eft as much from either thrombolysis or angi
oplasty.
c Agents. The two most commonly used thrombo
lytic agents are streptokinase (usually 1.5 million
units over 1 hour) and tissue plasminogen activa
tor (t-PA). usually 100 mg. If t-PA is used, hepa
rin must be given during or following therapy to
decrease the high reocclusion rate: no beneft of
additional heparin has been shown with strepto
kinase. Most studies have shown no difference
in outcome regardless of whether streptokinase
or t-PA was used, but the recent large GUSTO
trial found a 1% 30-day mortality beneft with
front-loaded t-PA (2/3 of the dose given in 30
minutes and 113 given over the next 60 minutes).
!
Although this difference is relatively small, there
may be slight advantages of one or the other
agent, depending on the clinical situation.
(1) t-PA. Young patients with anterior MIs who
present within 4 hours of the onset of symp
toms may beneft the most from t-PA. t-PA
is also preferred for patients who have had
1 The GUSTO Investigators: An international randomized trial comparing
four thrombolytic strategies for acute myocardial infarction. N Engl J Med
329:673, 1993.
Chapter
a recent streptococcal infection or received
strptokinase within the last 6 months, and
for patients with borderline low blood pres
sure (because t-PA causes less hypotension
than streptokinase).
(2) Streptokinase. Overall, t-P A is associated
with a slightly higher risk of hemorrhagic
stroke than streptokinase (approximately
0.7-0.8% versus 0.5%). Patients who are
older than 70 years and those with high blood
pressure (i.e .. a systolic blood pressure > 160
mm Hg) have a higher risk of hemorrhagic
stroke; therefore, streptokinase may be the
preferred agent in these patients.
d. General recommendations. The mortality beneft
decreases drastically with delay in therapy, so
speed is of the essence. Make sure a large-bore
peripheral intravenous catheter (usually 16-
gauge) is in place prior to therapy. and limit ve
nous and arterial blood draws. It is clear that the
type of agent used is less important than ensuring
that all patients who meet appropriate criteria
and do not have contraindications receive throm
bolytic therapy as rapidly as possible.
e. Signs of successful reperfusion include a prompt
decrease in chest pain. normalization of the ST
segment, an accelerated idioventricular rhythm,
or an early peak of the CK enzymes (within 12
hours).
C. What other treatments may beneft the patient? Specifc
forms of therapy with nitrates. f blockers, and calcium
channel blockers as well as potential contraindications
are outlined in Chapter 9. The coronary care unit (CCU)
is the best place to manage patients with MI. given the
need for frequent vital checks and continuous rhythm
monitoring.
1. General measures
a. Bed rest and a stool softener are usually pre
scribed.
b. SUbcutaneous heparin (5000 units twice daily) is
usually administered to prevent deep venous
thrombosis.
Co Analgesia. Initially, nitrates are usually gven to
relieve pain, but morphine sulfate (4-8 mg intra
venously) may be used for persistent pain (care-
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Myocardial Infarction (MI)
ful titration of dose may be needed i n patients
who have borderline low blood pressure).
2. Aspirin (usually 325 mg orally) has been shown to
have a mortality beneft, even in patients who receive
thrombolytics. Active bleeding is a contraindication.
3. Oxygen (e.g., 2-4 Llmin) is often administered, al
though the beneft in patients with normal oxygen
saturation is questionable.
4. Nitrates are usually gven unless the patient is hypo
tensive o has evidence of a low cardiac output.
5. f blockers have been shown to decrease mortality in
patients with MI, and are especially useful in patients
with tachycardia, hypertension, or both.
6 Calcium channel blockers have not been shown to
have a mortality beneft in patients with MI. and in
some studies have been associated with increased
mortality. Diltiazem has been shown to decrease the
reinfarction rate in patients with non-Q wave MI,
but does not decrease mortality. In general, these
agents should be avoided in the acute management
of M!.
7. Angiotensin-converting enzyme (ACE) inhibitors
have had mixed results in the acute treatment of MI,
but are useful in the chronic management of patients
with an ejection fraction less than 40% (see VII B 1 a).
8. Heparin may not be useful for the treatment of acute
MI unless it is being used with t-PA thrombolysis.
I
COMONS
A. Arrhythmias are most common during the initial
12-24 hours.
1. Tachyarrhythmias are evaluated and treated as dis
cussed in Chapter 6. Of note, prophylactic lidocaine
is assocated with higher rates of asystole, a poorer
outcome, and is no longer recommended. Lidocaine
is often reserved for patients with sustained or non
sustained ventricular tachycardia. Prophylactic mag
nesium is also not recommended.
2. Bradyarrhythmias are more common with inferior
wall MI because the sinoatrial (SA) and atrioventric
ular (A V) nodes are more dependent on blood fow
from the right coronary artery.
a. Intravenous atropine (0.5-1 mg every 3-5
minutes, up to 3 mg) is usually efective for sinus
82 Chapter 1 0
bradycardia and symptomatic Wenckebach
(Mobitz type 1) second-degree AV block.
b. Temporary pacing is generally indicated for pa
tients with acute MI and:
(1) Symptomatic sinus bradycardia and Wencke
bach block that is unresponsive to atropine
(2) Mobitz type 2 second-degree A V block or
third-degree A V block
(3) New bifascicuJar block, including alternating
left and right bundle branch block, right bun
dle branch block with left anterior or poste
rior fascicular block, and left bundle branch
block with frst-degree AV block
B. Recurrent ischemia following MI is usually an indication
for emergent angiography and revascularization.
C. Pump dysfunction. Severe lef ventricuJar failure is man
aged as outlined for cardiogenic shock. Intra-aortic bal
loon counterpulsation and lef ventricular assist devices
may also be used until more defnitive therapy (i.e., car
diac transplantation) can be carried out.
D. Right ventricular infarction shouJd always be suspected
when hypotension accompanies an inferior MI. Treat
ment involves large fuid boluses to increase right-sided
cardiac output and left ventricular flling. Inotropic
agents with hemodynamic monitoring may also be re
quired.
E. Mechanical complications usually occur 2-7 days post
infarction.
1. Cardiac tamponade from free wall rupture usually
leads to abrupt hypotension and death.
2. Ventricular septal defect or papillary muscle rupture
leading to acute mitral regurgitation
a. Clinical signs and symptoms
(1) These disorders are often heralded by hypo
tension, pulmonary edema, or both. Any
abrupt change in hemodynamics should in
crease clinical suspicion of one of these me
chanical complications.
(2) A holosystolic murmur may be present in
both conditions, but the location is usually
at the left sternal border in ventricular septal
defect and at the apex in papillary muscle
rupture.
b. Diagosis. An emergent echocardiogram is the
quick and easy way to make the diagnosis. Hemo
dynamic monitoring with a P A line is usually
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Myocardial Infarction (MI)
83
necessary [or treatment. and may also be used
diagnostically-an increased oxygen saturation
between the right atrium and pulmonary artery
is seen with ventricuJar septal defect, and both
disorders may display prominent v waves.
c. Treatment. Nitroprusside or aortic balloon
counterpulsation may be used to decrease the
afterload, thereby increasing the fraction of
blood ejected into the aorta compared with the
regurgitant fraction ejected into the right ventri
cle or left atrium. Emergent surgical repair is
usually indicated for defnitive therapy.
3. Left ventricular aneurysm or pseudoaneurysm
a. Left ventricular aneurysm most often occurs after
large anterior wall MIs. Warfrin therapy for 3-6
months is often administered to patients with
large anterior wall MIs. Left ventricular aneu
rysms may also be associated with refractory
heart failure or arrythmias, and require surgi
cal correction.
b. Pseudo aneurysms are distinguished by a rela
tively narrow neck and a predisposition [or an
inferior-posterior location; surgical correction is
generally performed to prevent delayed rupture.
RISK REDUCTION
A. General measures include aspirin therapy (usually 325
mg/day), which has a mortality beneft, and aggressive
risk factor reduction (see Chapter 9 I B).
B. Additional diagnostic testing and preventive therapy.
Because the major complications of MI are heart failure,
recurrent ischemia, and arrythmias, diagnostic testing is
aimed at identifying and treating these disorders (risk
stratifcation).
1. Echocardiography. The post-MI left ventricnlar
ejection fraction is an excellent predictor of future
complications and survival. For this reason, patients
usually receive echocardiograms prior to discharge
from the hospital.
a. ACE inhibitors have been shown to decrease
mortality in patients who have a left ventricular
ejection fraction of less than 4% post-MI.
b. f blockers decrease post-MI mortality. Patients
with the lowest left ventricular ejection fractions
who can tolerate { blockers may actually have
84 Chapter 1 0
the greatest survival advantage. f blockers may
decrease the likelihood of arrythmias and pro
gressive heart failure in these high-risk patients.
2. Stress testing (see Chapter 9)
e Patients usually undergo a submaximal or maxi
mal stress test approximately 1 week or 3-6
weeks, respectively, following the MI. Although
the maximal stress test is considered more sensi
tive, patients frequently undergo the former be
cause it can be used to evaluate the patient's risk
prior to hospital discharge.
b. Angiography with revascularization is usually in
dicated for patients with positive tests that show
signifcant ischemia (especially if the ischemia is
assoiated with non-Q wave MI or a depressed
left ventricular ejection fraction).
C. Arrhythmia monitoring
HOT
K E Y
Ventricular arrythmias that occur within 24 hours of
MI generally do not worsen the patient's long.term
prognosis; however, subsequent episodes are associ
ated with a higher mortality rate and often necessitate
chronic therapy.
1. Patients with sustained ventricular tachycardia or
symptomatic nonsnstained ventricular tachycardia
(three or more consecutive ventricular premature
beats lasting less than 30 seconds) generally re
quire treatment.
2. Patients with asymptomatic nonsustained ventricnlar
tachycardia may also be treated, although the beneft
from therapy is less clear.
3. The appropriate means of assessing risk in patients
without ventricular tachycardia (i.e., those with occa
sional or no ventricular ectopy) is even more unclear.
While patients with a normal left ventricular ejection
fraction and signal averaged EKG have a favorable
prognosis, the positive predictive value of abnormal
tests is generally not high enough to ensure a beneft
from additional evaluation (i.e., electrophysiologic
testing) and treatment.
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11. Congestive Heart Fail ure
******
INTRODUC1 ON
A. Defnition. Congestive heart failure (CHF) occurs when
the heart is unable to pump suffcient amounts of blood at
normal flling pressures to keep pace with the metabolic
demands of the body.
B. Clinical manifestations classically include fatigue, leth
argy, dyspnea on exertion or rest, paroxysmal nocturnal
dyspnea (PND), orthopnea. weight gain. and leg
swelling.
C. Incidence. CHF is a common disorder, primarily affect
ing older individuals (10% of the popul
tio
.
n of he
United States over 75 years of age carry thiS diagnOSIS).
There are 40 .00 new cases per year.
D. Mortality rates. The annual mortality rate for all patients
with CHF is 20%. For patients who are symptomatic at
rest, the mortality rate is 50%. For those with pure dia
stolic dysfunction, it is 8%.
ClSSIFICATION. There are many different classifcation
schemes. The most useful include the following:
A. New York Heart Association (NYHA) functional classi
fcation
1. Class I: Symptomatic only with greater than normal
physical activity
.
2. Clas II: Symptomatic during normal activity
3. Clas III: Symptomatic with minimal activity
4. Class IV: Symptomatic at rest
B. Left-sided versus right-sided filure. It is important to
decide if patients have evidence of left-sided failure, be
cause these patients can present with marked hypoxemia
and therefore may need to be treated urgently (see IV
D). The distinction between left-sided and ght-side
failure is based primarily on signs found dunng phYSI
cal examination.
1. Lef-sided failure. Signs of left-sided failure include
85
86 Chapter 1 1
a left-sided third heart sound (S3), rales, wheezes
("cardiac asthma," a manifestation of interstitial
edema), and tachypnea.
2. Right-sided failure. Signs of right-sided failure in
clude a right-sided S3 (i.e., one that increases with
inspiration), an elevated jugular venous pressure. ab
normal hepatojugular refux, ascites, peripheral
edema, and an enlarged liver.
HOT
K E Y
a. Most of the time, evidence of biventricular failure
is found during physical examination because the
most common cause of right-sided failure is lef
sided failure.
Occasionally, right-sided failure can lead to left-sided
diastolic dysfunction because of septal deviation into
the left ventricular cavity, thereby increasing the left
ventricular end-diastolic pressure and causing pulmo
nary edema.
b. Other causes of right-sided failure include:
(1) Mitral stenosis
(2) Pulmonary hypertension [most commonly
caused by chronic obstructive pulmonary dis
ease (COPD)]
(3) Right ventricular infarction (usually oc
curring in the setting of left-sided inferior
wall infarction)
(4) Right-sided endocarditis
C. SystoHc versus diastolic dysfunction. Left ventricular fail
ure can be either systolic or diastolic. This is the most
important distinction to make because it affects
treatment.
I. Systolic dysfunction means that the heart's ability to
pump is compromised. It implies that the ejection
fraction is below normal (usually <4%). Causes of
systolic dysfunction include:
a. Myocardial infarction and ischemic heart disease
b. "Burned out" hypertensive or valvular heart dis
ease. Initially, these disorders lead to diastolic
dysfunction, but with time, the heart dilates and
the ejection fraction decreases.
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Congestive Heart Failure
87
Common Causes of Dilated Cardiomyopathy
("PIPED")
Postmyocarditis
Idiopathic
Peripartum
Ethanol
Drugs (cocaine and herain)
c. Dilated cardiomyopathies (i.e., disorders of the
myocardium that are not caused by coro
nary artery disease, hypertension, or valvular
disease)
d. Myocarditis
2 Diastolic dysfnnction means that the heart is able to
pump, but its ability to relax a
d allow ade
uate
flling during diastole is compromIsed. These patIents
have a normal or supranormal ejection fraction.
Causes of diastolic dysfunction include:
a. Ichemia
b. Disorders that lead to lef ventrkular hypertro
phy, such as:
(1) Hyprtension
(2) Aortic stenosis
(3) Hypertrophic cardiomyopathy
c. Restrictive cariomyopathy. This disorder is usu
ally caused by infltrative diseases (e.g., hemo
chromatosis, amyloidosis, sarcoidosis L sclero
derma).
3. In most patients, evidence of both diastolic and
.
sys
tolic dysfunction coexist: however, 20% of patIents
have predominantly diastolic dysfunction. Both types
of dysfunction have similar clinical manifestations.
HOT
K E Y
CHF with a low ejection fraction systolic dysfunction.
CHF with a normal or high ejection fraction dia
stol ic dysfu nction.
88
Q
Chapter 1 1
ApPROACH TO THE PATI ENT
A. Assess how symptomatic the patient is.
B. On the basis of the patient's history, physical examina
tion fndings, and chest radiographs, categorize the fail
ure as predominantly left-sided, right-sided, or biventri
cular.
C. If the patient has left -sided CHF, determine whether the
dysfunction is predominantly systolic or diastolic, using
the ejection fraction as a basis for the determination.
Ejection fraction can be assessed using echocardiogra
phy. mUltiple gated acquisition (MUGA) scans, or car
diac catheterization. Remember, if a panent with a nor
mal ejection fraction has cardiogenic pulmonary edema,
then the dysfunction is diastolic.
D. Determine the underlying cause of the CHF (e.g., coro
nary artery disease, valvular disease, hypertension, car
diomyopathy).
E. If the patient's symptoms have worsened (this is usually
the scenario in patients evaluated in the emergency
room), you must decide what precipitated the CHF exac
erbation:
Factors that Can Exacerbate CHF ("FAILURE")
Forgot meds
Arrhythmia or Anemia
Infections, Ischemia, or Infarction
Lifestyle (e.g., increased sodium intake, stress)
Upregulators (e.g. , thyroid disease, preg
nancy)
Rheumatic valve or worsening of other valvu
lar diseases
Embolism (pulmonary)
TREATMENT
A. Goals of treatment for CHF (and most other diseases)
are two-fold:
1. Reduce symptoms
2. Reduce mortality
B. Chronic systolic dysfunction. Treatment primarily in
volves the "4 Ds."
1. Dilators. Peripheral arterial vasodilators [e.g., angio
tensin-converting enzyme (ACE) inhibitors, hydra-
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Congestive Heart Failure 89
lazine, isordil) are drugs that have been shown to
reduce both symptoms and mortality. The ACE in
hibitors are considered frst-line therapy for sys
tolic dysfunction.
2 Digoxin. This age-old treatment for CHF has been
shown to reduce symptoms but has never been shown
to decrease mortality. Digoxin should be used in
patients who are symptomatic in spite of other
therapy.
3. Diuretics are strictly for treating symptoms of fuid
overload (e.g., rales, peripheral edema). No mortality
beneft has ever been shown.
4. Diet. A low-salt diet is also primarily used for control
of fuid overload. The number of patients admitted
to the hospital for CHF exacerbations markedly in
creases the day after Thanksgiving, undoubtedly as
a result of increased salt consumption.
C. Chronic diastolic dysfnnction. There are only three op
tions in the treatment of chronic diastolic dysfunction.
Digoxin and vasodilators do not play a major role in the
treatment of patients with predominantly diastolic dys
function.
D.
L Diuretics
2 Diet
3. f blockers. The goal in treating diastolic dysfunction
is to enhance ventricular compliance. This is best
done by using agents that improve left ventricular
relaxation, such as calcium channel blockers (e.g.,
diltiazem. verapamil) and f blockers. These drugs
have never been shown to reduce mortality.
Acute pulmonary edema. If a patient experiencing acute
pulmonary edema is not treated correctly and promptly,
he or she may die. Both systolic and diastolic dysfunction
can lead to acute pulmonary edema; however, in the
beginning, initiating prompt therapy is more important
than determining the exact cause of the patient's rapid
decompensation. Reducing preload is the primary goal
of therapy in patients who are in acute pulmonary edema.
It is easy to remember how to treat "wet" patients:
90 Chapter 1 1
Treatment of Acute Pulmonary Edema {"MOIST
'N DAMP"}
Morphine (2-4 mg intravenously as long as
the blood pressure is adequate)
Oxygen (as much as necessary to raise the
oxygen sturation over 90%)
Intubation, if necessary (pul monary edema is
rapidly reversible, but i f the patient is tiring,
intubation can be lifesaving)
Sit 'em up (to reduce preload)
Tourniquet (rotating tourniquets to decrease
preload were once used)
Nitrates (acutely decrease preload)
Diuretics (20-40 mg furosemide intravenously
t first decrease preload and then induce a di
uresis)
Albuterol (may help bronchospastic patients)
More morphine, more nitrates, and morediuret
ics as needed
Phlebotomy (was once used to reduce preload)
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12. Shock
@
INTRODUCON
A. Defnition. Shock occurs when the arterial circulation
is unable to keep up with the metabolic demands of
the body.
B. Clinical manifestations of shock-regardless of etiol
ogy-usually include:
1. Hypotension
2. Tachycardia
3. Altered mental status
4. Decreased urine output
5. Cool skin
CAUSES OF SHOCK. The many causes of shock must be
remembered because treatment must address both the mani
festations of shock as well as its underlying cause.
The Causes of Shock ("SHOCK")
Sepsis
Hypovolemia
Obstruction to Flow
Cardiac
Kooky disorders
A. Sepsis is a common cause of shock. Bacteremia caused
by gram-negative rods (e.g., Escherichi coli, Klebsiella,
Proteus, Pseudomonas) or gram-positive cocci (e.g.,
Staphylococcus, Streptococcus) is the usual cause of sep
tic shock.
B. Hypovolemia. Any process that causes a marked reduc
tion in intravascular volume (e.g., trauma, gastrointesti
nal bleeding, hematoma, burns, pancreatitis, hyperosmo
lar states, vomiting, diarrhea) can lead to hypovolemic
shock.
91
92 Chapler 1 2
C Obstruction to fow. Disorders such as cardiac tampon
ade, pulmonary embolism. tension pneumothorax, and
severe aortic or mitral valve stenosis can lead to shock.
Tamponade and tension pneumothorax should always
be considered promptly because early treatment can save
the patient's life.
D. Cardiac causes. Cardiogenic shock is most commonly
the result of "pump failure," caused by a myocardial
infarction (of either the left or right ventricle) or dilated
cardiomyopathy. Other cardiac causes include tachy
or bradyarrhythmias, acute valvular regurgitation (mitral
or aortic), and rupture of the septum or ventricular
wall.
E. "Kooky" disorders. This category includes diseases only
a medical school "DEAN" could remember:
"Kooky" Disorders leading 10 Shock
("DEAN")
Drug toxicity (primarily vasodilaling drugs)
Endocrine disorders (adrenal insuficiency or
myxedema)
Anaphylaxis
Neurogenic (espcially afer spinal cord i nj ury)
ApPROACH TO THE PATIENT
A. Physical examination. The ABCs (airway, breathing, and
circulation) should be assessed frst.
1. The blood pressure should be verifed with a manual
cuff. Hypotension is usually defned as a systolic pres
sure that is Jess than 9 mm Hg.
2 Temperature. If the patient is febrile or hypothermic,
septic shock is likely.
3. The oxygen saturation (the "ffth vital sign") should
be obtained during the initial assessment.
4. Neck vein assessment. Elevated neck veins in a hypo
tensive patient are usually indicative of:
a. Tamponade
b. Tension pneumothorax
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Shock
B.
93
c. Pulmonary embolism (with right ventricular
failure)
d. Right ventricular infarct
e. Biventricular dysfunction (the only entity on this
list that will also cause rales)
5. Lung sounds
a. Rales usually indicates a cardiac cause.
b. Wheezing should increase suspicion of anaphy
laxis.
c. Disparate breath sounds may represent pneumo
thorax.
6. Cardiac auscultation. Important fndings include an
abnormal rate L rhythm, distant heart sounds, a
third heart sound (). or new murmurs.
7. Abdominal palpation is helpful in evaluating
whether pancreatitis, a perforated viscus, or an in
fected hepatobiliary source is the cause of shock.
8. Rectal examination is important, especially if a gas
trointestinal bleed is likely.
9. Skin inspection. A scarlatiniform rash may be indica
tive of toxic shock syndrome, whereas urticaria can
be a sign of anaphylaxis.
to. Neurologic examination is useful to assess mental
status and to ensure that the patient does not have
spinal cord compression.
Laboratory tests. Useful tests include:
1. A complete blood count (CBC)
2. A Chemistry panel, including blood urea nitrogen
(BUN) and creatinine levels
3. Liver function tests
4. Urinalysis
5. Blood cultures
6. Arterial blood gases
C. A chest radiograph and electrocardiogram (EKG) are
mandatory.
D. Other diagnostic modalities [e.g., computed tomography
(C), cocardiography. endoscopy, ventilation-perfu
sion (V/Q) scans, or evaluation of thyroid-stimulating
hormone (TSH) levels or serum cortisol] should be en
listed promptly if warranted by clinical suspicion.
E. Occasionally, patients are hypotensive but the cause is
not clear. In these situations. pulmonary artery (P A)
catheterization can be useful, especially in patients who
are both hypotensive and hypoxemic (Table 1 2-1).
94
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Shock 95
HOT
Hypotension Hypoxemia PA l ine
KEY
TREATMENT. The goal is to maintain the mean arterial pres
sure above 6 mm Hg, while treating the underlying disorder
causing the shock. Treatment is usually instituted even be
fore a defnitive cause of shock has been determined.
A. Place the patient in the Trendelenburg position (head
down).
B. Provide supplemental oxygen. Intubation may be nec
essary.
C. Administer fuids rapidly through two large-bore intrave
nous lines, unless the patient clearly has biventricular
failure.
D. Insert a Foley catheter to monitor urine output.
E. Consider vasopressor medications. The decision to use
"pressors" is often diffcult; usually, they are used i the
patient has not responded to a trial of aggressive fuid
resuscitation. The choice of which pressor to use depends
on the clinical situation and should be guided by hemody
namic monitoring.
L Mechanism of action. Vasopressors act on the auto
nomic nervous system. Once you understand what
each receptor does (Table 12-2). it is easy to remem
ber the actions of each pressor.
2 Agents. Table 12-3 contains the most commonly used
vasopressors, in order from ai-adrenergic agents to
Jz-adrenergic agents. Get used to remembering the
drugs in this order. [If you need a mnemonic to help
you, you can think of the following scenario: A pa
tient, Edward, who has severe congestive heart fail
ure (CHF). calls himself "Eddie." Unfortunately,
he is a poor speller, so he spells his name "Edi."
Every time you see him, you inquire whether he
has paroxysmal nocturnal dyspnea (PND). You ask,
"PND EDI?"]
--< He ,J5 npO,a:M >-- --<
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Sepsis, hypotensive cardiogenic shock
Pulseless arrest, sepsis
Cardiogenic shock (but not by itself if patient is
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Bradycardia
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13.Acute Dyspnea
@
INTRODUCTION. Acute dyspnea is a common cause of

emergency room visits, hospital admissions, and decompen
sation among hospitalized patients.
CAUSES OF ACUTE DYSPNEA. Dyspnea is often the chief
complaint of patients with a variety of disorders, many of
which can be immediately life threatening.
A. Pubnonary
1. Pneumothorax is a sudden event that is often accom
panied by very acute dyspnea and pleuritic chest
pain. This diagnosis should always be considered in
a patient on a ventilator.
2. Pulmonary embolism is a diffcult diagnosis to make
because of the lack of sensitivity and specifcity of
the history and physical examination. Therefore, you
should consider this possibility early in the evaluation
of most patients with acute dyspnea because special
ized testing is often required to confrm the diagnosis.
3. Bronchospasm should be suspected in patients with
known obstructive lung disease, such as chronic ob
structive pulmonary disease (COPD) or asthma.
Wheezing is the hallmark physical fnding; however,
COPD and asthma are not the only causes of wheez
ing. Congestive heart failure (CF), for example,
can also cause the patient to wheeze.
HOT
Not all that wheezes i s asthma!
K E Y
4. Aspiration should be suspected in patients with swal
lowing dysfunction or a diminished level of con
sciousness. Always ask family members or nurses
for information.
1 01
1 02
Chopter 13
5. Pneumonia. Patients will usually have other symp
toms of infection, including fever or hypothermia,
chills. or a productive cough.
6. Upper airway obstruction. A very acute onset of
symptoms or localized wheezing should prompt con
sideration of this diagosis.
7. Acute respiratory distress syndrome (ARDS). These
patients are usually hospitalized with another diag
nosis.
B. Cardiac
1. Myocardial ischemia or infarction. Dyspnea may oc
cur i the absence of chest pain and thus may repre
sent an anginal equivalent.
2. CHF. In hospitalized patients with CHF, acute dys
pnea i often precipitated by fuid administration
or ischemia.
3. Arrhythmias cannot be reliably diagnosed on physi
cal examination; a 12-lead electrocardiogam (EKG)
or a rhythm strip is required.
4. Pericardial tamponade is rare, but should always be
considered in a patient with right-sided heart failure
and no evidence of left-sided heart failure.
C. Metabolic
1. Sepsis. Dyspnea and an acute respiratory alkalosis
may be the earliest fndings in a patient with a severe
systemic infection.
2. Metabolic acidosis can be diagnosed on the basis of
an arterial blood gas.
D. Hematologic. Anemia can cause acute dyspnea, and can
easily be missed on history and physical examination.
E. Psychiatric. Anxiety can be a primary cause of acute
dyspnea; however, a diagnosis of primary anxiety should
be considered only after the more serious possibilities
have been ruled out. Many patients with dyspnea of an
organic cause are very anxious.
ApPROACH TO THE PATIENT. The key to evaluating a pa
tient with acute dyspnea is to focus on recognizing the most
serious disorders.
A. Patient history. There are four key areas of inquiry:
1. What was the speed of onset of the dyspnea?
2. Are there any associated symptoms (e.g., chest
pain, chills)?
3. What happened immediately before the onset of
the dyspnea? What medications or fuids was the
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Acute Dyspneo 103
patient receiving immediately before becoming
dyspneic?
4. What are the patient's other medical problems? If
already hospitalized, what is the admission diag
nosis?
B. Physical examination. Focus on fve key areas:
1. Vital signs. Markedly abnormal vital sigs in an
acutely dyspneic patient may sigify impending re
spiratory failure. An oxygen saturation should be ob
tained.
HOT
K E Y
Remember, C normol oxygen soturation does not ex
clude the possi bi l ity of C serious disorder!
2. Lungs. Pay particular attention to the symmetry of
breath sounds and the presence of wheezing or rales.
3. Heart. A complete examination should be per
formed, focusing on the fndings of right-sided and
left-sided heart failure.
4. Extremities. Look for edema (unilateral versus bilat
eral) and cyanosis.
5. Mental status. Evaluating the patient's mental status
is crucial for two reasons:
a. A markedly depressed level of consciousness
may necessitate intubation for airway protection.
b. The fnding of altered mental status as a result
of the dyspnea suggests a signifcant homeo
static insult.
C. Diagnostic studies. Four studies should be routinely per-
formed when the patient is acutely dyspneic.
a. 12-Lead EKG
b. Arterial blood gas analysis
c. Chest radiograph
d. Complete blood count (CEC)
TREATMENT
A. Supplemental oxygen. All patients with acute dyspnea
1 04
Chapter 1 3
should be administered supplemental oxygen. A history
of COPD or carbon dioxide retention should not prevent
oxygen therapy for hypoxemic patients; however, pa
tients at risk for carbon dioxide retention should be
closely monitored.
B. Diuretics. Any process associated with excess lung water
(e.g., pulmonary edema, ARDS. aspiration. pneumonia)
may improve with diuresis.
C. f Agonists. Regardless of the cause, wheezing will likely
unprove somewhat with nebulized f agonist therapy.
D. Mechanical ventilation. The need for immediate or po
tential intubation should be assessed. Indications for me
chanical ventilation include:
1. Refractory hypoxemia (Pa02 < 60 mm Hg despite
maximal oxygen therapy)
2. Ventilatory failure (generally manifested by an in
creasing Paco2 despite therapy)
3. Inability to protect the airway
4. Impending upper airway obstruction
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14. Massive Hemoptsis
@
INTRODUCTION. Hemoptysis, defned as the expectoration

of blood, can be an insignifcant symptom of a benig illness,
a frst manifestation of serious malignancy, or a fatal process
in and of itself. Hemoptysis is usually classifed as either
massive or nonmassive.
A. Massive hemoptysis is usually defned as > 200 ml blood/
24 hours and requires immediate evaluation: it is the
focus of this chapter.
B. Nonmassive hemoptysis, usually defned as < 200 ml
blood/24 hours. accounts for more than 90% of cases but
usually does not necessitate admission of the patient to
the hospital. Patients with massive hemoptysis have a
higher mortality rate than those with nonmassive hemop
tysis, but patients expectorating small amounts of blood
warrant close attention, because they may "open up"
(i.e., develop massive hemoptysis in an unpredictable
fashion).
CAUSES O HEMOPTSIS. The list of differential diagno
ses is long. The following mnemonic may help you to remem
ber the many causes of hemoptysis-think of soldiers in a
"BATTLE CAMP" coughing up blood.
Causes of Hemoptysis ("BATlE CAMP")
Bronchiectosis or Bronchitis
Asperg illoma'
Tumor"
Tuberculosis'
Lung abscess'
Emboli
Coagulopothy
Arteriovenous molformation, Arteritis, or Alve
oIar hemorrhoge
Mitral stenosis
Pneumonia
Most common causes of mssive hemoptysis
1 05
1 06 Chopter 1 4
A. Bronchitis is the most common cause of hemoptysis but
rarely causes massive bleeding.
B. Bronchiectasis is relatively rare because the number of
cases of tuberculosis and untreated pneumonia has de
clined: however, bronchiectasis is still seen commonly in
patients with cystic fbrosis.
C. Aspergilloma. Any cavitary fungal lesion can cause he
moptysis, but the "fungus ball" caused by Aspergillus
Jmigatus is most common.
D. Tubrculosis. Hemoptysis in patients with tuberculosis
is often caused by the rupture of Rasmussen's aneurysms
(i.e., dilated segments of pulmonary arteries that traverse
pulmonary cavities).
E. Emboli. Bland or septic emboli can cause lung infarction.
F. Coagulopathy is often associated with hemoptysis but is
not causative in and of itself. An underlying lesion should
be sought.
G. Arteriovenous malformation is usually congenital and is
often associated with hereditary hemorrhagc telangiec
tasia (Osler-Weber-Rendu syndrome).
F. Arteritis. Many vasculitides can involve the lungs
(e.g., Churg-Strauss syndrome, Wegener's ganuloma
tosis).
G. Alveolar hemorrhage can be caused by autoimmune pro
cesses that also involve the kidneys [e.g., Goodpasture's
syndrome, systemic lupus erythematosus (SLE)], as well
as idiopathic pulmonary hemosiderosis.
H. Mitral stenosis causing pulmonary hypertension can lead
to hemoptysis.
I. Pneumonia associated with hemoptysis is usually necro
tizing (e.g., that caused by Staphylococcus aureus or
Pseudomonas aeruginosa).
Q
A. Maintain airway patency and oxygenation. Arte
rial blood gas analysis and chest radiographs should
be performed immediately to assess oxygenation
and determine the extent of blood retained in the
lung. Because death from massive hemoptysis usually
results from alveolar fooding and hypoxemia, ensuring
adequate oxygenation is the most important first
step.
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Massive Hemoptysis 1 07
HOT
K E Y
To prevent aspiration of blood into the unaffected lung
i n a potient with massive hemoptysis, have the potient
lie in the lateral decubitus position with the bleeding
side down. How do you know which lung is bleeding?
Ask the patient; he or she may know.
1. If emergent intubation is indicated for airway man
agement, hypoxemia, or hypoventilation, a large
bore endotracheal tube (preferably 8 mm) should
be placed if possible, because the patient will most
likely need urgent bronchoscopy.
2. Intubation with a double-lumen endotracheal tube
allows ventilation of both lungs, while preventing
aspiration of blood from one side to the other. This
is a difcult technique with serious potential compli
cations; therefore, it should be performed only by
an experienced physician.
B. Identif the bleeding lesion
1. Ensure a bronchopulmonary source. It is necessary to
ensure that the patient truly has bronchopulmonary
bleeding. If the source of the bleeding is not obvious,
helpful techniques include the following:
a. Evaluation of the pH of the expectorated sub
stance can provide clues-gastrointestinal con
tents are usually acidic, whereas pulmonary ex
pectorations are usually alkaline.
b. Examination of the pharynx and larynx may re
veal the cause of the bleeding to be epistaxis.
2. Lung auscultation and chest radiogaphs can help to
localize the bleeding but may not be helpful i the
bleeding is diffuse or if blood has been aspirated
fom one lung into the other. A chest radiograph
may also show a mass lesion or cavity.
3. Urinalysis and assessment of renal function may pro
vide clues to an unsuspected vasculitis or pulmonary
renal syndrome.
4. Computed tomography (CT) is not always useful
but may reveal a space-occupying lesion (e.g., lung
cancer or abscess).
1 08 Chapter 1 4
5. Early bronchoscopy is indicated for most patients
for both therapeutic and diagnostic purposes.
6. Arteriography is useful for actively bleeding patients
for purposes of localization of the bleeding lesion
and therapy.
C. Control the hemorrhage
1. General measures indicated for all patients with mas
sive hemoptysis include bed rest, cough suppressants,
sedatives, and stool softeners or laxatives, which help
prevent sudden increases in intrathoracic pressure,
thereby minimizing intravascular pressure.
2. Coagulopathies should be sought and corrected if
present.
3. Intravenous vasopressin (0.2 U/min intravenously)
has been used as a nonspecifc vasoconstrictor but
may cause ischemic complications.
4. Bronchoscopy followed by maneuvers such as iced
saline irrigation, topical application of vasoconstric
tors or thrombin, or balloon tamponade may be
needed in some patients.
5. External radiation therapy may be effective for re
ducing bleeding from tumors.
6. Defnitive therapy can be achieved with angographic
arterial embolization and, if necessary, lung re
section.
HOT
K E Y
Consult a pulmanalagist i mmediately if the patient pre
sents with massive hemoptysis.
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lS.Approach to the Chest
Radiograph
@
INTRODUCTION. It is often necessary to rely on your own

interpretation of a chest radiograph pending a formal read
ing. The purpose of this chapter is to provide a consistent,
easy-to-use approach to the evaluation of a chest radiograph.
PREUMINARY CONSIDERATIONS
A. What kind of radiograph should I order?
1. A posterior-anterior (P A) view is always preferable
to an anterior-posterior (AP) view because the latter
exaggerates the size of the heart and other mediasti
nal structures. However, in an emergency situation,
an AP view is often the only option.
2. A lateral view should also be obtained to provide
supplemental information and to confrm fndings on
the PA view.
B. Is it a good flm? Assessing the quality of the radiograph
may help you avoid common misinterpretations.
1. Inspiration. Count the number of ribs; a good inspira
tion will reveal ten posterior ribs. A poor inspiration
may cause the lungs to look "squashed," resulting in
the false appearance of an "interstitial prominence."
This may lead to a misdiagnosis of pulmonary edema
or atypical pneumonia.
2. Rotation. Look at the clavicles and see i they are
asymmetrical (an indication of rotation). Rotation
often leads to erroneous estimates of cardiac, pulmo
nary artery, aortic, and mediastinal dimensions.
3. Penetration. You should be able to see individual
vertebrae in a flm that is appropriately penetrated.
Decreased penetration will make the lungs seem
denser. Mild pulmonary edema or a small infltrate
will appear to be marked pulmonary edema or a
large infltrate, and even normal interstitial markings
may appear abnormal.
C. Is there an old flm available for comparison? There is
no substitute for comparison with prior flms. A new
subtle area of consolidation may be found in a patient
with suspected pneumonia, a nodule may be unchanged
1 09
1 1 0 Chapter 1 5
for 10 years and therefore presumed to be benign, or
the mediastinum may be wider in a patient with sus
pected aortic dissection. In all cases, you need to make
sure the view was the same (i.e., AP versus PA). In
addition, you must "mentally adjust" for variations
in technique (i.e., inspiration, rotation, and pene
tration).
Q
THE OUTSIDE-IN APPROACH. The structures visible on
a chest radiograph can be evaluated in any order, but you
should be consistent every time you read a flm. The out
side-in approach is frequently used, and ensures that com
monly overlooked structures (e.g., bones) are not forgotten.
A. Bones. Look for lytic or blastic lesions that may signal
a metastatic malignancy. Evidence of osteoporosis or
compression fractures may also be found.
B. Lungs. Look at both lung felds in an orderly fashion.
Pay special attention to the diaphragms, the cardiac bor
ders, and the apices. Although symmetrical abnormali
ties may occur (e.g., with pulmonary edema or bilateral
pneumonia), asymmetrical fndings are particularly sus
picious. An infltrate may be blood. pus, or water; there
fore, hemorrhage, pneumonia, and pulmonary edema
are all considerations. It is also worth adding atelectasis
and acute respiratory distress syndrome (ARDS) to this
list of common infltrates.
1. Diaphragms
a. If one of the diaphragms is obscured, an infltrate
is present in the respective lower lobe.
b. The retrocardiac area is a notorious place for
missed diagnoses. You should be able to see the
left herdiaphrag behind the heart. An inabil
ity to appreciate the left hemidiaphragm usually
signals atelectasis or an infltrate, but may also
occur if the flm is underpenetrated.
c. Flattened diaphragms are often found in chronic
obstructive pulmonary disease (COPD).
d. Blunting of the costophrenic angles can be
caused by pleural effusions.
e. Look for fee air under the diaphragm in patients
presenting with abdominal pain.
2. Cardiac borders
M A lingular infltrate (lower portion of the upper
lobe) is present if the left cardiac border is ob
scured.
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Approach to the Chest Radiograph III
b. A right middle lobe infltrate is present if the
right cardiac border is obscured.
3. Apices
a. Apical pneumothoraces are easy to miss; always
look carefully for these in patients with chest
pain or shortness of breath. Follow the interstitial
markings to the chest wall to ensure that no pneu
mothorax is present.
b. Congestive heart failure (CHF) is characterized
by cephalization (redistribution of blood fow to
ward the apices). Other common fndings with
CHF include cardiomegaly, pleural effusions,
prominent pulmonary arteries, and Kerley B
lines (horizontal lines in the periphery).
c. Tuberculosis often presents in the apices. A lor
dotic view may be ordered i the apex is not
well visualized.
C. Heart
D.
1. Cardiomegaly. The cardiac silhouette should be less
than one half of the thoracic diameter on a P A flm;
anything larger indicates cardiomegaly.
2. Chamber enlargement
a. The left side of the cardiac silhouette represents
the left ventricle, whereas the right side repre
sents the right atrium. Prominence in either loca
tion may represent enlargement of the respec
tive chamber.
b. Left atrial enlargement may be signifed by:
(1) The loss of the normal concavity on the left
side of the hean
(2) An elevated left mainstem bronchus
(3) The "double-density" sign, which is seen as
two parallel lines on the right side of the
heart representing the right atrial and the
enlarged left atrial borders
c. Right ventricular enlargement is not visible on
P A or AP flms, but can be seen on a lateral flm
as flling of the retrosternal space.
3. Pulmonary hypertension. The diameter of the pul
monary artery should generally not exceed that of a
dime; an increase in this size may signify pulmo
nary hypertension.
Mediastinum
1. Aortic dissection. Mediastinal widening may signify
aonic dissection, but the sensitivity of this fnding is
not very high.
1 12 Chapter 1 5
2. Lymphadenopathy. A prominent paratracheal stripe
(usually seen as a wide stripe down the right side of
the trachea) and obliteration of the normal aortic
pulmonary window (a triangular space on the left
side) often signify lymphadenopathy.
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16. Hypoxemia
@
INTRODUCION
A. Hypoxemia is not a diagnosis; it is a manifestation of an
underlying disease.
B. Hypoxemia is common in hospitalized patients.
C. Patients with hypoxemia should always be evaluated
promptly.
@
CUNICAL VALUES
A. Arterial oxygen tension (Paoz). In strictest terms. one
needs to obtain an arterial blood gas report in order to
confrm the presence of hypoxemia. A normal Pao2 is
80-100 mm Hg.
HOT
To determine the normal Pa for a particular patient:
Subtract 1 mm Hg for eery decode of oge; subtract
3 mm Hg for every 1000 feet altitude.
K E Y
B.
c.
Oxygen (Oz) saturation. The Pao2 can be estimated using
the O2 saturation. An O2 saturation of 88% is roughly
equal to a Pa of 60 mm Hg. The O2 saturation has a
variability of ::4%.
Alveolar-to-arteral (A-a) gradient. The A-a gradient
helps determine the cause of the hypoxemia and provides
a rough estimate of how ill a patient is.
1. A normal A-a gradient is less than the patient's age
divided by 4 plus 4. For example, a 24-year-old pa
tient should have an A-a gradient less than 10.
2. Calculating the A-a gradient is easy using the alveo
lar gas equation and values fom the arterial blood
gas report.
M First, the alveolar oxygen tension (P A02) is calcu
lated using the alveolar gas equation:
1 1 3
1 1 4 Chapter 1 6
PA02 (P
b,.mt, - Pwa ...
) F102 - Paco2/0.8, where
Pba,.me,k the barometric pressure (760 mm Hg)
P wo; the vapor pressure of water at body
temperature (47 mm Hg)
F102 the fraction of oxygen i n the inspired gos
(0.21 on room air)
HOT
Remember, in order for the simpl ified equation t work,
the patient must be breathing room oir.
K E Y
Q
PaC02 the arterial carbon dioxide tnsion
Thus, the equation simplifes to:
The value for Paco2 is obtained from the arterial
blood gas report.
b. To calculate the A-a gradient, subtract the Pao2
(obtained fom the arterial blood gas report)
fom the P 1t_ (obtained from the alveolar gas
equation):
A-a gradient * PA02 - Pao2
MECHANISMS OF HYPOXEMIA. There are fve patho
physiologic mechanisms that al!se hypoxemia (Table 16-1).
A. Ventilation-perfusion (V/Q) mismatch accounts for
more than 95% of cases of hypoxemia. V/O mismatch
occurs when ventilation i regonal areas is decreased in
comparison to perfusion. This regional hypoxemia can
not be corrected because the oxygen-carrying capacity
in normal regons cannot be increased.
B. Right-to-Ieft shunting occurs when systemic venous
blood (PV02 40 mm Hg) enters the left side of the heart
without coming in contact with oxygen-rich alveolar air.
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Hypoxemio
TABLE 1 6- 1 : Causes of Hypoxemia
Pathaphysiologic Mechanism Clinical Examples
Ventilation-perfusion ( /0)
mismatch
Right-to-Ieft shunting
Diffusion defects
Hypoventilation
low inspi red O2 tension
Pneumonia, CHF, ARDS, atelecta
sis, tumor-filled alveoli
Any of the couses of V /0 mis
match if V /0 0, congenital
cardiac abnormalities, pulmo
nary arteriovenous malfor
mation
Interstitial lung diseose, Pneumo
cystis carinii pneumonia
capo, CNS disorder (damage to
respiratory neurons), mechoni
cal i mpirment of the breathing
opparatus (poliomyelitis, Guil
lain-Barre syndrome, myasthe
nio gravis, kyphoscoliosis, Pick
wickian syndrome)
High altitude
1 1 5
ARDS acute respiratory distress syndrome; CHF congestive heort failure;
CNS central nervous systm; capo chronic obstructive pulmonory
di seose; O2 oxygen.
1. Right-to-Ieft shunting may result fom cardiac abnor
malities (i.e., intracardiac shunts) or pulmonary ab
normalities (i.e., intrapulmonary shunts).
2. A shunt exists whenever ventilation equals zero but
perfusion continues.
HOT
K E Y
A shunt does not correct with 1 00% supplemental oxy
gen, unlike V /0 mismatch and diffusion defects.
1 1 6 Chapter 1 6
C. Difusion defects leading to hypoxemia are less common.
The usual causes include interstitial lung diseases (e.g.,
idiopathic pulmonary fbrosis), environmental lung dis
ease, and Pneumocystis carinii pneumonia. A clinical
clue to the presence of a diffusion defect is that often
the patient will become much more hypoxemic with am
bulation.
D. Hypoventilation is defned by an elevated Paco2' There
are many causes of this abnormality; in order to fnd the
cause, a systematic approach, starting at the head and
working to the lungs, is best (see Chapter 23 III B).
E. Low inspired oxygen tension. Unless the patient is at a
high altitude, this cause can be ruled out.
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17. Pulmonar Functon Test
@
INTRODUCTION
A. Uses. Pulmonary function tests can be used to:
1. Diferentiate obstructive lung disease fom restric
tive lung disease
2. Assess the severity of lung disease
3. Evaluate response to therapy
B. Types of infonnation assessed. Pulmonary function tests
allow assessment of three types of information:
1. Lung volumes
M The total lung capacity (TLC) is the volume of
air in the lungs after a maximal inspiratory effort.
b. The vital capacity (VC) is the maximal volume of
air that can be expelled from the lungs following a
maximal inspiration.
c. The residual volume (RV) is the volume of air
remaining in the lungs after a maximal expir
atory effort.
2. Expiratory fow rate. The forced expiratory volume
in 1 second (FEV1) is the most commonly used
screening test for airway disease. It is a fow rate that
represents the volume of the forced vita) capacity
(FVC) expired during the frst second of expiration.
3. Difusion capacity. Evaluation of the difusing capac
ity of the lungs for carbon monoxide (DLCO) indi
cates the adequacy of the alveolar-capillary mem
brane. Common causes of a decreased DLCO are
emphysema and interstitial lung disease.
C. Interpretation. An organized and systematic approach
to interpretation is required. When interpreting the re
sults of pulmonary function testing, it is important to
note both the observed values and the percent predicted.
The range of normal for all values wll vary slightly de
pending on the pulmonary function testing laboratory.
@
OBSTRUCTIVE VERSUS RESTRICIVE lNG DISEASE
A. The relationship between fow rate, lung volume, resis
tance, and compliance is as follows:
Flow Rate " Lung Volume/(Resistance)(Compliance)
1 1 7
1 1 8
Q
Chapter 1 7
Therefore, the fow rate (as measured by FEVl) will
decrease if the lung volume decreases (as seen in restric
tive disorders), resistance increases (as seen in asthma
or chronic bronchitis), or compliance increases (as seen
in emphysema).
B. Obstructive disorders cannot be distinguished from
restrictive disorders on the basis of the FEVl alone.
In order to distinguish between obstructive and restric
tive lung disorders, the lung volume must be eliminated
from the equation; dividing by the FVC will accomplish
this goal: FEV1(%) " FEV1 ' FVC. The FEVl(%) is the
percent of the forced vital capacity expelled in 1 sec
ond.
1. If the FEVl(%) is decreased 80%), then the pa
tient has obstructive disease.
2. If the FEVl(%) is normal or increased in the setting
of a low FEVj, then the patient has restrictive
disease.
ApPROACH TO THE INTERPRETATION OF PULONARY
FUNCTON TESTS
A. Look at the FVl frst.
1. If the patient has a normal FEVj, TLC, and DLCO,
the patient is doing well from a pulmonary stand
point.
2 If the FEVl is low, look at the FEVl(%) to distinguish
between obstructive and restrictive disease.
M If the FEVl (%) is normal, then the patient proba
bly has restrictive disease (which will be con
frmed by a low TLC).
b. If the FEVl(%) is less than 80%, then the patient
has obstructive disease.
(1) If the patient has obstructive lung disease,
then determine if it is reversible.
(a) If the FEVl improves by more than 15%
after bronchodilator administration, re
versible airway obstruction (i.e., asthma)
is implied. If there is signifcant improve
ment, then the patient has a component
of reactive airway disease and will proba
bly beneft from treatment with inhaled
corticosteroids.
(b) If there is no improvement following the
administration of bronchodilators, the
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Pulmonary Function Tests 1 1 9
patient probably has chronic obstructive
pulmonary disease (COPD).
B. Now look at the DLeo.
1. If the patient has restrictive disease, a low DLCO
implies that interstitial lung disease is the cause.
2. If the patient has obstructive disease, a low DLCO
implies the presence of emphysema.
18. Obstructive Lung Disease
@
INTRODUCION
A. Disorders. There are four major obstructive lung dis
eases:
1. Asthma
2. Chronic obstructive pulmonary disease (COPD)
3. Bronchiectasis
4. Cystic fibrosis
B. Defnitions. Asthma and COPD are by far the most com
mon obstructive lung diseases; therefore, these two disor
ders are the focus of this chapter. All obstructive diseases
are marked by abnormal expiration, characterized by a
low forced expiratory volnme in 1 second (FEV.) and a
low FEV1(%).
1. Asthma is characterized by widespread narrowing of
the airways as a result of increased responsiveness to
various stimuli. Pathologc changes include smooth
muscle hypertrophy, mucosal edema, and mucus
pluggng. The abnormal expiration is usually revers
ible with bronchodilators.
2. COPD. The abnormal expiratory fow of COPD is
usually not reversible. There are two types of COPD:
a. Chronic bronchitis, defned clinically as a produc
tive cough lasting for at least 3 months over 2
consecutive years
b. Emphysema, defned pathologically as perma
nent enlargement of the airspaces distal to the
terminal bronchiole with destruction of the walls
and without fbrosis
@
CUNICAL MANIFESTATIONS O ASTHMA AND COPD
A. Asthma is usually seen in children and young adults.
Clinical manifestations may include:
1. Episodic wheezing and chest tightness
2. Dyspnea and cough
3. Tachypnea and reliance on the accessory muscles
and intercostal retraction
4. A prolonged expiration phase and hyperresonance
5. Pulsus paradoxus
B. COPD usually presents in the ffth or sixth decade of
120
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Obstructive lung Disease 1 21
Q
life. Most patients have components of both chronic
bronchitis and emphysema.
1. Chronic bronchitis ("blue bloaters")
a. Stocky build
b. Prominent. productive cough
c. Mild dyspnea
d. Early hypoxemia and hypercarbia
e. Wheezes and rhonchi
2. Emphysema ("pink pufers")
a. Barrel-chested with a thin build
b. Mild cough with severe dyspnea
c. Hypoxemia and hypercarbia only in end-stage
disease
d. Diminished breath sounds on examination
DIAGNOSIS OF ASTHMA AND COPD. These disorders
are diagnosed on the basis of the patient's history, physical
examination fndings, and abnormal pulmonary function
test results.
A. Asthma. Remember, not all that wheezes is asthma. A
physician who "CARES" will always rule out other
causes of wheezing:
Other Causes of Wheezing ("CARES")
Cardiac asthma (i . e. , CHF) or Churg-Strauss
syndrome
Allergic bronchopulmonary aspergillosis
Refl ux esophagitis
Exposures (irritants, medications), Embolism
(pulmonary)
Sinusitis, Strongyloides infection
B. COPD. Patients often have a history of chronic cough,
sputum production, and dyspnea that may have been
present for many years. The etiology is almost always
prolonged cigarette smoking; however, OI-antitrypsin de
fciency should be suspected in patients who are younger
than 4 years of age.
TREATMENT. The treatment of acute exacerbations of both
asthma and COPD is very similar.
1 22 Chapter 1 8
A. Albuterol and ipratropium are the frst-line agents and
have similar effcacy. However, the ( agonists appear to
have a more rapid onset of action.
B. Steroids improve symptoms after 4-6 hours and should
be used for at least 5 days in patients with severe exacer
bations.
C. Theophylline is rarely used because of concerns regard
ing toxicity and proven effcacy of other agents.
D. Humidifed oxygen or oxygen administered by nasal can
ula should be used i most patients, but caution is needed
in those susceptible to carbon dioxide retention.
E. Magnesium (intravenously), although contro
,
ersial, has
been shown to be benefcial in patients wIth severe
asthma.
F. Antibiotics have been shown to occasionally beneft pa
tients with COPD exacerbations. Asthmatic patients
should be treated only if a bacterial infection is suspected.
Agents Used to Treat Exacerbations of Asthma
or COPD ("ASTHMA")
Albuterol or ipratropium (Atrovent)
Steroids (oral or i ntravenous)
Theophyl line
Humidified oxygen
Magnesium
Antibiotics
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1 9. Restrictive Lung Disease
Q
INTRODUCTION. Restrictive lung disease is an uncommon

but important disorder that is often diagosed by pulmonary
function testing to evaluate dyspnea or by an abnormal chest
radiograph. Occasionally, cases are diagnosed only after ve
tilatory failure has occurred, necessitating mechanical ventI

Lation. Ventilatory parameters suggest the diagnosis of re
striction.
A. Defnition. The sine qua non of a restrictive ventilatory
defect is a reduction in total lung capacity (TLC) and vital
capacity (VC). The FEVl(%) [i.e., the forced expirat
?
ry
volume in 1 second (FEVl) divided by the forced vItal
capacity (FVC)] may be increased, but this fnding is not
necessary to make the diagnosis.
B. Etiolog. Restrictive lung disease is only one type of
restrictive ventilatory defect. Restriction can also be
caused by diseases of the pleura, chest wall, and nervous
system. Use the following mnemonic to "PAINT" a men
tal picture of the causes of restrictive ventilatory defects.
Causes of Restrictive Ventilatory Defects
("PAINT")
Pleural (fibrOSis, effusions, empyema, pneumo
thorax)
Alveolar (edema, hemorrhage, inflammation)
Interstitial lung disease
Neuromuscular (myasthenia, phrenic nerve
dysfunction, myopthy)
Thoracic or extrathoracic (kyphoscol iosis, obe
sity, ascites, pregnancy)
CAUSES OF RESTRICTIVE LUNG DISEASE. Technically, re
strictive lung disease refers to restrictive disease resulting
from alveolar or interstitial processes.
A. Alveolar processes include edema, hemorrhage, and in
fammation.
B. Interstitial processes can be remembered using the mne-
1 23
124 Chapter 1 9
monic, "HITS FACED." (The mnemonic is easier to
remember when you place the "S" in front of the "H" .)
Causes of Interstitial Lung Disease ("HITS
FACED")
Histioytosis X or Hypersensitivity pneumonitis
Idiopathic pulmonary fibrosis
Tuberculosis or Tumors
Sarcoidosis
Fungal infection
Alveolar proteinosis
Collagen vascular disease
Environmental or Eosinophilia-associated
Drugs
1. Pulmonary histiocytosis X (eosinophilic granuloma)
is an idiopathic disorder that may progress to fbrosis.
a. Diagnosis. The typical patient is a 30- to 40-year
old smoker. The upper lung zones are most fre
quently involved. Bierberbach granules (X bod
ies) are seen within mononuclear cells on biopsy.
b. Treatment entails the administration of steroids.
2. Hypersensitivity pneumonitis is an immune-medi
ated infammation of the lung parenchyma that re
sults from repeated inhalation of organic dusts (e.g.,
mold, grain, bird droppings). The disease can be
acute, subacute, or chronic; unrecogized disease can
result in fbrosis. The disorder is not associated with
blood eosinophilia. The source of the antigen should
be avoided; treatment with steroids may be necessary
as well.
3. Idiopathic pulmonary fbrosis is the most common
diagnosis for patients presenting with interstitial
lung disease.
M Diagnosis. The disease presents in the sixth to
seventh decade with the insidious onset of dysp
nea and a cough. The chest radiograph has a
lower lobe predominance: however. biopsy is re
quired for defnitive diagnosis.
b. Treatment is supportive; steroids may help.
4. Tuberculosis. Interstitial infltrates can occur with
primary tuberculosis if the infection is disseminated
(i.e., miliary tuberculosis). More ofen, difuse infl
tration occurs during reactivation of disease. This
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Restrictive Lung Disease 125
scenario is often seen in immunocompromised hosts.
Treatment entails combination therapy for tubercu
losis.
5. Tumor. Lymphangitic spread of malignancy is diffuse
involvement of the pulmonary lymphatics by malig
nant cells as a result of extension from the lung capil
laries. The most common etiologies include lung and
breast cancer. Treatment depends on the malig
nancy.
6. Sarcoidosis is a systemic noncaseating granuloma
tous disease presenting in the third to fourth decade;
there is lung involvement in 90% of cases. The inci
dence is higher in African-Americans and in women.
a. Diagnosis. Associated findings may include
lymphadenopathy, rash, erythema nodosum, and
hepatosplenomegaly. Sarcoidosis can be associ
ated with an elevated angiotensin-converting en
zyme (ACE) level: however. this fnding is nei
ther sensitive nor specifc.
b. Treatment. Steroids may be appropriate for
some patients.
7. Fungal infections
M Histoplasmosis is found in the central and eastern
United States, and presents as diffuse interstitial
lung disease, often in a miliary pattern, during
reactivation in immunocompromised hosts. Am
photericin B is the drug of choice.
b. Coccidioidomycosis is endemic in the southwest
ern United States. Rarely, diffuse involvement
occurs during primary infection; it is more com
mon during reactivation in immunocompromised
hosts. Treatment is with amphotericin B.
8. Alveolar proteinosis is a rare disorder resulting from
deposition of phospholipid material in alveolar
spaces. The disease can be primary (idiopathic) or
secondary (postviral or post-tuberculous). Treat
ment entails periodic whole lung lavage by bron
choscopy.
9. Collagen vascular diseases. Interstitial lung disease
is only one manifestation of intrathoracic involve
ment in these disorders, and often a minimal compo
nent of a multiorgan process. Rheumatoid arthritis
and scleroderma are the two diseases most associated
with interstitial lung disease that ultimately lead to
fbrosis.
M Rheumatoid arthritis. Interstitial lung disease
1 26
Chapter 1 9
Eosinophilic
Drug-related
FUR 19- 1 . Major diseases that cause pulmonary infiltrates with eosin
ophilia. Just think of six piees of PIE!
can be primary or secondary to hypersensitivity
drug reactions to methotrexate or gold.
.
b. Scleroderma results in lung involvement m ap
proximately two-thirds of patients. Restriction
can result from pulmonary fbrosis or. rarely.
from fibrosis of the skin on the chest wall.
c. Systemic lupus erythematosus
.
(SL
.
E) in!
e
quently leads to chronic. progressIve mterstltlal
lung disease, but can cause a diffuse mfltrate
secondary to pneumonitis.
10. Environmental exposures can include organic dusts
(leading to hypersensitivit

yneumon
.
itis) or i
or
ganic dusts (e.g., asbestos. Slhca. beryllium). Particle
deposition leads to infammation, which can progress
to fbrosis. Treatment entails removal from the
source of exposure and supportive care.
11. Eosinophilia-associated pulmonary infltrates are
characterized by diffuse peripheral infltrates and
blood eosinophilia. Figure 19-1 is an easy way to
remember the major diseases that cause pulmonary
infltrates with eosinophilia (PIE).
12. Drugs. The most common causes a
e
ntineoplastic
drugs, antibiotics (sulfa drugs, pemcllhns) sulfonyl-
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Restrictive lung Disease 1 27
ureas, gold, phenytoin, penicillamine, and amiodar
one. Removal of the offending agent can lead to
cure, as opposed to the progressive fibrosis that can
result if the adverse effect is unrecognized.
A. Patient history and physical examination. The history
should focus on exposures to environmental agents and
drugs. Although the symptoms of cough and dyspnea
are of foremost concern to the patient, they are almost
universal and do not distinguish one disease from an
other. The review of systems should be comprehensive:
you are looking for symptoms of infection or evidence
of collagen vascular disease (e.g .. history of rash, arthral
gias. photosensitivity, ulcers).
B. Chest radiogaph. A chest radiogaph is helpful.
1. Pleural thickening or effusions in the absence of pa
renchymal disease will reveal the pleura as the cause
of the restrictive physiology.
2. A normal chest radiograph with evidence of restric
tion on pulmonary function testing suggests the pos
sibility of a neuromuscular disorder.
3. A chest radiograph may be diagnostic if normal pa
renchyma is seen in combination with spinal pathol
ogy (e.g., kyphoscoliosis) or small lung volumes (e.g.,
ascites, obesity).
C. Other tests. The most common dilemma occurs when
interstitial lung disease is seen on the chest radiograph
and an unrevealing history and physical are obtained.
Many tests are available, each with its own sensitivities
and specifcities. Tests should be selected according to
the patient's situation and the list of likely diagnostic pos
sibilities.
1. High-resolution computed tomogaphy (HReT) is a
logcal next step after the history, physical. and chest
radiograph. HRCT has been reported to have high
specifcities for the diagnosis of interstitial pulmo
nary fbrosis, lymphangitic spread of malignancy, sar
coidosis, silicosis, and interstitial pneumonias.
2. Bronchoscopy. Bronchoscopic lavage can reveal or
ganisms. malignant cells, lymphocytes, or neutro
phils.
a. Lymphocytes suggest sarcoidosis, tuberculosis,
or hypersensitivity pneumonitis.
b. Neutrophils are more common with interstitial
1 28
Chapter 1 9
pulmonary fbrosis, histiocytosis X, and ciga
rette smoking.
3. Transbronchial biopsy increases the risk of pneumo
thorax and hemorrhage, but enables diagnosis of dis
ease not refected in alveolar fuid and can be used
in patients who are too ill to tolerate open biopsy.
4. Open lung biopsy is the diagnostic gold standard.
H O T
K E Y
The yield is very high; however, diagosis oftreatable
conditions occurs in only a minority of cases. Thora
coscopic lung biopsy is a newer procedure with simi
lar yield but decreased risk. It involves the insertion
of a rigid scope into the pleural cavity to visually
biopsy the affected lung.
If the diagnosis is unclear, repeating the history and
physical examination (i.e., "the basics") wi l l often lead
to the diagnosis as quickly as ordering a battery of
invasive and expensive tests
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20. Communit-Acquired Pneumonia
++e++++e++++o++++=+++=++++++e+++e+=++++++e+=+++eo+++++e=+eeo=+o=eo+ee+eo+eo=eo
Q
INTRODUCTION
@
A. Epidemiology. Community-acquired pneumonia is a
leading cause of death and the number one cause of
infectious disease-related mortality in the United States.
Hospitalized patients with community-acquired pneu
monia have an in-hospital mortality rate of up to 25%.
B. Classifcation. Attempting to classify community-ac
quired pneumonia as "typical" or atypical" using clini
cal information is not very useful for predicting the un
derlying pathogen.
CLINICAL MANIFESTATIONS OF COMMUNITY
ACQUIRED PNEUMONIA
A. Symptoms commonly include subjective fever, cough,
sputum production, pleuritic chest pain. and dyspnea.
B. igns c
<
mmonly nclude fever, tachypnea (> 20 respira
tIons/mm), and SIgns of lobar consolidation (bronchial
breath sounds, egophony, dullness to percussion,
crackles).
CAUSES OF COMMUNITY-ACQUIRED PNEUMONIA
A. Organisms
1. Streptococcus pneumoniae is the most common or
ganism. Respect the "pneumococcus"-it can kill
quickly!
2. Haemophilus injuenzae is an especially common
cause of community-acquired pneumonia in patients
with chronic obstructive pulmonary disease (COPD).
3. Legionella species can cause severe pneumonia.
Gram staining usually reveals numerous polymor
phonuclear neutrophils (PMNs) but no organisms.
4. Aerobic gram-negative rods. For example, Klebsiella
infection is seen in alcoholics (where it can present
as a "bulging fssure" on a chest radiograph).
5. Staphylococcus aUus infection is usually seen in
patients who have infuenza or who are immunocom
promised.
6. Other. This category includes respiratory viruses
1 29
1 30 Chapter 20
(e.g., infuenza ViIS) , Mycoplasma pneumoniae,
Moraxela Ctarrhalis, Chlamydia pneumoniae
(TWAR), Mycobacterum tuberculosis, Peumo
cystis carinii, and fngi.
B. Polymicrobial aspiration must be considered in patients
with altered mental status or patients transferred from
a nursing home.
1. If aspiration occurs in the upright position, the lower
lobes are affected (the right side more often than
the left). This distribution makes sense according to
the laws of gravity.
2. It is more of a PUSL to remember which lobes
are involved if aspiration occurs during recum
bency-the posterior upper lobe and the superior
lower lobe.
ApPROACH TO TE
P
ATIENT
A. Diagnostic tests
1. Complete blood count (CBC)
2. Electrolytes, blood urea nitrogen (BUN), and creat.
inine
3. Peripheral blood cultures on samples drawn from
two separate sites should usual ly be performed.
4. Arterial blood gases
5. Chest radiograph [posterior-anterior (PA) and lat
eral views]
6. Sputum analysis
a. Gram staining and culture of even a properly
expectorated sputum sample may not be the best
way to detect or identify the responsible organ
ism; therefore, this test is not routinely recom
mended by some experts.
b. If there is concem that M. tuberculosis or P carinii
is the cause of the pneumonia, sputum analysis us
ing special stains should always be done.
7. Thoracentesis. If a pleural effusion is present, pleural
fuid may be sent for a cell count and differential.
Gram staining and culture, total protein, and lactate
dehydrogenase (LDH) levels to rule out an em
pyema.
B. Criteria for hospital admission. There are no absolute
criteria for hospital admission, but there are specifc risk
factors associated with a complicated clinical course, in
creased mortality, or both. The following mnemonic can
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Community-Acquired Pneumonia
1 3 1
help you remember some of the most imp0ant criteria
for admitting a patient: "ADMIT NOW"
Criteria for Hospital Admission of Patients with
Community-Acquired Pneumonia ("ADMIT
NOW")
Age > 65 years
Decreased immunity (e.g. , cancer, diabetes,
AIDS. splenectomy)
Mental status changes
I ncreased A-a gradient
Two or more lobes involved
No home (i.e., homeless patients)
Organ system failure (increased creatinine,
bone marrow suppression, severe hypoten
sion, liver failure)
WBC count greater than 30,000/mm3 or less
than 4000/mm3
Sometimes the most important criterion is the "eyeball"
test (i.e., how sick a person looks to an experienced phy
sician).
T
REATMENT. In general, patients admitted to the hospital
with community-acquired pneumonia should be treated with
parenteral antibiotics. Duration of therapy depends on the
organism, clinical scenario, and host defenses of the patient.
but. in general, therapy usually requires 7-14 days.
A. Empiric therapy
1. For most patients (except those in whom aspiration
or Legionella infection is a major concern), a third
generation cephalosporin (e.g., ceftriaxone, cefotax
ime) or a f lactamlf-lactamase inhibitor (e.g., ampi
cillin sulbactam) is appropriate solo empiric therapy.
2. If Legionella is a maj or concer, then an intravenous
macrolide (e.g., erythromycin) should be added.
3. In patients with probable aspiration, clindamycin
(because of its excellent activity against anaerobic
organisms) may be used.
B. If the organism is identifed, antibiotic susceptibility test
ing should guide further therapy.
21 . Pulmonary Hypertension
Q
@
INTRODUCTION
A. Pulmonary hypertension is diagnosed when pulmonary
artery pressures exceed 25/8 mm Hg (normal) or when
there is clinical, radiographic, electrocardiographic, or
echocardiographic evidence of increased pulmonary
pressures.
B. Untreated pulmonary hypertension carries a high mor
tality rate. but identifcation and treatment of reversible
causes can signifcantly beneft the patient.
CLINICAL MANIFESTATIONS OF PULONARY
HYPERTENSION
A. Symptoms include:
1. Progressive dyspnea
2. Chest pain (partially as a result of right ventricular
ischemia)
3. Fatigue
4. Syncope or near syncope
5. Peripheral edema (from right ventricular failure)
B. Signs. Pulmonary hypertension often presents with phys
ical examination fndings that refect right ventricnlar
failure.
H O T
K E Y
Evidence of right ventricular failure al most always indi
cates pulmonary hypertension.
The following fndings are typical:
1. Increased jugular venous pressure
2. A right-sided third or fourth heart sound (S, or S4)
3. A right ventricular lift
4. Pulmonic component of the second heart sound (Pz)
1 32
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Pulmonary Hypertension 1 33
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louder than the aortic component of the second heart
sound (Az)
5. Murmurs of tricuspid and pulmonary regurgitation
6. Peripheral cyanosis and edema
CAUSES OF PULONARY HYPERTENSION
A. Primary causes. Primary pulmonary hypertension (plex
ogenic pulmonary arteriopathy) is seen mostly in young
women who present with right-sided heart failure. Most
patients have a rapidly downhill course; the average sur
vival time is 2-3 years.
B. Secondary causes must be ruled out before diagnosing
the rarer and less treatable primary cause. To remember
the many secondary causes of pulmonary hypertension,
think "backwards" from the left ventricle to the lungs.
Anything that increases pressure "downstream" will
cause higher pressures upstream. When increased
pulmonary artery pressures are caused by increased
"downstream" pressure, the hypertension is called post
capillary pulmonary hypertension. When the increased
pulmonary pressures result from abnormalities within
or before the capillary bed, the hypertension is called
capillary/precapillary pulmonary hypertension.
1. Postcapillary causes
a. Left ventricular dysfunction. Disorders include:
(1) Systolic or diastolic dysfunction
(2) Constrictive pericarditis
b. Increased left atrial pressure with normal left
ventricular pressures. Disorders include:
(1) Mitral valve stenosis
(2) Balloon mitral valve
(3) Left atrial myxoma
(4) Cor triatriatum
c. Pulmonary veno-occlusive disease. Fibrotic
changes in the veins or venules are of unclear
etiology but may be associated with:
(1) Malignancy
(2) Chemotherapy
(3) Bone marrow transplantation
(4) No underlying disease
2. Capillary/precapillary causes
a. Obstructive lung disease
b. Restrictive lung disease
c. Vascular disease (i. e. , small vessel occlusion)
(1) Vasculitis
1 34
H O T
K E Y
(2) Pulmonary emboli
(3) Schistosomiasis
d. Miscellaneous causes
(1) Hypoxia
(2) Acidosis
(3) Polycythemia
(4) Hepatic cirrhosis
(5) Intracardiac left-to-right shunt
Chapter 2 1
Sleep apnea i s increasingly being recognized as a
cause of hypoxia and secondary pulmonary hyper
tension.
A. Preliminary evaluation
1. Physical examination findings
a. Carefully compare the second heart sound in the
left second interspace (Pz) to the one in the right
second interspace (Az). A Pz that is louder than
the Az should alert you to the possibility of pul
b. If you diagose pulmonary hypertension, listen
carefully for a left-sided S3 or S4, which may indi
cate left ventricular dysfunction (i.e., a postcapil
lary etiology). Also listen for left-sided murmurs
and "extra" heart sounds that may indicate mitral
stenosis or a lef atrial myxoma, respectively.
2. Laboratory fndings. Polycythemia is often present
with chronic hypoxia.
3. Radiographic fndings
M Pulmonary hypertension from all etiologies will
usually result in enlarged central pulmonary ar
teries visible on the chest radiograph. Right ven
tricular and atrial enlargement may also be seen
in severe, chronic cases.
b. Evidence of the underlying cause may also be
visible radiographically. For example:
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Pulmonary Hypertension 1 35
(1) In emphysema, there may be "pruning" of
distal vessels. hyperinfation, or fat dia
phragms.
(2) In left ventricular dysfunction, there may be
left ventricular or atrial enlargement or evi
dence of pulmonary edema.
4. Electrocardiographic fndings. The EKG typically
shows right axis deviation. Right ventricular hyper
trophy and right atrial enlargement are also common
fndings (see Chapter 4 IV; VI B and 0).
B. Confrmation. There are many invasive and noninvasive
diagnostic tests that may be used to further defne the
nature of the patient's pulmonary hypertension. Ob
taining tests in the following order is a reasonable way
to approach patients with pulmonary hypertension.
1. Echocardiography
a. Doppler echocardiogaphy. Measurement of pul
monary pressures can confrm or dispute the ini
tial clinical diagnosis.
(1) Right ventricular hypertrophy or enlarge
ment, paradoxical motion of the interventric
ular septum, and right atrial enlargement
may also accompany pulmonary hyper
tension.
(2) Echocardiography also permits evaluation of
the left side of the heart. The presence of left
ventricular dysfunction, mitral stenosis, or
left atrial myxoma confrms a diagnosis of
postcapillary pulmonary hypertension; no
additional workup is necessary and appro
priate treatment can be instituted.
b. Bubble study. A bubble study allows detection
of an intracardiac shunt.
2. Pulmonary function tests with arterial blood gases
a. Hypoxemia. a decreased difusing capacity for
carbon monoxide (OLeO), and a mild restrictive
defect are common fndings regardless of the
cause of pulmonary hypertension.
b. Severe obstructive disease in a long-time smoker
is the most helpful fnding because it usually es
tablishes COPD as the diagnosis; additional test
ing is usually unnecessary and treatment can be
aimed at the COPO and hypoxia.
3. Sleep studies are usually indicated in patients with
risk factors for sleep apnea (i.e., male sex, obesity,
and a history of snoring). However, sleep studies
1 36 Chapter 2 1
do not correlate well with the degree of pulmonary
hypertension, and may lad. to false-positive results.
4. Ventilation-perfusion (V/Q) lung scanning. If no
cause of postcapillary hypertension or COPO has
been found evaluation for chronic thromboembolic
disease is uually necessary (see Chapter 22 IV E).
5. Pulmonary angiography and right-heart catheteriza
tion. If the diagnosis is still elusive, invasive studies
become necessary. Although there is concer about
the safety of right-heart catheterization in the pres
ence of pulmonary hypertension, most studies have
not shown major morbidity or mortality and the con
sequence of ot diagnosing a treatable condition is
severe. These tests can often be done one right after
the other.
a. A positive pulmonary angiogram obviates the
need for right-heart catheterization.
b. Right-heart catheterization may be necessary to
rule out postcapillary pulmonary hypertension
(i.e., from diastolic dysfunction that may have
been missed on echocardiography) and an intra
cardiac shunt as etiologies. In addition, this pro
cedure may serve to guide vasodilator therapy.
T
REATMENT
A. Primary pulmonary hypertension
1. Oxygen therapy decreases pulmonary vasoconstric
tion in hypoxic patients. slowing the progression of
pulmonary hypertension.
2. Pharmacologc therapy. Some authorities recom
mend chronic anticoagulation or vasodilator therapy
(guided by pulmonary artery catheterization). Cal
cium channel blockers or prostacyclin infusions may
ofer the best medical treatment.
3. Heart-lung transplantation is being used with in
creasing frequency for patients with end-stage
disease.
B. Secondary pulmonary hypertension
1. General measures
a. Oxygen therapy should be initiated to counteract
hypoxia, regardless of the eti ology. More than
15 hours per day has a long-term mortality benefit
in hypoxic patients with COPO.
b. Phlebotomy. Patients showing polycythemia
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Pulmonary Hypertension
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with a hematocrit that exceeds 60% may undergo
phlebotomy to reduce blood viscosity.
c. Salt restriction, diuretics, and sometimes, digi
talis (controversial) are used to treat cor pul
monale.
2. Specifc measures. Treatment is always aimed at the
underlying disease.
a. Postcapillary pulmonary hypertension is gener
ally easier to treat than precapillary/capillary pul
b. Capillary/precapillary pulmonary hypertension
(1) COPD can be treated with smoking cessa
tion, bronchodilators, and oxygen therapy
when appropriate.
(2) Thromboembolic disease is treated with
chronic anticoagulation therapy. Thrombo
endarterectomy is often appropriate for pa
tients who develop pulmonary hypertension
as a result of major pulmonary artery oc
clusion.
(3) Sleep apnea can be treated with weight re
duction, avoidance of alcohol and sedatives,
and nighttime oxygen with or without contin
uous positive airway pressure (CP AP).
22. Pulmonar Embolism
Q
Q
INTRODUCTION. Pulmonary embolism causes more than
50,000 deaths per year; however, prompt treatment may sig
nifcantly reduce the mortality rate.
CAUSES OF PuLONARY EMBOUSM
A. Deep venous thrombosis. Most pulmonary emboli
(95%) arise from deep venous thrombosis of the lower
extremities. The highest risk for pulmonary embolism
occurs with proximal deep venous thrombosis (i.e.,
thrombosis of the popliteal, superfcial femoral, or
common femoral vein).
B. Other, less common, etiologies for pulmonary embolism
include upper extremity or pelvic venous thrombosis and
right atrial thrombi.
CUNICAL MNIFESATIOS OF PuLNARY EMSOUS.
The symptoms and sigs of pulmonary embolism are nonspe
cifc, occurring in many disorders.
A. Symptoms. The presence of chest pain. especially the
pleuritic variety, is the most common symptom, followed
closely by dyspnea. A feeling of apprehension or im
pending doom is frequently described.
B. Sigs. Tachypnea is present in most patients with pulmo
nary embolism. Tachycardia, low-grade fever. and evi
dence of lower extremity swelling or tenderness are other
important signs.
1 38
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H O T
K E Y
Risk factors for pulmonary embolism include:
Age greater thon 40 yeors
History of venous thromboembolism
Malignancy
Prolonged i mmobility
Congestive heart failure
Myocardial infarction
Stroke
Fracture of the lower extremity (including hip)
Obesity
Majory surgery (especially orthopedic)
Congenital or acquired abnormalities in hemostasis
ApPROACH TO THE PATIENT. Pulmonary embolism can
pose a substantial diagnostic challenge. The differential diag
nosis includes other cardiac and pulmonary disorders that
cause dyspnea, chest pain, and hypoxemia. Common compet
ing diagnoses are pneumonia. congestive heart failure
(CHF), asthma, chronic obstructive pulmonary disease
(COPD), pneumothorax, myoardial infarction, and aortic
dissection.
A. Patient history and physical examination are essential
to the diagnosis.
B. Chest radiogaph. The chest radiograph provides valu
able information in a patient with dyspnea, chest pain,
or hypoxemia.
1. A common misconception is that most patients with
pulmonary embolism have a normal chest radio
graph. In fact, approximately 90% of patients with
pulmonary embolism have an abnormal chest radio
graph. Atelectasis and parenchymal opacities are the
most common fndings.
2. There are several classic roentgenographic sigs of
pulmonary embolism:
a. Westermark's sig (i.e., a region of oligemia) is
visible as a radiolucent area.
b. Hampton's hump, a peripheral wedge-shaped
density, may refect pulmonary infarction.
c. Atelectasis, a small pleural efusion, an enlarged
central pulmonary artery, and an elevated hemi
diaphrag are other common signs.
1 40 Chapter 22
3. Unfortunately, these classic signs of pulmonary em
bolism are nonspecific and cannot dcfnitively estab
lish the diagnosis of pulmonary embolism. Therefore.
the main utility of a chest radiograph is its ability
to make apparent alterative diagnoses that would
explain a patient's symptoms (e.g., pneumonia. pneu
mothorax, or pulmonary edema).
C. Electrocardiogram (EKG). Most patients with pulmo
nary embolism will have an abnormal EKG. The fndings.
however, are nonspecific.
1. The most common fnding is sinus tachycardia; other
arrhythmias are rare.
2. The classic fndings of acute right-sided heart strain
are seen in only approximately 25% of patients.
These include:
a. Right bundle branch block
b. P pulmonale
c. Right axis deviation
d. SJQ3T3 (a large S wave in lead L a large Q wave
in lead III, and an inverted T wave in lead I1I)
remember, these patients are SiQ fom Thrombus!
D. Arterial blood gases. Patients with pulmonary embolism
may have alveolar hyperventilation (low Paco2), hypox
emia (low Paoz), a widened alveolar-to-arterial (A-a)
gradient, or any combination of the three. Although most
patients with pulmonary embolism have a widened A-a
gradient. up to 1 5% may have normal gradients. The
negative likelihood ratio (see Chapter 2 III B) for a
normal A-a gradient is 0.7: therefore, a normal A-a gradi
ent cannot rule out pulmonary embolism in most clini
cal circumstances.
E. Ventilation-perfusion (VIC)scanning. If the scan shows
perfusion defects in areas of normal ventilation. a pulrn
nary embolism ocluding blood fow is probable. V/Q
scans are interpreted as normal or showing low, interme
diate, or high probability of pulmonary embolism based
on standardized criteria.
1. The likelihood ratio for pulmon
,
ry embolism can be
calculated for each category of V/Q scan result. The
Prospective Investigation of Pulmonary Ebolism
Diagnosis (PIOPED) study evaluated V/Q scans
in comparison with pulmonary angograms in the
diagnosis ofplmonary embolism (Table 22-1 ).
2. Using the V/Q scan result, you can calculate the
probability of pulmonary embolism in a given pa
tient.
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TABLE 22- J : Correlotion of Ventilotion-Perfusion (V /0) Scans and
Likelihood Ratios
V / Q Scan Result Likelihood Ratio
High probability
Intermediate probability
Low probbi lity
1 3
1 . 1
0. 4
0. 1 Normal
Based an data from PIOPED investigators: Value of the venti lation/perfusion
scan in acute pulmonary embolism. JAMA 263:2753-9, 1 990.
F.
a. Generate the pretest probability of pulmonary
embolism. using the patient history, physical ex
amination fndings, and data provided by the
chest radiograph, EKG, and arterial blood gas
report.
b. Convert the pretest probability to posttest proba
bility using the method described in Chapter 2
III C 1. In general, a very low posttest probability
excludes the diagnosis of pulmonary embolism,
while a very high posttest probability confrms
the diagnosis.
3. Summary
a. A high-probability \/6 scan generally rules in
the diagnois
.
of pulmonary embolism.
b. A normal V/Q scan generally rules out the diag
nosis of pulmona
r
y embolism.
c. An intermediate \/6 scan is useless-the likeli
hood ratio is essentially 1. so this scan result does
not impact the post
.
tet probability.
d. A low-probability V/Q scan is diffcult to inter
pret. In this case, the pretest probability (clinical
assessment) is essential for interpreting scan re
sults. If the pretest probability is low, then pulmo
nary embolism is unlikely. However, ifthe pretest
probability is intermediate or high, the probabil
ity of pulmonary embolism is substantial. Addi
tional diagnostic testing should be undertaken.
Noninvasive lower extremity testing. Because most pul
monary emboli arise from proximal lower extremity deep
venous thromboses. one strategy in a patient with clini
cally suspected pulmonary embolism is to evaluate the
1 42
Chapter 22
legs for deep venuus thrombusts. Because the treatment
of deep venous thrombosis and pulmonary embolism
is basically the same, documentation of deep venous
thrombosis is adequate reason to stop diagnostic testing
and initiate anticoagulation therapy. Two noninvasive
tests for detecting lower txtremity deep venous thrombo
sis are available: impedance plethysmography and Dop
pler ultrasound.
1. In patients with symptomatic deep venous thrombo
sis (i.e., leg swelling or pain), both tests have very
high sensitivity and specifcity.
2. In asymptomatic patients, the sensitivity of these
tests is much lower (in the 50% range).
G. Spiral computed tomography (Cf) scanning appears to
be highly accurate for the diagnosis of central pulmonary
emboli. The utility of spiral CT for peripheral embuli may
be much lower. In the setting of a low- or intermediate
probability V/O scan, spiral CT remains an unproven
diagnostic modality. Until further study is completed.
spiral CT scanning should not replace conventional diag
nostic strategies.
H. Pulmonary angiogram. Pulmonary arteriography is the
gold standard for diagnosing pulmonary embolism; how
ever, the associated risks of death. major complications.
and minor complications are approximately 0.5%, 1 %,
and 5%, respectively. Major complications include con
trast-induced renal fail ure. In patients with angiographi
cally documented pulmonary embolism, approximately
one third have negative venograms and one half have
negative noninvasive lower extremity testing. In these
patients, the entire lower extremity thrombus probably
embolized to the lungs.
T
REATMENT. The treatment of pulmonary embolism is anti
coagulation with heparin, followed by warfarin for 4-6
months. Inferior vena cava ( lYC) flter is an alternative for
patients with absolute contraindications to heparin.
A. Anticoagulation is the standard treatment for buth deep
venous thrombosis and pulmonary embolism.
1. Intravenous heparin should be administered initially.
The recurrence of venous thromboembolism in
creases with delayed or inadequate anticoagulation,
so rapid achievement of a partial thromboplastin
time (PTT) of 1.5-2.0 times control is desirable. Hep
arin is usually continued for 5 days.
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Pulmonary Embolism 1 43
2. Or warfarin should be started on diagnosis. The
effcacy and safety of early warfarin initiation has
been well documented. The duration of therapy is
not completely certain. but most exptrts recommend
4-6 months of anticoagulation to achieve an interna
tional normalized ratio (INR) of 2.0-3.0.
B. Ive flter. For patients with absolute contraindications
to anticoagulation, an IYC flter may be placed percuta
neously via the femoral vein. These flters prevent a
lower extremity thrombus from traveling to the lungs.
lowering the risk of recurrent pulmonary embolization.
C. Thrombolytic agents (e.g .. urokinase. tissue plasminogen
activator) can dissolve a clot present in the circulation
and result in more rapid resolution of perfusion abnor
malities than standard heparin therapy, but the benefts
of thrombolysis are transient. Use of these agents does
not improve the mortality rate and there is a substantial
risk of excess bleeding associated with these agents. For
these reasons, thrombolytic agents are not used routinely
in the treatment of pulmonary embolism. In patients
with massive pulmonary embolism characterized by he
modynamic instability or respiratory failure, thrombo
Iytics may be tried.
23. Respiratory Fail ure
Q
Q
INTRODUCTION. Respiratory failure is a common admit
ting diagnosis in the intensive care unit (ICU). There are
two underlying mechanisms of respiratory failure:
A. Failure to oxygenate. The patient's Pa is less than 6U
mm Hg on rOom air.
B. Failure to ventilate. The patient's Pacoz is greater than
50 mm Hg.
CAUSES OF RESPIRATRY FAILURE
A. Failure to oxygenate (see Chapter 16 III). Of the follow
ing fve mechanisms of hypoxia, the last two rarely cause
respiratory failure.
1. Ventilation-perfusion (V/Q) mismatch
2. Diffusion defect
3. Hypoventilation
4. Right-to-Ieft shunt
5. Low inspired partial pressure of oxygen
B. Failure to ventilate. Hypercapnia is caused by hypoventi
lation. You can organize your list of differential diagno
ses by starting with the brain (the breathing center) and
moving to the alveoli (where carbon dioxide is excreted).
Any problem along the way can result in carbon dioxide
retention and. therefore. a respiratory acidosis. Causes
include:
1. Centrdl nervous system (CNS) disorders
a. Sedating drugs (e.g., heroin)
b. Brain tumor
c. Stroke
2. Neuromuscular disorders (e.g., botulism, Guillain
Barre syndrome, amyotrophic lateral sclerosis, myx
edema)
3. Chest wall disorders (e.g .. obesity, kyphoscoliosis)
4. Upper airway obstruction (e.g., epiglottitis. laryn
gospasm)
5. Lower airway obstruction [e.g., asthma, chronic ob
structive pulmonary disease (COPD), sleep apnea]
6. Dead space ventilation. Signifcant damage to the
1 44
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Respiratory Fai l ure 1 45
lungs (e.g., from infection) can increase dead space
ventilation and lead to carbon dioxide retention.
ApPROACH T THE PATIENT
A. Assess the urgency of the situation.
1. If respiratory failure is immediate, then you must
evaluate the patient quickly and decide on a therapy.
2. If the failure is chronic, you can approach the patient
a bit more leisurely. The rest of the chapter deals
primarily with acute respiratory failure.
B. Assess the need for intubation.
C.
1. If the patient has any of the following signs, you
should get prepared to intubate soon:
a. A markedly elevated respiratory rate (> 30 respi-
rations/min)
b. Fatigue and labored respiration
c. Use of the accessory muscles to breathe
d. Stridor (suggests impending upper airway ob
struction)
e. Agonal breathing (implies impending respira
tory arrest)
2. Indications for intubation are:
a. Severe hypoxemia despite supplemental oxygen
b. Acute hypercapnia (especially if mental status
is altered)
c. Need for airway protection
d. Impending upper airway occlusion
e. Therapeutic hyperventilation (in cases of in-
creased intracranial pressure)
Attempt to defne the cause of the respirdtory failure.
1. Patient history. Take a directed history.
2. Physical examination
a. Obtain a full set of vitals (including oxygen satu
ration).
b. Note the presence or absence of the following:
(1) Alteration in mental status, gag refex
(2) Expiratory wheezes, rales, diminished or ab
sent breath sounds, dullness to percussion
(3) Third heart sound (S3) with a sustained point
of maximal impulse (PMI), elevated jugular
venous pressure, dependent edema
(4) Abdominal tenderness, bowel sounds
3. Diagnostic studies. The following studies should be
performed immediately in most patients with acute
respiratory failure:
1 46 Chapter 23
a. Chest radiograph
b. 12-Lead electrocardiogram (EKG)
c. Arterial blood gas analysis l to assess serum pH,
oxygenation (Paoz). and ventilation (Paco2)]
HOT
K E Y
An arterial blood gas i s essential i n order to distinguish
failure to oxygenate from failure to ventilate.
Low Paez Fail ure to oxygenate
High Pac02 Fail ure to ventilate
d. Complete blood count (CBC), serum electro
lytes. blood urea nitrogen (BUN), and creatinine
TREATMENT. General therapeutic measures for patients in
acute respiratory failure are outlined in Chapter 13 IV. A
general approach to mechanical ventilation is described in
Chapter 24.
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24. Mechanical Ventilation
Q
INTODUCTION
A. Defnition. A ventilator is simply an air pump that deliv
ers a set volume Or pressure of air.
B. Phases of ventilatory support. The three main phases of
ventilatory support can be compared to a plane fight:
initiation (take off), maintenance (cruising), and wean
ing (landing).
1. Initiation. Chapter 23 III B describes guidelines for
making the decision to intubate.
2. Maintenance. The goal is to achieve a balance be
tween making the patient comfortable and allowing
him to exercise the muscles used during respiration.
Any of the modes of ventilation detailed in this chap
ter may be appropriate.
3. Weaning is often the trickiest part (as is landing
an airplane). The ventilator settings and method of
weaning should be tailored to the patient. depending
on the patient's underlying disease, mental status,
and degree of comfort.
Q
MODES OF POSITIVE-PRESSURE VENTILTION
A. Volume-cycled modes
1. Synchronized intermittent mandatory ventilation
(SIMV). The ventilator delivers a set tidal volume
at a set rate, but delivers no tidal volume for patient
initiated breaths above the set rate. Ventilator
breaths are synchronized with patient-initiated
breaths but the ventilator also delivers a breath when
the patient does not initiate one. Pressures vary.
a. Advantages. SIMV offers maximum control of
ventilation.
b. Disadvantages
(1) It is diffcult for the patient to overcome resis
tance of the tubing when breathing over the
set rate.
(2) High pressures may be needed to deliver the
set tidal volume.
2. Assist control (AC). The ventilator delivers a set
tidal volume at a set rate, and delivers the same tidal
1 47
1 48
Chapter 24
volume for patient-initiated breaths above the set
rate. Ventilator breaths are synchronized with pa
tient breaths. Pressures vary.
a. Advantages. The patient receives assistance for
every breath.
b. Disadvantages
(1) The patient may develop respiratory alkalo
sis because every patient-initiated breath re
ceives a full tidal volume.
(2) High pressures may be needed to deliver the
set tidal volume.
B. Pressure-cycled modes. [n the pressure control (PC)
mode, the ventilator delivers a constant pressure at a set
rate, and delivers the same pressure for patient-initiated
breaths above the set rate. Tidal volumes vary.
1. Advantages. This mode can be used when peak
airway pressures are too high (e.g., > 40 cm H20)
on SIMV or AC.
2. Disadvantages. The patient may not receive ade
quate tidal volumes.
C. Flow-cycled modes
L. Pressure support (PS). The ventilator delivers a set
pressure only when the patient initiates a breath.
Pressure support ceases when fow decreases to 25%
of maximum inspiratory fow.
a. Advantages. Because this method is more physi
ologic than many of the others, patient comfort
is enhanced.
b. Disadvantages
(1) The patient must trigger every respiration.
(2) The patient may not receive adequate tidal
volumes.
2. Noninvasive positive-pressure ventilation (NPPV).
Ventilation is delivered through a face mask rather
than through an endotracheal tube. NPPV is trig
gered by air fow, and delivers a constant pressure
throughout inspiration.
a. Advantages
(1) Patients with hypercapnic ventilatory failure
[e.g., an acute exacerbation of chronic
obstructive pulmonary disease (COPD)]
may respond well to this mode of ventila
tion.
(2) NPPV may help delay or avoid endotra
cheal intubation.
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Mechanical Ventilation
1 49
M
b. Disadvantages
(1) The face mask may be uncomfortable for
the patient.
(2) It is diffcult to deliver high levels of oxygen.
D. Combined modes. In SIMV + PS, the ventilator delivers
a set tidal volume at a set rate and delivers a set pressure
for patient-initiated breaths above the set rate.
1. Advantages. This mode maintains control of ventila
tion with S[MV while maximizing patient comfort
with pressure-supported breaths.
2. Disadvantages. The patient may develop respiratory
alkalosis because every patient-initiated breath re
ceives pressure support assistance.
E. Weaning modes
1. Continuous positive airway pressure (CPAP). The
ventilator delivers a continuous pressure, usually 5
cm H20, throughout inspiration and expiration.
a. Advantages. The patient does the work of
breathing.
b. Disadvantages. It is diffcult to overcome the re
sistance of ventilator tubing, so patients can
tire easily.
2. T-piece. The endotracheal tube is attached to a
T-shaped piece of tubing that delivers only oxygen.
The patient is not attached to a ventilator.
a. Advantages. The patient does the work of
breathing.
b. Disadvantages. Because the patient is not
attached to a ventilator, no alarms will sound if
the patient becomes apneic.
INITIAL VENTILTOR SmlNGS are summarized in Table
24- L .
WEANING
A. Methods. Weaning can be accomplished in several ways.
L SIMV. The set rate is turned down gradually.
2. PS. The level of pressure support is turned down
gradually.
3. CPAP. The patient is placcd on CPAP for a limited
time each day.
B. Criteria
1. Reversal of condition that required ventilation
2. Awake and cooperative patient
1 50
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3. Fraction of inspired oxygen (FIOz) . 0.5 [with an
arterial oxygen tension (Paoz) > 60 mm Hg]
4. Positive end-expiratory pressure (PEEP) < 5 cm H20
5. Minute ventilation (VE) . 10 Llmin*
6. Maximum inspiratory force (MIF) < -20 cm H20
7. Spontaneous respiratory rate/spontaneous tidal vol
ume (VT) < 100 breaths/L
Most I mportant Weaning Criteria ("WEANS
NOW")
Wake (patient must be awake!)
Electrolytes OK (i. e., no hypomagnesemia or
hypophosphatemia)
Acidosis (metabolic) or Alkalosis (metabolic)
absent
Neuromuscularly intact (beware of prolonged
ami noglycoside or steroid use or neuromuscu
lar blockade)
Suctioning and Secretion controlled
Nutriti onally i ntact
Obstruction of the airways reduced
Weaning parameters
MIF -20 em H20
VT > 300 ml
VE 1 0 L
Respiratory rate/VT 1 00 breaths/L
VENTILTOR EMERGENCIES
H O T
K E Y
Always disconnect the patient from the ventilator and
bag the patient with 1 00% oxygen until the problem
is resolved.
VE tidal volume (VT) ? respiratory rate.
1 52 Chapter 24
A. Low airway pressure alann. Differential diagnoses in-
clude the following.
1. Disconnected tubing
2. Air leak around the cuff (e.g., balloon rupture or
tracheal dilatation)
3. Extubation (e.g., tube has slipped into the oro-
pharynx)
4. Tracheo-esophageal fstula
B. High airway pressure alarm. Differential diagnoses in-
clude the following:
1. Kinked tube
2. Tube out of position (e.g., right main-stem bron-
chus intubation)
3. Airway is obstructed by secretions (e.g., mucous
plug)
4. Pneumothorax
5. Bronchospasm
6. Worsening of lung disease
7. Patient resistance to the ventilator
C. Apnea alarm. Differential diagnoses include the fol-
lowing:
1. Sedatives
2. Central nervous system (CNS) depression
3. Muscle weakness
4. Neurologic defect
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PART IV
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25.Abdominal Pain
eeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeepeeeeeeeeeeeeeeeeeeeeee
Q
INTRODUCTON
A. The evaluation of a patient with abdominal pain is com
plicated by the overabundance of potential diagnoses,
the frequency of nonspecifc signs and symptoms, and
the limitations of radiographic studies.
B. Life-threatening conditions can easily "hide" in the ab
domen, initially causing few, if any, symptoms. The con
sequences of wrongly attributing the pain to a benign
condition ( e.g., gastritis) can be catastrophic. Remember.
"Always respect the belly."
CAUSES OF ADOMINAL PAIN. The list of diseases that
can cause abdominal pain is almost endless and includes
diseases of the liver, gallbladder, pancreas. spleen. kidneys,
abdominal aorta, and the entire gastrointestinal tract (includ
ing the appendix). Pain can also be referred from the thorax
(e.g., myocardial infarction or pneumonia) and pelvis [e.g.,
pelvic infammatory disease (PIO), testicular torsion]. A
thorough approach to abdominal pain consists of the follow
ing three steps:
A. Consider the abdominal organs. By remembering that
infection, obstruction, or ischemia may cause abdominal
pain in any intra-abdominal organ, you will form a broad
differential diagnosis.
B. Rule out referred pain from the thorax and pelvis.
C. Consider metabolic and systemic causes of abdominal
pain. These can be remembered using the following mne
monic.
1 55
1 56
Chapter 25
Metabolic and Systemic Causes of Abdomi nal
Pain ("Puking My BAD LUNCH")
Porphyria
Mediterranean feer
Black widow spider bite
Addison's disease or Angioedema
Diabetic ketoacidosis
Lead pOisoning
Uremia
Neurogenic (impingement of spinal nerves or
roots, diabetes, syphi l is)
Calcium (hypercalcemia)
Herpes zoster
APROACH TO THE PATIENT
A. Patient history
1. E
p
idemiologic factors have an important impact on
the likelihood of a particular diagnosis (e.g., intrave
nous drug use suggests hepatitis; alcohol abuse sug
gests pancreatitis or alcoholic hepatitis; hypertension
suggests myocardial ischemia or abdominal an
eurysm).
2. Time course. The progression of certain symptom
complexes is critical. For instance, in appendicitis,
pain almost always precedes nausea and vomiting.
3. Symptoms
a. Pain
(1) Quality. Judgments regarding the quality of
the pain are often misleading or useless, given
the signifcant variation and overlap among
diagnoses. However, acute abdominal pain is
often more of a cause for concern than
chronic pain. and the chances of fnding pa
thology are significantly higher.
(2) Location. The location of the pain is ex
tremely important and may help order your
differential diagnosis (Table 25-1). Because
there is a great deal of overlap, you can never
be faulted for being too careful (e.g., check
ing a urinalysis in a patient who has upper
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1 58
Chapter 25
quadrant symptoms, but lacks the classic cos
tovertebral angle tenderess).
b. Other symptoms. Common symptoms and asso
ciated organs or organ systems are summarized
in Table 25-2. Remember to ask about cardiac.
pulmonary, and pelvic symptoms as well.
B. Physical examination
1. Auscultation may not provide much information,
because the presence or absence of bowel sounds
usually dos not narrow the differential diagnosis.
2. Palpation. Always move gently toward the area of
the patient's complaint.
3. Rectal and pelvic examination. Always perform a
rectal examination (with stool guaiac) and a pelvic
examination in patients with abdominal pain. Pain
during rectal or pelvic examination may indicate
pelvic pathology Or a disorder involving a lower
intraabdominal structure (e.g, a retrocolic appen
dix).
C. Diagnostic tests
1. Basic tests. The results of the following tests provide
a starting point for narrowing the list of possible diag
noses.
a. Complete blood count (CBC). Look for leukocy
tosis or anemia.
b. Renal panel. Electrolyte disturbances can be the
cause or result of the illness. Elevated blood urea
nitrogen (BUN) and creatinine levels may sug
gest volume depletion or renal pathology.
TABLE 252: Symptoms and Associated Organ Systems
Symptom Likely Site of Pathology
Dysuria, frequency
Nausea, vomiting, diarrhea
Jaundice, pruritis
Pain that decreases upon sitting up
Abrupt onset of midline pain that
i s out of proportion to the exam
Kidney, bladder
Gastroi ntestinal troct
liver, gallbladder
Pancreas
Mesenteric vessels
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Abdominal Pain
1 59
c. Liver function tests screen for liver or biliary pa
thology.
d. Amylase. Evaluating the lipase level in addition
to the amylase level may increase the sensitivity
and specifcity for pancreatitis.
e. Urinalysis is helpful to rule uut diabetic ketoaci
dosis and renal pathology.
f. Urine pregnancy test. If the patient is a woman
of childbearing age, a pregnancy test should be
performed regardless of how probable pregnancy
seems to the patient.
2. Ancillary tests. Given your initial diagnostic impres
sions. the fullowing tests may be indicated.
a. Serum calcium. This evaluation can rule out
hypercalcemia as a possible diagnosis.
b. Serum albumin. A low value may increase suspi
cion of an intraabdominal malignancy.
c. Fecal white blood cell (WBC) count. A fecal
WBC count should be performed to screen for
bowel infammation in any patient with di
arrhea.
d. Radiologic examination of the abdomen. Flat
and upright views are useful for evaluating
bowel obstruction or the presence of kidney
stones.
e. Radiologic examination of the chest. Posterior
anterior (P A) and lateral views are indicated
when the patient is experiencing upper abdomi
nal pain (to rule out a lower lobe pneumonia)
or when there is any suspicion of peritonitis (to
rule out free air).
t
(1) A lateral radiograph sometimes demon
strates free air not seen on the P A flm. The
patient should remain upright for at least 5
minutes prior to P A and lateral radiographs
to increase the sensitivity for detecting air
beneath the diaphragm. In a patient who can
not sit up (e.g., because of pain or hypoten
sion). a lef lateral decubitus view can be used
to evaluate for free air.
(2) Enlargement of the aortic or cardiac silhou
ette may suggest an abdominal aortic aneu
rysm or a cardiac cause of the pain.
Abdominal ultrasound is often the best way of
evaluating gallbladder. biliary, and renal pathol
ogy; diseases in the liver, spleen, pancreas, ab-
1 60 Chapter 25
dominal aorta, and some intraabdominal ab
scesses can also be detected.
g. Abdominal computed tomography (eT) scan.
An abdominal CT scan is better than ultrasound
for evaluating most intra abdominal structures
(except for the biliary tree, and perhaps the kid
ney). Triple-contrast studies (intravenous, oral,
and rectal) are usually performed. yielding much
fner detail. For patients with elevated creatinine
levels, intravenous contrast can sometimes be
avoided if the bowel is of primary concern; how
ever, abscesses will often be missed unless intra
venous contrast is used. [Abdominal magnetic
resonance imaging (MRI) is an option for pa
tients in whom radiocontrast dye is contraindi
cated.J
h. Paracentesis. If the patient has ascites, you
should always perform a paracentesis to rule
out peritonitis.
i. Electrocardiography. Every patient with a his
tory of cardiac disease or risk factors and abdomi
nal pain (especially upper abdominal pain)
should have an electrocardiogram (EKG) to rule
out myocardial ischemia. Inferior wall myocar
dial ischemia is the type of ischemia most likely
to cause abdominal pain.
D. General guidelines for the management of a patient with
abdominal pain
1. The patient should have nothing by mouth during the
initial evaluation because surgery may be necessary.
2. Associated conditions (e.g., severe volume depletion
or electrolyte imbalances) should be corrected while
the diagnostic workup is proceeding.
3. In the past, it was thought that the use of painkillers
(e.g., opiates) during evaluation of the patient would
"mask" potential diagnoses. However, it is now gen
erally considered inappropriate to withhold medica
tion in a patient with severe pain. The use of short
acting opiates (e.g., fentanyl) allows careful titration,
which helps prevent hypotension.
4. A nasogastric tube is indicated in patients with severe
vomiting or bowel obstruction.
5. Early consultation with a surgeon when certain disor
ders are suspected clinically (e.g., appendicitis. peri
tonitis, cholecystitis) can prevent long delays and
unnecessary tests.
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Abdominal Pain
1 61
6. When an etiology is not apparent and the patient
appears ill (e.g., fever, diaphoresis, resting tachycar
dia, abdominal tenderness), observation in the hospi
tal is usually necessary. In these situations, there is
no substitute for frequent follow-up exams and the
tincture of time.
26. Liver Tests
Q
Q
INTRODUCTION. The liver has been called "the custodian
of the milieu interieur." Hepatic disorders, therefore, have
far-reaching effects on homeostasis. Fortunately, there are
several tests that can help determine the cause of the injury
and allow assessment of the liver's remaining synthetic ca
pacity.
GENERAL ApPROACH
A. Synthetic function
1. Albumin. The liver is an important site of protein
synthesis. Assessment of albumin levels can tell us
how well the liver is making proteins in general. If
dietary intake is constant and the liver fails, it can
take several weeks for albumin levels to fall. There
fore, in a patient with acute liver failure, the albumin
level may be normal.
2. Prothrombin time (PT). The PT is a function of
plasma levels and the activity of factors I. II, V, VII,
and X. The half-lives of some of these proteins are
much shorter than that of albumin; therefore, the PT
increases within hours of a signifcant decrease in the
synthetic function of the liver.
3. Total bilirubin levels can also be used to assess liver
function. Clinical jaundice is usually apparent with bi
lirubin levels that exceed 3 mgldL A complete discus
sion of bilirubin fonnation and elimination is beyond
the scope of this chapter, but, briefy, bilirubin is
formed by the breakdown and cleavage of the heme
ring. The bilirubin is then glucuronidated (conju
gated) in the liver and excreted in the bile. Elevations
can be thought of as being predominantly unconju
gated or conjugated. Most are a mix of both.
a. Unconjugated (indirect). Levels of unconjugated
bilirubin increase if production increases (for ex
ample, as a result of hemolysis or hematoma) or
hepatic uptake or conjugation decreases (as seen
in Gilbert's syndrome and Crigler-Najjar syn
drome).
b. Conjugated (direct). Levels of conjugated biliru
bin increase with decreased secretion of bilirubin
1 62
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liver Tests 1 63
into bile canaliculi (as seen in Dubin-Johnson
syndrome and Rotor's syndrome). Biliary epithe
l
i
al damage (as a result of hepatitis, toxins, or
cirrhosis) or ductal obstruction (as a result of
biliary stones, cholangitis. or pancreatic cancer)
can also increase conjugated bilirubin levels.
4. Glucose levels may be decreased in patients with
severe liver dysfunction.
B. Injury patter. The two predominant patterns of liver
injury are cholestatic and hepatocellular.
1. Cholestatic patter. The cholestatic pattern is charac
terized by elevations in alkaline phosphatase and y
glutamyl transpeptidase (GGT).
a. Alkaline phosphatase is an enzyme that hydro
lyzes organic phosphate esters. Alkaline phos
phatase is found primarily in liver and bone, but
may also be found in the small intestine, kidney,
placenta, and leukocytes. In the liver. alkaline
phosphatase is found primarily on the surface of
the bile canalicular membrane. Disproportionate
elevations of alkaline phosphatase occur with any
disease that obstructs bile fow (e.g., biliary
stones, cholangitis, pancreatic cancer) or diseases
that infltrate the liver causing micro-obstruction
or damage (e.g., tuberculosis, sarcoidosis, meta
static cancer).
b. GGT is an enzyme found in many tissues, but
notably, not bone. Therefore, it is most useful
for evaluating the cause of an elevated alkaline
phosphatase level. If both enzymes are elevated,
the liver is a likely source, whereas elevation of
alkaline phosphatase with a normal GGT sug
gests a bone source. GGT is also elevated in
patients with alcoholic liver disease.
2. Hepatocellular patter. The hepatocellular pattern
is associated with elevations in aspartate aminotrans
ferase [AST, serum glutamate oxaloacetate transam
inase (SGOT)]. alanine aminotransferase [ALT, se
rum glutamate pyruvate transaminase (SGPT)], and
lactate dehydrogenase (LDH).
a. AST is an enzyme found in the cytosol and mito
chondria of hepatocytes. It is also found in car
diac muscle; renal, brain, pulmonary, and pancre
atic tissue; leukocytes; and erythrocytes. AST is
a sensitive indicator of hepatic injury but is not
specifc.
1 M
Q
Chapter 26
b. ALT is an enzyme found i n the cytosol of hepato
cytes. Because it is found only in the liver, AL Tis
a very specifc indicator of hepatocellular injury.
L= LOU is an enzyme that is found in many tissues;
isoenzyme 5 (LDH-5) is found in the liver. LDH
levels increase with any hepatocellular injury.
Couses of Markedly Increased (> 1 000 U/L)
A5T ond Al Levels ("Tainted Mushrooms Con
Couse Bod Hepatitis, 50 Watch Out!")
Tylenol or Tetracycline toxicity
Mushrooms (Amanita phaloides)
Carbon tetrachloride toxicity (rare)
Congestive hepatopathy
Budd-Chiari syndrome
Hepatitis (viral)
Shock liver (due to hypotension of any couse)
Wilson's di sease (subtype associ oted with f
minant hepatic necrosis)
Other toxi ns (e. g. , halothane, valproic acid,
vitami n A)
COMMON LIVER FUNCTION TEST ABNORMALITIES
summarized in Table 26-1.
are
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27.Acute Diarrhea
M
Q
Q
INTRODUCTION. Though we might think of diarrhea as pri
marily a nuisance, over 5 million deaths per year worldwide
can be attributed to this ailment.
A. Defnition. Diarrhea is the excretion of more than 200
g of stool per day. Diarrhea is not a subjective experience
of increased frequency or quantity of stool.
B. Classifcation. Diarrhea can be classifed as acute 3
weeks in duration) or chronic (> 3 weeks in duration).
Because acute diarrhea is seen more often in hospitalized
patients, it is the focus of this chapter.
CAUSES OF ACUTE DIARRHEA
A. Infection. Diarrhea of an infectious etiology is by far the
most common type.
B. Infammation. Diarrhea resulting from an infammatory
process (e.g., infammatory bowel disease. ischemic
bowel disease) often presents with blood and pus in
the stool. In order to make this diagnosis, an infectious
etiology must be ruled out.
C. Drugs, including laxatives, antacids containing magne
sium, antibiotics, and colchicine, are an often overlooked
cause of diarrhea.
D. Toxins, including heavy metals, seafood toxins, and
mushroom toxins, can cause acute diarrhea.
A. Evaluate volume status. Physical examination fndings
suggestive of dehydration include resting tachycardia,
orthostatic hypotension, dry mucous membranes, and
skin tenting.
B. Most cases of acute, infectious diarrhea are self-limited
and do not need work-up. only supportive care. Figure
27-1 can help you differentiate which patients need a
diagnostic work-up and which patients need antimicro
bial treatment.
TREATMENT
A. Bland diet. Dairy foods, spicy foods, and caffeine should
he avoided. Ohserve the BRAT diet: bananas, rice, ap
plesauce, toast.
1 66
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Acute Diarrhea
History of fever; rectal blood, mucus or pus;
recent antibiotic use; or recent travel
Yes
Presence of fecal PMNs,

guaiac-positive stools, or
No
Observation
Rehydration
?Mri"9' pa,
Yes No

Medical disease --. Oisease-
(l BO, specific
ischemic bowel therapy
Escherichia coli
(EI EC, EHEC)
Shigella
Salmonela
Yersinia
enterocolitic
Campylobacter
Aeromonas
Clostrdium
difcile
Amoeba
Antibiotic
therapy
Consider fecal O&P x 3
I \
(+) (-)
+
Giardia
Amoeba
Cryptosporidium
+
Antibiotic
Virus
Escherichia coli
(ETEC, EPEC)
Vibrio species

1 67
Obsere and institute
general therapy, but if
severe or perSistent,
consider stool culture,
Clostrdiumdftoxin,
flex sig with biopsy,
and/or EGO
FIGURE 27- 1 . Algarithm for evoluating patients with acute diarrhea.
IBD inflammatory bowel disease; O&P ova and parasites; PMNs
polymarphonuclear neutrophils; EGO esophagogastroduodenoscopy;
EIEC enteroinvasive Escherichia coli; EHEC enterohemarrhagic
E. coli (serotype 01 57: H7); EPEC " enteropathogenic E. coli;
ETEC enterotoxigenic E. coli; Rex sig flexible sigmoidoscopy.
1 68 Chapter 27
B. Rehydration. Intravenous fuids may be necessary if the
patient is unable to take liquids orally.
C. Pharmacologic therapy
1. Antimotility agents. In some patients with infectious
diarrhea. antimotility agents pose a theoretical risk
of toxic megacolon and prolongation of illness.
2. Bismuth subsalicylate has antisecretory and antimi
crobial properties and can be useful for traveler's
diarrhea or viral diarrhea.
3. Antibiotics, if necessary, are usually given for 5- to
7-day courses.
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28.Acute Gastrointestinal Bleeding
M
INTRODUCTION. Gastrointestinal bleeding is both a com
mon and serious problem in the United States.
A. Classifcation. Gastrointestinal bleeding is traditionally
classifed as "upper" or "lower," depending on whether
the bleed originates above or below the ligament of
Treitz.
B. Defnitions
1. Hematemesis is blood, including "coffee grounds,"
in the vomitus. Hematemesis clearly represents an
upper gastrointestinal source.
2. Hematochezia is blood in the stool. Hematochezia
can occur with lower gastrointestinal bleeds as well
as rapidly bleeding upper gastrointestinal bleeds.
H O T
K E Y
I n 1 0% of patients with hematochezia, the source of
bleeding is the upper gastrointesti nal tract.
3. Melena is black, tarry stool resulting from digested
blood. Melena usually indicates an upper gastroin
testinal bleed because the blood has been digested
to hematin, but small bowel and right-sided colonic
hemorrhages can also produce melena.
H O T
K E Y
Bismuth subsal icylate, iron, spinach, and charcoal can
also produce black stools.
1 69
1 70 Chapter 28
Q
CAUSES OF GASTROINTESTINAL BLEEDING
A. Upper gastrointestinal source. There are many causes of
upper gastrointestinal tract bleeding; the most common
can be easily remembered using the mnemonic, "G UM
BLEEDING." (The frst three causes are the most
common. )
Gastroi ntestinal Bleeding-Upper Gostrointes
tinal Sources ("GUM BLEEDING")
Gastritis (secondary to NSAIDs, olcohol, or
stress)
Ulcers (often caused by Helicobacter pylori
or NSAIDs)
Mallory-Weiss tear (often secondary to exces
sive vomiting)
Biliary (hemobilia, usually secondary to
trauma)
Large vorices (seen in patients with portal hy
pertension)
Esophagitis or Esophageal ulcer
Enterooortic fistula (usually seen in patients with
aortic grafts)
Duodenitis or Dieulafoy's lesion (an ectatic ar
tery in the stomach)
Inflammatory bowel disease (upper tract
Crohn's disease)
Neovascularization (arteriovenous malforma
tion), usually seen in the elderly; more com
monly causes lower gastroi ntesti nal bleeding
Gastric cancer
B. Lower gastrointestinal source. Use the following mne
monic to remember the causes of lower gastrointestinal
tract bleeding-you may need a "DRAIN" to collect
the blood.
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Acute Gostroi ntesti nal Bleeding 1 71
Gastrointestinal Bleeding-Lower Gastroi ntes
tinal Sources ("DRAIN")
Diverticulosis
Radiation colitis
Arteriovenous malformation (angiodysplasia)
Ischemia, Inflammation, or Infection
Neoplasm
1. Diverticulosis is the most common cause of lower
gastrointestinal bleeding. The disorder is painless
and is almost never a cause of chronic blood loss.
2. Radiation colitis can occur at any time following
radiation therapy.
3. Arteriovenous malformations (angiodysplasia) oc
cur primarily in the elderly and may cause both acute
and chronic blood loss.
4. Ischemic colitis. The patient experiences pain out of
proportion to the examination.
S. Infammatory bowel disease is usually accompanied
by diarrhea and rarely causes massive bleeding.
6. Infectious colitis is also usually accompanied by di
arrhea.
7. Neoplasms (benign or malignant) usually cause
chronic, rather than acute, blood loss.
Q
APPROACH TO THE PATIENT
A. Patient history. The history is helpful for distinguishing
between an upper and lower source of bleeding, but poor
for determining the exact cause of the bleeding. It is
important to inquire about the following:
1. Number of episodes
2. Most recent episode
3. Use of nonsteroidal antiinfammatory drugs (NSAIDs)
and aspirin
4. Anticoagulant use
S. Cirrhosis
6. Alcohol abuse
7. Vomiting prior to hematemesis
8. Presence and location of abdominal pain
9. Prior aortic surgery
B. Physical examination
1. Vital signs. Check orthostatics-if your patient
1 72 Chapter 28
"tilts" (i.e., moving from a supine posItIon to an
upright position causes his pulse to increase by more
than 20 beats/min or his systolic blood pressure to
decrease by more than 10 mm Hg), then his intravas
cular volume is 1%-20% helow normal.
H O T
K E Y
Patients on f blockers might hove a "normal" pulse
rate, despite a large volume loss.
2. HEENT. Check for scleral icterus, which may indi
cate liver disease with associated varices. Rule out
epistaxis and oral lesions as a source of upper gastro
intestinal tract bleeding.
3. Lungs and heart. Check for evidence of left ven
tricular dysfunction. which can affect fuid adminis
tration.
4. Abdomen. Given the cathartic nature of blood, the
absence of bowel sounds may suggest an intraabdom
inal catastrophe. Look carefully for rigidity, involun
tary guarding, and rebound tenderness, which may
suggest peritonitis.
S. Rectum. Palpate for rectal masses. A stool guaiac
should be performed if the stools are not clearly
bloody.
6. Neurologc examination. Check for asterixis (evi
dence of liver disease).
7. Skin. Look for signs of liver disease, such as jaundice,
spider angiomata, and palmar erythema.
C. Diagnostic tests. Important initial tests to run include:
1. Blood typing and cross-matching
2. Complete blood count ( (,BC) with platelets
3. Electrolyte panel
4. Blood urea nitrogen (BUN) and creatinine levels
S. Liver tests
6. Prothrombin time (PT) and partial thromboplastin
time {PIT)
7. Chest and abdominal radiographs
8 Electrocardiogram (EKG)
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Acute Gastrointestinal Bleeding 1 73
D. General guidelines for the management of a patient with
gastrointestinal bleeding. In a patient with gastrointesti
nal bleeding, do not delay management because you have
not fgured out the cause of the bleeding! Gastrointesti
nal bleeding is one situation in internal medicine where
the initial management is usually the same regardless of
the exact cause.
1. Ensure that the ABCs (airway, breathing, circula
tion) are in place.
2. Begin fuid replacement. Intravenous access should
be obtained immediately, preferably with two large
bore (18-gauge or larger) intravenous lines.
3. Insert a nasogastric tube if there is any possibility of
an upper gastrointestinal bleed. Bolus with 50 cc of
water, then withdraw-keep a tab of how much water
it takes for the aspirate to become almost clear.
The nasogastric tube aspirate may be negative,
even in the presence of upper gastrointestinal
bleeding, if:
(1) The source of the bleeding is below the end
of the nasogastric tube (e.g., if the nasogastric
tube ends in the stomach, bleeding from a
duodenal ulcer may not be apparent in the as
pirate).
(2) The bleeding is transient.
b. The tube should be kept in place if there is active
bleeding or signs of a small bowel obstruction.
4 Hold antihypertensive or diuretic therapy. In addi
tion, the patient should receive nothing by mouth.
S. Decide whether or not to admit the patient to the
intensive care unit (ICU).
a. If your patient needs to take a trip to the ICU, she
will need a "VISA." Patients generally require
admission if any of the following criteria are met:
Criteria for Admittance to ICU with a Gastroin
testinal Bleed ("VISA")
Variceal bleeding (suspected or confirmed)
Instabi l i ly of vital signs
Serious comorbid conditions (e. g. , coronary
artery disease, COP D)
Active gastrOi ntesti nal bleeding
1 74
Chapter 28
b. All patients admitted to the ICU should be seen
hy a gastroenterologist immediately.
6. Stabilize the patient.
a. Transfusion
(1) Elderly patients or thuse with coronary ar
tery disease are usually transfused to keep
their hematocrit greater than 30%. At least
two units of typed and cross-matched packed
red blood cells (RBCs) should be kept in the
blood bank at all times.
(2) In a patient with active bleedi
g, consider a
platelet transfusion if the patient's platelet
count is less than 50.000/mm
>
. Fresh frozen
plasma should be used if the patie
t's inter
national normalized ratio (INR) IS greater
than 1 .5.
H O T
K E Y
A unit of blood entering or leaving the body should
change the patient's hemoglobin by approximately
1 g/di.
b. Intravenous H2 blockers are usually adminis
tered.
c. Vitamin K should be administered if the patient's
PT or PTT is abnormal.
7. Perform ancillary tests if necessary.
a. A technetium-99 (ro)-Iabeled red blood cell
scan can be performed if a slow (i.e., 0. 1 -1 ml!
min) lower gastrointestinal bleed is present.
.
b. An angiogram may be indicate wh
n a rapid
(i.e., > I mllmin) lower gastromtestmal bleed
is suspected.
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29. Splenomegaly
e
M

INTRODUCTION
A. Splenomegaly is enlargement of the spleen.
1. A normal spleen is 12 em by 7 em and weighs less
than 200 grams. It is surrounded by a thin capSUle.
The spleen is usually not palpable unless it is en
larged; therefore. a palpable spleen is always ab
normal.
2. Massive splenomegaly occurs when the spleen
weighs more than 3000 grams.
B. Hypersplenism is the term given to any clinical situation
in which the spleen inappropriately removes excess
amounts of leukocytes, platelets. or erythrocytes from
the circulation.
1. Hypersplenism and splenomegaly are not synony
mous. Patients with hypersplenism all have spleno
megaly; however, only a small percentage of those
with splenomegaly have hypersplenism.
2. Characteristics of hypersplenism include the fol
lowing:
a. Splenomegaly
b. Splenic destruction of one or more cell lines
c. Normal or hyperplastic bone marrow
d. Reversal of the cytopenia following splenectomy
CLINICAL MANIFESTATIONS OF SPLENOMEGALY
A. Nonacute splenomegaly is most common. Clinical pre
sentations include:
1. Early satiety (because of impaired gastric flling);
may lead to weight loss
2. Cytopenia (as a result of hypersplenism); may
lead to infections, bleeding. or fatigue
3. Symptoms of the underlying disease
B. Acute splenomegaly
1. Clinical signs include the sudden onset of left upper
quadrant pain and a tender. enlarged spleen.
2. Differential diagnoses
a. Subcapsular hematoma
b. Splenic rupture due to trauma (even remote) or
an infectious process (e.g., malaria, mononucleo
sis, typhoid fever)
1 75
1 76 Chapter 29
c. Splenic infarct due to sickle cell disease or em
bolism
d. Hemorrhage into a splenic cyst
Q
CAUSES OF SPLENOMEGALY
A. Congestive causes. This category includes any disease
that leads to disordered splenic blood fow, so that the
blood "backs up" in the spleen. Think of causes that
anatomically head away from the spleen.
1. Splenic vein obstruction
2. Portal vein obstruction
3. Hepatic schistosomiasis
4. Cirrhosis
5. Hepatic vein obstruction
6. Constrictive pericarditis
7. Congestive heart failure (CHF)
.
B. Reactive causes. This category includes those diseases
that lead to splenic hyperplasia. Because the spleen is a
lymphoid gland, many diseases that cause a systemi
.
c
immunologic response can cause splenomegaly. In addi
tion, blood disorders that lead to hemolysis can also
cause the spleen to enlarge.
1. Infections
a. Bacterial (e.g., endocarditis, tuberculosis, sus
tained bacteremia)
b. Viral (e.g., mononucleosis, viral hepatitis)
c. Parasitic (e.g., malaria, leishmaniasis, trypanoso
miasis)
d. Fungal (e.g., disseminated histoplasmosis)
2. Collagen vascular diseases
.
a. Rheumatoid arthritis. Felty's syndrome 1h the
triad of ganulocytopenia, rheumatoid arthritis,
and splenomegaly.
H O T
K E Y
Rheumatoid arthritis-like congestive heart fai l ure, sys
temic lupus erythematosus, endocarditis-usually
causes mild splenomegaly.
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Splenomegaly
1 77
b. Systemic lupus erythematosus (SLE)
3. Serum sickness. This immune complex disorder
usually caused by a drug hypersensitivity reaction
occurs 1 -3 weeks following primary exposure (or
within 36 hours of re-exposure) to an offending
agent.
Cl i nical Manifestations of Serum Sickness
("SALT")
Skin rosh (morbilliform, urticarial, or palpo
ble purpura)
Arthralgias or Arthritis
Lymphadenopathy
Temperature i ncrease
4. Work hypertrophy can be caused by hemolysis.
C. Infltrative causes
1. Benign
H O T
K E Y
U= Sarcoidosis
b. Amyloidosis
c. Gaucher's disease, an autosomal recessive disor
der characterized by an accumulation of sphin
golipid within phagocytic cells throughout the
body
Hip fracture + Polpable spleen Eastern European
descent Goucher's di sease
2. Malignant
a. Lymphomas
b. Leukemias
c. Myeloproliferative disorders
d. Primary splenic tumors
e. Metastatic tumors
1 78
Chapter 29
Causes of Massive Splenomegaly ("Hopefully,
My Medical Students Can learn Gastroenter
ology")
Hairy cell leukemia (uncommon, resembles
chronic lymphocytic leukemia)
Malaria
Myeloid metaplasia with myelofi brosis (one of
four myeloproliferative di sorders)
Srcoidosis
Chronic myelogenous leukemio (onother mye
loproliFerative disorder)
Lymphomo (primarily splenic lymphoma)
Gaucher's disease
A. Patient history. When taking the history, you
.
should
focus on searching for an underIymg cause. Thmgs to
look for include:
1. Alcohol use or cirrhosis
2. CHF
3. Febrile illness (current or recent)
4. Arthralgias, arthritis, or joint stiffness
5. Fever, weight loss, diaphoresis, or lymph node
swelling
6. Family history of anemia or splenomegaly
B. Physical examination. Look for evidence of hepatomeg
aly, lymphadenopathy. skin rash, subcutaneous nodules,
CHF, liver disease, or an infectious process.
C. Laboratory tests usually include a complete blood count
(CBC) and analysis of the peripheral smear and liver
tests.
D. Other tests. Blood cultures may be warranted. An ultra
sound is useful to confrm the presence of splenomegaly
and evaluate the liver size. Bone marrow biopsy, lymph
node biopsy, serologies, exploratory laparotomy, and
other imaging studies may also be performed.
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30. Ascites
ee e
M
Q
INTRODUCTION. Ascites is the accumulation of excess fuid
within the peritoneal cavity.
CAUSES OF ASCITES. Ascites may occur as part of ana
sarca (generalized edema) or as an isolated fuid collection.
A. Anasarca. The causes of a generalized edematous state
can be remembered as the "osis group"-nephrosis, cir
rhosis, cardiosis, and hypothyroidosis.
8. Isolated fluid collection. There are three primary mecha
nisms of ascites production. In addition. there are miscel
laneous disorders that cause ascites by various mecha
nisms.
1. Increased hydrostatic pressure in the splanchnic cap
illaries may result from diseases that produce ele
vated venous pressure. One way of thinking about
the causes of increased hydrostatic pressure is to
trace the venous blood from the heart down.
a. Cardiac. Right-sided heart failure and constric
tive pericarditis lead to elevated venous pressure
and can cause ascites.
b. Hepatic
(1) Postsinusoidal obstruction includes inferior
vena cava obstruction, hepatic vein obstruc
tion (i.e., Budd-Chiari syndrome), or hepatic
venule obstruction (i.e .. veno-lIcclusive dis
ease).
(2) Sinusoidal obstruction is the most common
cause of ascites and usually results from cir
rhosi<.
(3) Presinusoidal obstruction may be caused by
schistosomiasis or portal vein thrombosis.
(Portal vein thrombosis may cause variceal
bleeding, but only rarely produces ascites.)
2. Oecreased oncoti( pressure may result from de
creased albumin intake (i.e .& starvation), decreased
albumin production (i.e., severe liver disease). or
increased loss of alhumin (e.g., nephrotic syndrome,
protein-losing enteropathy).
3. Increased capillary permeability may occur with in
fection (e.g., tuberculosis) or maligancy.
1 79
1 80
Q
Chapter 30
4. Miscellaneous causes
a. Hypothyroidism. Myxedema usually produces
anasarca, not isolated ascites.
b. Pancreatitis may cause pancreatic ascites.
c. Lymphatic obstruction from trauma, tumor. or
infection (e.g., flariasis, tuberculosis) may cause
chylous ascites.
A. Patient history and physical examination. A complete
history and physical examination (including recal and
pelvic examinations) are necessary. B y rem
mbenng the
underlying mechanisms, you can systematically pursue
the diagnosis.
1. Increased hydrostatic pressure
a. Right-sided heart failure or constrictive pericar
ditis. Ask about symptoms of left-sided heart fail
ure (the most common cause of right-sided heart
failure). Perform a careful cardiac examination
and evaluate the jugular venous pressure.
b. Budd-Chiari syndrome may be suggested by right
upper quadrant pain and an enlarged liver in a
patient with a myeloproliferative disorder.
.
c. Hepatic veno-occJusive disease should be consid
ered in patients with ascites and a history of che
motherapy Or bone marrow transplantation.
d. Cirrhosis is the most common cause of ascites.
Inquire about risk factors, including alcohol con
sumption and hepatitis exposures (e.g., i
?
trve
nous drug use). Look for signs of chromc liver
disease (see Chapter 32).
.
2. Low oncotic pressure in the absence of severe liver
disease may be suggested by a history of starvation
or by the presence of nephrotic syndrome.
3. Increased capiJJary permeability may be suggested
by a history of fevers or weight loss, which could
suggest infection or malignancy.
4. Miscellaneous mechanisms
a. Pancreatic ascites should be considered when
ever pancreatitis is a possibility.
b. Lymphatic obstruction is suspected on the basis
of the "milky" appearance of chylous ascites.
c. Myxedema. If myxedema is the etiology, the pa
tient will usually have other symptoms of hypo
thyroidism (see Chapter 74).
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Ascites 1 8 1
B. Laboratory tests. Routinely performed laboratory tests
include a complete blood count (CBC) with differential,
an electrolyte pane!, blood urea nitrogen (BUN) and
creatinine levels, prothrombin time (PT) and partial
thromboplastin time (PT) , and liver function tests with
serum albumin. A urine dipstick test for protein and
thyroid function tests are also frequently performed, es
pecially when anasarca is present.
C. Diagnostic paracentesis is almost always needed to make
a diagnosis. Even when the diagnosis seems apparent,
diagnostic paracentesis is still indicated to rule out sec
ondary processes [e.g., spontaneous bacterial peritoni
tis (SBP)].
I. Procedure
a. Make sure that the patient has emptied his blad
der before the procedure. Alternatively, a Foley
catheter may be inserted.
b. A midline approach (i.e., 1-2 cm directly below
the umbilicus) may be preferable because this
region is avascular. However, prior midline sur
gery ofen necessitates a lateral approach be
cause the bowel may be adherent to the perito
neal wall.
c. A small needle (19-gauge or smaller) is usually
used.
2. Evaluation. A cell count with differential, bacterial
Gram stain and cultures, and an albumin level should
be obtained on the fuid sample. Lactate dehydroge
nase (LDH) and glucose levels may provide addi
tional information. An amylase or triglyceride level
should he ordered if there is a possibility of pancre
atic or chylous ascites, respectively.
H O T
K E Y
Remember to order a serum al bumi n level at approxi
mately the same time the ascitic flUid i s obtai ned.
3. Interpretation. Table 30-1 contains likely etiologies
of ascitcs and their characteristic fluid findings.
Cirrhosis 2 l.1 < 250 (mesothelial) Moderate Abnormal liver function tests
Spontaneous bacterial 2 l.1 > 250 (PMNs) Moderate Culture may be positive
peritonitis (SBP)
Congestive heart failure ; 1.1 < 1000 (mesothelial) High Elevated neck veins, gallops, abnormal EKG
Hypothyroidism 211 < 250 (variable) Variable Decreased free T., increased TSH
liver malignancy (pri- ; l.1 Variable Moderate Elevated serum AFP with primary malignancy
mary or secondary)
Nephrotic synd rome <1.1 < 250 (mesothelial) low Positive urine dipstick and 24-hour collectian far
protein
Tuberculous ascites < l.1 > 1000 (variable) High Ascitic acid-fast bacillus stain occasionally positive
Secondary peritonitis <1.1 > 250 (PMNs) Moderate Very low ascitic glucose, palymycrobial
Pancreatic ascites < 1.1 > 1000 (PMNs) Maderate Increased serum and fluid amylase
Peritoneal malignancy < 1.1 > 1000 (variable) High Cytology, CT scan, peritoneal biopsy may be
useful
AFP = a-fetoprotein; EKG = electrocardiogram; PMNs = polymorphonuclear neutrophils; T. = thyroxine; TSH = thyraid-stimulating
hormone.
* Total protein is considered low if it is less than 1 g/ dl, moderate if it is 1-3 g/ dl, and high if it is >3 g/ dl.
c
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Ascites
HOT
KEY
183
Remember that the fndings given are only general
izations and will not apply in all cases. Furthermore.
the presence of two or more disorders may skew the
fuid analysis.
a. Cell count. The cell count can be used to evaluate
the possibility of SBP, tuberculosis, or malig
nancy.
(1) SBP. Empiric treatment for SBP is usually
indicated when the absolute neutrophil count
exceeds 250 celiS/il. Counts greater than 500
cells/p, are more specifc but less sensitive
for SBP.
(2) Tuberculosis or malignancy. A cell count that
exceeds 250 cells/ILl and is lymphocyte pre
dominant often implies tuberculous or malig
nant ascites.
b. Serum-ascites albumin gradient. Subtract the as
citic fuid albumin value from the serum albu
min value.
(1) If the result is greater than or equal to 1.1,
portal hypertension is implicated (i.e., a hy
drostatic etiology is responsible).
(2) If the value is less than 1.1, capillary perme
ability is probably abnormal (i.e., infection
or malignancy may be implicated).
If portol hypertension is occompanied by onother disor
der that produces increased copillary permeobility, the
gradient will usually remain greoter than or equal to
1 .1 . SBP usually occurs in potients with portal hyperten
sion; therefore, the gradient is usually greater than or
equal to 1.1 in these patients.
c. Gram stain and culture of ascitic fuid should be
performed if peritonitis is suspected.
d. LDH and glucose levels. An elevated LDH or
low glucose level may indicate tuberculosis or
malignancy.
e. Amylase and triglyceride levels. Elevated amy
lase or triglyceride levels may indicate pancreatic
or chylous ascites, respectively.
184 Chapter 30
D. Additional testing may be necessary when the ascitic
fuid contains an elevated cell count with a lymphocyte
predominance, increasing suspicion for tuberculous or
malignant ascites.
1. Purified protein derivative (PPD) test. A positive
PPD test will increase suspicion for tuberculous peri
tonitis.
2. Acid-fast bacillus stain and culture of ascitic Huid.
These are relatively insensitive tests, but sending a
large volume of fuid (e.g., ] L) may increase the
yield.
3. Ascitic Huid cytolog is also of relatively low yield
unless a large volume of fuid is sent.
4. Abdominal computed tomography may reveal an in
tra-abdominal malignancy.
5. Laparoscopy with peritoneal biopsy is often per
formed to make an expedient diagnosis.
TREATMENT. The general management of ascites is dis
cussed in Chapter 33 IV B 4; other specifc therapies are
tailored to the underlying etiology and will not be dis
cussed here.
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31.Acute Pancreatitis
@
INTRODUCTION. Pancreatitis implies inHammation of the
pancreas.
A. Acute pancreatitis results from the leakage of pancreatic
enzymes into pancreatic tissue, leading to autodigestion.
Because acute pancreatitis is more common than chronic
pancreatitis, acute pancreatitis is the focus of this chapter.
B. Chronic pancreatitis. Causes are varied and ultimately
lead to destruction of the pancreatic tissue.
CUNICAL MANIFESTATIONS OF ACUTE PANCREATIIS
w
A. Symptoms usually include the abrupt onset of epigastric
pain that lasts for hours to days and radiates to the back,
nausea and vomiting, sweating, weakness, and anxiety.
The patient typically feels better when sitting up and
leaning forward.
B. Physical examination fndings
1. The patient may be febrile, tachycardic, tachypneic,
and hypotensive.
2. The skin of the periumbilical area may be discolored
(Cullen's sign), or fank ecchymoses (Turner's sign)
may be present.
3. The abdomen is hypoactive with mild distention (be
cause of ileus). Upper abdominal tenderness (usually
with0ut rebound or rigidity) is present.
C. Laboratory fndings
1. Elevated serum amylase and lipase are the hallmarks
of acute pancreatitis.
2. Other fndings may include leukocytosis (12.000-
15,OOO/mm ) hypoalbuminemia, hyperglycemia, and
elevated aspartate aminotransferase (AST, SGOT),
alkaline phosphatase, and bilirubin.
CAUSES OF ACUTE PANCREATITIS. There are numerous
causes of pancreatitis. The simplest way to remember the
most important of these causes is with the mnemonic, "BAD
HITS." (HINT: If you move the "S" in front of the "H,"
the mnemonic will be easier to remember, but more diffcult
to utter in public.)
185
1 86 Chapter 3 1
Common Causes of Acute Pancreatitis ("BAD
HITS")
Biliary stones
Alcohol abuse
Drugs
Hyperlipidemia or Hypercalcemi o
Idiopathic or Infectious
Trauma
Surgery (post-ERCP) or Scorpion sting
A. Biliary stones are the most common cause of acute pan
creatitis in suburban hospitals.
B. Alcohol abuse is the most common cause in urban hos
pitals.
C. Drugs. Many drugs can cause acute pancreatitis, includ
ing thiazide diuretics, sulfa antibiotics, pentamidine, and
some antiretroviral agents.
D. Hyperlipidemia (types I, IV, V). Pancreatitis usually does
not occur in hyperlipidemic patients until their serum
triglyceride level exceeds 10 mg/dl.
E. Idiopathic causes. In 15% of patients, no obvious cause
of the pancreatitis is identifed; however, some authors
implicate pancreas divisum (a congenital defect) as the
cause.
F. Infectious etiologies include mumps, cytomegalovirus
(CMV), HIV, and infections caused by Escherichia coli.
G. Trauma. Blunt, rather than penetrating, trauma is most
often responsible.
H. Surgical. Post-surgical pancreatitis occurs in 2% of pa
tients undergoing endoscopic retrograde cholangiopan
creatography (ERCP).
I. Scorpion sting. This cause is really only important to
know for resident's report or on attending rounds.
ApPROACH TO THE PATIENT. The diagnosis is based on
fnding elevated serum amylase or lipase l evels in the context
of an appropriate clinical setting. Imaging studies that may
be helpful include abdominal ultrasound and computed to
mography (CT). When a patient presents with pancreatitis,
you should:
A. Determine the LW of the pancreatitis.
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Acute Pancreatitis
187
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B. Assess the severity and estimate the prognosis. Because
the serum amylase and lipase levels do not correlate with
severity, Ranson's criteria are used to assess severity
and prognosis.
1. Ranson's criteria are assessed at admission and dur
ing the initial 48 hours.
Ranson's Criteria at Admission ("WAGlS")
White blood cell (WBC) count > 16,OOO/mm3
Age > 55 years
Glucose > 200 mg/dl
Lactate dehydrogenase (LDH) 350 U/l
SGOT > 250 U/l
Ranson's Criteria During the Initial 48 Hours
("BaCH wosn't an SOB")
Base deficit > 4 mEq/l
Calcium < 8 mg/dl
Hematocrit decrease > 1 0%
Sequestration of fluid > 6 l
Oxygen < 60 mm Hg
Blood urea nitrogen (BUN) increase of
> 5 mg/dl
2. In general, as the number of criteria increases, so
does the mortality rate.
TREATMENT is primarily supportive and includes bowel rest,
volume resuscitation, and management of respiratory dis
tress and renal failure. If gallstones are thought to be the
cause, cholecystectomy should be considered.
COMPUCATIONS
A. Pancreatic abscess should be suspected when patients
worsen after initial improvement.
188 Chapter 31
B. Pancreatic pseudocyst occurs in 10%-20% of p.nicnts
and usually does not require specifc trC<tment unless it
has been present for longer than 6 weeks. is greater
than 5 centimeters in diameter, or is accompanied by
signifcant symptoms.
C. Renal failure and respiratory failure are the two most
common systemic complications.
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32.Alcoholic Liver Disease
@
INTRODUCTION
A. The amount of alcohol required to produce liver disease

in a given patient is variable. Women may be more sus
ceptible than men. but men are more often affected be
cause of higher alcohol consumption rates.
B. There are three degrees of alcoholic liver disease. Often
these three syndromes overlap in a given patient.
1. Fatty liver
2. Alcoholic hepatitis
3. Micronodular (Laennec's) cirrhosis
CLINICAL MANIFESTATIONS OF ALCOHOLIC LIVER
DISEASE. Table 32-1 summarizes the clinical fndings that
accompany the various degrees of alcoholic liver disease.
A. Fatty liver is usually diagnosed in patients with a history
of alcohol consumption accompanied by mildly abnormal
liver function tests, hepatomegaly, or both. A defnitive
diagnosis may be made by biopsy but is rarely necessary.
Other possible causes of fatty liver include obesity, diabe
tes, hyperlipidemia, steroids (endogenous or exogenous),
starvation, parenteral nutrition, and toxins (e.g., car
bon tetrachloride).
B. Alcoholic hepatitis can be very mild or life-threatening.
The patient often presents with the signs and symptoms
summarized in Table 32-1 after a "drinking binge"; often
the onset of symptoms coincides with the cessation of
drinking. Although alcoholic hepatitis is a common dis
ease in alcoholics, other diseases (e.g., cholecystitis and
cholelithiasis) may mimic alcoholic hepatitis quite
closely. To avoid missing other pathology, have a low
threshold for getting an abdominal ultrasound in an alco
holic patient with right upper quadrant pain.
C. Cirrhosis. Alcoholism is the most common cause of
cirrhosis in the United States. The diagnosis is usually
obvious clinically-the major task is determining the
cause (or causes) of the cirrhosis (see Chapter 33 III B).
189
190
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Alcoholic liver Disease 191
TREATMENT
A. Fatty liver. Abstinence is the mainstay of therapy. Exer
cise and nutritional counseling are advisable for patients
with obesity, diabetes, or hyperlipidemia.
B. Alcoholic hepatitis. The long-term prognosis depends on
liver function and the patient's ability to abstain from
consuming alcohol.
1. Supportive therapy includes correction of fuid and
electrolyte status and observation for alcohol with
drawal, seizures. and delirium tremens.
2. Steroid therapy may beneft some patients with ex
tensive liver dysfunction.
C. Cirrhosis. Abstinence is critical to prevent worsening of
liver function.
33. Liver Failure
@
Q
INTRODUCTION
A. Acute liver failure is defned by the presence of encepha
lopathy and coagulopathy associated with acute hepatic
disease. It is often classifed as fulminant or sub fulminant,
depending on whether it develops within 2 months of,
or as many as 6 months after, the onset of illness.
B. Chronic liver failure occurs over a longer period of time.
CLINICAL MANIFESTATIONS OF LIVER FAILURE
A. Acute liver failure is characterized by the rapid develop
ment of nonspecifc symptoms (e.g., nausea, malaise),
jaundice, and altered mental status, usually in a pre
viously healthy patient.
1. Central nervous system (CNS, signs
a. Altered mental status. Encephalopathy produces
an alteration in mental status that ranges from
mild obtundation (grade I l II) to stupor or
coma (grade III or IV). Patients may also present
with agitation and delusions, which are uncom
mon in chronic liver failure. Unlike chronic liver
disease, acute liver failure may not be clinically
obvious; it is therefore important to consider he
patic failure in all patients with altered mental
status.
b. Asterixis is frequently noted on examination.
c. Cushing's reflex (hypertension and bradycardia),
abnormal pupillary reflexes, and increased mus
cle tone progressing to decerebrate posturing are
signs of cerebral edema, which may accompany
encephalopathy in the majority of grade IV pa
tients. Cerebral edema occurs more commonly
with fulminant liver failure, whereas renal failure
and ascites are more often associated with a sub
fulminant course.
2. Hematologic signs. Elevation of the prothrombin
time CPT) is universally present and may be accompa
nied by an elevated partial thromboplastin time
(PT). Thrombocytopenia may also occur.
3. Cardiovascular signs may include hypovolemia, a de-
1 92
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Liver Fai lure 1 93
crease in systemic vascular resistance associated with
hypotension, and an increase in cardiac output. Be
cause these fndings may also indicate sepsis, infec
tion should be considered and ruled out.
4. Metabolic changes
a. Hypoglycemia may aggravate the alteration in
mental status.
b. Hypokalemia can result from respiratory alkalo
sis induced by liver failure.
c. Hyponatremia and hypophosphatemia may also
occur.
5. Complications
a. Hemorrhage. Thrombocytopenia is a strong risk
factor for gastrointestinal or other bleeding.
b. Infections. Defects in neutrophil function as well
as humoral and cell-mediated immunity may re
sult in bacterial or fungal infections.
c. Renal failure is an ominous complication.
(1) Hepatorenal syndrome should be considered
in patients with severe liver disease, declining
renal function, and prerenal physiology (i.e.,
a low urinary sodium level). Hepatorenal
syndrome is distinguished from hypovolemia
by the patient's failure to respond to a fuid
challenge. Hepatorenal syndrome must also
be distinguished (on the basis of clinical crite
ria) from other causes of kidney failure that
result in prerenal physiology (see Chapter
37).
(2) Acute tubular necrosis may also occur.
d. Hepatopulmonary syndrome. Intrapulmonary
shunting of blood leads to hypoxia. Typically,
patients are more symptomatic when they are
sitting up, as opposed to lying down (i.e., they
are platypneic), because sitting up increases
blood fow to the lower lobes where more
shunting is known to occur.
B. Chronic liver failure. Clinical manifestations of chronic
liver failure are summarized in Table 32-1.
CAUSES OF LIVER FAILURE
A. Acute liver failure
1. Infection
a. Viral hepatitis is probably the most common
cause of acute liver failure.
194 Chapter 33
(1) Hepatitis A is a rare cause of ful minant hepa
titis, and never produces chronic disease.
(2) Hepatitis B causes fulminant liver failure in
approximately 1 % of infected patients.
(3) Hepatitis C usually causes only chronic dis
ease, but at a high rate (approximately 50%).
(4) Hepatitis D causes coinfection or superinfec
tion only in the presence of hepatitis B SUr
face antigen (HBsAg), and may account for
more than 50% of the cases of fulminant dis
ease caused by hepatitis B.
(S) Hepatitis E is endemic in Mexico and parts
of Asia; the mortality rate is high among
pregnant women.
(6) Epstein-Barr virus, cytomegalovirus (CMV),
and herpesvirus occasionally cause acute
liver failure.
2. Drugs and toxins
HOT
K EY
a. Drugs
(1) Direct hepatotoxicity
(a) Acetaminophen overdose. Alcoholics
and malnourished patients have a higher
risk of hepatotoxicity as a result of acet
aminophen overdose.
Remember the "rule of 1405" when confronted with
the possibility of ocetami nophen overdose: the approx
i mate toxic dose is 140 mg/kg, C blood level that
exceeds 140 Jg/ml 4 hours ofter ingestion may be
toxic, and the first dose of ocetylcysteine (the antidote)
is 140 mg/kg orally or by nasogastric tube (often
followed by 70 mg/kg every 4 hours for 17 doses).
(b) Heavy metals, phosphorus, vitamin A,
valproic acid, and tetracyclines may also
be directly hepatotoxic.
(2) Idiosyncratic reactions may also result in
acute liver failure. Isoniazid, halothane. phe
nytoin, and sulfonamides are some examples
of drugs that can cause idiosyncratic hepato
toxicity.
b. Toxins. Amanita phalloides (the death-cap
mushroom) and carbon tetrachloride (found in
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liver Failure 195
B.
industrial cleaning solvents) can both produce
acute liver failure.
3. Vascular abnormalities
a. Inadequate arterial supply, as a result of cardiac
pathology (e.g., cardiac arrest, myocardial in
farction, cardiomyopathy), infltrating malignan
cies, or sepsis, may cause liver failure.
b. Venous obstruction
(1) Veno-occlusive disease. Intrahepatic ob
struction of the hepatic venules may be asso
ciated with bone marrow transplantation,
chemotherapy, or oral contraceptive use.
(2) Inferior vena cva obstruction or hepatic vein
obstruction (i.e., Budd-Chiari syndrome) of
ten results from thrombosis associated with
a myeloproliferative disorder or hypercoagu
lable state or from direct tumor invasion.
4. Inherited metabolic disorders. Wilson's disease usu
ally presents in younger patients (20-40 years of age)
and may result in acute or chronic liver failure.
S. Miscellaneous causes
a. Pregnancy. Both acute fatty liver and the
HELLP (Hemolysis, Elevated Liver enzymes,
Low Platelets) syndrome may complicate preg
nancy.
b. Reye's syndrome. Children younger than 15
years may develop Reye's syndrome, which is
usually associated with viral illness and concomi
tant salicylate use.
Chronic liver failure
1. Infections, including viral hepatitis (primarily hepati
tis B and C), schistosomiasis, and toxoplasmosis
2. Drugs and toxins. Alcoholism accounts for almost
50% of all cases of chronic liver failure.
3. Vascular abnormalities (e.g., as a result of cardiac
failure, tumors, or venous obstruction)
4. Inherited metabolic disorders, including Wilson's
disease, hemochromatosis, at-antitrypsin defciency,
and glycogen storage disease
S. Miscellaneous causes
a. Primary biliary cirrhosis. Women between the
ages of 40 and 60 years are most often affected.
Pruritus, markedly elevated serum alkaline phos
phatase, and the presence of antimitochondrial
antibody are typical features (antimitochondrial
antibody is noted in 95% of cases).
196 Chaptr 33
b. Secondar biliary cirrhosis may result from
stones or strictures causing chronic hil iary trad
ohstruction.
c. Autoimmune hepatitis is most common in young
women. Patients may have other manifestations
of autoimmunity; antinuclear and anti-smooth
muscle antihodies are found in 20%-40% and
60%-80% of patients, respectively.
A. Patient history. A thorough history is critical if a drug
or toxin exposure is thought to he the cause of the liver
failure. Vascular disorders may also he suggested hy the
history (e.g., right upper quadrant pain may imply Budd
Chiari syndrome; weight loss may suggest an intra-ah
dominal malignancy).
B. Laboratory tests
1. General tests. The following tests are usually per
formed to evaluate liver function and screen for asso
ciated metaholic or hematologic derangements and
complications (e.g., bleeding, infection, or renal
failure ).
a. Complete blood count (CBC) with differential
and platelets
b. Electrolyte panel with blood urea nitrogen
(BUN), creatinine, and glucose levels
c. Evaluation of PT and PT
d. Liver tests [i.e., aspartate aminotransferase
(AST), alanine aminotransferase (ALT), alka
line phosphatase, total bilirubin J
2. Specifc tests can be used to help determine the eti
ology.
a. Hepatitis serologies, induding hepatitis A and C
antibodies, HBsAg, and hepatitis B surface and
core antibodies are often ordered.
b. Acetaminophen level. An acetaminophen level
should be obtained in all patients with signs of
acute liver failure. A salicylate level and toxicol
ogy screen are also commonly performed.
c. Serum ceruloplasmin. Wilson's disease should
be considered in patients younger than 50 years
of age with acute or chronic liver failure. A low
serum ceruloplasmin level is a sign of Wilson's
disease; other findings include a high urinary cop-
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liver Fail ure 197
per level or the presence of Kayser-Fleischer
rings on slit-lamp examination.
d. Transferrin saturation and ferritin levels are high
in patients with hemochromatosis, a cause of
chronic liver failure.
e. at-Antitrypsin level. Defciency may result in
chronic liver failure.
f. Antibody tests. Antinuclear, anti-smooth mus
cle, and antimitochondrial antibodies may be
sent to evaluate the possibility of autoimmune
hepatitis or primary biliary cirrhosis.
C. Liver biopsy or imaging studies may be performed when
the diagosis is still in question.
TREATMENT
A. Identify and treat any treatable causes.
1. Acute liver failure
a. Acetaminophen overdose can be treated with
acetyicysteine. Early treatment is desirable, and
empiric therapy may be indicated when a toxic
dose is suspected. Patients may beneft even
when the ingestion occurred as many as 36 hours
prior to therapy.
b. Mushroom poisoning may be treated with peni
cillin, silybin, or both.
c. Pregnancy-related liver failure is often resolved
by delivering the baby.
2. Chronic liver failure. Regardless of the etiology,
chronic liver failure is usually not reversible. If ad
ministered early in the course of the disease, how
ever, specifc treatments may prevent the progression
to chronic liver failure. For example:
a. Hemochromatosis may be treated with phlebot
omy l deferoxamine chelation therapy.
b. Wilson's disease may be treated with penicilla
mine chelation therapy.
c. Autoimmune hepatitis is extremely sensitive to
steroid therapy.
d. Chronic hepatitis B or C may be treated with
interferon-a.
B. Prevent or treat complications.
1. Infections, such as spontaneous bacterial peritonitis
(SBP), must be aggressively treated. A third-genera
tion cephalosporin is often the initial therapy and is
administered for at least 5 days. The combination
198 Chapter 33
of ampicillin and gentamicin is often used to treat
possible entcrococcal infection in extremely ill pa
tients or patients who do not respond to the initial
therapy. Following therapy, norfoxacin may be used
to decrease the rate of recurrent spontaneous bacte
rial peritonitis.
2. Hemorrhage
a. Patients who are not actively bleeding are usually
administered vitamin K subcutaneously in case
vitamin defciency is partially responsible for
the coagulopathy.
b. Fresh frozen plasma and blood products may be
required for patients with active bleeding (see
Chapter 60 IV B).
3. Bleeding esophageal varices
a. Treatment
(1) Pharmacologic treatment involves the intra
venous administration of octreotide or vaso
pressin plus nitroglycerin.
(2) Injection sclerotherapy and band ligation are
effective procedures but may not be techni
cally feasible in all patients.
(3) Transjugular intrahepatic portosystemic
.
shunting (TIPS) or surgical shunting may be
used for refractory bleeding.
b. Prophylaxis. Propranolol (20-80 mg orally twice
daily) is often given to patients who are stable
after a variceal bleed (usually days later) and to
those with very large varices.
4. Ascites and edema are often treated with a sodium
restricted diet and diuretics.
a. Spironolactone. The initial dose is often 50 mg
orally twice daily; this amount is increased by
]0 mglday every few days while following the
serum and urine electrolytes. Reversal of the nor
mal urinary sodium and potassium concentra
tions (i.e., urinary sodium exceeds urinary po
tassium) indicates an aldosterone antagonist
effect, and should prompt frequent evaluations
for hyperkalemia.
b. Furosemide may also be added to the regimen to
increase diuresis. Cardul monitoring of volume
status and electrolytes is always required.
c. Large-volume paracentesis is often necessary for
patients with massive ascites who are refractory
to medical therapy or symptomatic. Intravenous
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liver Failure 199
albumin is often given just before large-volume
paracentesis is performed to maintain the intra
vascular volume (especially in patients without
peripheral edema).
d. TIPS is being increasingly used for patients with
refractory ascites.
5. Hepatic encephalopathy may be precipitated by in
fections, overly aggressive diuresis, electrolyte ab
normalities, gastrointestinal bleeding, or drugs (e.g.,
sedative-hypnotics, narcotics). Management usually
involves treating precipitating factors and the admin
istration of lactulose (often 30 ml orally three times
daily or by nasogastric tube, titrated to maintain two
loose stools per day). Cerebral edema is often present
in patients with high-grade encephalopathy and may
be treated with mannitol (usually 0.3-0.4 g/kg body
weight). Head-up tilting, steroids, and hyperventila
tion are ineffective in patients with acute liver failure.
Pentobarbital may be used to lower intracranial pres
sure, but may also lower cerebral perfusion pressure
by decreasing the systemic blood pressure.
HOT
Intracerebral hemorrhage is always a possibilily in
patients with coagulopathy and altered mental status
and may requi re further evaluation [e.g., with com
puted tomography (CT)].
K EY
C.
6. Hepatorenal syndrome. No therapy has been shown
to have a consistent beneft; renal vasodilators. in
cluding low-dose dopamine and calcium channel
blockers, are still sometimes tried.
7. Metabolic derangements
a. Hypoglycemia may require the intravenous ad
ministration of a 10% glucose solution.
b. Hypokalemia and hypophosphatemia may re
quire electrolyte replacement.
c. Hyponatremia may require free water restric-
tion.
Consider the appropriateness of liver transplantation.
Liver transplantation may be performed in patients with
acute or chronic liver failure.
200 Chaptr 33
1. In the acute setting, liver transplantation is usually
indicated when a variety of prognostic factors (e.g.,
PT, grade of encephalopathy, etiology) suggest a
poor chance of survival without it. Because safe
transport to a specialized facility is easier when pa
tients have low-grade encephalopathy, a liver trans
plant should be considered as soon as possible follow
ing a diagnosis of acute liver failure.
2. The 5-year survival rate after liver transplantation
may be as high as 60%-80%.
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PART V
Renal/Acid-Base
,aHHblJ CKaH npe,lH03Ha'eH lJWb ,lR :
MCA ST pOHT.PY
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34. Oeriew of Nephrology
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Q
INTRODUCTION
A. In nephrology, there are many syndromes, each with a
set of diseases capable of causing it. Often, specifc dis
eases are capable of causing more than one syndrome.
B. Know the clinical manifestations and lab data that corre
spond to each renal syndrome and then think of the
diseases that could cause that syndrome. The differential
diagnoses for most of the renal syndromes are easy to
remember; just match the diagnosis with the patient's
complaints and data and you're set.
RENAL SYNDROMES. The renal syndromes are discussed
in more detail in Chapters 35-38. Table 34-1 provides an
overview.
203
204
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Chapter 34
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35.Acute Renal Failure
@
INTRODUCTION
A. Defnition. Acute renal failure is defned as a rapid de
crease in renal function that results in inappropriate ni
trogen waste accumulation (azotemia). Because nitrogen
accumulation is initially asymptomatic, the diagnosis is
commonly made when the serum creatinine level rises
abruptly (i.e., by 0.5 mg/dl or more) during a 24-hour
period.
HOT
Although serum creatinine i s almost solely filtered and
therefore provides a good estimate of the glomerular
filtration rote (GFR), it i s actually slightly secreted. Some
drugs (e.g., cimeti dine) con block this secreti on, raise
the serum creati nine, and couse an underestimation
of the actual GFR and, therefore, renal function.
K EY
Q
B. Epidemiology. Approximately 5% of all hospitalized pa
tients are diagnosed with acute renal failure; the inci
dence can be as high as 20% in the intensive care unit
(lCU).
C. Clinical manifestations. Symptoms of acute renal failure
usually are present when the blood urea nitrogen (BUN)
exceeds 100 mg/dl, but may occur at lesser values. Clinical
manifestations include cardiovascular complications
(e.g., arrhythmias, volume overload, pericarditis), neuro
logic abnormalities (e.g .. altered mental status, seizures).
or gastrointestinal complications (e.g., bleeding, nau
sea, vomiting).
CAUSES OF ACUTE RENAL FAILURE. The causes of acute
renal failure can be conveniently classifed as prerenal, renal,
or postrenal (Figure 35-1).
A. Prerenal causes account for most of the cases of acute
renal failure. Prerenal is actually preglomerular. Any
disease state that results in a decrease in blood fow
to the glomerulus will result in decreased glomerular
205
206
Acute renal failure
Glomerular
Tubular
Interstitial
Vascular
Chapter 35
FIGUR 35-1. The causes of acute renal failure can be categorized as
prerenal, renal, or postrenal.
fltration and. consequently, an elevated serum creati
nine level. One way to remember the prerenal causes of
acute renal failure is to begin with the flling of the left
ventricle and work your way distally toward the glo
merulus.
1. Decreased flling of the left ventricle results in de
creased cardiac output and, therefore, decreased fow
to the glomerulus. Hypovolemia is the most common
cause, but right ventricular failure and mitral stenosis
can also result in poor left ventricular flling and
subsequent pre renal azotemia.
2. Decreased lef ventricular function results in de
creased cardiac output even with normal or elevated
left ventricular flling.
3. Aortic stenosis. Even with normal left ventricular
flling and function. critical aortic stenosis can block
forward fow to the kidney.
4. Renal artery stenosis from fbromuscular dysplasia
or atherosclerotic disease decreases fow to the glo
merulus. (Fibromuscular dysplasia leading to renal
artery stenosis is most often seen in young women.)
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Acute Renal Failure
207
5. Narrowing of the aferent arteriole from vasocon
striction, infammation, or thrombosis can result in
pre renal azotemia.
a. Sepsis can lead to constriction of the afferent
arteriole via infammatory mediators.
b. Nonsteroidal anti-infammatory drugs (NSAIDs)
can lead to narrowing of the afferent arteriole by
inhibiting prostaglandins. which normally dilate
the vessel.
c. Contrast dye can also lead to constriction of the
afferent arteriole and cause a prerenal picture.
d. Microangiopathic hemolytic anemias (see Chap
ter 56) are rare causes of a prerenal azotemia.
e. Hepatorenal syndrome, through unclear mecha
nisms, shunts blood away from the afferent arte
riole, causing prerenal azotemia.
B. Postrenal causes account for approximately 10% of all
cases of acute renal failure. Because one kidney can
adequately compensate for the other, renal failure will
only occur if both kidneys are not functioning properly.
C.
1. Bladder neck obstruction is the most common post
renal cause of acute renal failure. Common causes
of bladder neck obstruction include:
a. Prostatic hypertrophy or malignancy
b. Neurologic disorders (e.g., neuropathy)
c. Anticholinergic medications
2. Ureteral obstruction
a. Unilateral ureteral obstruction (e.g., from stones,
blood clots, or pus) can result in acute renal fail
ure in a patient with only one kidney.
b. Bilateral ureteral obstruction may result from
retroperitoneal fbrosis, malignancy, or lymph
adenopathy.
Renal causes. Think of the causes in terms of the compo
nents of a kidney (i.e., glomeruli, tubules, interstitium,
vessels).
1. Acute glomerulonephritis affects the glomeruli. The
many causes of acute glomerulonephritis are dis
cussed in Chapter 37 II.
2 Acute tubular necrosis (ATN) affects the tubules.
a. Shock from all causes, but particularly septic
shock, can lead to AT.
b. Contrast dye agents used for radiographic studies
are toxic to the tubules. but usually only result
in renal failure in patients with underlying renal
disease (e.g., diabetics).
208
Chapter 35
c. Endogenous pigments (e.g., myoglobin, hemo
globin), crystals, and proteins. Myoglobinuria
(from rhabdomyolysis) or hemoglobinuria (from
intravascular hemolysis). uric acid deposition
(from tumor lysis), and Bence Jones proteins
(from multiple myeloma) can all cause tubule
injury and result in ATN.
d. Medications (e.g., aminoglycosides) and toxins
(e.g., heavy metals) can be directly nephrotoxic.
e. Surgery or trauma. Ischemic injury (as a result
of hypotension), tissue destruction (from myo
globin), or a combination of the two can lead
to ATN.
HOT
The most common causes of ATN are sepsis, contrast
dye agents, and nephrotoxic drugs.
K EY
3. Acute interstitial nephritis affects the interstitium.

Medications (e.g., {-lactam antibiotics, sulfa antibi
otics. furosemide, thiazide diuretics, NSAIDs) are
the most common causes of acute interstitial ne
phritis.
4. Vasculitis and microangiopathic hemolytic anemias
affect the blood vessels (see Chapters 56 and 70).
Do not be confused by the fact that many of the
vasculitides are listed as causes of glomerulonephritis
(i.e., infammation of the glomerulus)-because the
glomerulus contains a capillary bed, vasculitis can
result in glomerulonephritis.
ApPROACH TO THE PATIENT. Using data gleaned from
the patient history, physical examination, and basic labora
tory tests and procedures, you can classify the cause as pri
marily prerenal, postrenal, or renal.
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Acute Renal Failure 209
HOT
The same di sorder may cause more than one type of
acute renal failure.
K EY
A. Obtain a patient history.
L. Prerenal. A history of congestive heart failure (CHF)
or of new or increased use of diuretics or NSAIDs
often signifes a prerenal etiology.
B.
2. Postrenal. A history of benign prostatic hypertrophy,
kidney stones, nephrectomy, or a retroperitoneal ma
lignancy may alert you to postrenal causes.
3. Renal
a. Glomerulonephritis. The causes of glomerulone
phritis can help guide your questions regarding
relevant symptoms. For example, a recent sore
throat or skin infection may suggest poststrepto
coccal glomerulonephritis.
b. ATN or acute interstitial nephritis. The medica
tion history (including use of over-the-counter
NSAIDs) may suggest a tubular or interstitial eti
ology.
c. Vasculitis. Ask about rashes. arthralgias. and fe-
vers (see Chapter 70).
Perform a physical examination. Always assess the vital
signs, including oxygen saturation and urine output.
l. Blood pressure. Hypotension often denotes a prere
nal cause; additional evaluation and treatment are
aimed at the underlying etiology.
2. Temperature. High or low temperatures often indi
cate sepsis (although interstitial nephritis or vasculi
tis may also be associated with temperature abnor
malities).
3. Oxygen saturation. Hypoxia may signal impending
pulmonary edema (e.g .. from renal failure with vol
ume overload).
4. Urine output measurements will help you classify
the renal failure as oliguric 400 ml/day) or nonoli
guric (> 400 ml/day). Nonoliguric renal failure is
associated with lower mortality and dialysis rates. In
210
Chapler 35
patients with ATN, nonoliguric renal failure often
follows oliguric failure. heralding the return of re
nal function.
5. Heart and lung examination. A complete physical
examination is important, with special attention
given to the heart and lungs. Heart and lung examina
tion may provide information about the cause of the
acute renal failure (e.g., critical aortic stenosis, severe
left ventricular dysfunction) and also permits assess
ment of some of the consequences of the renal failure
(e.g., volume overload, pericarditis).
6. Auscultation. Renal bruits may indicate renal ar
tery obstruction.
7. Palpation. Increased bladder size and tenderess of
ten signify postrenal obstruction.
C. Rule out obstruction.
1. Postvoid residual (PVR). A PVR is often performed
before laboratory tests because if obstruction is the
cause, a diagnosis can be made quickly and an exten
sive workup is avoided. This procedure is especially
useful in older men, in whom obstruction from be
nign prostatic hypertrophy is not uncommon. The
PVR is measured by catheterization after the patient
has "emptied" his bladder.
a. If the PVR is greater than 200-250 ml, obstruc
tion is diagnosed and a Foley catheter should be
left in place.
b. If the patient already has an indwelling catheter,
make sure to fush the catheter to evaluate ob
struction by pus or blood clots.
2. Ultrasound. The PVR does not help you evaluate
the upper urinary tract. In patients with one kidney
or suspected bilateral obstruction, renal ultrasound
should be performed early in the workup.
o. Perform laboratory stndies to help determine the diagno
sis and the consequences of the renal failure.
t. Complete blood count (CBC) with platelets. The
white blood cell (WBC) count helps assess the possi
bility of infection or interstitial nephritis. Anemia
may indicate more chronic renal failure or bleeding
from uremia.
2. Electrolyte panel (including Na+, K, Cl-, HCOI,
Ca
2
+, P04, Mg
2
+, and glucose). Common electrolyte
or metabolic derangements include hyponatremia,
hyperkalemia, hypocalcemia, hyperphosphatemia,
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Acute Renal Failure
211
and hypermagnesemia, and a mixed anion and non
anion gap acidosis.
3. Blood urea nitrogen:creatinine (BUN:Cr) ratio. A
normal BUN: Cr ratio is 10. In prerenal states, urea
gets reabsorbed from the tubules while creatinine
does not; therefore, a BUN: Cr ratio higher than
10 (and certainly one greater than 20) supports a
pre renal diagnosis.
4. Urinalysis. A urinalysis is an essential part of the
evaluation because an active urinary sediment im
plies an intraparenchymal cause of renal failure.
a. Red blood ceU (RBC) casts or dysmorphic red
ceUs often imply glomerulonephritis or vasculitis.
b. WBC casts are usually a sign of infection (i.e . .
pyelonephritis) or infD ation (i.e., intersti
tial nephritis).
c. Tubular casts or "muddy" granular casts may
signify AT.
5. Urine electrolytes are also a very useful diagnostic
test i patients with acute renal failure.
a. Urnary sodium and chloride can be used to help
delineate a prerenal cause from an intrarenal
one. Values less than 20 mEq/L imply a prerenal
etiology; values lower than 10 mEq/L are even
more specifc.
(1) It is worth noting that early obstruction can
also result in a low urine sodium or chlo
ride level.
(2) With a concomitant metabolic alkalosis. the
urinary chloride is a better indicator of a pre
renal state because sodium may be excreted
with bicarbonate to maintain electroneu
trality. In this situation, the urinmy sodium
may be falsely increased, although prerenal
physiology is present.
b. Fractional excretion of sodium (FENa). FENa
is another way of diagnosing prerenal physiology,
and can also help you evaluate tubulointerstitial
dysfunction. To calculate the FENa. remember
"UP . . . UP" with "sodium over creatinine":
FENa ~
Urine Na /Plasma Na'
? 100%
Urine Cr /Plasma Cr
Normal values are between 1% and 3%.
21 2 Chapter 35
(1) A value less than 1 % signifes prerenal physi
ology, whereas one greater than 3% indicates
tubulointerstitial disease (because there is a
defect in sodium resorption).
(2) A normal value provides no evidence of these
entities, but does not rule them out either
(i.e., there may be mixed disorder).
6. Creatine kinase. Evaluation of the creatine kinase
level is helpful if the urine dipstick is positive for
blood, but no or few RBCs are noted microscopically.
This implies that urinary myoglobin (from rhabdo
myolysis) or hemoglobin (from intravascular hemo
lysis) is present. Evaluate the possibility of rhabdo
myolysis frst; then consider working up intravascular
hemolysis. Creatine kinase levels greater than 6000
I U (and often more than 15,000 I U) are usually
needed to cause tubular necrosis; however, creatine
kinase levels may be normal if the rhabdomyolysis
and ATN occurred a few days prior to the workup.
7. Ancillary tests. If glomerulonephritis or vasculitis is
suspected or diagnosed, additional tests need to be
ordered (see Chapters 37 and 70). Liver function tests
are ordered when the hepatorenal syndrome is sus
pected, but the clinical diagnosis is usually obvious.
E. Perform additional diagnostic studies if the diagnosis
remains unclear.
1. Renal ultrasound. In addition to ruling out obstruc
tion, renal ultrasound helps to distinguish acute from
chronic renal failure.
a. The kidneys are usually normal in size in patients
with acute renal failure.
b. They are usually small in patients with chronic
renal failure. It is easy to remember the chronic
diseases that lead to enlarged kidneys because
the SHAPE is large:
Chronic Diseases that Lead to Enlarged
Kidneys ("SHAPE")
Scleroderma
HIV nephropathy
Amyloidosis
Polycystic kidney disease
Endocri nopathy (diabetes)
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Acute Renal Failure
21 3
2. Renal biopsy is usually unnecessary but is indicated
for unresolving acute renal failure of unknown eti
ology.
TREATMENT
A. Disease-specifc
1. PrerenaI causes
HOT
K EY
2.
a. Fluids are usually indicated because hypovo
lemia is the predominant pre renal cause of acute
renal failure.
Remember -If the cause of the acute renol failure is
cardiac in origin (e.g., CHF, critical aortic stenOSis),
giving fluids may not be appropriate. Consider these
possibilities before giving fluids!
(1) Administration of small, defned boluses
(e.g., 250 ml) can prevent volume overload.
(2) Re-evaluate the patient frequently. The goal
urine output is at least 30 mllhour. Boluses
can be continued with that goal in mind as
long as the oxygen saturation is maintained
and the lungs remain clear (i.e., there is no
evidence of pulmonary edema).
b. Other treatments tailored to the specifc etiology
may also be necessary (e.g., discontinuing medi
cations, administering antibiotics for sepsis).
Postrenal causes
a. Catheterization. A Foley catheter should be
placed. if one has not been placed already.
(1) Clamp the catheter if more than 750 cc drains
acutely to prevent the patient from becoming
hypotensive. I f. after 30 minutes, no hypoten
sion develops, you can allow more drainage.
while monitoring the blood pressure.
(2) Observe for postobstructve diuresis. If the
blockage has been present for a few days,
a postobstructive diuresis often ensues. This
may result from urea accumulation with an
osmotic diuresis as well as salt accumulation
214 Chapter 35
with a physiologic diuresis. Although postob
structive diuresis is partly a physiologic phe
nomenon, transient tubular dysfunction can
contribute to severe volume depletion unless
fuids are replaced.
(a) Fluid replacement. It is customary to give
back approximately two-thirds of the uri
nary losses with half normal saline. Giv
ing normal saline will only exacerbate the
problem by adding to the salt overload.
(b) Electrolyte replacement. Depletion of
electrolytes, particularly potassium and
magnesium, occurs frequently in postob
structive diureses.
b. Percutaneous drainage through a percutaneous
nephrostomy tube may be needed in cases of
upper tract obstruction.
3. Renal causes are treated based on the specifc pathol
ogy, but there are general treatments that are com
mon to all.
a. General measures
(1) Fluid restriction. Fluids may need to be re
stricted to 1 Uday. Volume status should be
monitored using daily weights and input/out
put measurements.
(2) Diet. The diet should be low salt. low po
tassium, and low protein.
(3) Adjust medication dosages. The dosages of
medications that are excreted renally should
be adjusted. Magnesium-containing antacids
should be avoided.
b. Specifc measures
(1) Glomerulonephritis. Treatment is discussed
in Chapter 37.
(2) ATN
(a) Fluids may help prevent oliguric renal
failure (by "washing out" tubular casts
that may precipitate in the nephron) and
may also dilute the effects of certain tox
ins (i.e., myoglobin, contrast dye).
(b) Furosemide in high doses is sometimes
successful in converting oliguric to non
oliguric renal failure; however, main
taining volume status and appropriate re
nal blood fow is critical and the patient
should never be "on the dry side."
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Acute Renal Failure
215
(c) Mannitol is an antioxidant and osmotic
diuretic that is sometimes used to convert
oliguric to nonoliguric renal failure. It
may precipitate CHF, however, and
should be avoided in susceptible pa
tients.
(3) Acute interstitial nephritis is usually treated
by discontinuing ofending medications and
administering fuids as tolerated.
(4) Vasculitis. Treatment is discussed in Chap
ter 70.
B. Acute dialysis. The following indications are usually ap
plicable regardless of the cause of the renal failure.
Indications for Acute Dialysis ("AEIOU")
Acidosis
Electrolytes (e.g., hyperkalemia)
Intoxication
Overload
Uremia
1. Acidosis. Dialysis is usually necessary when the pa
tient is experiencing complications of a metabolic
acidosis (e.g., arrhythmias, left ventricular dysfunc
tion) or if the serum pH starts to fall below 7.2.
Sodium bicarbonate is sometimes used as a temporiz-
ing measure until dialysis can be initiated.
2.
3.
4.
Severe, refractory hyperkalemia (usually >6.5-7
mEq/L) or hyperkalemia with persistent electrocar
diogram (EKG) changes is an indication for acute
dialysis. Albuterol nebulizers or the administration
of intravenous calcium_ sodium bicarbonate or insu
lin and glucose are sometimes used as teporizing
measures. Sodium polystyrene sulfonate can also be
given orally or rectally to decrease potassium levels
over several hours.
Intoxication. Dialysis may be necessary when acute
renal failure results from a dialyzable, toxic ingestion
(e.g., salicylates, ethylene glycol).
Overload. Volume overload that is refractory to di
uretics is an indication for dialysis. Temporizing mea
sures include nitrates and furosemide (which cause
21 6 Chapter 35
venodilation and may therefore decrease pulmo
nary edema).
5. Uremia. Altered mental status, seizures, pericarditis,
intractable nausea and vomiting, and uncontrolled
bleeding from platelet dysfunction are all indications
for acute dialysis.
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36. Nephrotic Syndrome
@
INTRODUCTION
A. Pathophysiologic mechanism. Nephrotic syndrome re
sults from increased glomerular permeability to serum
proteins.
B. Clinical manifestations of nephrotic syndrome. Onset
is insidious and renal function may be normaL Gross
hematuria and red blood cell (RBe) casts occur infre
quently. Clinical fndings include proteinuria, low serum
albumin. hyperlipidemia, and edema.
Characteristics of the Nephrotic Syndrome
("PALE")
Protei nuria (> 3. 5 grams/24 hours)
Albumin (low)
Lipids (elevated)
Edema
Q
CAUSES OF NEPHROTIC SYNDROME
A.
B.
Primary renal disease. Nephrotic syndrome is caused by
primary renal disease in two-thirds of patients. Primary
glomerular diseases associated with nephrotic syndrome
in adults include:
1. Membranous nephropathy
2. Minimal change disease
3. Focal glomerulosclerosis
4. Membranoproliferative glomerulonephritis
5. Rapidly progressive glomerulonephritis (as well as
other types)
Secondary causes. Nephrotic syndrome occurs secondary
to a systemic disease in the remainder of patients.
Though there is a long list of possible secondary causes,
most can be remembered easily using the mnemonic,
"THIS LAD HAS nephrotic syndrome."
21 7
21 8
Chapter 36
Secondary Causes of Nephrotic Syndrome
Tumors
L A D H A S
nephrotic syndrome
Heroin, Heavy metals, and toxi ns
Infection
Hepatitis B and C
AIDS
Subacute bacterial endocarditis, Syphilis,
Schistosomiasis
Systemic di sorders
Lupus
Amyloid
Diabetes
1. Tumors. Many cancers can cause nephrotic syn
drome. In elderly patients with unexplained ne
phrotic syndrome, an underlying malignancy is a real
concern. Both hematologic malignancies (e.g.,
lymphoma, leukemia) and solid tumors can cause
nephrotic syndrome.
2. Heroin, heavy metals, and toxins. "Street" heroin,
organic gold, mercury, antivenin, antitoxins, and con
trast media can cause nephrotic syndrome.
3. Infections. There are many infections that can cause
nephrotic syndrome; some important ones are hepa
titis B and C, AIDS. subacute bacterial endocrditis,
syphilis, and schistosomiasis.
4. Systemic disorders. Major causes of nephrotic syn
drome include systemic lupus erythematosus (SLE),
amyloid, and diabetes.
APPROACH TO THE PATIENT. Once it has been deter
mined that a patient has nephrotic syndrome, the search for
the underlying cause begins. Depending on the suspected
cause, the following laboratory tests and procedures can
be useful:
A. Electrolyte panel, including blood urea nitrogen (BUN),
creatinine, and glucose values
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Nephrotic Syndrome
21 9
B. Antinnclear antibody (ANA) assays
C. Hepatitis serologies
D. Rapid plasma reagin (RPR) or Venereal Disease
Research Laboratory (VDRL) test for syphilis
E. mV test
F. Fat pad or rectal biopsy (to look for amyloidosis)
G. Blood cultures (to rule out endocarditis)
H. Renal biopsy
TREATMENT focuses on the underlying disorder. General
management strategies include:
A. A diet low in sodium and saturated fat
B. Adequate protein intake (approximately 1 glkglday)
C. Diuretics for edema and hypertension
D. Fluid restriction (if hyponatremia is present)
COMPUCATIONS
A. Infections. Patients with nephrotic syndrome are prone
to peritonitis, sepsis. and cellulitis.
B. Thrombosis (both arterial and venous) can occur.
C. Hypovolemia may be a consequence of overdiuresis.
D. Wasting results from protein depletion.
E. Atherosclerosis may result from hyperlipidemia.
37. Nephritic Syndrome
@
Q
CLINICAL MANIFESTATIONS OF ACUTE NEPHRITIC
SYNDROME (ACUTE GLOMERULONEPHRITIS) . Acute ne
phritic syndrome is characterized by the sudden onset of
hematuria, proteinuria (usually <3 g/24 hours), rising creati
nine levels. and salt retention. (Compare with the clinical
manifestations of nephrotic syndrome, described in Chapter
36 I B. )
A. The presence of red blood cell (RBC) casts or dysmor
phic RBC is usually diagnostic. White blood cells
(WBCs) or WBe casts may also appear in the urine.
B. The bematuria may be microscopic, but it is often macro
scopic (patients complain of dark or "smoky" urine).
C. The edema usually appears initially in areas of low tissue
pressure (e.g., the periorbital region), but may progress
to pleural effusions and ascites.
D. Hypertension results from salt and water retention.
CAUSES OF ACUTE NEPHRITIC SYNDROME
A. Hypocomplementemic acute nephritic syndrome. Acti
vation of the complement system by immune complexes
is the cause of low complement (C3) levels.
1. Systemic diseases
a: Systemic lupus erythematosus (SLE). Comple
ment levels are decreased in 75%-90% of patients
with SLE. Usually other manifestations of lupus
are present as well.
b. Subacute bacterial endocarditis. More than 90%
of patents have low complement levels. Blood
cultures confrm the diagnosis.
c. "Shunt" nephritis is usually caused by infection
of a ventriculoperitoneal shunt used to relieve
hydrocephalus. As with bacterial endocarditis.
sustained bacteremia is the cause of the nephritis.
d. Cryoglobulinemia. Complement levels are de
creased in 85% of these patients. Serum cryoglo
bulin levels are easily available and will confrm
this diagnosis.
2. Renal causes
a. Poststreptococcal glomerulonephritis is the pro-
220
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Nephritic Syndrome 221
totype for acute glomerulonephritis. Nephritis
usually occurs 1-2 weeks after a pharyngeal or
cutaneous infection with a group A (J-hemo
lytic) streptococcus. Ninety percent of patients
recover fully.
b. Membranoproliferative glomerulonephritis
(MPGN) is a disease of children and young
adults.
(1) It can be classifed as type I (the most com
mon type) or type II (which has a higher
incidence of hypocomplementemia).
(2) MPGN can also present as the nephrotic syn
drome and has a variable clinical course.
Causes of Hypocomplementemic Acute Ne
phritic Syndrome ("She Sow Solly Cook Poi
soned Macaroni")
SLE
Subacute bacterial endocarditis
Shunt nephritis
Cryoglobulinemia
Postslreptococcal glomerulonephritis
MPGN
B. Normocomplementemic acute nephritic syndrome
1. Systemic diseases
a. Vasculitis syndromes (see Chapter 70). Polyarte
ritis nodosa, hypersensitivity vasculitis (including
Henoch-Schonlein purpura), and Wegener's
granulomatosis can cause acute glomerulone
phritis.
b. Goodpasture's syndrome is characterized by pul
monary hemorrhage and acute glomerulonephri
tis. It is caused by serum antibodies that react
with glomerular and alveolar basement mem
branes.
2. Renal diseases
a. IgA nephropathy (Berger's disease), the most
common primary glomerular disease in the
United States, is considered a monosymptomatic
form of Henoch-Schonlein purpura.
(1) IgA nephropathy presents as gross hematuria
(lasting 2-6 days) that often follows an upper
respiratory tract or gastrointestinal infection.
222 Chapter 37
(2) Progression to renal failure occurs in l5% of
patients within 6 months. and in up to 50%
within 20 years.
b. Rapidly progressive glomerulonephritis (RPGN)
is the term applied to any glomerulopathy that
is characterized by the combination of a rapid
decline in renal function (due to acute glomerulo
nephritis) and extensive crescent formation in
multiple glomeruli.
(1) RPGN may occur secondary to systemic dis
eases or may occur alone as a primary dis
order.
(2) Primary RPGN affects older individuals (the
average age is 60 years) and often has a pro
drome that resembles a viral illness. Diagno
sis is based on a characteristic renal biopsy.
(3) The prognosis is quite poor.
A. Make the diagnosis. The most important aspect of mak
ing the diagnosis of acute glomerulonephritis (after tak
ing the history and performing a physical examination)
is to personally examine a fleshly voided urine specimen,
preferably before attending rounds! A 24hour urine col
lection for creatinine (to calculate creatinine clearance)
and protein (to assess for the nephrotic syndrome) is
also important.
HOT
K E Y
The best way to increase the chance of finding RBC
costs i s to obtai n on early morning specimen after the
patient has placed a pillow behind the lumbar spine
a few mi nutes after waking up.
B. Categorize and stage the glomerulonephritis. Once the
diagnosis is made. the search for the underlying cause
begins.
L Laboratory studies. The serum complement (C3)
level allows classifcation of the glomerulonephritis
as hypocomplementemic or normocomplementemic.
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Nephritic Syndrome 223
Other tests that may be useful, depending on the
clinical setting, include anti-streptolysin 0 (ASO).
antinuclear antibody (ANA), anti-glomerular base
ment membrane (anti-GBM) antibody, antineutro
phil cytoplasm antibody (ANCA) titers, serum
cryoglobulin, blood cultures, and erythrocyte sedi
mentation rate (ESR).
2. Renal biopsy is the defnitive procedure for diagnos
ing acute glomerulonephritis.
TREATMENT
A. Infammatory renal disorders should be treated with ste
roids and cytotoxic agents. If the glomerulonephritis is
secondary to a systemic disease, the primary disorder
should be treated as well.
B. Indications for hemodialysis are given in Chapter 35
IV B.
C. The patient's electrolyte status [including blood urea
nitrogen (BUN) and creatinine levels], volume status,
and blood pressure should be monitored frequently. Hy
pertension should be treated.
38. Renal Tubular Defects
@
INTRODUCTION
A. The various diseases, congenital and acquired, that cause
renal tubular defects have one thing in common: they
tend to affect the tubules to a greater extent than the glo
meruli.
B. Defects may be anatomic or physiologic.
L Diseases that cause anatomic defects are usually he
reditary and include polycystic renal disease, medul
lary sponge kidney, and medullary cystic disease.
Anatomic defects can be diagnosed by intravenous
pyelography (or sometimes ultrasound).
2. Diseases that cause physiologic defects in tubular
transport usually present as polyuria, electrolyte im
balance, or a non-gap metabolic acidosis. This chap
ter focuses on the most confusing aspect of physio
logic tubular defects. renal tubular acidosis.
Q
RENAL TUBULAR AOOOSIS
A. Defnition. Renal tubular acidosis results from a net de
crease in tubular hydrogen secretion or bicarbonate re
absorption, causing a non-gap metabolic acidosis.
B. Classifcation. Most patients with a non-gap metabolic
acidosis who do not have diarrhea will have one of the
three types of renal tubular acidosis (Table 38-1).
1. Type 1 renal tubular acidosis occurs as a result of
defective hydrogen ion secretion; therefore, urinary
pH will be elevated.
2. Type 2 renal tubular acidosis occurs as a result of
decreased bicarbonate reabsorption. Initially. the
urinary pH will be elevated because of bicarbonate
loss; with continued bicarbonate loss, however, the
serum bicarbonate and, thus, the urine bicarbonate
concentrations will decrease and urinary pH will
fall.
224
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Renal Tubular Defects
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226
Serum potassium
Elevated
Low
Urinary pH
P 5.3
< 5.3
Uinar pH determination should
be performed immediately after
obtaining a urine specimen.
Chapter 38
8
8
FIGURE 38-1. Algorithm far determining the type of renol tubular aci
dosis.
3. Type 4 renal tubular acidosis is usually caused by
aldosterone defciency or resistance. Hyperkalemia
occurs for the same reason hyperaldosterone states
cause hypokalemic metabolic alkalosis.
C. Determining the type of renal tubular acidosis (Figure
38-1)
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39. Urinary T raet Infections (UTls)
@
Q
INTRODUCTION. Urinary tract infections (UTIs) are ex
tremely common, and include cystitis, pyelonephritis, and
urosepsis.
A. Etiology. Escherichia coli accounts for approximately
80% of all infections. Staphylococcus saprophyticus,
Klebsiella species, Prteus mirabilis, Enterococcus spe
cies, and other bacteria account for the rest.
B. Epidemiology
L Women are more susceptible than men to UTIs be
cause the female urethra is shorter, facilitating bacte
rial access to the bladder .
a. Sexual intercourse and the use of diaphragms
and spermicide are predisposing factors.
b. In postmenopausal women, estrogen defciency
may predispose patients to acute cystitis (from
increased colonization with E coli).
2. Uncircumcised men are at higher risk than circum
cised men.
CLINICAL MANIFESTATIONS OF UTls
A. Dysuria (i.e., pain or buring with urination) is usually
present and is commonly associated with other iritative
symptoms (i.e., urinary freqnency, Mgency, and noctu
ria). Although dysuria often indicates acute cystitis, it is
important to remember that other disorders may also
present with dysuria. There is a FUND of irritative symp
toms that may indicate the presence of a UTI:
Irritative Symptoms Suggestive of UTI
("FUND")
Frequency
Urgency
Nocturio
Dysuria
227
228
M
Chapter 39
B. Suprapubic or costovertebral angle pain or tenderness
is usually indicative of cystitis or pyelonephritis, respec
tively.
C. Fever usually indicates pyelonephritis. Hypotension and
altered mental status may herald urosepsis.
DIFFERENTIAL DIAGNOSES OF DYSURIA. Dysuria does
not always signal acute cystitis. It is especially important to
consider the alternative causes of dysuria in men. because
acute cystitis is less common in men than in women. Non
UTI causes of dysuria include the following:
A. Women
1. Infectious causes
a. Urethritis (e.g., from Neisseria gonorrhea, Chla
mydia trachomatis. or herpes simplex virus) may
also cause dysuria. Compared with the dysuria
of acute cystitis, the dysuria of urethritis usually
evolves gradually, is less severe. and is less often
accompanied by urinary frequency and urgency.
A history of vaginal discharge or a new sexual
partner also raises suspicion for urethritis.
b. Vaginitis (e.g., from Candida or Trichomonas)
usually presents with a malodorous vaginal dis
charge. The patient may also complain of dyspa
reunia.
2. Noninfectious causes
a. Interstitial cystitis presents with dysuria, urinary
leukocytes, and a negative urine culture.
b. Chemotherapy and pelvic irradiation may cause
symptoms that mimic UTI.
B. Men
1. Bladder pathology may result in dysuria in both men
and women, but the relative paucity of UTIs in men
increases the likelihood that some other diagnosis is
responsible. Both bladder stones and tumors should
be considered.
2. Prostate syndromes. With the exception of acute
bacterial prostatitis, which usually results in dysuria
that is accompanied by marked systemic toxicity.
prostate syndromes may be easily confused with cys
titis. Laboratory testing is usually needed to differen
tiate among these disorders (see V F).
3. Urethritis from gonorrhea or chlamydia is often asso
ciated with penile discharge.
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Urinary Tract Infections (UTls) 229
LBORATORY STUDIES. Not all of the following tests need
to be obtained in every patient. The indications for tests are
discussed in V.
A. Urine dipstick testing allows for the determination of
the urinary pH, leukocyte esterase, nitrite, blood, and
protein levels.
1. Urinary pH. An alkaline urine may indicate a urease
splitting organism (e.g., Proteus).
2. Leukocyte esterase usually indicates the presence of
infammatory cells [i.e., white blood cells (WBCs)],
and therefore, infection. The sensitivity may exceed
75%. False-positives may occur with urinary contami
nation.
3. Nitrite is detected when bacteria are present. The
sensitivity is relatively low, and false-positives are
noted with bacterial contamination.
4. Blood in the urine may indicate myoglobin, hemoglo
bin, or intact red blood cells (RBCs). Cystitis can
cause hematuria, but other causes of bladder pathol
ogy should also be considered.
5. Protein in the urine may indicate a glomerulopathy.
Large numbers of WBCs may lead to a falsely posi
tive protein determination.
B. Urine microscopic analysis. The presence of more than
5 leukocytes per high-power feld denotes pyuria, and
is indicative of some urinary tract abnormality. Gram
staining may also be performed, but is not a sensitive
test for UTI. Sterile pyuria (i.e .. pyuria with a negative
urine culture) may occur with contained bacterial infec
tions (renal abscesses), systemic bacterial infections (en
docarditis). nonbacterial infections (miliary tuberculo
sis), infammatory processes (interstitial nephritis), and
partially treated UTI.
C. Urine culture provides the gold standard for diagnosing
UTI. The presence of as few as 100 colonies may sig
nal infection.
D. Prostatic secretion analysis. Prostatic secretions may be
elicited through prostatic massage. In elderly men with
possible chronic prostatitis, a urinalysis with culture is
often sent before and after prostatic massage.
E. Urine pregnancy test. Because pregnant patients are of
ten treated with different antibiotics and with a longer
course of therapy, a urine pregnancy test should be ob
tained in all patients for whom pregnancy is a possibility.
F. Renal ultrasound. In patients who are systemically ill,
230 Chapter 39
and especially in those with a history of kidney stones
or a presentation compatible with urolithiasis, an ultra
sound may be obtained to rule out " pus under pressure"
(i.e., an infection behind an obstruction that mimics an
abscess).
A. Uncomplicated cystitis
1. Women. In women who present with the classic
symptoms of UTI without any evidence of pyelone
phritis (i.e., no systemic symptoms, such as fever.
costovertebral angle pain, or nausea), a urinary dip
stick is usually the only test that is required. If the
urinary dipstick is negative or the patient has pelvic
pain or abnormal vaginal discharge, a pelvic exami
nation and a urine culture are often indicated as well.
2. Men. A urine dipstick and culture is generally per
formed prior to therapy.
B. Uncomplicated pyelonephritis. Patients usually present
with irritative symptoms associated with fever, costover
tebral angle pain or tenderness, or both. The urinar
dipstick is usually positive, and a urine culture is usually
sent for defnitive diagnosis.
C. Recurrent cystitis (e.g., three or more episodes per year)
is more common in women than men. Prior to diagnosing
recurrent cystitis, rule out relapse.
1. Relapses typically occur early after the completion
of therapy, the same species and strain of organism
is isolated, and additional urologic evaluation is usu
ally necessary.
2. Recurrences typically occur later. a different organ
ism is usually isolated, and additional evaluation is
often unnecessary.
D. Complicated UTls may occur in men or women and are
often suspected in patients who relapse or do not im
prove with initial therapy. A complicated infection re
sults when a patient has an anatomic or functional abnor
mality of the urinary tract, or a resistant infection. A
urine culture is always recommended.
E. Asymptomatic bacteriuria. In most patients, screening
for asymptomatic bacteriuria is unnecessary. Exceptions
include the following.
1. Pregnant women often are screened and treated if
the bacteria count is 10,000 or more (to decrease the
risk of pyelonephritis).
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Urinary Tract Infections (UTls) 23 1
2. Patients undergoing urologic surgery also beneft
from screening.
F. Prostate syndromes. The presence of obstructive symp
toms (i.e., hesitancy, difficulty starting and stopping the
stream. decreased urinary fow) may favor a diagnosis
of chronic prostatitis or prostatodynia. Of note, prostate
tenderness on examination is not a sensitive marker for
these disorders. If a prostate syndrome is suspected, a
urine sample is obtained for urinalysis and culture, and
then a second sample is obtained following prostate
massage.
1. Chronic bacterial prostatitis. An increase in leuko
cytes usually occurs with massage: culture of prostatic
secretions is positive.
2. Chronic nonbacterial prostatitis usually demon
strates an increase in leukocytes after massage, but
the culture is negative. Ureaplasma or Chlamydia
may be the cause.
3. Prostatodynia (a misleading term because the pros
tate is normal) is a diagnosis of exclusion that is
made when the patient has typical symptoms, but no
increase in leukocytes with massage and a negative
culture.
TREATMENT
A. Uncomplicated cystitis. Empiric therapy is generally ap
propriate when the urine dipstick test is positive. It may
also be appropriate for patients with no alternative diag
nosis and a high clinical suspicion for UTI.
B.
1. Trimethoprim (TMP)/sulfamethoxazole (SMX)
(e.g., TMP 160 mg/SMX 80 mg ) is often adminis
tered orally twice daily for 3 days. A longer course
of therapy (e.g., 7 days) may be appropriate in higher
risk patients (e.g., patients with diabetes, elderly pa
tients). Men are usually treated for 7 days.
2. Fluoroquinolones. A fuoroquinolone can be substi-
tuted if the patient has a sulfa allergy.
3. Amoxicillin is indicated if the patient is pregnant.
Uncomplicated pyelonephritis
1. Outpatient treatment is appropriate for many pa
tients. TMP/SMX (TMP 160 mg/SMX 800 mg orally
twice daily) may be prescribed for 14 days.
2. lnpatient treatment may be necessary for diabetic
patients, the elderly, and in patients who appear se
verely ill or are unable to maintain hydration second-
232 Chapter 39
ary to nausea and vomiting. Inpatient treatment is
also recommended for pregnant patients. A third
generation cephalosporin or the combination of am
picillin and gentamicin is often used. The former may
be more appropriate for patients with renal dysfunc
tion, whereas the latter may be better suited for se
verely ill patients and those in whom an enterococcus
species is suspected to be the causative organism.
C. Recurrent cystitis is often an indication for prophylaxis.
1. General recommendations. Postmenopausal women
may beneft from topical estrogen to help prevent
E coli colonization. Women who use diaphragms or
spermicide should consider alternative methods of
birth control. These measures may obviate the need
for prophylaxis.
2. Prophylaxis
a. Postcoital prophylaxis is often used in patients
who relate their UTls to sexual intercourse. One
tablet of TMP/SMX may be taken following in
tercourse, and patients should be advised to uri
nate soon after intercourse.
b. Daily or three-times-per-week prophylaxis with
TMP/SMX may be used in patients with recur
rent UTIs unrelated to sexual intercourse.
3. Early therapy may be preferred in patients who have
infrequent recurrences (e.g., two episodes per year).
Patients initiate their own 3-day treatment with the
onset of symptoms.
D. Complicated UTIs. If a resistant infection is the cause
therapy is generally aimed at the organism and ofte
given for an extended period (e.g., 10-14 days or longer).
A fuoroquinolone is often given to outpatients. while
broad-spectrum intravenous antibiotics may be required
for initial inpatient therapy.
E. Prostate syndromes
1. Chronic bacterial prostatitis. Prolonged treatment
(often with TMP/SMX for 6 weeks or more) is gener
ally given.
2. Chronic nonbacterial prostatitis. Empiric treatment
against Ureaplasma or Chlamydia (e.g., with erythro
mycin) is often initiated.
3. Prostatodynia. L Blocking agents may be helpful.
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40.Approach to Acid-Base
Disorders
@
INTRODUCTION
Q
A. All acid-base disorders can be placed in one of the
following categories:
L Metabolic acidosis
a. Nonanion gap
b. Anion gap
2. Metabolic alkalosis
a. Chloride-responsive
b. Chloride-unresponsive
3. Respiratory acidosis
4. Respiratory alkalosis
B. Often, there is more than one metabolic derangement,
which can make interpretation more diffcult. However,
the approach discussed in this chapter will enable you
to diagnose most acid-base disorders.
STEPS IN THE EVALUATION OF ACID-BASE DISORDERS.
l
An arterial blood gas and electrolyte panel are needed to
fully evaluate all acid-base disorders.
A. Decide whether the patient is acidemic or alkalemic.
Although a pH of 7.35-7.45 is considered "normal,"
mixed disorders or the body's compensatory mechanisms
(see IV) may hide signifcant acid-base derangements
within this range. It is therefore useful to decide on
acidemia or alkalemia simply on the basis of whether
the pH falls below or above 7.4.
1. Acidemia is diagnosed when the pH is less than 7.4.
2. Alkalemia is diagnosed when the pH is greater
than 7.4.
B. Determine whether the acid-base abnormality has a
metabolic or respiratory cause. You can make this deter
mination by looking at the arterial carbon dioxide ten-
Modifed with permission from Haber RJ: A practical approach to acid
base disorders. West J Med 155(2):146-51, 1991.
233
234 Chapter 40
sion (Paco2)' A high Paco2 causes an acidosis, whereas
a low Paco2 causes an alkalosis.
1. Acidemia
a. If the patient is acidemic and the Paco
2
is high,
you have diagnosed a respiratory acidosis.
b. If the patient is acidemic and the Paco
2
is low, you
have diagnosed a metabolic acidosis (because the
Paco
2
does not account for the acidosis).
2. Alkalemia
a. If the patient is alkalemic and the Paco
2
is low.
you have diagnosed a respiratory alkalosis.
b. If the patient is alkalemic and the Paco2 is high,
you have diagnosed a metabolic alkalosis.
C. Calculate the anion gap. The anion gap equals the mea
sured cations minus the measured anions [i.e .. Na+ -
(Cl- + HC03-)]. Because the measured cations are nor
mally more than the measured anions, the unmeasured
anions must be greater than the unmeasured cations by
exactly the same amount in order to maintain electroneu
trality. Any disorder that increases unmeasured anions
will decrease measured anions and cause an increased
anion gap.
a. Normal is 8-12.
b. If the anion gap is more than 20, an anion gap aci
dosis is present. The body does not compensate
for a respiratory alkalosis with an anion gap acido
sis; therefore, the presence of an anion gap acido
sis represents a primary abnormality (see III A 2).
c. If the anion gap is 12-20, there still might be an
underlying anion gap acidosis.
D. Calculate the corrected serum bicarbonate
1. The purpose of this calculation is to determine what
the serum bicarbonate would be if no anion gap
existed (i.e., the corrected serum bicarbonate).
a. If correcting the anion gap results in an elevated
serum bicarbonate (i.e., > 28), the patient has
an underlying metabolic alkalosis.
b. If correcting the anion gap results in a reduced
serum bicarbonate (i.e., < 23), the patient has
an underlying nonanion gap acidosis.
c. If correcting the anion gap results in a normal
serum bicarbonate, then the decreased serum bi
carbonate is completely explained by the anion
gap acidosis.
2. The following formula can be used to calculate the
corrected serum bicarbonate:
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Approach to Acid-Base Disorders 235
CB * Mesure AG Normal AG + Mesure HC03-
(CB " corred bicaronat md AG mion gap
By subtracting the normal anion gap from the mea
sured anion gap, you have a measurement of the
"extra acid" that is present. Because each extra acid
titrates approximately one base, this calculation ap
proximates the amount of bicarbonate consumed in
titrating the anion gap acidosis. By adding this value
to the measured bicarbonate value, you correct the
bicarbonate for the effect of the anion gap acidosis.
HOT
Steps for Determi ni ng Acid-Base Abnormalities
Determi ne whether the pH is greater than or less

than 7.4
look at the Pac02
Calculate the anion gap

K EY
Calculate the corrected serum bicarbonate

M
DIFFERENTIAL DIAGNOSES. Once you have completed the
four steps described in II, you will have identifed most possi
ble acid-base disorders. Three disturbances at the same time
(the "triple ripple") is the maximum because respiratory
alkalosis and respiratory acidosis cannot exist simultane
ously. The following differentials can help you arrive at a
cause for the patient's acid-base disorder or disorders.
A. Metabolic acidosis
1. Nonanion gap. The common causes of non anion gap
acidosis include two renal, two gastrointestinal, and
two "post" causes.
a. Renal
(1) Renal failure usually causes a mixed anion
and nonanion gap acidosis.
(2) Renal tubular acidosis (see Chapter 38)
b. Gastrointestinal
(1) Diarrhea. Bicarbonate loss can result in a
nonanion gap metabolic acidosis.
(2) Colo vesicular fstula or ileostomy can also
cause bicarbonate loss.
236 Chapter 40
c. "Post" disorders
(1) Post-hyperventilation. The kidney compen
sates for a respiratory alkalosis by "spilling"
bicarbonate to generate a nonanion gap
metabolic acidosis. If the respiratory alkalo
sis ceases (e.g., following treatment for heart
failure), a nonanion gap acidosis may remain
until the kidney can regenerate bicarbonate.
(2) Post-anion gap acidosis. In order for the kid
ney to maintain the body's electroneutrality,
the increase in measured anions that accom
panies an anion gap acidosis is associated
with chloride loss, producing a hypochlore
mic acidosis. If a signifcant volume loss ac
companies the anion gap acidosis (e.g., dia
betic ketoacidosis with an osmotic diuresis
from hyperglycemia), the kidney will try to
correct by reabsorbing salt and water. In do
ing so, chloride is reabsorbed and a hyper
chloremic (i.e., nonanion gap) acidosis may
occur until the kidney can replace the con
sumed bicarbonate (this often takes a few
days).
2. Anion gap. Metabolic anion gap acidoses result from
an increase in unmeasured anions. Armed with the
following mnemonic. "MUDPLIERS," you can zero
in on the cause Or causes of an anion gap aci
dosis.
Causes of Anion Gap Acidosis ("MUDPLlERS")
Methanol intoxication (through conversion into
formic acid)
Uremia (urea is an anion)
Diabetic or alcoholic ketoacidosis
Paraldehyde (a medicine no longer in use)
Lctte (usually from anaerobic metabolism
during shock or extensive tissue inj ury)
Isoniazid or Iron overdose
Ethylene glycol intoxication (antifreeze in
gestion)
Rhabdomyolysis
Salicylate intoxication
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Approach to Acid-Base Di sorders 237
a. Uremia. Check the BUN.
b. Rhabdomyolysis. Check creatine kinase.
c. Diabetic ketoacidosis. Diabetic ketoacidosis can
be ruled out on the basis of a negative urine
dipstick for ketones.
d. Salicylate overdose. A salicylate level should
be obtained for all unexplained anion gap aci
doses.
e. Methanol or ethylene glycol intoxication. A si
multaneous blood sample for osmolarity, serum
electrolytes, and ethanol level is especially im
portant in patients with altered consciousness
and in alcoholics with an anion gap acidosis be
cause the probability of a methanol or ethylene
glycol ingestion is increased.
(1) Calculate the osmolar gap. All alcohols (in
cluding ethanol, isopropyl alcohol, methanol,
and ethylene glycol) can produce an osmolar
gap (a difference between measured and cal
culated osmolarity), but only methanol and
ethylene glycol lead to osmolar gaps with
signifcant anion gap acidoses. Calculate the
osmolar gap as follows:
Calculated osmolarity 2 ? Na BUN/2. 8
gl ucose/18
Osmolar gap ~ Actual osmolarity - Calculated
osmolarity
(2) Correct for ethanol. The ethanol level di
vided by 4.6 equals the amount of osmoles
that ethanol is contributing to the gap.
(3) Calculate the remaining osmolar gap. Sub
tract the osmoles due to ethanol from the
original osmolar gap. The remaining osmolar
gap is still unexplained. A value greater than
5 mOsmlkg H20 is concerning (but not spe
cifc) for a toxic ingestion of another alcohol
(e.g., methanol or ethylene glycol). Other
clinical evidence that may confrm your suspi
cion includes visual disturbances (with meth
anol ingestion) and urinary oxalate crystals
(with ethylene glycol ingestion).
238 Chapter 40
f. Lactate. Often a lactic acidosis is diagnosed on
a clinical basis (e.g., obvious sepsis) or by exclu
sion. An elevated lactate level confirms your clin
ical suspicion.
g. Alcoholic ketoacidosis is probably much more
common than we think, but deserves to be a
diagnosis of exclusion so that other potentially
treatable and life-threatening conditions are
not missed.
B. Metabolic alkalosis. To determine the cause of meta
bolic alkalosis, frst obtain a urine chloride level. Causes
are referred to as chloride-responsive or chloride-unre
sponsive.
1. Urine chloride < 20 mEqlL. The metabolic alkalosis
resulting from the following causes will correct with
sodium chloride administration.
a. Prerenal states (e.g., severe heart failure). Most
metabolic alkaloses are generated by the kidney
reacting to a decrease in renal blood fow. Any
of the prerenal states (see Chapter 35 II A) can
lead to a metabolic alkalosis. Mechanisms by
which a prerenal state produces a metabolic alka
losis include:
(1) Increased proximal bicarbonate reabsorp
tion. Avid reabsorption of sodium in the
proximal tubule induces increased bicarbon
ate reabsorption in order to maintain electro
neutrality.
(2) Increase
d
distal acid secretion. A pre renal
state results in higher renin and aldosterone
levels, which increases sodium uptake in the
distal tubule while leading to potassium and
hydrogen ion secretion.
b. Gastric fuid loss (from vomiting or a nasogastric
tube) can lead to a metabolic alkalosis.
c. Prior diuretic therapy leading to volume deple
tion can result in a metabolic alkalosis.
2. Urine chloride > 20 mEq/L. The metaholic alkalosis
resulting from the following causes will not correct
with sodium chloride administration. The most com
mon causes can be easily remembered if you think
of the frst four letters of the alphabet:
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Common Causes of Chloride-Unresponsive
Metabolic Alkalosis (" ABCD")
Aldosteronism (primary)
Bartter's syndrome
Cushing's syndrome
Depletion of magnesium
a. Primary hyperaldosteronism increases excretion
of potassium and hydrogen ion at the distal tu
bule, resulting in hypokalemia and alkalosis.
b. Bartter's syndrome presumably results from a
defect in salt reabsorption in the thick ascending
portion of the tubule. Salt and water loss trigger
aldosterone production, which causes hypoka
lemia and alkalosis (hypomagnesemia may also
be seen).
c. Cushing's syndrome may produce hypokalemia
and alkalosis by mechanisms similar to those of
primary hyperaldosteronism.
d. Depletion of magnesium may result in po
tassium wasting. Hypokalemia may cause hydro
gen ions to shift intracellularly, and may also
result in increased excretion of hydrogen at
the distal tubule; both mechanisms may lead
to alkalosis.
Bartter's syndrome and magnesium depletion are gen
erally associated with normal or low blood pressure,
whereas primary hyperaldosteronism and Cushing's
syndrome are generally associated with hypertension.
240 Chapter 40
HOT
K E Y
Diuretics often produce a confusi ng picture because
although the urinary chloride is 20 mEq/l, the meta
bolic alkalosis is usually responsive to sodi um chlo
ride admi nistration.
C. Respiratory acidosis (hypoventilation). See Chapter 23
II B.
D. Respiratory alkalosis (hyperventilation). There are eight
common etiologies:
1. Primary CNS disorders
2 Pubnonary disease (including all causes of hypoxia)
3. Metabolic acidosis
4. Sepsis
HOT
K E Y
Respi ratory alkalosis can be the first acid-base abnor
mality seen in patients with sepsis.
5. Pregnancy
6. Drugs (e.g .. salicylates)
7. Liver disease
8. Pain or anxiety
COMPENSATION
A. Clinicians look at compensatory mechanisms for two
reasons:
t. To determine whether compensation is occurring or
if there is another primary abnormality
2. To estimate the acuity of an acid-base abnormality
B. Compensation refers to the body's natural mechanisms
of counteracting a primary acid-base disorder. For ex
ample, the lungs will compensate for the kidneys through
hyperventilation during metabolic acidosis and, to a
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lesser extent. hypoventilation during metabolic alkalosis.
The kidneys will compensate for the lungs by excreting
or retaining bicarbonate when respiratory alkalosis or
acidosis, respectively, is present.
HOT
K E Y
For every change of 10 mm Hg i n the Paco2 (up or
down), the pH changes 0.08 if the process i s acute
and 0. 03 if the process i s chronic (in the opposite
di rection of the Paco2) .
41 . Hyponatremia
@
INTRODCTION
A. Defnition. Hyponatremia refers to a serum sodium con
centration of less than 135 mEq/L. Hyponatremia is a
very common problem in hospitalized patients.
B. Action of antidiuretic hormone (ADH). Understanding
the action of ADH is essential to understanding hypona
tremia.
1. Normally, the body regulates osmolality very closely
by increasing or decreasing ADH secretion. When
the effective circulating volume (ECV) decreases.
the body senses that there is a lack of intravascular
fuid and secretes ADH to help expand intravascular
volume at the expense of osmolality.
2. Hyponatremia is usually caused by either an:
a. Appropriate increase in ADH (as seen with hy
povolemic or hypervolemic causes), or an
b. Inappropriate increase in ADH [as seen in the
syndrome of inappropriate ADH secretion
(SIADH)]
C. Clinical manifestations of hyponatremia depend on the
cause, level, and rapidity of hyponatremia; they include
confusion, muscle cramps, nausea, and lethargy that may
progress to seizures and coma.
D. Approach to the patient
1. The initial step in evaluating patients with hypona
tremia is to check the serum osmolality to ensure
that the patient does not have isotonic or hyper
tonic hyponatremia.
a. Isotonic hyponatremia (pseudohyponatremia) is
caused by hyperlipidemia or hyperproteinemia.
and is attributable to laboratory error.
b. Hypertonic hyponatremia is caused by hypergly
cemia or hypertonic infusions [e.g .. mannitol. to
tal parenteral nutrition (TPN)].
2. If the serum osmolality is low 280 mOsm), the
next step is to evaluate the patient's fuid status. With
this information, it is possible to narrow down the
possible causes of the hypotonic hyponatremia.
242
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Hyponatremia 243
@
HYPOTONIC HYPONATREMIA
A. Hypovolemic
1. Physical examination will reveal signs of volume
depletion (e.g., orthostasis, resting tachycardia, poor
skin turgor, dry mucous membranes, low jugular ve
nous pressure).
2. Causes are summarized in Table 41-1.
3_ Treatment entails intravascular fuid expansion (usu
ally with normal saline) and treatment of the underly
ing cause. The initial goal of treatment for any cause
of hyponatremia is to increase the sodium only half
way during the frst 24 hours.
B. Hypervolemic
1. Physical examination reveals signs of volume expan
sion (e.g., peripheral edema, ascites, pleural efu
sions, pulmonary edema).
2. Causes are summarized in Table 41-2.
TABLE 41 - 1 : Causes of Hypotonic Hypovolemic Hyponatremia
5erum Uric
Common Causes FENa Acid
Skin loss <1 % >5 mg/dl
Gastroi ntestinal loss <1 % >5 mg/dl
lung loss <1 % >5 mg/dl
Third spacing of fluids <1 % >5 mg/dl
Adrenal insufficiency >1 % >5 mg/dl
Renal loss (diuretics, tubular damage) >1 % >5 mg/dl
FENa ~ fractional excretion of sodium (see Chapter 35) .
TABLE 41 -2: Causes of Hypotonic Hypervolemic Hyponatremia
.
Serum Uric
Nephrosis (i.e., nephrotic syndrome)
Ci rrhosis
Cardiosis (i .e. , congestive heart foilure)
FENo ~ fractional exertion of sodium.
<1 %
<1 %
<1 %
>5 mg/dl
>5 mg/dl
>5 mg/dl
244 Chapter 41
TABLE 41 -3: Causes of Hypotonic Euvolemic Hyponatremia

Serum Uric
SIADH >1 %
Variable
Variable
>1 %
<4 mg/dl
<5 mg/dl
>5 mg/dl
>5 mg/dl
Water intoxication (polydipsia)
Hypothyroidism
Renal dysfunction
FENa ~ fractional excretion of sodi um; SIADH ~ syndrome of inappropriate
antidi uretic hormone secretion.
3. Treatment usually involves a combination of fuid

restriction and diuretics.
C. Euvolemic
1. Physical examination is notable for the lack of signs
indicative of volume depletion or expansion.
2. Causes of euvolemic hypotonic hyponatremia are
summarized in Table 41-3.
3. Treatment involves fuid restriction plus treatment
of the underlying cause.
SIADH is often a difcult but important diagnosis to make.
Because the management of SIADH usually requires fuid
restriction in a hospitalized patient (who may be NPO, fe
brile, or both), it is important to be fairly sure ofthe diagnosis
to prevent dehydration. If a hyponatremic patient meets all
(or at least most) of the following fve criteria. you can feel
reasonably confdent about treating the patient for SIADH:
A. The patient should have H underlying reason to have
SIADH. The most common causes are malignancies,
central nervous system (eNS) and pulmonary disease,
and various drugs.
B. The patient should be euvolemic, but may be slightly hy
pervolemic.
C. The patient should have normal renal, adrenal, and thy
roid function.
D_ The patient's urine osmolality is inappropriately in
creased and is usually greater than the serum osmolality.
E. The patient should have low serum uric acid_ Of all the
causes of hyponatremia, only two-SIADH and primary
polydipsia-are characterized by hypo uricemia. In these
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Hyponatremia 245
two disorders, the intravascular volume is actually ex
panded (even though the disorders are categorized as
euvolemic). The kidney handles uric acid the same way
it handles sodium; therefore, in Slates of intravascular
expansion, sodium and uric acid elimination are en
hanced.
42. Hypernsion
@
@
INTRooalON
A. Defnition. Patients who consistently have a systolic
blood pressure > 140 mm Hg or a diastolic blood pres
sure > 90 mm Hg are considered to be hypertensive.
B. Hypertension is an extremely Common disorder in both
outpatients and hospitalized patients. In general, hyper
tension in inpatients is a major concern primarily when
patients present with hypertensive urgencies or emer
gencies.
CAUSES OF SECONDARY HYPERTENSION. Although 95%
of hypertensive patients have essential (primary) hyp
.
erten
sion. causes of secondary hypertension must be consIdered
in patients with characteristic signs or symptoms, onset of
hypertension at a very young or old age, or when the blood
pressure is refractory to medical therapy. The causes of sec
ondary hypertension can be remembered using the following
memory aid:
Causes of Secondary Hypertension
One anatic cause
Two renal causes
Three adrenal causes
Four CENTs
Ethanol abuse or Estrogen use
Neurologic disease
Thyrotoxicosis
A. One anatomic cause. Aortic coarctation, a congenital
disorder characterized by aortic constriction at the origin
of the left subclavian artery. usually presents in children
or young adults and can lead to hypertension.
B. Two renal causes
1. Intrinsic renal disease. Almost any parenchymal kid
ney disorder can lead to hypertension, usually as a
result of increased intravascular volume and in-
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Hypertension 247
creased activity of (he renal-angiotensin-aldoste
rone system.
2. Renal artery stenosis, a relatively common cause of
secondary hypertension, is usually caused by fbro
muscular dysplasia in young adults and atherosclero
sis in older patients. The stenosis leads L decreased
renal blood fow. which leads to increased renin re
lease and hypertension.
HOT
K E Y
Always consider renal artery stenosis as the cause of
hypertenSion when a patient shows a dramatic in
crease i n serum creati ni ne after starting angiotensin
converting enzyme (ACE) i nhibitor therapy.
C. Three adrenal causes
1. Primary hyperaldosteronism, an uncommon cause of
secondary hypertension, is caused by an aldosterone
secreting adenoma or bilateral adrenal hyperplasia.
HOT
K E Y
Suspect primary hyperaldosteronism if a hypertensive
patient is hypokalemic and not taking diuretics.
2. Cushing's syndrome. Excess glucocorticosteroids (as
a result of any cause) will often cause the patient to
be hypertensive. Usually the other clinical manifesta
tions of glucocorticoid excess will be present to aid
in making the diagnosis.
3. Pheochromocytoma is a norepinephrine- and epi
nephrine- secreting tumor that may be malignant and
can also lead to headaches and glucose intolerance.
D. Four CENTs
1. Calcium. Hypercalcemia is an uncommon cause of
hypertension but should be considered in those who
248 Chapter 42
have underlying diseases apt to lead to hypercalcemia
(see Chapter 71 III).
2. Ethanol abuse or estrogen use. The most common
causes of secondary hypertension are the use of alco
hol and oral contraceptive agents. Pregnancy can also
lead to hypertension.
3. Neurologic disease. Any process that leads L in
creased intracranial pressure can lead to the triad of
hypertension, bradycardia, and irregular respiration
(known as Cushing's triad).
4. Thyrotoxicosis. Patients with hyperthyroidism can
also be hypertensive.
HYPERTENSIVE CRISES: URGENCIES AND EMERGENCIES

A. Hypertensive urgencies are situations in which the pa
tient has a systolic blood pressure > 220 mm Hg or a
diastolic blood pressure > 120 mm Hg and no evidence
of end-organ damage. Urgencies are usually treated with
oral antihypertensive agents (e.g., nifedipine, clonidine,
or captopriI) in the emergency room. Once the blood
pressure is decreased to an acceptable level, these pa
tients can usually be discharged but warrant very close
follow-up.
HOT
K E Y
Sublingual nifedipine should be avoided i n al most
all patients.
B. Hypertensive emergencies are those situations in which
the elevated blood pressure leads to end-organ damage.
1. Examples. The following situations qualif as hyper
tensive emergencies:
M Hypertensive encephalopathy (altered mental
status)
b. Intracranial hemorrhage
Malignant hypertension is an outdated term that implies hypertension
associated with encephalopathy (or neuropathy) and accompanied by pap
illedema. It is a form of hypertensive emergency.
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Hypertension 249
c. Aortic dissection
d. Myocardial infarction
e. Unstable angina
f. Hypertensive nephropathy (progressive acute re
nal failure with proteinuria and hematuria)
2. Treatment for hypertensive emergencies usually re
quires admission to the intensive care unit (ICU) and
the administration uf parenteral antihypertensives
(e.g., nitroglycerin, nitroprusside, labetalol).
MCA ST pOHT.PY
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PART VI
I nfectious Disease
MCA ST pOHT.PY
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43.Approach to Fever
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INTRODUCTION
A. Normal body temperature. The normal oral temperature
is 36C-37.4C (average 36.7C).
1. The range includes 95% of the population. Any tem
perature higher or lower is considered abnormal.
2. The average rectal temperature is O.soC higher and
the average axillary temperature is O.soC lower than
the oral temperature.
HOT
Think of the three temperatures (axillary, oral, and
rectal) i n alphabetical order to remember which is
lowest and which is highest: A < 0 < R.
K E Y
B. Causes. Fever (an elevated temperature) may be a mani
festation of infection, malignancy, connective tissue dis
orders, drug reactions, central nervous system ( CNS)
disorders, or other diseases.
Remember:
HOT
Patients who are elderly, i mmunocompromised, or

taking steroids or nonsteroidal antiinflammatory
drugs (NSAIDs) may not mount a fever, even in
the presence of a severe infection.
K E Y
The degree of fever is of little predictive value in

assessing the severity of an underlying illness in
a given patient.
Hypothermia often signals the presence of an over

whelming infection, and should therefore be evalu
ated as thoroughly as hyperthermia.
@
ApPROACH TO THE PATIENT. In many cases. the etiology
of the fever is clinically obvious; other times, fever can be
253
254 Chapter 43
the initial manifestation of an elusive illness. This chapter
will provide you with a way to approach patients with recent
onset of fever from an obscure source. If the fever persists
for weeks without a diagnosis, a fever of unknown origin
(FUO) may be present (see Chapter 46).
A. Patient history
1. Immune status. Is the patient immunocompromised
(e.g .. as a result of leukemia. chemotherapy, ste
roid use)?
2. Medical history. Patients with a known illness may
have a fever caused by their underlying illness (e.g.,
tumor fever fom a lymphoma or a fever from a lupus
fare); however. these patients often have superim
posed infections, which always need to be systemati
cally ruled out.
3. Medication history. What prescription drugs is the
patient taking? The medication history is aimed at
discovering drugs that cause immunosuppression
(e.g., steroids) and those that may result in drug fever
(e.g., neuroleptics, anticholinergics, anesthetic, anti
biotics).
4. Social history. What is the patient's travel and
sexual history? Is there a history of illicit drug use
or other HIV risk factors? Positive answers may
trigger a search for parasites, sexually transmitted
diseases, abscesses or endocarditis, or HIV-re
lated diseases.
HOT
K E Y
Fever should be presumed to be secondary to an infec
tion until proven otherwise, because i nfections cause
the majority of fevers and can be l ifethreatening.
B. Top to bottom approach. One way of determining the
infectious cause of a fever is to start at the patient's
head and work your way down. Characteristic signs and
symptoms (shown in parentheses) may increase your
suspicion for the following disorders:
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Approach to Fever 255
1. Meningitis (headaches, neck stiffness, photophobia)
2. Sinusitis (sinus tenderness)
3. Otitis (ear pain. diminished hearing)
4. Pharyngitis (sore throat, lymphadenopathy)
5. Pneumonia (cough, pleurisy, dyspnea)
6. Endocarditis (recent dental or other procedure, new
skin lesions)
7. Abdominal processes (pain, change in bowel habits.
nausea or vomiting)
8. Urinary tract infection (UTI) or pyelonephritis (dys
uria, frequency, suprapubic or costovertebral angle
tenderness)
9. Pelvic infection (discharge, dysuria)
10. Prostatitis (lower abdominal pain, tender prostate)
11. Perirectal abscess (pain, tenderness, swelling)
1. Cellulitis (erythema, pain, swelling)
13. Joint infections (pain, warmth, swelling)
14. Local intravenous catheter site infection (pain, pus)
HOT
I n patients exposed to broad-spectrum anti biotics and
presenting with diarrhea, always consider Clostridium
dificile colitis.
K E Y
C.
D.
Physical examination. A complete physical examination
is necessary. Pelvic and rectal examinations are useful for
evaluating the possibility of pelvic infammatory disease
(PID), prostatitis, and perirectal abscesses as potential
causes of fever.
Laboratory studies. The history and physical examina
tion may provide you with enough information to make
a diagnosis. Quite commonly, however, you may remain
unsure about the etiology of the fever. The following
laboratory tests will help you assess the likelihood of an
infection, and may also help to localize the source.
1. Complete blood count (CBC) with platelets
a. Neutropenia with fever is a medical emergency,
and requires hospitalization and broad-spec
trum antibiotics.
256 Chapter 43
b. A leftward shifted white blood cell (WBC) count
often implies signifcant bacterial infection.
c. A low WBC count may be just as worrisome as
a high one: the WBC count may not be elevated
in alcoholics, the elderly, and other immunocom
promised patients in the presence of a serious
infection. On the other hand, African-American
patients normally have WBC counts slightly be
low the given "normal" range.
2. Electrolytes with blood urea nitro
en (BUN an
.
d
creatinine. The presence of an amon gap aCIdosIs
may indicate sepsis.
3. Prothrombin time (P) and partial thromboplastin
time (PIT). Abnormal coagulation studies may indi
cate disseminated intravascular coagulation (DIC),
which may accompany serious infection.
4. Liver tests (e.g., bilirubin, alkaline phosphatase, and
transaminase levels) help evaluate the possibility of
hepatobiliary disease (e.g .. cholecystitis. ascending
cholangitis, liver abscess, hepatitis).
5. Amylase levels may be helpful if pancreatitis is sus
pected.
6. Urinalysis should always be done to evaluate the
possibility of UTI.
7. Urine pregnancy test. A pregnancy test should be
considered in all women of childbearing age.
8. Cultures
a. Blood cultures provide the gold standard for di
agnosing endocarditis and bacteremia. and are
therefore always required in intravenous drug
users presenting with fever. Patients who require
blood cultures are usually admitted for close fol
low-up.
b. Urine cultures should be obtained whenever the
fever is unexplained.
L Sputum evaluation may be useful for patients
with respiratory tract symptoms.
d. Throat culture may be useful in patients with
pharyngitis.
.
e. Cerebrospinal fuid (CSF) analysis and culture IS
necessary in patients with meningeal symptoms
or signs, altered mental status, or HIV infection
and an unexplained fever.
f. Body fuid analysis and culture. Patients with a
fever accompanied by ascites, a pleural or joint
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Approach to Fever 257
effusion, or any other type of fuid collection
need a diagnostic tap.
HOT
Patients that present with fever and rash should have
a skin biopsy unless the diagnosis i s straightforward.
K E Y
E. Radiographs
1. Chest. Posterior-anterior (PA) and lateral views
should be taken on all patients with unexplained
fever.
2. Abdomen. Flat and upright views are useful when
the patient has a fever and abdominal pain. Make
sure to look for air-fuid levels, bowel distention,
kidney stones, and free air.
F. Ancillary studies. At this point. you have systematically
ruled out most of the possible infections from head to
toe. If a diagnosis still has not been made, you need to
consider the easiest place for an infection to hide-the
abdomen and pelvis.
1. Computed tomography (CT). A CT scan is the best
radiographic test in this situation. It provides a thor
ough evaluation of the intra-abdominal organs, and
is more sensitive than ultrasound for detecting oc
cult abscesses.
2. Ultrasound. Abdominal ultrasound is often inade
quate for ruling out intra-abdominal abscesses and
other pathology, but may be better than a CT scan
for evaluating the gallbladder and bile ducts (e.g.,
for cholecystitis or ascending cholangitis).
3. Other tests (e.g . u bone marrow biopsy, indium or
gallium scans, bone scns) may be obtained if the
cause of the fever is still in question (see Chapter 46).
TREATMENT. If a potentially dangerous infection is sus
pected, admission to the hospital is warranted. Patients who
are elderly. immunocompromised. or have other organ sys
tem disease may also require admission.
258 Chapter 43
A. General measures
t. Fluids need to be administered to keep up with in
creased insensible losses.
2. Discontinuing medications that may be responsible
for a fever can be both diagnostic and therapeutic.
B. Empiric antibiotic therapy
1. Patients hospitalized for fever and neutropenia or to
rule out endocarditis and other potentially serious
infections are often treated empirically pending cul
ture results.
2. A low threshold for giving empiric antibiotics should
also be used for patients who are immunocompro
mised, including those with HIV infection, diabetes,
alcoholism, or liver or renal disease, and patients
who are asplenic or taking steroids or immunosup
pressants.
C. Antipyretic therapy
1. Acetaminophen (325-650 mg every 4 hours) is usu
ally frst-line therapy.
2. Indomethacin (25-50 mg every 8 hours) and cold
sponge baths may be useful for persistent fevers.
3. Evaporative cooling is often employed for patients
with a temperature greater than 41C. In this tech
nique, the patient is sprayed with cool water while
fans move ambient air across his body.
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44. Approach to Microbiology
W
OVERVIEW OF MICROBIOLOGY. The simplest way to ap
proach microbiology is to divide the organisms into six major
categories (based on Gram stain. morphology, and aerobic
requirements) and consider the most important diseases each
organism can cause.
A. Gram-positive cocci
1. Streptococcus
a. Group A streptococci cause "strep throat," scar
let fever, rheumatic fever, erysipelas, cellulitis,
and pneumonia.
b. Group B streptococci cause mainly perinatal in
fections and a variety of infections in adults [e.g.,
urinary tract infection (UTI). sepsis].
c. S. pneumoniae causes pneumonia (usually lo
bar), meningitis, and endocarditis.
d. Viridans streptococci are the most common cause
of subacute bacterial endocarditis.
2. Enterococcus causes UTIs. intra-abdominal infec
tions, endocarditis, and nosocomial i nfections. Infec
tions caused by Enterococcus can be diffcult to
treat.
3. Staphylococcus
a. S. aureus (coagulase-positive) causes skin infec
tions, toxic shock syndrome, endocarditis (espe
cially in drug users), intravascular line infections,
osteomyelitis, septic arthritis, pneumonia, and
nosocomial infections. S. aureus is virulent to
begin with; methicillin-resistant strains are even
more diffcult to eradicate.
b. S. epiderm idis (coagulase-negative) causes intra
vascular line infections and prosthetic valve en
docarditis.
c. S. saprophyticus (coagulase-negative) causes
UTls.
B. Gram-positive rods
1. Clostridium (anaerobic) can cause tetanus, botulism,
food poisoning, antibiotic-associated colitis, cellulitis
and skin infections, gas gangrene, abscesses, and sep
ticemia.
259
260
Chopter 44
2. Bacillwi can cause cutaneous and pulmonary an
thrax (woolsorter's disease). Most cases in the
United States are cutaneous; pulmonary anthrax is
usually fatal. B. cereus is a very common cause
of diarrhea.
3. Nocardia usually causes pulmonary disease that may
disseminate (in immunocompromised hosts), leading
to brain abscesses and subcutaneous nodules. Nocar
dia species are weakly acid-fast.
4. Actinomyces (anaerobic) causes cervicofacial infec
tions (following dental infection or trauma). chronic
pneumonia, abdominal infections (which may be
confused with Crohn's disease) and pelvic infamma
tory disease (PID) associated with the use of an intra
uterine contraceptive device (IUD).
5. Listeria monoctogenes causes sporadic cases of
meningitis and bacteremia as well as food-borne out
breaks in elderly or immunocompromised adults.
6. Erysipelothrix causes three types of human illness:
erysipeloid (a localized skin lesion); a diffuse skin
eruption accompanied by systemic illness; and bac
teremia (usually associated with endocarditis). Ery
sipelolhrix is acquired through skin abrasions follow
ing contact with infected swine, fsh, turkeys, ducks,
and sheep.
7. Corynebacterium
a. C. diphtheriae causes cutaneous, nasopharyn
geal, and oropharyngeal infections. Infections
of the respiratory tract are characterized by a
thick, gray membrane over the pharynx and
tonsils.
b. C. jeikeium (group JK) causes sepsis, primarily
in hospitalized, neutropenic cancer patients who
are on multiple antibiotics and have some type
of skin disruption.
c. "Diphtheroids" are common, nonpathogenic
skin contaminants.
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Approach to Microbiology 261
Gram-Positive Rods ("Clumsy BActeria NOr
mally ACt like ERrorprone COrnballs")
Clostridium
Bacillus
Nocardia
Actinomycosis
Listeria monocytogenes
Ersipelothrix
Cornebacterium
C. Gram-negative cocci
1. Neisseria
a. N meingitidis causes meningitis (in children
and young adults), meningococcemia (30%-50%
of patients have meningococcemia without men
ingitis). and sinusitis.
b. N gonorhoeae commonly causes urethritis (in
both men and women) and endocervicitis, which
may progress to PID or disseminated gonococcal
infection (DOl). N. gonorrhoeae also causes
pharyngitis and conjunctivitis.
2. Moraxella (Branhamella) catarrhalis causes sinus
itis, bronchitis, and pneumonia; however, it is often
diffcult to distinguish colonization from actual in
fection.
D. Gram-negative rods comprise the largest category of
pathogenic organisms. Infections can involve many dif
ferent systems, including the genitourinary, hepatobili
ary, gastrointestinal, and respiratory systems. Sepsis in
volving gram-negative rods is a major cause of mortality,
especially for neutropenic or otherwise immunocom
promised patients. A partial list of pathogens in this
category follows.
1. Escherichia coli causes the majority of UTls and can
cause intra-abdominal and biliary infections-all of
which may lead to sepsis.
2. Klebsiella causes the same diseases as E coli, as well
as sinusitis and pneumonia (especially in alcoholics).
3. Pseudomonas is a destructive organism that can lead
to sepsis following a variety of illnesses (e.g., skin,
ear. sinus, eye, urinary tract, or lung infections). Pseu
domonas infection is often nosocomial and usually
occurs in the setting of local tissue damage or im
paired host defenses.
262 Chapter 44
4. Haemophilus injuenzae causes pneumonia, bacter
emia (especially in patients who have undergone
splenectomy), cellulitis, otitis media, epiglottitis, si
nusitis, chronic bronchitis, and meningitis (primarily
in children).
5. Bordecellapercussiscauses whooping cough (primaI'
ily in children) and prolonged bronchitis in adults.
6. Brucella causes an insidious febrile illness character
ized by easy fatigability, headache, cervical and axil
lary lymphadenopathy, hepatosplenomegaly, and
lymphocytosis. Acquisition of brucellosis is usually
via animal contact or following ingestion of contami
nated milk.
7. Frandsella (Pasteurella) tularensi causes tulare
mia, a multisystemic disorder (fever, headache,
lymphadenopathy, prostration) usually acquired via
rabbit or tick contact.
8. Yerinia pestis causes the plague and is acquired via
fea or rodent bites.
9. Salmonella, Shigella, Campylobacler, Yer;nia en
terocolitica, and Vibrio species can all cause an in
fectious diarrhea.
E. Anaerobes. The anaerobes Actinomyce and Clostrd
ium are discussed with the gram-positive rods. Bacteroi
des fragilis, B. (Prevotella) melaninogenicus, Pepto
streptococcus, and Fusobacterium are also anaerobes.
1. In general, anaerobes are implicated (either alone
or in combination) in gingivitis, sinusitis, otitis, ab
scesses (dental, brain, lung, intra-abdominal), aspira
tion pneumonia, empyema, skin and soft tissue infec
tions, and pelvic infections.
2. As a rule of thumb. treatment of an abscess primarily
depends on drainage and only secondarily depends
on antibiotics.
F. Miscellaneous organisms
1. Rickettsia. Infections include Rocky Mountain spot
ted fever, murine (endemic) typhus fever, louse
borne (epidemic) typhus fever, and Q Fever.
2. Mycoplasma pneumoniae is the most common cause
of pneumonia ("walking pneumonia") in young
adults.
3. Chlamydiae. Infections include chlamydia (the most
common sexually transmitted disease in the United
States), lymphogranuloma venereum (LGV), tra
choma, conjunctivitis, psittacosis, and pneumonia (in
young adults).
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Approach to Microbiology
263

ANTIMICROBIAL THERAPY. The best wa

t
?
I
arn antibiot
ics is to know the organisms that each
nt1blOhc (
?
r class
f
antibiotics) covers well and which organ
.
ls
s ar

mlss
d. ThiS
information can be found in many antImIcrobIal gUIdes.
A. List the three or so most com
on or potentially lethal
organisms that can cause the Illness that you are con-
fronted with. .
B. Select an antibiotic that cover

the
?
rgamsm
k
.
s that :
most likely responsible for the mfectIon, ra 109 su

consider cost, convenience, and coverage of potentIally
life-threatening pathogens.
H O T
K E Y
If a patient is very ill, elegant antibiotic combinations
are less i mportant than broad coverage to protect
against a potentially lethal organism.
4S. Fever and Rash
@
INTRODUCTION. Like chest pain, the symptom complex of
fever and rash may represent an acute, life-threatening dis
ease or a benign condition.
@
SEVEN KILLER CAUSES OF FEVER AND RASH. Though
there are many causes of fever and rash, you must frst
consider the diseases that may kill the patient within hours.
A SMARTTT physician can easily remember these seven
killer causes:
Seven Killer Causes of Fever and Rosh
("SMARm")
Sepsis
Meningococcemia
Acute endocarditis
Rocky Mountain spotted fever
Toxic erythemas
Toxic epidermal necrolysis (TEN)
Travel-related infections
A. Sepsis. Fever accompanied by a generalized erythema
tous rash may signal impending sepsis (usually caused
by Gram-negative organisms).
B. Meningococcemia. Patients usually appear acutely ill. A
petechial rash develops in most patients.
H O T
K E Y
Disseminated gonococcal infection (DGI) is a less dan
gerous Neisseria infection that may also produce fever
and rash. DGI often presents with palpable purpuric
pustules, and may be associated with fever, tenosyno
vitis, polyorthralgias, or septic arthritis.
c. Acute endocarditis should be considered in all patients
264
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Fever and Rosh 265
with fever and a petechial rash. A careful cardiac exami
nation is always necessary.
D. Rocky Mountain spotted fever. After 2-6 days of a fu
like febrile illness, a macular rash usually appears over
the ankles or wrists. The rash spreads centrally and may
evolve into a petechial rash.
E. Toxic erytbemas include toxic shock syndrome (TSS),
staphylococal scalded skin syndrome (SSSS), scarlet fe
ver, and scarlatiniform eruptions.
H O T
Common features of toxic erythemas include fever; on
erythematous rash that is most marked i n the flexural
flds and later desquamates; and, frequently, mucocu
taneous involvement.
K E Y
E.
1. TSS results in a diffuse erythematous rash that
blanches easily; desquamation occurs after 1-2
weeks (see Chapter 83). Both Staphylococcus aureus
and Streptococcus pyogenes can cause TSS.
2. SSSS results in generalized erythema and desqua
mation.
3. Scarlet fever follows S. pyogenes pharyngitis. Al
though it may not be immediately life-threatening,
scarlet fever should always be considered when the
patient presents with a toxic erythema. Scarlatini
form eruptions resemble the rash of scarlet fever and
are usually caused by S. aureus.
Toxic epidermal necrolysis (TEN) is caused by a reaction
to drugs. It is a "SNAP" to remember the drugs that
commonly cause TEN:
Drugs That Commonly Couse TEN ("SNAP")
Sulfonamides
Nonsteroidal anti-inflammatory drugs (NSAIDs)
Allopurinol
Phenytoin
266 Chapter 45
TEN results in large areas of erythema and desquama
tion, and may be clinically indistinguishable from SSSS.
F. Travel-related infections. Fever and rash in a recent trav
eler should alert you to the possibility of a potentially
life-threatening viral illness. Most of these dangerous
viruses are acquired in Latin America, Africa, or Asia.
Hemorrhagic fevers are the most worrisome, and include
Ebola, Lassa, and Hanta virus infection. These disorders
are often characterized by petechiae or purpura as well
as other types of bleeding, and are associated with a high
mortality rate.
A. Rule out the seven killer causes of fever and rash. In
general, you will be able to rule out these life-threatening
causes of fever and rash by paying attention to the patient
history and the clinical manifestations of disease, includ
ing the rash.
1. Patient history. Always remember to obtain a medi
cation and travel history. A negative drug and travel
history usually rules out TEN and hemorrhagic fever
as potential etiologies.
2. Clinical manifestations
a. III appearance. Patients with meningococcemia,
Rocky Mountain spotted fever, or sepsis usually
appear systemically ill.
b. Cardiac murur. Acute endocritis usually is
accompanied by a cardiac murmur (see also
Chapter 48).
c. Rash
(1) Desquamating rashes often signal a toxic ery
thema or TEN.
(2) Petechial rashes should always alert you to
the possibility of meningococcemia, Rocky
Mountain spotted fever, or endocarditis.
3. Helpful data
a. Laboratory evaluation to assess other organ sys
tems may be necessary when toxic shock is still
a consideration (e.g., in a patient who appears
ill or has low blood pressure).
b. Most of the toxic erythemas (with the exception
of SSSS) can usually he ruled out on clinical
grounds; however, a skin biopsy is always indi
cated to differentiate SSSS from TEN. A split
epidermis (i.e., intra epidermal separation) is
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Fever and Rash 267
TABLE 45 1: Types of Cutaneous Lesions
Lesion Description
Macules
Papules
Vesicles
Bullae
Pustules
Nodules
Plaques
Purpura
Petechiae
Ecchymoses
Discolored, flat lesions
Raised lesions; <0.5 cm in diameter
lesions l Ied with clear Auid; <0.5 cm i n di
ameter
large vesicles (i . e. , >0.5 cm in diameter)
Pus.fi lled vesicles
Raise lesions >0.5 cm in diameter and depth
Raised lesions >0.5 cm in diameter, but without
depth
Purple, nonblanchable lesion
Purpuric lesions <3 mm in diameter
Purpuric lesions >3 mm in diameter
found in SSSS, whereas total epidermal separa
tion (i.e., subepidermal separation) is seen in
TEN.
B. Address other diagnostic possibilities
1. Types of lesions. One way to establish a concise dif
ferential diagnosis of a fever and rash is to frst deter
mine the type of primary lesion (Table 45-1).
2. Diferential diagnoses. Some common etiologies for
each primary lesion associated with a fever are pro
vided below.
a. Macules and papules (or a maCUlopapular rash)
(1) Drug reactions commonly present with a pru
ritic, confuent eruption over the trunk that
usually occurs within 1 week of starting a new
medication. Fever is usually absent.
(2) Viral infections (e.g., measles and other
childhood viral exanthems, infectious mono
nucleosis, primary HIY) usually result in
rashes that are nonpruritic. Fever and other
viral symptoms are often present.
(3) Toxic erythemas are usually accentuated in
268
Chapter 45
the fexural folds. are not pruritic, and may
have mucous membrane involvement.
(4) Connective tissue diseases [e.g .. systemic lu
pus erythematosus (SLE), Still's disease] of
ten present with rash in association with other
characteristic symptoms (e.g., arthralgias).
(5) Bacterial infections are less likely causes.
(a) Lyme disease may cause erythema chron
icum migrans.
(b) Secondary syphilis most often results in
scaling papules that are present on the
palms and soles.
(c) Typhoid fever can cause "rose spots."
which are usually seen as an individual
papule on the trunk that fades with
pressure.
b. Vesicles and bullae
Differential Diagnoses for Vesicles ond Bulloe
Acompanied by Fever ("VESICLES")
Viral i nfections (e.g., voricellazoster, herpes
simplex, coxsackie)
Erythema multiforme
SSSS
Impetigo (bullous)
Contact dermatitis
LESs likely etiologies (e.g., porphyria cutonea
torda, bullous pemphigoid, pemphigus vul
goris, dermatitis herpetiform is)
c. Pustules
Differential Diagnoses for Pustules Accompa
nied by Fever ("Very Ful l of PUS")
Viral infections (e.g., varicella-zoster, herpes
simplex)
Fungal infections (e.g., candidiasis)
Pustular psoriasis
Urethritis-related (i . e. , DGI)
Syphi l is
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d. Nodules and plaques
(1) Nonpainful
(a) Fungal infections
(b) Lymphoma
(2) Painful
269
(a) Erythema nodosum presents with tender
nodules on the lower legs. It is often asso
ciated with another illness (e.g., tubercu
losis, coccidioidomycosis, sarcoid, post
streptococcal infection) or pregnancy.
(b) Sweet's syndrome should be suspected in
patients with fever, neutrophilia, and red
brown lesions (usually on the head and
upper extremities). The syndrome may
be associated with leukemias (usually
acute myelogenous leukemia), lympho
mas, myelodysplasia. or other malignan
cies. Infltration of neutrophils into the
dermis is seen on biopsy.
e. Purpura
H O T
K E Y
(1) Palpable purpura is pathognomonic for vas
culitis (see Chapter 70).
(2) Nonpalpable purpura. Petechiae usually in
dicate a bleeding disorder (e.g., thrombocy
topenia) and ecchymoses often result from
vessel fragility (e.g., actinic purpura), but
overlap does exist [e.g., necrotic ecchymoses
may occur with disseminated intravascular
coagUlation (DIC)].
Purpuric lesions i n a patient with fever may be the
harbinger of a l ife-threatening i l l ness. Hemorrhagic
fever, meni ngococcemia, Rocky Mountain spotted fe
ver, endocarditis, sepsis, and vasculitis all need to be
carefully considered and ruled out.
46. Fever of Unknown Origin (FUO)
*************=****************************
@
@
INTODUCTON. Fever of unknown origin (FUO) is de
fned as a temperature greater than 38.3C for more than 3
weeks that eludes diagnosis even after 1 week of in-hospital
evaluation. This defnition was designed to exclude common
undiagnosed viral syndromes, but it is somewhat arbitrary. If
your patient has an undiagnosed fever of prolonged duration,
there is no need to make her wait 7 days in the hospital
before proceeding with an effcient work-up.
COMMON CAUSES OF FUO (Table 46- 1 )
A. Infections account for many FUOs (although possibly
fewer than in the past, due to better diagnostic tests).
1. Bacterial infections
a. Intra-abdominal abscesses (e.g., in the liver.
spleen, or kidney) are especially common causes
of FUO.
b. Osteomyelitis and sinusitis are other localized
infections that may elude initial diagnosis.
c. Bacteremias from culture-negative endocarditis,
salmonellosis, and brucellosis can cause FUO.
2. Mycobacterial infections
a. Tuberculosis is a common cause of FUO. HIV
infected patients have a higher rate of extrapul
monary tuberculosis.
b. Mycobacterum av;um complex infections may
be the leading cause of FUO in patients with
AIDS and a CD4 count less than 100 celis/Il.
3. Viral infections
a. Cytomegalovirus (CMV) infection is a serious
consideration in immunocompromised patients.
b. Epstein-Barr virus infection causes mononucleo
sis (especially in adolescents and young adults).
4. Fungal infections
a. Histoplasmosis and coccidioidomycosis can
cause FUO in immunocompetent patients.
b. Candidiasis and aspergillosis are opportunistic
fungal infections that may cause FUO.
5. Parasitic infections. Amebiasis, malaria, and toxo
plasmosis may cause FUO.
270
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Fever of Unknown Origin (FUO)
TABLE 46- 1: Common Causes of Fever of Unknown Origin (FUOI
Disease Categor . Examples
Infectious
Neoplastic
Bacterial, mycobacterial, viral, fngal, para
sitic, spirochetal, rickettsial
Lymphomas, leukemias, hepatic cancer, re
nal cancer, atrial myxoma
271
Connective tissue
disorders
Miscellaneous
Systemic lupus erythematosus (SLE), rheuma
toid arthritis, Still's disease, vasculitides
Inflammatory bowel disease, granuloma
tous heptitis
@
6. Spirochetal infections. Secondary syphilis, lep
tospirosis, and Lyme disease should be considered.
7. Rick
.
ettsial inections include the typhus group (epi
demiC, endemiC, and scrub typhus), the spotted fever
group (Rocky Mountain spotted fever. rickettsial
pox, and tick fever), and other similar illnesses (Q
fever, [rench fever, and ehrlichiosis).
B. Neoplasms. Lymphomas. leukemias, hepatic and renal
cancers, and atrial myxomas are often associated with
febril e syndromes. Concurrent infection should always
be ruled out.
C. Connective tissue disorders. Systemic lupus erythemato
sus (SLE), rheumatoid arthritis. Still's disease and the
vasculitides (see Chapter 70) can all cause FUO.
D. Other causes. Infammatory bowel disease and granulo
matous hepatitis may cause a prolonged FUO (i.e., one
that lasts more than 6 months).
ApPROACH TO THE PATENT. Because the cause of an
FUO is elusive (by defnition), there is a tendency to try to
"net the diagnosis" by ordering every test under the sun.
Proceeding in a logical, stepwise fashion will decrease the
number of tests your patient must undergo. the cost of the
toal work-u
p
, a
.
nd the incidence of false-positive results.
Pnor to delVing Into an extensive evaluation rule out facti
tious (patient induced) fever by observing th elevated tem
perature reading yourself.
A. Go
.
were th

money is! The best bet for making a diag
nosIs IS pursumg any symptoms, signs, or abnormal labo-
272 Chapter 46
ratory test results that present along with the fever. Make
sure to always go down the list of possibilities from head
to toe as outlined in Chapter 43. For example:
1. Persistent headaches with a normal cerebrospinal
fuid analysis. A computed tomography (C) scan
or magnetic resonance imaging (MRl) may b indi
cated to rule out an intracranial abscess or sinusitis.
2. Cardiac murmurs associated with negative blood cul
tures may be evaluated with echocardiography
(transthoracic or transesophageal).
3. Hemoptysis or chronic cough in the presence of an
unremarkable chest radiograph may be further eval
uated with a chest CT scan or bronchoscopy.
4. Hematuria may prompt an intravenous pyelogram
or ultrasound to evaluate the possibility of renal car
cinoma.
5. Lymphadenopathy may be evaluated by biopsy.
6. Bone pain can be pursued with radiographs and a
bone scan.
7. Cytopenias can be evaluated by bone marrow biopsy.
H O T
K E Y
I n HIV-i nfected patients, you can use the CD4 count to
help predict the disease processes a patient is l i kely
t have (see Chapter 49). Mycobacterium<vium com
plex infections and CMV infections are common causes
of an FUO in AIDS patients with low CD4 counts (less
than 1 00 celiS/Il).
B. Diagnostic studies
1. Initial considerations
a. Abdominal and pelvic CT scan. There is no
better place for an infection (e.g., an abscess) or
malignancy (e.g., liver or renal carcinoma) to
hide than in the abdomen or pelvis; therefore.
performing this test early in the diagnostic work
up may be valuable.
b. Screens for tuberculosis, Epstein-Barr virus, and
syphilis may be performed with a purifed protein
derivative (PPD) test, a heterophil antibody test,
and a serum Venereal Disease Research Labora
tory (VDRL) test, respectively.
c. Rheumatologic work-up. An antinuclear anti-
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Fever of Unknown Origin (FUO)
273
H O T
K E Y
body (ANA) assay, rheumatoid factor assay, and
an erythrocyte sedimentation rate (ESR) are of
ten requested early in the evaluation. Any rashes
that are purpuric should be biopsied to rule out
vasculitis (see Chapter 70).
d. Other tests may be ordered based on epidemio
logic exposures. For example:
(1) Thick and thin blood smears examined every
8 hours for 2-3 days are appropriate if the
patient has traveled to areas where malaria
is endemic.
Fever i n a traveler should be considered malaria until
proven otherwise.
(2) Stool for culture or ova and parasite (O&P)
examination is also useful in patients with an
appropriate travel history.
(3) Amebic titers can help evaluate chronic intes
tinal amebiasis in patients with a remote
travel history because O&P stool examina
tion is usually negative in patients with
chronic disease.
(4) Toxoplasmosis titers are approximately 85%
sensitive for end-organ toxoplasmosis.
(5) Specifc serologies or cultures for brucellosis,
leptospirosis, Lyme disease, Rocky Moun
tain spotted fever. and other spirochetal and
rickettsial diseases may be sent, depending
on the geographic region, exposures to ani
mals or the outdoors, and the clinical presen
tation.
(6) Mycobacterium avium complex blood cul
tures may be performed in HIV-positive pa
tients with low CD4 counts.
2. Secondary considerations
a. Radionuclide studies
274
Chapter 46
(1) Gallium scans and indium-labeled white
blood cell (BC) scans are often used when
no etiology has been found. Gallium scans
may have an advantage in that they
.
de
ect
both infection and neoplasm, whereas Illdmm
scans only detect infection. Both tests are
limited by low specifcity.
(2) Bone scans may be performed to ru
e out
osteomyelitis and primary or metastatIc ma
lignancies of bone.
b. Invasive tests
(1) Bone marrow biopsies are generally of low
diagnostic yield, but are low-risk
n
?
a
f
ten performed when the diagnosIs IS stIli M
question.
.
'
.
o
(2) Liver biopsies have a higher Yield | patlents
with abnormal liver tests.
(3) Endoscopy (upper and lower) should be per
formed earlier in the work-up if there are
any gastrointestinal symptoI?
'
signs. or su
gestive laboratory abnormaht
es (e.g., a
P
OSI
tive fecal occult blood test, non defCiency
anemia).
(4) Exploratory laparotomy is of questionable
beneft, but should be considered in patients
with a negative work-up who are clinically de
teriorating.
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47.Acute Rheumatic Fever
@
INTRODUCTION
A. Defnition. Acute rheumatic fever is a systemic, immune
mediated disorder that occurs as a sequela to group A
streptococal pharngeal infection. (Skin infections are
not associated with rheumatic fever.)
B. Epidemiology. Acute rheumatic fever most commonly
occurs in school-age children, 2-4 weeks after an acute
throat infection.
1. Acute rheumatic fever rarely occurs in patients
younger than 5 years of age or older than 40 years
of age.
2. It is uncommon in the United States, but can be seen
in recent immigrants.
C. Rheumatic fever "bites the heart and licks the joints"
[i.e., chronic arthritis is not a sequela of rheumatic fever,
but valve disease and congestive heart failure (CHF) can
be]. The incidence of valve involvement varies depending
on the valve:
1. The mitral valve is affected in the majority of cases.
2. The aortic valve is affected in less than half of cases
(but almost never as the sole valve).
3. The tricuspid and pulmonary valves are affected in
less than 5% of cases, usually in association with
mitral valve involvement.
@
DIAGNOSIS
A. Jones criteria. Diagnosis of rheumatic fever is based on
evidence of a preceding streptococcal pharyngitis [e.g.,
a positive anti-streptolysin 0 (ASO) titer or culture],
plus two major Jones criteria or one major and two minor
Jones criteria.
1. Major
W Arthritis. The arthritis takes the form of a migra
tory polyarthritis that tends to involve the large
joints sequentially, however, adults may have
only single joint involvement. The arthritis re
solves spontaneously within 1 month and there
are no residual joint deformities.
275
276 Chapter 47
b. Heart involvement. Evidence of carditis includes
pericarditis, myocarditis, cardiomegaly, conges
tive heart failure, and mitral or aortic regurgi
tation.
c. Nodules. Small, frm. nontender subcutaneous
nodules occur over areas of bony prominence.
Nodules are rarely seen in adults.
d. Erythema marginatum is the classic rash; it be
gins as a macule that rapidly enlarges to form a
ring with a clear center.
e. Sydenham's coreathe most diagnostic of the
major criteria-is characterized by involuntary
choreoathetoid movements of the upper half of
the body.
2. Minor
Major Jones Criteria ("J INES")
Joints (arthritis)
I Involvement
Nodules
Erythema marginatum
Sydenham's chorea
a. Prolongation of the PR interval on the electro-
cardiogram (EKG)
b. Increased erythrocyte sedimentation rate (ESR)
c. Fever
d. Polyarthralgias
e. History of rheumatic fever
f. Positive C-reactive protein
B. Clinical presentation. Rheumatic fever usually presents
in one of three ways:
1. Insidious carditis
2. Acute-onset polyarthritis
3. Chorea (least common)
TREATMENT
A. Bed rest. The patient should be confned to bed until
the fever, tachycardia, and EKG changes resolve.
Aute Rheumatic Fever
277
B. Salicylates will rapidly decrease fever and joint swelling,
but do not affect the natural course of the illness. If
salicylates do not provide symptomatic relief, steroids
should be considered.
C. Antibiotics
1. Penicillin (or erythromycin) should be administered
if the streptococcal infection is still present.
2. rophylactic antibiotics should be prescribed for pa
tients younger than 25 years of age to prevent recur
rent episodes.
48. lnfective Endocarditis
eeeeeeeeeeeeee+e+eeeeeeeeeqeeeeeeeeeeeeeeeeeeee
@
@
INTRODUCTION
A. Appropriately diagnosing and treating infective endocar
ditis usually leads to a good outcome, whereas failure to
deliver proper therapy often results in serious morbidity
and mortality.
B. Typically, acute endoarditis results from Staphylococcus
aureus infection of previously normal valves, and may
result in rapid valvular dysfunction and death. Subacute
endoarditis is usually caused by a streptococcal viridans
infection of previously abnormal valves, and has a slower
course; however, overlap between these two presenta
tions does occur.
C. "Rule out endocarditis" in patients with fever and a
history of intravenous drug use (IVDU) is a common
hospital admitting diagnosis. This chapter will help you
approach the "shooter with a fever," as well as other
patients with suspected or proven endocarditis.
CAUSES OF INFECTIE ENDOCARDlTIS
A. Streptooccal viridans (Streptococcus salivarius, Strepto
coccus sanguis, Streptococcus mitior, and Streptococcus
milleri), enterococci, and Streptococcus bovis (nonen
teroccocal group D streptococci) account for most cases
of native valve endocarditis in patients without a history
of IVDU.
B. Staphylococcus aureus and Staphylococcus epidermidis
are the most common causes of IVDU-related endocar
ditis and prosthetic valve endocarditis, respectively.
C. Gram-negative bacteria can cause endocarditis, usually
in association with genitourinary or gastrointestinal pro
cedures or surgery.
D. Culture-negative organisms may cause endocarditis in
patients who have recently received antibiotics or who
have certain types of infections.
1. HACEK group organisms. Haemophilus, Actinobac
illus, Cardiobacterium, Eikenella, and Kingella are
Gram-negative organisms that often grow slowly
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Infective Endocarditis 279
over weeks; therefore, ask the laboratory to save

the blood cultures for a prolonged period if culture
negative endocarditis is suspected .
2 Fungi. Large vegetations are often found in patients
with endocarditis associated with Candida or Asper
gillus infection. An intravascular source is frequently
noted (e.g., an indwelling intravenous catheter). Spe
cifc fungal cultures may be required.
3. Rickettsia (Coxiella buretii) and chlamydia (Chla
mydia psittaci and Chlamydia trachomatis) are rare
causes of culture-negative endocarditis.
CUNICAL MNIFESTATIONS OF INFE ENDRDIS.
The clinical manifestations of endocarditis are variable,
but most closely depend on which organism is involved
and whether the patient has left-sided (aortic or mitral) or
right-sided (usually tricuspid) disease.
A. Fever occurs in almost all patients; however, elderly pa
tients and patients taking steroids or nonsteroidal anti
infammatory drugs (NSAIDs) may be afebrile.
B. Murmurs. With the possible exception of tricuspid dis
ease (which is usually associated with IVDU), a murmur
is almost always present. Murmurs are often not promi
nent; therefore, their signifcance may b underesti
mated.
C. Low back pain, arthralgias, and myalgias are very
common.
D. Splenomegaly may occur with subacute endocarditis.
E. Classic fndings, including Osler's nodes, Janeway le
sions, Roth spots (retinal hemorrhages), petechiae ofthe
palate or conjunctiva, and splinter hemorrhages (be
neath the nailbed) are not often found.
H OT
Although Osler's nodes are Iypi cally violaceous lesions
located on the tips of the Fingers or toes, and Janeway
lesions are Ipically erythematous and found on the
palms or soles, the predominant distinction beleen
the Iwo is that Osler's nodes are painful whereas Jane
way lesions are painless.
K E Y
280
Chapter 48
COMPUCATIONS OF INFECTIVE ENDOCARDITIS
A. Congestive heart failure (CHF). Pulmonary edema and
hypotension may occur with signifcant left-sided (aortic
and mitral) valve dysfunction, whereas peripheral edema
may result from right-sided (tricuspid) disease.
.
B. Myoardial abscess formation can lead to bradycardIa
with varying degrees of heart block.
C. Emboli. Left-sided endocarditis may result in peripheral
infarcts, whereas right-sided endocarditis may cause sep
tic emboli with pulmonary infarction, abscess formation,
or both.
A. Patient history
1. Infective endocarditis is a diagnosis that is often
missed; therefore, always make sure to include endo
carditis in the "head to toe" approach to fever (see
Chapter 43).
2. Be sure to ask the patient about risk factors for
endocarditis (i.e., IVDU, known valvular disease, re
cent procedures or surgery).
B. Physical examination. In addition to performing a com
plete physical examination, pay special attention to the:
1. Fundoscopic examination (to search for Roth spots)
2. Cardiac examination (to detect murmurs)
3. Skin examination (to search for Osler's nodes, Jane
way lesions, and petechiae)
C. Laboratory studies. Patients who have an unexplained
fever, a low clinical probability of endocarditis, and are
conscientious concerning follow-up can sometimes be
evaluated as outpatients. Active intravenous drug users
with a fever (with or without a murmur) and no obvious
alternative source of infection are almost always admit
ted to rule out endocarditis.
1. Blood cultures are the gold standard for diagnosis.
Two sets of aerobic and anaerobic cultures are usu
ally obtained; however, three sets may increase the
sensitivity to over 90%.
a. Different venous sites are usually used to avoid
confounding skin contamination.
b. Cultures should always be taken prior to initiat
ing empiric antibacterial therapy.
2. Echoardiography. Because the duration of therapy
may differ depending on which side of the heart
(left or right) is involved, echocardiography is often
Infective Endocarditis
281
performed to defne which valve is infected. Trans
thoracic echocardiography is often performed frst,
followed by transesophageal echocardiography in
cases where the diagnosis is still in question, but the
cost effectiveness of this approach is unclear.
a Transthoracic echocardiography (TIE), with a
sensitivity of approximately 60%, is not sensitive
enough to rule out endocarditis. In addition, TE
is notoriously poor for ruling out mitral valve
disease.
b. Transesophageal echocardiography (TEE) in
creases the sensitivity to approximately 95%, and
is markedly better for evaluating the mitral valve.
TREATMENT
A. Empiric therapy
1. Suspected acute endocarditis is a common consider
ation in intravenous drug users with a fever. S. aureus
can destroy the valve rapidly, so therapy is initiated
immediately after blood cultures are drawn.
HOT
KEY
a. Nafcillin plus gentamicin is often used in regions
where the incidence of MRSA is low.
b. Vancomycin plus gentamicin may be adminis
tered in regions where the incidence of MRS A
is high.
The benefits of added gentamicin include the fl
lowing:

Synergy against S. aureus, which decreases the
duration of bacteremia
Broader coverage against gram-negative and
multi-organism infections, an i mportant advantage
in intravenous drug users.
2. Suspected subacute endocarditis may be treated with
penicillin and an aminoglycoside. Because the conse
quences of not treating S. aureus infection can be
severe, this regimen should only be considered in
patients with a chronic and very stable course.
3. Suspected prosthetic valve endoarditis may be
treated with vancomycin and an aminoglycoside.
This regimen will cover methicillin-resistant S epi-
282 Chapter 48
dermidis (a common offender) while treating possi
ble enterococcal infection as well.
B. Organism-specifc therapy. The duration of therapy may
vary depending on whether disease is right- or left-sided,
and on the minimal inhibitory concentration (MIC) of
the antibacterial needed to inhibit organism growth.
1. Streptococcal viridans infections are usually treated
with penicillin and an aminoglycoside. Therapy may
range from 2-6 weeks, depending on the MIC.
2. Enterococcal infections usually require prolonged
therapy and are often treated with penicillin and an
amino glycoside for 4-6 weeks.
3. Staphylococcal infections
a. Methicillin-sensitive S. aureus (MSSA) infec
tions may be treated with nafcillin with or with
out an aminoglycoside.
b. Methicillin-resistant S. aureus (MRSA) infec
tions may be treated with vancomycin with or
without an aminoglycoside.
C. Surgery. Valve replacement is often indicated when:
1. Fungal infection is strongly suspected
2. A prosthetic valve is infected
3. Complications [e.g .. myocardial abscess or acute val
vular dysfunction associated with congestive heart
failure (CHF)] have developed
4. Medical therapy has failed
5. The patient has experienced more than one em
bolic event
FOLLOW-UP
A. Frequent examinations are essential. Listen carefully for
a new or changing murmur, look closely for embolic
phenomena, and watch for widening of the pulse pressure
(which should alert you to possible aortic regurgi
tation).
1. Bilateral disease. Although intravenous drug users
more commonly have right-sided disease, they may
also have left-sided or bilateral endocarditis. You
should therefore continue to assess possible left
sided involvement.
2. Persistent fever. Defervescence usually occurs within
1 week, but more prolonged fevers may be noted
with S. au reus infection. Drug reactions are the most
common cause of persistent or recurrent fever, hut
myocardial and metastatic abscess formation should
I
I
I
I
I
I
I
Infective Endocarditis
283
always be considered (especially with S. aureus infec
tions).
B. Electrocardiograms (EKGs). Lengthening of the PR in
t
rval should
rompt an echocardiogram to evaluate pos

s
ble myocardIal abscess formation (TEE is more sensi

tIve). An EKG should be obtained on admission and
often on a daily basis thereafter (especially with S.
aureus infection).
49. CD4 Counts and Complications
of HIV Infection
M
INTRODUCTION. In HIV -positive patients. the list of differ
ential diagnoses for an opportunistic infection or malg?
cy
is extensive. In addition to the multitude of possibilities.
patients who are HIV -infected often present with prot
an
symptoms (such as fever or weight loss) that make shorte
.
nmg
the list of differential diagnoses diffcult. However. patients
infected with HIV acquire opportunistic infections and ma
lignancies at relatively predictable CD4 counts, and by
.
sim
ply noting a recent CD4 count, you can make a relatively
short list of the likely causes of a new symptom.
HOT
Remember that a CD4 count obtai ned during an acute
illness may be falsely low or falsely high. It is therefore
best to use recent CD4 counts if they are available.
KEY
Q
DIFFERENTIAL DIAGNOSES ACCORDING TO CD4
COUNT. CD4 counts should only be used as a general guide
because there is a great deal of variability among patients.
Common diseases that occur as the C4 count falls are
discussed here.
A. CD4 count < 800 cells! /l
1. Bacterial infection. Pneumococcal pneumonias are
common.
2. Extrapulmonary or pulmonary tuberculosis. Extr
pulmonary tuberculosis is much more common In

HIV -infected patients. Central nervous system
(CNS), abdominal, lymphatic, pleural, bone, and mil-
iary tuberculosis are all possibilities.
. .
3. Lymphoma. In patients with CD4 counts m thiS
range, lymphomas are systemic. not the primary CNS
lymphomas that occur with lower counts.
284

t
,
CD4 Counts and Complications of HIV Infection
TABLE 49- 1 : Summary: CD4 Counts and Likely Differential
Diagnoses for Symptoms in HIV-Infected Patients
CD4 Count (celis/ill) Likely Infctions and Malignancies
<800
<500
<200
<1 00
Any CD4 count
Bacterial infection, tuberculosis,
lymphoma, Kaposi's sarcoma
Coccidioidomycosis, histoplasmosis, candi
diasis
Pneumocystis carinii pneumonia, toxoplas
mosis, Crptococcus infection
Mycobacterium avium complex infection,
cytomegalovirus infection, primary CNS
lymphoma, baCillary angiomatosis
Hepotitis, syphilis, herpes virus infec
tion, influenza virus infection
285
4. Kaposi's sarcoma. Patients may have pulmonary and
gastrointestinal involvement as well as the typical
skin lesions.
B. CD4 connt < 500 ceUs! /l
1. Coccidioidomycosis may be manifested as pneumo
nia, meningitis, or skin and soft tissue infection.
2. Candidiasis
a. Oral candidiasis and esophagitis a very common.
b. Disseminated disease is more likely in patients
with neutropenia or intravascular catheters, or
in those taking broad-spectrum antibiotics.
3. Histoplasmosis can cause pulmonar disease or dis
seminate and cause a sepsis-like picture.
C. CD4 connt < 200 cells! /l
1. Pneumocystis carinii pneumonia (see Chapter 50)
2. Toxoplasmosis often manifests with CNS disease
(see Chapter 52)
3. Crptococcu infection is a common cause of menin
gitis.
D. CD4 connt < 100 cells!/l
1. Mycobacterium alium complex infection usually
causes fever, cytopenias, and cachexia.
2. Cytomegalovirus (CM) infection. Retinitis, esoph
agitis, colitis, AIDS cholangiopathy, and polyradicu
lopathy may all be seen with CMV infection.
286
Chapter 49
3. Primary CNS lymphoma (see Chapter 5
)
4. Bacillary angiomatosis usually presents WIth
utne
ous lesions; disseminated disease ma

result m liver
involvement that is usually accompanIed by a mark
edly elevated alkaline phosphatase level.
I
l
I
l
I
l
I
50. Pulmonar Disese in
HIV -Infected Patients
M
Q
INTRODUTION. At least two-thirds of patients with HIV
have symptomatic pulmonary disease al some time during
their lives. One way to approach respiratory complaints in
HI V-infected patients is to:
A. Consider the organisms that can cause disease based on
the patient's CD4 count (see Chapter 49).
B. Narrow the list of possible diagnoses by considering the
appearance of the chest radiograph (Table 50-I). These
patterns are not mutuaHy exclusive, and each pattern
can be caused by many disorders. When it comes to HIV
disease, there are few absolute truths-use Table 50-1
as a starting point, and modify it based on your clini
cal experience.
C. Further narrow the list based on the clinical picure,
laboratory data and results of diagnostic testing.
PNEUMOYSTIS CARINI PNEUMONIA (PCP). When
ever a patient with HIV disease presents with respiratory
complaints, the diagnosis of PCP should always be consid
ered because P. carinii is an extremely common pathogen.
A. The following questions are important to ask when con
sidering PCP as a possible diagnosis:
L. What is the CD4 count? The CD4 count will indicate
the patient's risk for PCP; those with CD4 counts>
200 cells/p.l are at much less risk.
2. Is the patient on PCP prophylaxis? Compliant pa
tients are less likely to have PCP.
3. What is the clinical scenario? Patients with PCP usu
ally present with a subacute onset of shortness of
breath (especially on exertion) that is associated with
fever. fatigue, weight loss, and a dry cough. Commu
nity-acquired pneumonia. on the other hand, usually
presents with the acute onset of a productive cough.
fever, and evidence of consolidation on lung exami
nation.
287
288 Chapter 50
TABLE 50- 1 : Radiographic Paterns in HIV-Associated Pulmonary
Disease
Radiographic Patern Common Disease
Normal Pneumocstis carin iii pneumonia
(PCP)
Diffuse interstitial infiltrates
Pulmonary embolism
PCP
Focal conso/idotion
Pleural effusion
* Usually patchy i nfiltrates.
Dissemi nated fungal infection
Tuberculosis
Kaposi's sarcoma*
Congestive heart failure (CHF)
Viral and atypical pneumonia
Baterial pneumonia
Kaposi's sarcoma
Tuberculosis
Tuberculosis
Lymphoma
Bacterial pneumonia
Kaposi's sarcoma
CHF
Disseminated fungal infection
4_ Does the physical examination reveal evidence of a
diferent disorder (e.g., tuberculosis, lymphoma, or
Kaposi's sarcoma)?
5. Does the chest radiograph reveal difuse interstitial
infltrates? Diffuse interstitial infltrates are the clas
sic fnding; patients may, however, present with mini
mal changes or atypical fndings (t.g., pleural effu
sions).
6. Are the patient's alveolar-to-arterial (A-a) gradient,
serum lactate dehydrogenase (LDH), and erythro
cyte sedimentation rate (ESR) increased? The
blood gas report allows defnition of the degree of
hypoxia, as well as evaluation for the necessity of
steroid therapy in patients with PCP. (Patients with
an A-a gradient> 35 usually beneft when treated
with corticosteroids.) An elevated LDH and ESR
have also been shown to correlate with the likeli
hood of PCP.
i
i
f
i
I
I
Pulmonary Disease in HIV-Infected Patients
289
HOT
?xygen saturation monitoring can be very useful. Pa
tients who exhibit dramatic desaturation on ambulation
usually have PCP.
KEY
7. !s the sputum purulent? Finding P. carinii organisms
IS extremely diffcult in purulent sputum.
Symptoms consistent with PCP
Incrased A-a gradient or
CXA compatible with PCP
Positive
Negative
Treat for PCP

Positive
Treat for PCP

Normal A-a gradient and
Normal CXA
Obsere
Negative
Treat specific disease

FIGURE 50- . A!g
.
<
rithm for the assessment of patients with suspected
Pneu
oCYSfS corm" pneumonia (PCP. A- gradient alveolar-to-arterial

gradient; CXR chest radiograph.
290
Chapter 50
8. Is the patient's difusing capacity decreased? Patients
with PCP tend to have a decreased DLCU on pulmo
nary function testing.
B. There are many ways to evaluate patients f
r the
possibility of PCP. The alg
?
rithm in Figure 50-1 I.S. o
?
e
approach; it should be modifed based on the sensl
lvlt
?
and specifcity of the various tests available at your mstJ
tution.
51.Gastrointestinal Manifestations
of HIV Disease
M
Q
INTRODUCTION. More than 50% of HIV-infected patients
develop a gastrointestinal illness during the course of their
disease. Esophagitis, enterocolitis, and hepatobiliary disease
are commonly seen in these patients.
ESOPHAGmS usually presents with dysphagia, odynopha
gia, or a substernal sensation of pain or burning.
A. Causes of HIV-related esophagitis. Common causes in
clude the following:
1. Infectious
a. Candida
b. Cytomegalovirus (CMV)
c. Herpes simplex virus
2. Noninfectious
a. Pill-induced
b. Aphthous ulcers (possibly HIV-related)
B. Approach to the patient
1. Empiric antifungal therapy. Patients with symptoms
of esophagtis and oral thrush are usually treated
empirically for candidal oral thrush. Ketoconazole
(often 200 mg orally twice daily) may be administered
for 1-2 weeks. In patients who fail to show rapid
improvement, fuconazole (often 20 mg orally once
daily) may be substituted.
2. Upper endoscopy is usually indicated for patients
without oral thrush and for those who are unrespon
sive to empiric antifungal therapy. Upper endoscopy
usually leads to a diagnosis.
C. Treatment
1. Fungal esophagitis
a Oral ketoconazole or fuconazole is usually the
frst-line treatment, depending on which, if any.
empiric therapy has been attempted.
b. Intravenous amphotericin (0.1-0.3 mglkglday)
may be necessary in patients who are unable
to swallow.
291
292
M
Chapter 51
c. Maintenance therapy may be given as one-half
of the treatment doses (e.g., ketoconazole-200
mg once daily, fuconazole-100 mg once daily).
2. Viral esophagitis
.
a CMV esophagitis is usually treated WIth gan
ciclovir (often 5 mglkg intravenously twice daily
for 2-3 weeks). The maintenance dose is often
5 mg/kg intravenously daily.
. w
b. HSV esophagitis is usually treated with acyclovir.
Intravenous therapy may be necessary in patients
who are unable to swallow and in those who are
very ill (e.g., in patients with esophageal bleeding
or fevers).
c. Unresponsive viral esophagitis may be treated
with foscarnet, which may also be given to pa
tients with CMV esophagitis who are unable to
tolerate ganciclovir therapy.
3. Noninfectious esophagitis may be treated with ste
roids (often prednisone, 4 mg orally daily with a 2-
to 3-week taper).
ENTEROCOUTIS. More than 50% of HIV-positive patients
develop diarrhea at some time during their illness.
A. Causes of HlV -related enterocolitis
1. Opportunistic infection
a. Bacteria. Salmonella, Shigella, Yerinia, and
Campylobacter are common causes of acute diar
rhea in HIV-positive patients. Clostrdium dif
cite is an important consideration in patients ex

posed to antibiotics.
b. Protozoa. Commonly implicated organisms in
clude Entamoeba histolytica, Giardia lamblia,
Crptosporidium, Microsporidia, and Isospora
belli.
c. Viruses. CMV and adenovirus are common
causes of enterocolitis in HIV-infected patients.
d. Mycobacterium avium complex
2. AIDS enteropathy is a diagnosis of exclusion and
may be directly related to the effect of HIV on
the colon.
1. Laboratory studies
a Fecal white blood cell (WBC) count. A fecal
WBC should be performed.
b. Stool culture may be performed to rule out bacte
rial infection.
Gastrointestinal Manifestations of HIV Disease
293
c. Stool ova and parasites (O&P). Three samples
are generally sent to increase the yield. The eval
uation for Cryptosporidium and Microsporida is
enhanced by an acid-fast stain and a modifed
trichrome stain, respectively.
d. Enzyme-linked immunosorbent assay (ELISA)
for C difcite toxin. Three specimens are gener
ally ordered to increase the yield. Because HIV
infected patients frequently receive antibiotics
C difcile may be a commonly missed diagnosis:
e. Blood and stool cultures for Mycobacterium
avium complex should be considered in patients
with a C4 count of less than 100 cells/ILl.
2. ndoscopy is often necessary when symptoms con
tmue and no etiology has been identifed.
a. CMV is a very common pathogen that is often
missed by the initial screening studies.
b. Colonoscopy (followed by upper endoscopy with
small bowel biopsy if colonoscopy fndings are
normal) may be performed, although the yield
for fnding a treatable pathogen is generally low.
e. Treatment
1. Empiric antibacterial therapy (e.g .. ciprofoxacin 500
mg orally twice daily for 5 days) is often initiated in
patients who present acutely with fever, diarrhea or
positive fecal WBCs.
'
2. Specifc therapy depends on the causative organism.
HEPATOBIUARY DISEASE. Many HIV-infected patients
have asymptomatic alterations in their liver transaminase or
alkali
e phospatase levels. When symptoms occur, they

?
ten mclude nght upper quadrant pain, nausea, and vom
ItIng.
A. Causes of HIV -related hepatobiliar disease
1. Viruses. including hepatitis B, hepatitis C, and CMV
2. Mycobacterium avium complex
3. Lymphoma
4. Medications, including sulfa drugs, isoniazid, rifam
, ketoconazole, and fuconazole, can cause hepa

titis.
5. Sclerosing cholangitis (i.e., AIDS cholangiopathy)
often presents with right upper quadrant pain accom
panied by a marked elevation in the alkaline phos
phatase level that is out of proportion to transaminase
elevations. Infection with CMV or Cryptosporidium
may be involved in the pathogenesis.
294
Chapter 51
Less common canses of hepatobiliary pa
hology
.
i
-
6.
elude fungal disease (e.g., histoplasmosIs1 c
?
c CId
oidomycosis), Kaposi's sarcoma, tubercu OSIS. an
peliosiS hepatis from Rochalimaea henselae or Ro-
chalimaea quintana.
.
uld b b
1 Patent history. A medication hIstOry sho
.
e
?
-
tained to search for potentially hepatotoxIc medIca-
tions.
Physical examination. A skin examination may
2
.
disclose evidence of bacillary angiomatosis or
Kaposi's sarcoma.
a Hepatitis Band C serologies a
e ofte

sent.
b. Blood cultures for Mycobacterum avrum com-
plex may be ordered.
.
4. Imaging studies. Although
.
i
itia
f
l
t
evalua
c
t
l
l
e
o
a
n
r w
m
t
cover a potential etiology, It IS 0
n un
that disease is an incidental fndmg or
he caus of
the hepatobiliary process. Imaging st
dl es are o
(
ten
r d to rule out other dIsorders e.g.,
pe orme
lymphoma).
I t
Ultrasound may be especially useful for eva ua -
a.
.
the bile ducts. and is therefore often chosen
; patients suspected of having biliary obstrc
tion (e.g., those with an elevated serum alkahne
phosphatase level).
b. Computed tomography (C
h
T)
I
.
A CT SC
n
a
C
y
p
vides better resolution of t e !Ver pare
.
'
and is useful for patients suspected of havtng
parenchymal disease.
Endoscopic retrograde cholangiop
ncrea
!
ogra-
c.
phy (ERCP) may be used for th
.
e
.
dIagnos
s a
d
treatment of sclerosing cholangttIs. In hIS dIS
ease, intraluminal irregularties of the Ile ducts
are often accompanied by dl
tal narrowI
g of the
common bile duct (i.e., papIllary ste
osl s) .
.
5. Liver biopsy may be conside
ed for patIents WIth a

negative evaluation and perslstent
.
sympt
?
ms.
Treatment depends on the cause. In patIents WIth scler-
C.
ing cholangitis, papillary sphincterotomy may provi e
symptomatic beneft.
I
I
I
I
E
J
C
I
E
G
F

U

5
L
I
0
0
3
C
5
3
C
I
I
I
I
I
5
C
|
C
I
L
F
|
0
3
I
I
52. Neurologic Manifestations
of HIV Disease
M
INTODTON. HIV -infected patients frequently develop
neurologic disorders, which can be divided into fve clinical
categories: meningitis, space-occupying lesions, encephalop
athy, myelopathy, and peripheral neuropathy.
MENINGIS
A. Causes of meningitis. The following are common causes
of meningitis in HIV-positive patients.
B.
1. Bacteria ( see Chapter Rl II A)
2
.
Viruses. Herpes simplex virus, cytomegalovirus
(CMV), and the JC virus may cause aseptic meningi
tis as well as encephalitis. HIV itself may cause cere
brospinal fuid ( CSF) pleocytosis and elevated CSF
protein even without clinical meningitis.
3. Fungi. Cryptococcal meningitis is common, often
presenting as fever and a headache without neck
stiffness or photophobia.
4. Spirochetes. The incidence of central nervous system
( CNS) syphilis is increased in HIV-infected patients.
5. Mycobacteria. Tuberculosis is the most common my
cobacterial cause of CNS disease in HIV -positive pa
tients.
6.
Malignancy. Lymphomatous meningitis is the most
common malignant etiology.
Approach to the patient. In general, the approach to an
HIV-positive patient with suspected meningitis is the
same as that for other patients ( see Chapter Sl IV).
However, the increased likelihood of certain etiologes
leads to a few specifc considerations for HIV-infected
patients with possible meningitis.
1. A serum or CSF cryptococcal antigen (CRAG) titer
should be obtained in HIV -infected patients who are
being evaluated for possible meningitis. The serum
CRAG is more sensitive than the CSF CRAG. but
the sensitivities of each may exceed 90%.
2. A CSF Venereal Disease Research Laboratory
(VORL) test is often performed to evaluate the pos
sibility of neurosyphilis.
295
296
@
Chapter 52
3. The presence of an unexplaine CSF l
p
?ocytic
pleocytosis or evidence of a basd
r memngl tl s (
.g.,
meningitis with cranial nerve fndmgs) usually r
lses
suspicion of meningitis related to tuberculosIs or
lymphoma.
a CSF analysis. Multiple CSF sampl
s shoul
.
d
.
be
sent for cytology and acid-fast bacillus stammg
and culture.
b. A tuberculin purifed protein derivatve (PPD)
skin test may be performed to evaluate exposure
to tuberculosis.
c. Magnetic resonance imagi
g RI) i
.
s often use
ful to look for basilar memngtIs; a bIOpsy of the
brain or meninges is sometimes necessary for
defnitive diagnosis.
C. Treatment depends on the cause.
SPACE-OCCUPYING LESIONS may present as headaches,
seizures, focal sensory or motor defcits, visual feld defects,
or altered mental status.
A. Causes of space-occupying lesions. Although all of the
following causes should be considered in a patient
ho
presents with signs and symptoms of a spa
e-occupym

lesion, the frst two are the most common m HIV -POSI
tive patients.
1. Toxoplasmosis
2. Primary CNS lymphoma
3. Bacterial abscess
4. Cryptococcoma
5. Tuberculoma
6. Nocardiosis
1. Imaging studies. A computed tomogr
phy (CT) or
MRI scan is often useful for evaluatmg suspected
CNS disease in HIV-infected patients.
a. C sa. Many space-occupying lesions are b
t
ter seen with contrast enhancement, which
should be used in the absence of contraindica
tions.
b. MRI is generally a more sensitive te
t and may
reveal multiple lesions when only a smgle leSIOn
is seen on CT scan.
a. A serum CRAG titer is frequently ordered.
Neurologic Manifestations of HIV Disease
297
HOT
KEY
b. Blood cultures and a PPD test may also be ob
tained, depending on the clinical situation.
c. Toxoplasmosis titers have limited utility.
lumbar punctures are rarely useful for evaluating
space-occupying lesions i n HIV-infected patients.
3. Stereotactic brain biopsy. This procedure may be
performed early in the diagnostic work-up in the
following types of patients:
a Those with an increased risk for processes other
than toxoplasmosis (e.g., intravenous drug users,
who have an increased risk of a brain abscess)
b. Those with single lesions on MRI (because find
ing a single lesion makes toxoplasmosis less
likely)
c. Those with progressive neurologic defcits or
mass effect on imaging (because appropriate
treatment is needed immediately)
d. Those who do not have regression of the space
occupying lesion or lesions after 2 weeks of em
piric toxoplasmosis therapy
C. Treatment depends on the cause. Because toxoplasmosis
is the most common etiology, an empiric trial of sulfadia
zine (or clindamycin) combined with pyrimethamine is
often given for 2 weeks, followed by repeat brain im
aging.
ENCEPHALOPATHY
A. Any alteration in mental status requires a thorough eval
uation to rule out reversible causes (see Chapter 76).
An imaging study (preferably an MRI) and spinal fuid
analysis are necessary to rule out infectious or malignant
processes. Neuropsychiatric testing is frequently per
formed to help rule out depression.
298 Chapter 52
B. Many patients are ultimately diagnosed as having AIDS
dementia, an illness that occurs late in the course of HIV
infection and is often characterized by memory defcits,
word finding diffculties, and motor slowing. Imaging
studies frequently reveal brain atrophy. Zidovudine is
usually prescribed in an attempt to slow progression of
the dementia.
MYELOPATHY usually presents with progressive lower ex
tremity weakness that may be accompanied by blader or
bowel incontinence. Evidence of upper motor neuron dIsease
with a spastic paraparesis and hyperrefexia are usually noted
unless a peripheral neuropathy is also present.
A. Causes of myelopathy. Spinal cord disease often results
from infection, external compression injury (i.e .. cord
compression) or miscellaneous insults.
. .
1. Infection. Viruses (CMV, herpes sImplex vIruS, and
HIV), fungi (Cryptococcus), spirochetes (Treponema
paWdum), and parasites (Toxoplasma) can infect the
spinal cord, leading to myelopathy.
2. Cord compression may result from epidural ab
scesses (e.g., from bacterial infection or tuberculosis)
or from malignancy (e.g., CNS lymphoma).
3. Miscellaneous causes
a Vascular insults (e.g., vasculitis)
b. Vitamin B\2 defciency
c. HIV -related vacuolar myelopathy is a diagnosis
of exclusion and usually occurs late in the course
of HIV infection. Motor weakness and decreased
proprioception often refect preferential loss of
myelin from the lateral and dorsal columns, re
spectively. There is no proven therapy.
.
.
1. Imaging studies. MRI of the Involved area of spmal
cord helps to rule out spinal cord compression.
a. Spinal fuid analysis with CRAG titers (serum,
CSF or both) and a CSF VR should be ob
tained.
b. Culture and serology for CMV may be useful to
evaluate the possibility of CMV polymdiculopa
thy (see VI A).
c. A vitamin BI2 level should be obtained.
PERIPHERAL NEUROPATHY is fairly common i patients
with AIDS.
Neurologic Manife5tatian5 of HIV Di sease
299
A. Causes of peripheral neuropathy. All causes of periph
eral neuropathy should be cunsidered (see Chapter 77);
however, common causes and patterns of peripheral neu
ropathy in patients with AIDS are given here.
1. Polyneuropathy
a. Predominantly sensory neuropathies are the
most commonly seen peripheral neuropathies in
AIDS patients. The typical presentation is the
development of painful dysesthesias late in the
course of the disease. Treatment may involve
changing antiretroviral medication, and symp
tomatic therapy with tricyclic antidepressants,
carbamazepine, and/or topical capsaicin.
b. Predominantly motor neuropathies
(1) CMV polymdiculopathy may cause progres
sive lower extremity weakness associated
with a CSF neutrophilic pleocytosis (in the
absence of bacterial infection). Therapy with
ganciclovir may result in clinical im
provement.
(2) An infammatory demyelinating polyneurop
athy may result in severe motor weakness
and markedly depressed nerve conduction
velocities. The clinical scenario resembles
that of the more acute Guillain-Barre syn
drome. Plasmapheresis is often used as
treatment.
2. Mononeuropathy is much less common than poly
neuropathy. Although HIV itself is an etiology, other
infections (e.g., CMV. herpes zoster virus) and malig
nancies (e.g., lymphoma) should be ruled out.
B. Approach to the patient. Other potentially reversible
causes of peripheral neuropathy should be considered
(see Chapter 77).
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53. Pancyopenia
eeeee+&e&+e++eeeeeeeeee&+&+eeeeeeeeeeeee
@
INTRODUCTION. Pancytopenia is defined as a decrease in

all blood cell lines.
CUNICAL MANIFESTATIONS OF PANCYOPENIA
A. Pancytopenia usually presents with signs and symptoms
that are related to a decrease in each cell tine.
1. Anemia can result in increased fatigue, shortness of
breath, lightheadedness. and pallor.
2. Thrombocytopenia
a Patients with platelet counts greater than 90,000
cells/ pJ have normal bleeding times (unless plate
let function is abnormal), and are usually asymp
tomatic.
b. Easy bruisability may be noticed as the platelet
count approaches 50,000 cellS/.
c. Counts below 20,000 cells/ pJ can be associated
with petechiae, mucosal bleeding, and spontane
ous internal bleeds.
3. Neutropenia predisposes patients to bacterial infec
tions, but patients usually present with symptoms
related to anemia or thrombocytopenia frst. The risk
of infection increases substantially once the neutro
phil count falIs below 500 cells/ JI.
B. Disease-specifc symptoms (e.g., neurologic symptoms in
vitamin BIl defciency, cachexia in malignancy) may also
be present.
HOT
KEY
Pancytopenia is a great reminder that even mild, non
specific symptoms can be the harbinger of a serious
illness. You should therefore consider getting a com
plete blood count (eBC) on all patients with a pro
longed or recurring illness.
303
304
M
Chapter 53
CAUSES OF PANCYOPENIA. Many textbooks attempt to
differentiate causes of decreased production from those of
increased destruction. For pancytopenia. this distinction is
not very useful because both processes are often involved.
The mnemonic "PANCYTO" can help you remember the
most common causes of pancytopenia.
Common Causes of Pancytopenia
("PANCYTO")
Paroxysmal nocturnal hemoglobinuria (PNH)
Aplastic anemia
Neoplasms and Near neoplasms
Consumption
Vitami n deficiencies (the "Y" looks l i ke a "Y")
Toxins, drugs, and radiation therapy
Overwhelming infections
A. PNH is a disorder of stem cells that results in an increased
sensitivity for complement-mediated cell ly
is.
.
.
B. Aplastic anemia is one of the misnomers In medICIne
because it involves a disorder of stem cells, and therefore
afects all cell lines. An immune mechanism is probable.
Exposures and disorders associated with aplas!ic anemia
are listed below; many cases of aplastic anemIa have no
identifable association.
1. Fanconi's anemia is an autosomal recessive disease
that usually appears in childhood and is often associ
ated with other congenital abnormalities (e.g., car
diac and renal malformations, hypoplastic thumbs,
hyperpigmented skin).
2. Drugs and toxins. Chemotherapeutic agents, chlor
amphenicol, sulfa drugs, and benzene have been as
sociated with aplastic anemia.
3. Infections. Hepatitis (espcially hepatitis C), Ep
stein-Barr virus infection, and other viral infections
have been associated with aplastic anemia.
4. Immune disorders may be associated with aplastic
anemia.
C. Neoplasms (e.g., leukemia, metastatic malignancies) and
near neoplasms (i.e., myelodysplasia) can cause pancyto
penia.
D. Consumption
I
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Pancytopenia
305
1. Hypersplenism (see Chapter 29 I B), regardless of
the cause, can result in pancytopenia.
2. Immune-mediated destruction usually results in de
creases of one or two cell lines. but can also cause
pancytopenia.
E. Vitamin defciencies (e.g .. vitamin Bt2 and folate def
ciencies) should always be considered in patients with
pancytopenia.
F. Toxins, drugs, and radiation therapy. For example, etha
nol use may result in pancytopenia.
G. ve
helming infections. Sepsis, tuberculosis, or fungal

InfectIOn can cause pancytopenia. HIV infection can also
result in pan
ytopenia. from the infection itself, superim

posed InfectIOns, or medications used to treat the in
fection.
HOT
KEY
Pancytopenia should be considered leukemia until
proven otherise.
A. Patient history. Inquire about medications, exposures,
and HIV risk factors. Perform a review of systems. asking
the patient about cachexia and other symptoms of an
occult malignancy.
B. Physical examination. Carefully examine the spleen and
lymph nodes. The presence of splenomegaly increases
the likelihood of malignancy and essentially rules out
aplastic anemia.
C. Laboratory studies. Although a bone marrow biopsy is
usually indicated and diagnostic, there are some potential
clues to the diagnosis that can be obtained on a routine
peripheral blood smear. Other tests may also be indi
cated in certain patients.
1. Peripheral blood smear
a. Megaloblastosis increases the likelihood of vita
min Bt2 or folate defciency.
306
Chapter 53
b. Blasts implicate a possible leukemia.
c. Leukoerythroblastic smear. A leukoerythroblas
tic smear, which reveals early (nucleated) red
blood cells (RBCs) and early white blood cells
(WBCs) [i.e., bands, metamyelocytes, myelo
cytes]. implies marrow invasion by m
.
alignancy,
fbrosis, or infection. Teardrop cells (I.e., RBCs
shaped like a teardrop from being "squeezed"
out of the bone marrow) are fequently seen with
leukoerythroblastosis.
.
.
.
d. Pelger-Huet anomaly (i.e., neutrophds wIth bI
lobed nuclei) is seen in patients with myelodys
plasia (see Chapter 64).
2. Vitamin BIZ and folate levels are often obtained.
3. HIV test. An HIV test should be performed in pa
tients with risk factors.
4. PNH workup. PNH results in intravascul

hemolysis
that can cause iron defciency from unnary losses;
therefore, PNH should be ruled out in all patients
with pancytopenia and suspected iron defciency
[e.g., when the mean corpuscular volume (MCV) is
low]. The sucrose hemolysis te
t assesses th

.
suscep
tibility of RBCs to lysis and IS both senSItIve and
specifc for PNH.
D. Bone marrow biopsy. Because a "dry tap" may occur
(i.e .. one in which bone marr
w aspirat is unobtainable
as a result of aplasia, fbroSIS, or malignancy), a core
biopsy is essential in order to determine the etiology
<
f
the pancytopenia. Patients with HIV and pancytopema
often still undergo bone marrow biopsy to rule out a
contributing infection or malignancy.
1. Increased cellularity suggests peripheral destruction
(hypersplenism, PNH. im
.
m
ne-mediated dis
?
rders)
or ineffective erythropOIeSIs (myelodysplasIa). Of
note, PNH and myelodysplasia may also display de
creased cellularity.
2. Decreased cellularity is the more common fnding
and may implicate aplastic anemia.
3. Other fndings. Evidence of malignancy, infection,
or myelodysplasia may also be found.
TREATMENT
A. General treatment is aimed at preventing the complica
tions associated with a decrease in each cell line.
L Packed RBC transfusions are usually gven to main-
Pancytopenia 307
tain the hematocrit above 30% in symptomatic pa
tients and older patients with known or suspected
coronary artery disease. Younger patients may toler
ate a much lower hematocrit.
2 Platelet transfusions may be necessary (see Chap
ter 54).
3. Infection prevention and treatment
a. Granulocyte-macrophage colony-stimulating
factor (GM-CSF) is sometimes used to increase
neutrophil counts.
b. Neutropenic precautions (e
.
g., hand washing,
minimizing injections, avoiding unpeeled fruit).
The risk from neutropenia is highest when the
patient's absolute neutrophil count is less than
500 cellslpJ. Neutropenic precautions should be
used for these patients. Prophylactic antibiotics
in the absence of signs or symptoms of infection
are not recommended.
c Broad-spectrum antibiotics shOUld be used for
patients with fever and neutropenia, which
should be treated as a medical emergency.
B. Specifc treatment is aimed at the underlying illness. Spe
cifc treatments for most of the causes of pancytopenia
are found in the relevant chapters. Therapies for PNH
and aplastic anemia will be briefy discussed here.
L PNH carries approximately a 4% lifetime risk of
thrombosis. (The mechanism is unclear.) Bleeding
from thrombocytopenia can also occur; approxi
mately 50% of patients with PNH die from one of
these two complications. Spontaneous remission may
occur in approximately 15% of patients.
a. Chronic anticoagulation therapy is indicated for
all patients with a history of thrombosis and
should also be considered prophylactically for
patients without severe thrombocytopenia.
b. Bone marrow transplantation may be curative
for the small group of eligible. young patients.
2. Aplastic anemia
a. Removal of potential etiologies (e.g., medica
tions) is always important.
b. Pharmacologic therapy
(1) Antithymocyte globulin (ATG) is usually the
frst-line pharmacologic treatment.
(2) Androgens are sometimes useful for patients
with mild aplasia, but are generally not effec
tive in patients with more severe disease.
308
Chapter 53
c. Bone marrow transplantation may cure 80% of
the young. eligible patients seected. ec
use
transfusions may increase the nsk of
eJectIon,
transplant candidates should only receIve trans
fusions when it is absolutely necessary, and trans
fusions from potential donors should never be
given.
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54. Thrombocyopenia
@
M
INTRODUCTION. Thrombocytopenia, a common disorder
in hospitalized patients, is defned as a platelet count less
than 10,000 cells! ,..1.
CLINICAL MANIFESTATIONS OF THROMBOCYTOPENIA.
Signs and symptoms are related to the degree of thrombocy
topenia (in the absence of concomitant disorders of coagula
tion or platelet dysfunction).
A. Platelet count 50,000-90,000 cells! ,.1. Clinical manifesta
tions are usually absent.
B. Platelet count 20,000-50,000 cells!,. 1. Patients may re
port easy bruisability, but spontaneous bleeding is usu
ally not seen.
C. Platelet count < 20,000 cells! ,. 1. Patients are at increased
risk for spontaneous bleeding (e.g., petechiae, gastroin.
testinal bleeding).
CAUSES OF THROMBOCYTOPENIA. It is easiest to remem
ber the causes of thrombocytopenia if you classify them
according to the underlying mechanism: decreased produc
tion, splenic sequestration, or increased destruction (Figure
54- 1).
A. Decreased production. Because diseases of the bone
marrow are involved, there is often a decrease in other
cell lines as well. The causes of decreased platelet produc
tion are almost identical to those of pancytopenia (i.e ..
"PANCYTO"; see Chapter 53 III), with the exception
of consumption ('C").
Causes of Decreased Platelet Production
("PANYTO")
Aplasia
Vitamin deficiencies (the "V" looks like a "Y")
Overwhelming infection
309
3 1 0
Chapter 54
PNH
Aplasia
Neoplasms,
Medications
Infections
Rheumatologic
MAHA
PNH
near neoplasms
Vitamin deficiency
Toxins, drugs, radiation
Overwhelming infections
disease
Idiopathic
Figure 54- 1 . Causes of thrombocytopenia. MAHA microangio
thi

hemolytic anemia (MAHA); PNH paroxysmal nocturnal hemoglablnurla.
1. PNH is more commonly associated with increased
destruction, but may also be associated with a pro
duction defect.
2. Aplasia. Aplastic anemia causes pancytopenia; rare
constitutional diseases that result in isolated de
creased megakaryocytic proliferation include con
genital amegakaryocytic hypoplasia and thrombocy
topenia and absent radii (the TAR syndrome).
3. Neoplasms and near neoplasms include leukemia,
metastatic malignancies, and myelodysplasia.
4. Vitamin defciencies, including vitamin BI2 and folate
defciency, are rare causes of isolated thrombocyto
penia.
5. Toxins, drugs, and radiation therapy. Ethanol. thia
zide diuretics, estrogens, and chemotherapeutic
agents can cause throm bocytopenia.
6. Overwhelming infections. including sepsis. tubercu
losis, fungal infection, and H I V disease, can cause
thrombocytopenia.
t
Thrombocytopenia 3 1 1
B. Increased splenic sequestration can result from hyper
splenism of any cause, leading to thrombocytopenia.
C. Increased destruction is probably the most common
cause of isolated thrombocytopenia. Disorders that cause
increased destruction of platelets can be classifed as
nonimmunologic or immunologic.
I. Nonimmunologic
a. Microangiopathic hemolytic anemia (MAHA)
may cause platelet destruction as a result of
shearing in small vessels (see Chapter 56).
h. PNH predisposes all cell lines to complement
mediated lysis and is therefore a rare cause of
isolated thrombocytopenia.
2. Immunologic. Destruction may be related to medica
tions, infections, or rheumatologic disease, or it may
be idiopathic [e.g., idiopathic thrombocytopenic pur
pura (ITP)].
A. Exclue
.
pseud
thrombocytopenia. Pseudothrombocy
topema IS an artIfact of platelet clumping in the test tube
in EDTA-anticoagulated blood. Examining the periph
eral blood smear may alert you to the problem. and
s
ding a heparinized specimen will confrm your sus

pICIOn.
B. Try to determine the cause of the thrombocytopenia.
1. Patient history. Pay particular attention to the pa
tient's medications. Risk factors for HIV or a history
of substance abuse (e.g., alcohol) also deserve atten
tion. A review of systems and asking about "B symp
toms" (i.e., fevers, night sweats, and weight loss) may
help reveal an occult malignancy.
2. Physical examination. A complete physical examina
tion is always necessary.
a. Examination of the spleen is of particular impor
tance (see Chapter 29 IV).
b. In addition, a thorough examination for lymph
adenopathy shOUld be performed (see Chapter
62 II).
a. Peripheral blood smear. A peripheral blood
smear is often helpful.
(1) Large platelets. This fnding implies in
creased destruction and early release from
the bone marrow. ITP is classically associated
3 1 2 Chapter 54
with fnding large platelets on the peripheral
blood smear.
(2) Schistocytes. The fnding of fragmented red
blood cells (RBCs) implies a microangio
pathic hemolytic anemia.
(3) Other abnormalities that may offer clues are
discussed in Chapter 53 IV C 1.
b. Prothrombin time (PT), partial thromboplastin
time (PTT), and lactate dehydrogenase (LOU)
may be used to evaluate the possibility of a
MAHA. Blood urea nitrogen (BUN) and creati
nine levels should be obtained when hemolytic
uremic syndrome/thrombotic thrombocytopenic
purpura (HUSrrTP) is a consideration.
c. Serologic studies. Antinuclear antibody (ANA),
HIV. and other specifc viral serologies are useful
for evaluating the possibility of immunologic de
struction associated with systemic lupus erythe
matosus (SLE) or infections with HIV or an
other virus.
(1) An HIV test is especially necessary in pa-
tients with HIV risk factors.
(2) Epstein-Barr virus, cytomegalovirus (CMV),
hepatitis, and toxoplasmosis serologies are
most useful when the patient has systemic
symptoms. lymphadenopathy. or splenomeg
aly on examination.
d. Vitamin B12 and folate levels and tests for PNH
are sometimes performed, but are usually not
helpful because these disorders are rarely associ
ated with isolated thrombocytopenia.
e. Anti-platelet antibody testing is not necessary to
make the diagnosis of lTP, and is therefore usu
ally not performed.
4. Bone marrow biopsy is performed in many patients
with thrombocytopenia. If the cause of the patient's
thrombocytopenia is readily identifiable (e.g., thia
zide diuretic therapy), a trial of removing the possible
inciting agent may be both diagnostic and therapeu
tic, and obviate the need for a bone marrow biopsy.
Pertinent findings on bone marrow biopsy include
the following.
a Decreased megakaryocytes are diagnostc of one
of the production problems. Evidence of the spe
cifc cause of the decreased production may also
be found (e.g., malignancy, infection).
3
C
p
y
I
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Thrombocytopenia
3 1 3
b. Increased megakaryocytes are found when in
cr
ased destruction or sequestration is the mech

amsm of thrombocytopenia. Increased megakar
r
ocyt
.
es on bone marrow biopsy without other
Identifable causes of increased destruction or
sequestration is usually diagnostic for ITP.
c. Evidence for myelodysplasia can also be seen on
bone marrow biopsy (see Chapter 64).
TREATMENT
A. General treatment
1. Oisco
tinue medications that may cause thrombocy

topema.
a. Usually, the platelet count will return to normal
in 7-10 days.
b. He
I
arin-induced thrombocytopenia and throm
bOSIS (HITT) is a disorder where immune-medi
ate thromboc
topenia and. paradoxically, sys

teml

thrombosl

coe
ist. Increasing the heparin

dose In these patients IS contraindicated; the only
therapy is heparin withdrawal.
2. Iatelet transfusions. Unnecessary platelet transfu
lOns shoul be avoded

.
because they may induce
Immune resistance; If thiS complication occurs hu
man leukocyte antigen (HLA)-matched platelet can
be administered.
HOT
KEY
a. Platelet transfusions usually are not indicated for
patients with platelet counts greater than 20,000
cells/pJ and no evidence of bleeding.
I gene
.
ral, platelet transfusions in asymptomatic pa
hents With TP should be avoided because transfusions
may worsen the patient's condition.
b. Indications. Platelet transfusions are indicated in
the following situations:
(1) Prior to surgery. The platelet count is usually
maintained above 50,000 cells/,l when sur-
3 1 4 Chapter 54
gery is to be performed, although in patients
with ITP, this may be hoth impossible and
unnecessary. When neurosurgery is to be per
formed, the platelet count is usually main
tained above 90,00 cells/ pJ in an attempt to
normalize the bleeding time.
(2) In a patient with active bleeding
(a) Severe bleeding. The platelet count is al
ways maintained above 50,000 cells/,l
and is sometimes increased to 90.000-
10,000 cells/,l.
(b) Mild bleeding o petechiae. The platelet
count should be maintained above 20,000
cells/,l.
(3) To prevent spontaneous bleeding. The plate
let count is usually kept above 10,000-20,00
cells/ ,l, depending on physician preference.
B. Specifc treaments for ITP (including HIV-associated
ITP) are discussed here; specifc treatments for other
causes are discussed in the relevant chapters.
1. Observation is often appropriate for patients with
platelet counts greater than 20,000 cells/,l and no
evidence of bleeding. Children frequently have an
acute form of ITP that is usually related to a viral
illness and resolves spontaneously over 3-6 months.
In adults, [TP usually follows a chronic course.
2. Pharmacologic therapy
a. Steroids will beneft approximately two thirds of
patients, leading to an increase in platelet count
in approximately 3 weeks.
b. Intravenous gammaglobulin often increases the
platelet count faster than steroids; it is therefore
useful for actively bleeding patients and those
with extremely low counts in the "window" be
fore steroids take effect.
c. Immunosuppressive agents can be used for pa
tients with ITP associated with SLE or other
connective tissue disorders.
d. Danazol is sometimes useful for patients with
refractory ITP.
e. Zidovudine may be useful in patients with HIV
associated ITP.
3. Splenectomy is reserved for patients in whom steroid
therapy fails or for those that relapse following a
steroid taper.
I
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55. Thrombocosis
M
Q
INTRODUCTION. Thrombocytosis is defned as a platelet
count greater than 450,000 celis/Jd.
CLINICAL MANIFESTATIONS OF THROMBOCYTOSIS
A. Primary. If the thrombocytosis is caused by a myelopro
liferative disorder, the platelets are frequently abnormal
and the patient may be prone to both bleeding and clot
ting events.
B. Secondary. If the thrombocytosis is secondary to another
disorder (reactive). even patients with extremely high
platelet counts (e.g., greater than 1,000,000 cells/,l) are
usually asymptomatic.
CAUSES OF THROMBOCYTOSIS
A. Primary causes. Any of the four myeloproliferative disor
ders can increase the platelet count through clonal prolif
eration of the stem cells (see Chapter 64).
B. Secondary causes. Reactive thrombocytosis is the most
common cause of thrombocytosis.
1. Malignancies
2. Infections
3. Connective tissue disorders
4. Iron defciency anemia
5. Splenectomy
A. Patient history
1. A history of gastrointestinal bleeding may imply pos
sible iron defciency.
2. Fevers, night sweats, or weight loss may implicate
malignancy or chronic infection (e.g., tuberculosis).
A complete review of systems should be performed
to help identify the presence of an occult malignancy
or infection.
3. A history of recent splenectomy may provide a sim
ple explanation for the thrombocytosis.
3 1 5
3 1 6 Chapter 55
B. Physical examination. Perform a thorough physical ex
amination. including pelvic and rectal examinations. Pay
special attention to the spleen and lymph nodes because
enlargement may signal malignancy or infection.
C. Laboratory studies can further narrow the differential di
agnosis.
1. Serum ferritin. The serum ferritin level will help eval
uate the possibility of iron defciency anemia and
is especially important in patients with a history of
gastrointestinal bleeding, guaiac-positive stools. or a
low mean corpuscular volume (MCV).
2. Hematocrit and white blood cell (WBq count. The
hematocrit and WBe count are often elevated in
patients with myeloproliferative disorders, although
essential thrombocytosis may result in an isolated
elevation of the platelet count.
3. Other tests may be performed if a reactive thrombo
cytosis is suspected [e.g., a purifed protein derivative
(PPD) test for possible tuberculosis, a computed to
mography (CT) scan for suspected intra-abdominal
malignancy].
TREATMENT
A. Primary causes. Myeloproliferative disorders may pre
dispose the patient to both bleeding and thrombosis as a
result of abnormal platelet function. Hydroxyurea should
be considered in those patients with marked throm
bocytosis (i.e., a platelet count greater than 70,000
cells/pJ). or if symptomatic thromboses occur.
B. Secondary causes. Most causes of reactive thrombo
cytosis do not require treatment to lower the platelet
count. The platelet count usually returns to normal fol
lowing treatment of the underlying disorder.
::
II
l
o
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56.Anemia
M
INTRODUCTION. Anemia is a common disorder among hos
pitalized patients.
A. Defnition. Anemia is defned as a decrease in the volume
of red blood cells (RBCs) as refected by the hematocrit.
Anemia is a manifestation of disease, not a disease in
and of itself
B. Normal values
1. In men, a hematocrit of less than 40% is consid
ered anemic.
2. In women, a hematocrit of less than 37% is consid
ered anemic.
C. Clinical manifestations of anemia. Patients with anemia
may be asymptomatic or complain of fatigue, dyspnea
on exertion, or exertional angina. Signs and symptoms
of the underlying disorder may also be present.
D. Classifcaton. Anemia is classifed as microcytic, normo
cytic, or macrocytic using the mean corpuscular volume
(MCV) as a basis.
1. The normal MCV is 80-100 p3.
2. If more than one disorder is present, the MeV may
be an average of the different populations of RBC,
producing a normal MeV. In mixed disorders, the
red cell distribution width (RDW) will be increased.
Q
MICROCYTIC ANEMIA (MeV <80 Jm3)
A. Causes of microcytic anemia
1. Iron defciency is a very common cause of microcytc
anemia and is important to diagnose because it may
be indicative of an underlying gastrointestinal malig-
nancy.
2. Thalassemia
3. Anemia of chronic disease (A CD) is associated with
infammatory diseases (e.g., rheumatoid arthritis, se
rious infection, carcinoma).
4. Sideroblastic anemias are a heterogenous group of
disorders that have in common various defects in the
porphyrin pathway that lead to an increase in cellular
iron uptake. Congenital sideroblastic anemia causes
microcytosis, whereas other etiologies may lead to a
variable MCV. Causes of sideroblastic anemia include:
3 1 7
3 1 8 Chapter 56
TABLE 56 1 : Serum Ferritin Values and Corresponding Likelihood
Ratios
Serum Ferritin Ilg/L) Likelihood Ratio
>1 00
25-1 00
1 5-24
<1 5
0. 1
Not helpful
1 0
50
Based on data fram: Guyatt GH, Oxman AD, Ali M, Willan A, Mcilroy W,
Patterson C: laboratory diagnosis of iron-deficiency anemia: on overview.
J Gen Infer Med 7(2): 1 45-53, 1 992.
a. Heredity
b. Drugs and toxins (e.g.. Lead. Isoniazid.
Ethanol-LIE)
c. Malignancy (e.g., leukemia, lymphoma, myelo
fbrosis, multiple myeloma, solid tumor)
d. Collagen vascular disease (e.g., rheumatoid ar
thritis)
B. Approach to the patient. It is important to differentiate
iron ?efciency from the other causes of microcytic
anelll1a.
1. Iron defciency versus thalassemia. Iron defciency
can be distinguished from thalassemia using the tha
lassemia index [i.e., the MCV divided by the RBC
count]. A thalassemia index of less than 13 suggests
thalassemia; one greater than 13 suggests iron def
ciency.
2. Iron defciency versus other etiologies
a. Determine the probability that a patient has iron
defciency. The pretest probability is based on
c1
.
il!ical factors. By estimating the pretest proba
bIlIty and using likelihood ratios for a given ferri
tin level (Table 56-1), you can estimate the post
test probability (see Chapter 2 H C 1 ).
b. Laboratory studies
(1) Serum ferritin. This test may be less helpful
in patients with liver disease. Like most tests
the ferritin is most useful when the pretest
probability is approximately 50%.
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Anemia
3 1 9
(a) If the serum ferritin is less than 1 5 Jg/L,
it practically guarantees that the patient
has iron defciency.
(b) Similarly, a value greater than 100 Jg/L
essentially rules out the diagnosis.
(2) Serum transferrin is occasionally helpful be
cause it is usually elevated in iron defciency
and decreased in ACD, probably because
transferrin is a protein.
c. Bone marrow biopsy remains the gold standard
test to diagnose iron deficiency.
HOT
KE Y
If iron deficiency is di agnosed in a patient, endoscopy
of the upper and lower gastrointestinal tract may need
to be performed because of the possibil ity of on under
lying gastrointesti nal malignancy.
@
MCROCYIC ANEMIA (MeV > 1 0 Jm3)
A. Megaloblastic anemias are caused by various defects in
DNA synthesis that lead to hematologic abnormalities.
Causes of megaloblastic anemia include:
1. Vitamin B12 defciency
2. Folate defciency
3. Drugs (e.g., methotrexate, azathioprine)
4. Miscellaneous (e.g., Lesch-Nyhan syndrome, thia
mine-responsive or pyridoxine-responsive ane
mias)
HOT
KE Y
The finding of hypersegmented polymorphonuclear
neutrophils (PMNs) on the peripheral blood smear
strongly suggests megaloblastic anemia.
320 Chapter 56
B. Chronic liver disease causes a macrocytosis as a result
of ineffective erythropoiesis.
C. Alcoholism produces erythrocyte membrane abnormali
ties. leading to macrocytic anemia.
D. Hypothyroidism causes macrocytic anemia via an un
clear mechanism.
E. Retculocytosis. An MCV greater than 110 f.m3 is usually
not due to reticulocytosis alone.
F. Myelodysplasia. There are fve myelodysplastic syn
dromes (see Chapter 64).
HOT
KEY
Practical ly all HIV-infected patients taking zidovudine
will have an elevated MCV; therefore, this finding can
aid i n gauging compliance with medications.
NORMOCYIC ANEMIA. An absolute reticulocyte count is
the initial test to order in a patient with normocytic anemia,
because the absolute reticulocyte count allows the anemia
to be classifed as proliferative or hypoproliferative (Figure
56-1).
A. Proliferative normocytic anemia is characterized by
erythrocyte loss.
L Hemolysis. Clues that hemOlysis may be present in
clude elevated lactate dehydrogenase (LDH) and
increased total bilirubin levels. If hemolysis is a con
cern, the peripheral smear must be examined. Based
on the morphology of the erythrocytes (e.g., schisto
cytes, sickle cells) the cause of the hemolytic anemia
may be determined. Microangiopathic hemolytic
anemia (MAHA) is an important cause of hemolysis
and is characterized by intravascular shearing of
RBCs, which leads to schistocyte formation. A few
of the important causes of MAHA are listed here.
a Disseminated intravascular coagulation (DIC).
In acute DIC, the major concern is bleeding,
whereas in chronic DIC, thrombosis is more of
a problem.
I
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Anemia
Hypoproliferative
Pancytopenia ACO
Renal
disease
Hereditary AIHA
spheroytosis
Proliferative
(RBC loss)
321

Hemolysis
Sickle
cells
1
Sickle cell
anemia
Hemorrhage
Other:
G6PO deficiency
PNH
Schistocytes
(MAHA)
Elevated
Hear valve OIC
abnormalities
HUS / TTP
VaSCUlitis
Severe HTN
HELLP
Figure 56-1 . Determining the cause of narmocytic anemia. ACD ane
mia of chronic disease; AIHA autoimmune hemolytic anemia; DIC
disseminated intravascular coagulation; G6PD glucose-6-phosphate de
hydrogenase; HELLP Hemolysis, Elevated liver enzymes, and low Plate
let count syndrome; HTN = hypertension; HUS/P hemolytic-uremic
syndrome/thrombotic thrombocytopenic purpura; MAHA microangio
pathic hemolytic anemia; PNH paroxysmal nocturnal hemoglobinuria;
PT= prothrombin lime; PI porial thromboplastin time; RBC red
blood cell; WBC white blood cell.
322
Causes of DI C ("MOIST")
Malignancy
Obstetric complications
Infection
Shock
Trauma
Chapter 56
b. Hemolytc-uremic syndrome (HUS)/thrombotic
thrombocytopenic purpura (TIP). The triad of
HUS is hemolysis, uremia, and thrombocyto
penia. TIP is hemolytic-uremic syndrome plus
fever and neurological changes. In general. if ure
mia is the primary disorder, the disease is re
ferred to as HUS. If the central nervous system
(CNS) manifestations are more signifcant, then
TTP is the appropriate term.
HOT
KEY
An lDH level less than 1 000 U/I makes HUS/TTP
very unlikely.
2. Hemorrhage. If hemorrhage is suspected, the source
of the blood loss must be determined (e.g., the gastro
intestinal tract).
B. Nonproliferative normocytic anemia. Low white blood
ceU (WBC) and platelet counts indicate pancytopenia,
whereas normal or high counts usually indicate AC or
renal disease.
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57. Polycythemia
************************************
@
Q
M
INTRODUCTION. A hematocrit greater than 54% in men or
51 % in women constitutes polycythemia.
A. Absolute polycythemia is characterized by an increase
in red blood cell (RBC) mass.
B. Relative polycythemia is characterized by a decrease in
plasma volume.
CUNICAL MANIFESTATIONS OF POLYCYTHEMIA
A. Patients are often asymptomatic if the hematocrit is
lower than 60%. Higher hematocrits may cause va so
occlusive episodes resulting in headaches, blurry vision,
dizziness, strokes, cardiac ischemia, and peripheral
thromboses. A "ruddy" cyanosis may be found on physi
cal examination.
B. Symptoms specifc to polycythemia vera are described
in Chapter 64.
CAUSES OF POLYCYTHEMIA. Polycythemia may be a sec
ondary, physiologic response to another disorder (e.g.,
chronic hypoxia), or it may herald a primary. more malignant
disorder (e.g., polycythemia vera or an erythropoietin-secret
ing tumor).
A. Absolute polycythemia. There are fve common causes
of absolute polycythemia. Remember, "Hypoxia Can
Cause Polycythemia Every Time."
Causes of Absolute Polycythemia ("Hypoxia
Can Cause Polycytftemia Every Time")
Hypoxia (chronic)
Carboxyhemoglobinemia
Cushing's syndrome or Corticosteroids
Polycythemia vera
Erythropoieti nsecreting Tumors
323
324 Chapter 57
1. Hypoxia. Chronic hypoxia, as a result of cardiopul
monary disease or high altitude, can lead to polycy
themia.
2. Carboxyhemoglobinemia or methemoglobinemia.
Carboxyhemoglobin, methemoglobin, and other
high-afnity variants cause a lefward shift of the
hemoglobin dissociation curve, decreased oxygen de
livery to the tissues, and a compensatory polycythe
mia. Smoking is a common cause of carboxyhemo
globinemia.
3. Cushing's syndrome or corticosteroid therpy. Corti
costeroids have an erythropoietic effect, which can
lead to polycythemia.
4. Polycythemia vera causes polycythemia by clonal
proliferation of stem cells independent of erythro
poietin.
5. Erythropoietin-secreting tumors are primarily renal.
cerebellar, or hepatic.
B. Relative polycythemia. There are two main causes of
relative polycythemia.
1. Dehydration (e.g., from vomiting, diarrhea, sweat,
or diuretic) can deplete plasma volume, leading to
a relative polycythemia.
2. Stress erythrocytois (GaisbOck's polycythemia) ac
tually results from contraction of the plasma volume,
and is therefore a misnomer. This benign disorder is
seen most often in hypertensive, obese men.
AP OACH TO THE PATIENT
A. Rule out hypoxia and carboxyhemoglobinemia. These
are common, relatively easy to evaluate causes of polycy
themia. If abnormalities signifcant enough to result in
the polycythemia are found, the need for additional
work-up may be eliminated. An arterial blood gas with
carboxyhemoglobin level is necessary for all patients who
smoke, and is more accurate than oxygen saturation mea
surements. The methemoglobin level can also be checked
if there is clinical suspicion.
B. Look at the patient's hematocrit.
1. Greater than 60% in men or 55% in women
a. A hematocrit greater than 60% in men or 55%
in women essentially rules out steroid excess,
which usually causes a mild polycythemia. Fur
thermore, because an elevated RBC mass is
found in 99% of these patients, decreased plasma
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3
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Polycythemia 325
volume is unlikely, and an RBC mass study is
usually not necessary.
b. A hematocrit greater than 60% in men or 55%
in women usually reduces the list of possible diag
noses to either polycythemia vera (more com
mon) or an erythropoietin-secreting tumor (less
common). The following criteria may be used
to
.
help diagnose polycythemia vera. In patients
without a defnitive diagnosis, the possibility of
an erythropoietin-secreting tumor should be con
sidered.
(1) Polycythemia vera
(a) Polycythemia associated with spleno
megaly, thrombocytosis, and a normal
oxygen saturation i diagnostic for poly
cythemia vera.
(b) An increased leukocyte alkaline phos
phatase (LAP) score, concomitant iron
defciency anemia, and/or increased vita
min BJ2 level ofer additional evidence
for polycythemia vera (see Chapter 64).
(c) A decreased erythropoietin level is also
useful (almost all patients with polycy
themia vera have a level less than 20
mU/mI).
(d) A marrow erythroid progenitor cell cul
tUre shows independent growth with
polycythemia vera, but not with other
forms of secondary polycythemia. How
ever, this test is often not routinely
available.
(2) Erythropoietin-secreting tumors
(a) An abdominal computed tomography
(CT) scan may help rule out renal pathol
ogy (including cancer) and hepatic malig
nancies.
(b) Brain imaging [preferably with magnetic
resonance imaging (MRI)] may be per
formed if there is any clinical suspicion
of a cerebellar lesion.
2. Hematocrit less than 60% in men or 55% in women.
An RBC mass study should be performed to rule out
decreased plasma volume, which is responsible for the
polycythemia in approximately 50% of cases. In general,
secondary causes will account for far more cases than
polycythemia vera.
326 Chapter 57
TREATMENT is aimed at the underlying disorder. Stress
erythrocytosis requires no treatment. General therapeutic
measures include the following.
A. Oxygen therapy is useful in patients with an arterial
oxygen tension (Pa02) lower than 60 mm Hg.
B. Smoking cessation is encouraged (especially in patients
with carboxy hemoglobinemia ).
C. Hydration is recommended for patients with evidence
of dehydration.
D. Phlebotomy to lower the hematocrit is usually only indi
cated for patients with polycythemia vera (see Chap
ter 4).
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F
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3
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58. Lukocyosis
@
INTRODUCTION
Q
A. The circulating pool of white blood cells (WBCs, leuko
cytes) consists of:
1. Neutrophils
2. Lymphocytes
3. Monocytes
4. Eosinophils
5. Basophils
B. Defnitions
1. Leukocytosis. In leukocytosis. the total WBC count
exceeds 11,000 cells/mm3 (11 x 1091).
2. Leukemoid reaction. A leukemoid reaction is said
to occur when the leukocyte count exceeds 30,000
cells/mm3 and there is no evidence of immature
WBCs or nucleated red blood cells (RBCs) on the
peripheral smear. This process refects a healthy bone
marrow that is reacting to some type of stress (e.g.,
trauma, infammation, infection, malignancy).
3. Leukoerythroblastosis. This term is used when there
is evidence of immature WBCs and nuceated RBCs
on the peripheral smear, regardless of the total WBC
count. Leukoerythroblastosis usually implies bone
marrow infltration.
C. Because each cell type can be increased in response to
various stimuli. determining the predominant cell type
in patients with leukocytosis may offer some insight into
the cause.
NEUTOPHIUA is defned as a neutrophil cOUnt that exceeds
7500 cells/mm3
A. Causes of neutrophilia. Neutrophilia can be caused by
many of the major disease categories learned in Chapter
1 (Table 58-1).
B. Approach to the patient. When evaluating patients with
neutrophilia. the most important initial consideration
shOUld be infection. If this and other benign disorders
are excluded, a search for malignancy (which may include
a bone marrow biopsy) is usually warranted. Acutely
infected or injured patients have elevated levels of en
dogenous glucocorticoids, which, in turn, will lead to
327
328 Chapter 58
TABLE 58- 1 : Common Causes of Neutrophilia
Category of Disease Specific Causes
Hematologic
Pregnancy-related
Drugs/ toxi ns
Hemolytic anemia, splenectomy
Pregnancy-induced neutrophilia
Corticosteroids, lithium, mercury, ethyl-
ene glycol
Metabolic/ endocrine
Inflammatory
Infectious
Hyperthyroidism, ketoacidosis
Rheumatoid arthritis, vasculitis, gout
Bacteria, vi ruses, fungi , parasites
Myeloproliferotive disorders, myelodys- Neoplastic
plastic syndromes, gastrointesti nal or
renal malignancy, melanoma, Hodg
kin's disease
Trauma Insect bites, jellyfish stings, crush i nj uries,
electric shock
M
low levels of eosinophils and basophils. The presence of
eosinophils and basophils in acutely ill patients usually
indicates one of the following:
1. Concomitant adrenal insufficiency
2 Granulocyte-macrophage colony-stimulating factor
(GM-CSF)-secreting tumor
3. Hematologic malignancy
LYMPHOCYTOSIS is defned as a lymphocyte count that ex
ceeds 5000 cells/mm3
A. Causes of lymphocytosis (Table 58-2). The severity of
the lymphocytosis may indicate possible causes.
1_ The frst step in evaluating a patient with lymphocy
tosis is to look for leukoerythroblastosis on the pe
ripheral smear. If leukoerythroblastosis is present.
bone marrow biopsy is necessary.
2 In patients without evidence of leukoerythroblasto
sis, a benign cause shoUld be sought. If none of these
causes can be reasonably diagnosed, the patient
should have a bone marrow biopsy to exclude neo
plasm.
MONOCYTOSIS is defned as a monocyte count that ex
ceeds 500 cells/mm3
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leukocytosis
TABLE 58-2: Common Causes of Lymphoytosis
Type of Lymphoytosis Specific Causes
Mild to moderate
(5000-1 5,000/
mm3)
Severe (> 1 5,000/
mm3)
Viral i l lness (mononucleosis, hepatitis)
Secondary to other infections (e.g. , tu
berculosis, toxoplasmosis, syphilis)
Malignancy (e.g., Hodgkin's disease,
early CLl)
Mononucleosis
Hepatitis
Pertussis
late Cll
All
329
All acute lymphocytic leukemia; CLl chronic lymphocytic leukemia.
TABLE 58-3: Common Causes of Monocytosis
~~~
Category of Disease Specific Cause
Infectious
Neoplastic
Inflammatory
Tuberculosis, endocarditis, brucellosis,
syphilis, fungal or protozoal infections,
listeriosis
Hodgkin's disease, leukemia, carcinoma
Inflammatory bowel disease, sarcoidosis
A. Causes of monocytosis (Table 58-3). Monocytes are very
important. not only in the killing of obligate intracellular
parasites (e.g., fungi, parasites, yeast), but also i n granu
lomatous infammation.
B. Approach to the patient. If the levels of monocytes are
extremely high. a hematologic malignancy should be
strongly suspected.
59. Eosinophilia
@
INTRODUCTION
A. Eosinophils, a type of white blood cell (WBC), normally
dwell in tissues. Eosinophils:
1. Play a major role in defending the body against multi
cellular. helminthic parasites
2. Elaborate mediators that promote mucus secretion
and alter vascular permeability in allergic diseases
3 Induce mast cells and basophils to release allergic
mediators
B. Eosinophil count. The normal range of eosinophils in the
blood is 0- 450 cells/mm3 (0%-4%). Counts are highest in
the moring and fall during the day, as glucocorticoid
levels increase.
1. Eosinopenia is commonly seen in bacterial and viral
infections and with exogenous corticosteroid use.
2. Eosinophilia is associated with many diseases (see
II).
Q
CAUSES OF EOSINOPHILIA
A. Pulmonary diseases. Many primary lung disorders can
lead to eosinophilia, including Lafer's syndrome and
eosinophilic pneumonia.
B. Helminthic infections
1. Filariasis
2. Ascariasis
3. Schistosomiasis
4. Strongyloidiasis
HOT
Dissemi nated strongyloides sometimes does not couse
eosinophilia because of the superimposed bacterial
infection that may occompany parasitic dissemination.
KEY
5. Trichinosis
330
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Eosinophilia 33 1
C. Other infections
L Allergic bronchopulmonary aspergillosis
HOT
Invasive aspergi llosis does not couse eosinophi l i a.
KEY
2. Coccidioidomycosis
3. Tnberculosis, especially chronic tuberculosis
D. Contaminated L-tryptophan can cause eosinophilia
myalgia syndrome.
E. Immunologic disorders [e.g., vasculitis (especially Churg
Strauss syndrome), severe rheumatoid arthritis, eosino
philic fasciitis 1
F. Addison's disease
G. Cutaneous disorders (e.g., bullous pemphigoid, scabies,
eosinophilic cellulitis)
H. Allergic disorders (e.g., asthma, alIergic rhinitis, atopic
dermatitis. drug reactions, acute urticaria)
I. Neoplasms. Solid tumors, lymphoma, and leukemia can
lead to eosinophilia.
332
Causes of Eosinophil ia
P H l l i A C A N

A C T F A S T
Pulmonary disease
Helminthic infections
Filariosis
Ascariasis
Chapter 59
Schistosomiasis or Stron
g
yloides infction
Trichinosis
Infections, other
Coccidioidomycosis
Tuberculosis (especially chronic)
L-T ryplophan
Immunologic disorders
Addison's disease
Cutaneous disorders
Allergic disorders
Neoplasms
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60. Bleeding Disorders
@
Q
M
INTRODUCTION. A predisposition to bleeding can result
from problems with platelets (either number or function) or
problems with coagulation (factor defciency or factor inhib
itors)_
CLINICAL MANIFESTATIONS OF BLEEDING DISORDERS
A. Recurrent bleeding since childhood or a family history
of bleeding suggests an inherited problem.
B. Mucocutaneous petechiae or ecchymoses are usually in
dicative of platelet problems.
C. Spontaneous deep bleeding into hematomas or joints
(hemarthroses) or delayed bleeding after surgery or
trauma is suggestive of coagulation problems.
APROACH TO THE PATIENT. Figure 60-1 summarizes the
general approach to a patient with a bleeding disorder-
A. Platelet count. The platelet count must be less than
90,000 celIs/JI to prolong the bleeding time. Therefore,
mildly decreased counts are not responsible for clinical
bleeding, and a concurrent problem of platelet function
or coagulation should be considered.
B. Prothrombin time (PT)/partial thromboplastin time
(PTT). There are three types of PT/PIT abnormalities:
increased PT/normal PIT, increased PT/increased P,
or normal PT/increased PIT.
1. Increased PT/normai PT
a. Diferential diagnoses
(1) Early disseminated intravascular coagula-
tion (DIC)
(2) Liver disease
(3) Warfarin therapy
(4) Vitamin K defciency
(5) Factor VII defciency (isolated factor VII de
ficiency is a rare cause of an elevated PTI
normal P)
b. Recommended work-up
(1) Patient history. Ask about medications and
note factors that may predispose a patient
to vitamin K deficiency (e_g., malnutrition,
333
334
l PT 1
normal PT
Early DIC
Liver disease
Warfarin
therapy
Vitamin K
deficiency
Factor VII
deficiency
Chapter 60
Obtain PT 1 PT and platelet count
l PT 1 1PT Normal PT 11 PT Normal
Severe DI C Coagulation
Severe factor deficiency
liver disease Coagulation
Warfarin factor inhibitor
overdose Antiphospholipid
Severe antibodies
vitamin K
deficiency
Factor I I , V,
or X deficiency

o

Factor XI I I deficiency
Dysfi brinogenemia
Deficiency of inhibitors
to fibrinolysis
Acquired:
Severe renal disease
Severe liver disease
Myeloproliferative
disorders
Paraproteinemias
Autoantibodies
DIC
Acqui red storage
pool disease
PT I PT,
platelet count
> 90,00 cells!"
Inherited:
vWD
Bernard-Soulier
syndrome
Glanzmann's
thrombasthenia
Storage pol
disease
A platelet count less than 90,000 celis/ill may reslt in an increased
bleeding time and a bleeding disorder. Patients with platelt counts
greater tan 90,000 cells/Ill may still b thromytopenlc (I.e., a
platelet count less than 1 50,000 celis/ill), bu thiS !evel of thrombo
cytopenia is usually not the cause of a bleeding disorder; therefore,
other causes should be considered.
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Bleeding Disorders
335
pancreatic insufciency, recent antibiotic
use).
(2) DIC panel (D-dimers, fbrinogen) and periph
eral smear. Evidence for DIe may include a
low fbrinogen level 150 mg/dI), elevated
D-dimers, or schistocytes on the peripheral
blood smear. D-Dimers can also be elevated
in cirrhosis or with clinical bleeding, and hy
pofbrinogenemia may also ocur with severe
liver dysfunction; therefore, the presence of
schistocytes may be the only distinguishing
feature for DIe in a patient with concomitant
liver failure.
(3) Liver tests (bilirubin, albumin, and transami
nase levels) are often obtained.
(4) Factor VB level. A factor VI level is rarely
necessary but can be obtained i the cause of
the increased P is still unknown.
2. Increased PT/increased P1T
a. Diferential diagnoses. The differential diagno
ses for this abnormality are generally the same
as those for an isolated elevated P, but the con
ditions are more severe:
(1) Severe DIC
(2) Severe liver disease
(3) Warfarin overdose
(4) Severe vitamin K defciency
(5) Factor II, V, or X defcienc (extremely rare
causes of an elevated PT/PTT)
b. Recommended work-up. The recommended
evaluation is the same as that for increased PT/
normal PIT, except that on the extremely rare
ocasion of a completely negative work-up, dif
ferent factor levels need to be tested.
3. Normal PT/increased PIT
a. Diferential diagnoses. After excluding the obvi
ous cause (i.e., heparin therapy), you need to
consider three possibilities.
* Heparin therapy can also cause an elevated PT/Pl, but the PT is usually
only mildly increased.
Figure 60- 1 . Approach to the patient with a bleeding disorder.
ole dissemi nated intravascular coagulation; PT
p
rothrombi n time;
PTT portial thromboplastin time; vWD von Wille
b
rand's disease.
336 Chapter 60
(1) Coagulation factor defciency
(2) Coagulation factor inibit
r
.
.
(3) Antiphospholipid an"bodle

(m
IUI
?
g lu
pus anticoagulant and antlcardlohpm an-
tibody)
b. Recommended work-up
(1) Patient history. The patient history
an pro
vide valuable information. If the patIent has
a history of bleeding, a factor defci
ncy or
a factor inhibitor is likely. If the patIent has
a history of clotting, an antiphospholipid syn-
drome is implicated.
. .
(2) 50: 5 mixing study. Only 30% factor actI
Ity
is needed to have a normal PTf. By mlxmg
the patient's blood with an equal amount
?
f
blood with a normal PTf, enough factor WIll
be provided to correct any factor defciency
(if that is the problem).
(a) If the PIT corrects (and star
:
corr
te?
on later testing) a factor defCiency IS dI
agnosed. The most common fact
?
def
ciencies are factor VIII (hemophIlIa A),
factor IX (hemophilia B), and factor X
defciencies; therefore, factor VIII, IX,
and X levels should be drawn frst.
(b) I the PIT does not correct with mixing,
an antiphospholipid antibody or a fator
inhibitor is present. Send laborat
ry te
ts
for l upus anticoagulant and
.
antIcardlO
lipin antibody. A Russell's vIper venom
time (see III D 1) can also e sent to
evaluate the presence of an antlphospho
lipid antibody.
(c) If the PIT initially corrects, ut
.
ro
longs on later testing, a or mhlbd
r
is probably present. ImtIally. there IS
enough factor present to normalize the
PTT but the inhibitor "eats up" the
factr until the level decreases to below
30%, prolonging the PT. Factor VIII
inhibitor is the most common and should
be checked frst.
C. Bleeding time. If the platelet count and PT!PT
.
are
normal, the next step in the work-up of a paIent
with a suspected bleeding disorder is to obtam a
bleeding time.
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Bleeding Disorders
337
1. I the bleeding time is prolonged with a platelet
count over 90,000 cells! /l, platelet dysfunction is i
plicated.
HOT
KEY
a. Acquired platelet dysfunction
(1) Diferential diagnoses. Acquired platelet dis
orders are usually systemic.
(a) Severe renal disease (i.e .. uremia)
(b) Severe liver disease
(c) Malignancy. Myeloproliferative disor
ders, multiple myeloma, and Walden
strom's macroglobulinemia (from para
proteinemias) can all lead to platelet
dysfunction.
(d) Autoantibodies [e.g., caused by { lactam
antibiotic therapy or idiopathic thrombo
cytopenic purpura (ITP)] can coat plate
lets and increase the bleeding time even
with a normal platelet count.
(e) DIC. The fbrin split products producd
in DIC inhibit platelet function.
(f Acquired storage pool disease. Cardio
pulmonary bypass surgery or vasculitis
can cause platelets to release all their
granules. resulting m dysfunctional
platelets.
(g) Aspirin irreversibly inhibits platelet func
tion for the life of the platelet (7-10
days); other nonsteroidal anti-infamma
tory drugs (NSAIDs) reversibly inhibit
platelet function and the effect is more
transient.
The bleeding lime may be prolonged with aspirin or
NSAIDs, but will only become abnormal if another
underlying cause of platelet dysfunction i s present.
(2) Recommended work-up
(a) Patient history. A medication history
(including all over-the-counter drugs)
338
Chapter 60
should always be obtained. Immune-me
diated platelet dysfunction may be sus
pected with the use of certain
.
media
tions, a history of ITP, or with mild
thrombocytopenia accompanied by obvi
ous platelet dysfunction (prolonged
bleeding time). Acquired storage pool
disease is suspected if the clinical setting
is appropriate.
(b) Complete blood count (CBC) with differ
ential. A CBC with di fferential will help
evaluate the possibility of a myeloprolif
erative disorder (see Chapter 64).
(c) DIC panel. A DIC panel can help evalu
ate the possibility of DIe.
(d) Liver tests and a blood urea nitrogen
(BUN) level will help you exclude liver
and renal disease, respectively.
(e) Protein electrophoresis may be used to
evaluate the presence of a paraprotein
emia (see Chapter 67).
b. Inherited platelet dysfunction. Platelets need to
frst adhere to the endothelium during injury, and
then to aggregate by binding fbrinogen.
(1) Diferential diagnoses. The frst two disor
ders involve problems with platelet adher
ence, and the second two involve problems
with platelet aggregation.
(a) von Willebrand's disease (vWD). von
Willebrand's factor (vWF) is elaborated
by megakaryocytes and endothelial cells,
and circulates in the plasma in multimers
of varying size bound to factor VIII
(which vWF stabilizes). vWF binds to
the glycoprotein Ib receptor on platelets,
and helps platelets adhere to endo
thelium.
(i) In type I vWD (8% of cases), the
amount of vWF is decreased.
(ii) In type m vWD, vWF is com
pletely lacking.
(iii) In type U vWD, there is a qualitative
decrease in vWF activity. In type Ua
vWD, the qualitative defect results
from a decrease in the large multi
mers of vWF, the active forms in
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Bleeding Disorders
339
platelet adhesion. In type lIb vWD,
there is also a decrease in the large
multimers of vWF; however, type
lIb vWD differs from type IIa vWD
in that the decrease is caused by
abnormal vWF adherence to plate
lets.
(b) Berard-Soulier syndrome results fom
a loss in the platelet receptor for vWF
(glycoprotein Ib).
(c) Glanzmann's thrombasthenia results
from the loss of the I1a-I1Ib glycoprotein
platelet receptor, which leads to de
creased fbrinogen binding and, there
fore. defective platelet aggregation.
(d) Storage pool disease is caused by defec
tive release of platelet granules [espe
cially adenosine diphosphate (ADP),
which results in decreased platelet aggre
gation.
(2) Recommended work-up
(a) Patient history. vWD is an autosomal
dominant disorder, and Bernard-Soulier
syndrome and Glanzmann's thrombas
thenia are autosomal recessive disorders;
therefore, obtaining the family history
is important.
(b) vWD panel. Screen for vWD frst because
vWD is the most common inherited dis
order of platelet function. A vWD panel
includes the following tests:
(i) Ristocetin cofactor activity. The pa
tient's plasma is mixed with normal
platelets and ristocetin. Ristocetin
should cause plasma vWF to bind
to the platelet surface (via the gly
coprotein Ib receptor), resulting in
platelet aggregation. The absence
of platelet aggregation implies a
quantitative or qualitative decrease
in vWF.
(ii) Factor VIII antigen is another way
to assess the vWF level.
(iii) Factor VIII activity may be de
creased with a decrease in vWF level
and may cause a prolonged PTT.
340
Chapter 60
HOT
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Type I vWD often shows a parallel decrease in al l
parts of the panel, while type I I I vWD demonstrates
no activity in any part of the panel. In type II vWD,
there will b decreased ristocetin cofactor activity out
of proportion to the decreased factor VIII antigen level.
(c) Ristocetin aggregation test. The patient's
plasma and platelets are mixed with risto
cetin. Berard-Soulier syndrome is diag
nosed by a normal vWD panel, but an
abnormal ristocetin aggregation test.
(d) Platelet aggregometry is used to diagnose
Glanzmann's thrombasthenia and stor
age pool diseases.
(i) In storage pool diseases, platelets
will not aggregate with low doses of
ADP, but higher doses will result in
aggregation.
(ii) In Glanmann's thrombasthenia, nei
ther low nor high doses of ADP will
induce aggregation because the neces
sary IIb-IlIa receptor is missing.
2. If the bleeding time is not prolonged in a patient
with a normal PIT and platelet count, but there
is still clinical suspicion of a bleeding diathesis, a few
rare disorders stilI need to be considered. AU of these
involve a defect in cross-linking of fbrin.
a. Diferential diagnoses
(1) Factor XIII ("fbrin-stabilizing factor") def
ciency
(2) Dysfbrinogenemia
(3) Defciency of inhibitors to fbrinolysis (i.e ..
plasminogen activator inhibitor or 02 plas
min inhibitor)
b_ Recommended work-up
(1) Increased clot solubility in urea demonstrates
factor XIII defciency.
(2) Increased thrombin time is evidence of a pos
sible dysfbrinogenemia.
(3) Rate of clot lysis tests and direct measure
ments of 02 plasmin inhibitor levels can be
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Bleeding Disorders
D. Other tests
341
performed to evaluate defciency of inhibi
tors to fbrinolysis.
1. Russell's viper venom time. Russell's viper venom
activates factor X without the usual help of factor
V, but stilI requires phospholipid. The Russell's viper
venom time may therefore be prolonged when anti
phospholipid antibodies are present.
2. Thrombin time measures the time for the blood to
clot afer thrombin is directly added, and therefore
assesses thrombin's conversion of fbrinogen to f
brin. The thrombin time will be prolonged when
thrombin is inhibited (as in heparin therapy). when
there is low fbrinogen (as in afbrinogenemia or
DIC), or when there is abnormal fbrinogen (as in
dysfbrinogenemia ).
3. eptilase i
e is just like thrombin time, except it

IS not sensItIve to the effect of heparin. If the throm
bin time is prolonged, but the reptilase time is nor
mal, ten heparin efect is diagnosed. If the repti
lase tIme IS also prolonged, then afbrinogenemia,
DIe. Or dysfbrinogenemia should be considered.
TREATMENT
A. Platelet problems
1. Quantitative problems. The treatment of thrombocy
topenia is discussed in Chapter 54.
2. Qualitative problems are usually only treated when
the patient is acutely bleeding or surgery is planned.
Specifc therapies may include dialysis for uremia,
myelosuppression for myeloproliferative disorders
or steroids for immune disorders. Other commonl;
used treatments include:
a. Desmopressin (0.3 J1g/kg per day) works presum
ably by increasing the release of stored vWF fom
en?othelial cells, and is useful as prophylaxis
pnor to surgery in patients with type I vWD. For
unclear reasons, it is also useful in other disorders
of platelet dysfunction (e.g., uremia, storage
pool disease).
(1) Stores of vWF are depleted in 2-3 days, so
desmopressin is usually only effective as
short-term treatment.
(2) Desmopressin is ineffective in type IIJ vWD.
In type lIb vWD, large muItimers of vWF
342
Chapter 60
are already stuck to platelets, and exposure
to desmopressin can trigger paradoxical
thromboses and thrombocytopenia (from
splenic removal). Therefore, the use of des
mopressin should be avoided in patients with
these sUbtypes.
b. Cryoprecipitate (10-15 units every 12 hours) is
effective in raising vWF levels 30%-50% (ap
proximately 3% per unit), and is therefore useful
in patients with vWD.
c. Platelet transfusions can be used for refractory
bleeding.
B. Coagulation problems
1. Increased PT/normai PIT and increased PTlin
crased PTT
a. With signifcant acute bleeding
(1) Fresh frozen plasma is given to normalize the
PT/PTT regardless of the underlying eti
ology.
(2) Cryoprecipitate can be used for patients with
DIe to restore the fbrinogen level to over
150 mg/dl.
(3) Vitamin K (10 mg subcutaneously daily for
3 days) should be routinely administered in
case vitamin K defciency plays a primary or
contributing role in the patient's coagu
lopathy.
HOT
KEY
Fresh frozen plasma contains 011 fadors, but only small
amounts of fibrinogen. Cryoprecipitate contains corr
centrated fador VIII, vWF, and fibrinoen.
b. Without signifcant acute bleeding. The treat
ment takes into account the underlying cause.
(1) DIC. In patients with DIe but no acute
bleeding, the elevated PT is not treated. In
stead, treatment is aimed at the cause of the
DIe (e.g., antibiotics for sepsis).
(2) Warfarin therapy
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Bleeding Disorders 343
HOT
KEY
(a) If the PT is higher than desired, the war
farin dose is usually decreased or with
held, and the PT is rechecked daily.
Remember, there is approxi mately a 2 to 3-day log
between the changes in dose and the changes in the
PT. If you have withheld the warfarin, do not wait until
the PT is in the appropriate range to resume therapy
because the PT will continue to drop. Therapy i s best
reinitiated when the PT is slightly higher than desired.
(b) Low doses of vitamin K (e.g., 1 mg by
mouth) can be administered to gradually
lower the PT in patients with marked
PT elevations.
(3) Vitamin K defciency or liver failur. Fre
quently, it is unclear whether the patient's
Ievat
d PT is from vitamin K defciency,

lIver dIsease, or both (especially in alcoholics,
who are prone to both disorders). Vitamin
K therapy is often both diagnostic and thera
peutic.
(4) Factor defciency is rare and not treated un
less bleeding is present or surgery is planned.
2. Normal PTnncreased PTT
a. Factor defciency is only treated if the patient is
acutely bleeding or about to undergo surgery.
Hemophilia A and B are treated with factor VIn
and IX concentrates respectively; other factor
defciencies are replaced with fesh fozen
plasma.
b. Factor inhibitors
(1) Acute treatment. Factor inhibitors associated
with active bleeding can be extremely diff
cult to treat.
(a) Aggressive factor replacement (to "over
whelm" the inhibitor) and/or plasma
pheresis (to remove the inhibitor) are
used.
(b) Activated factor IX can be used in the
presence of factor VIII inhibitors (i.e., to
bypass the step where factor VI II is
needed).
344
Chapter 60
(2) Chronic treatment. Steroids and/or immuno
suppressant agents (usually cyclophospha
mide) may be administered as chronic
therapy.
c. Antiphospholipid antibodies have a tendency to
cause thromboses, not bleeding. Therefore, treat
ment is anticoagulation therapy if signifcant clot
ting occurS (see Chapter 61).
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61. Hypercoagulable States
@
INTRODUCTION
M
A. Defnition. Hypercoagulabk states are clinical disorders
of the blood that increase the patient's risk for devel
oping thromboembolic disease.
B. Pathogenesis. Homeostasis in blood clotting is main
tained by interrelationships between coagulant and anti
coagulant proteins in the vascular endothelium and
blood. The pathogenesis of thrombus formation is sum
marized by Virchow's triad:
1. Defects in blood fow (stasis)
2. Defects in vascular endothelium
3. Defects in blood coagulation (leading to hypercoagu
lability)
CUNICAL MANIFESTATIONS OF HVPERCOAGULBLE
STATES. A hypercoagulable state should be suspected in a
patient who develops:
A. Multiple or recurrent clots
B. Clots in unusual locations (e.g., the upper extremities,
mesenteric vessels, arteries)
C. Thromboembolic disease at an early age
CAUSES OF HvPERCOAGULBLE STATES can be primary
or secondary. The causes of the most important hypercoagu
lable states (both primary and secondary) can be recalled
using the mnemonic, "DAMN THROMBUS."
345
346 Chapter 61
Causes of Hyprcoagulable States ("DAMN
THROMBUS")
Deficiencies or alterations in coagulation fac
tars (e.g., protein C, protein S, antithrombin
I I I , fador V, fibrinogen, plasminogen)
Antiphaspholipid antibody syndrome
Malignancy (e.g., Trousseau's syndrome)
Nephrotic syndrome (because of urinary loss
of protein C and S)
Trauma
Homoysti nuria or Heparin-induced thrombo
cytopenia and thrombosis (HIlT) or Hemo
globinuria [i .e., paroxysmal noturnal hemo
globinuria (PNH))
Rheumatologic causes (i.e. , vasculitis)
Oral contraceptives
Myeloproliferative disorders
Baby-carriers (i . e. , pregnancy)
Unknown
Surgery or postoperative states (particularly
neurosurgical and orthopedic)
A. DITT, an acquired disorder associated with the forma
tion of arterial or venous thrombi in the presence of
thrombocytopenia, occurs in a small percentage of pa
tients receiving intravenous or subcutaneous heparin
therapy. Heparin should be stopped promptly if throm
bocytopenia develops.
B. Antiphospholipid antibody syndrome is marked by the
presence of antiphospholipid antibodies, hypercoagula
bility, and recurrent spontaneous abortions. Among
the specifc antibodies associated with the syndrome
are anti cardiolipin antibodies and the lupus anticoagu
lant.
A. In a patient with a new deep venous thrombosis, the
patient history, physical examination, complete blood
count (CBq, urinalysis, prothrombin time (PT) and par
tial thromboplastin time (PIT), and chest radiograph
are suffcient to rule out most secondary causes of hyper
coagulability.
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Hypercoagulable States 347
B. The following laboratory studies may help exclude spe
cifc causes of hypercoagulability:
1. A factor V mutation test
2. Assays for anticardiolipin antibodies, lupus antico
agulant, and homocysteine level
3. Functional and quantitative assays for proteins C and
S, antithrombin III, and fbrinogen
HOT
KEY
When checking protein C and S levels, draw serum
before warfarin therapy is i nitiated. Warfarin reduces
protein C levels before those of all other vitami n K-de
pendent fadars because protein C has the shortest
half-life. Therefore, warfarin can lead to a falsely low
result on a protein C assay.
TREATMENT
A. Patients with thrombosis resulting from stasis, endothe
lial injury, or an idiopathic cause
1. Anticoagulation therapy
a Initial therapy of a patient presenting with deep
venous thrombosis or pulmonary embolism con
sists of both heparin and warfarin. Because pro
tein C has the shortest half-life of all the vitamin
K-dependent factors, warfarin therapy alone can
lead to a defciency of protein C relative to the
other procoagulant factors (i.e., factors II, VII,
IX, and X). Patients with an underlying protein
C defciency who are placed on warfarin may be
susceptible to a transient hypercoagulable state.
leading to " coumadin necrosis." Coumadin ne
crosis can be avoided by administering heparin
along with the warfarin. In addition, the concomi
tant use of heparin ensures that the patient rap
idly becomes anticoagulated. which may prevent
further extension of the clot.
b. Long-tenn therapy. Heparin is continued for ap
proximately 5 days and until the PT reaches the
therapeutic range [i.e., an international normal
ized ratio (INR) between 2 and 3]. Warfarin is
usually continued for 3-6 months.
348 Chapler 61
2. Inferior vena cava (IVC) filter. In patients at high
risk for bleeding with anticoagulation therapy, an
IVC filter may be placed.
3. Low molecular weight heparin therapy may replace
traditional therapy.
B. Patients with thrombosis resulting fom a hypercoagula
ble state often require lifelong anticoagulation therapy
with heparin or warfarin. Pure antithrombin III may be
useful in patients with antithrombin III defciency.
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62. Lymphadenopathy
@
@
INTRODUCTION
A. Defnition. Lymphadenopathy occurs when the lymph
nodes are of an abnormal consistency or incrased in
size. Lymphadenopathy can be regional (i.e., only one
group or a few contiguous groups of nodes are involved)
or generalized (i.e., involving more than two separate
sites).
B. Lymphadenopathy usually signals the presence of dis
ease and therefore warrants medical evaluation.
A. First, make sure the lymph nodes are tuly abnormal.
Certain lymph nodes (e.g., the submandibular and ingui
nal nodes) are commonly palpable.
B. Once the lymphadenopathy is deemed abnormal, gener
ate a diferential diagnosis based on the location of
the lymphadenopathy, the HIV status of the patient,
the clinical scenario, and the physical attributes of the
node. This information helps to guide the need for
laboratory tests and other studies [e.g., complete blood
count (CBC) and peripheral smear evaluation, mono
spot test, hepatitis serologies, serum lactate dehydroge
nase (LDH), erythrocyte sedimentation rate (ESR),
Venereal Disease Research Laboratories (VDRL) test,
chest radiographs].
1. Location of the lymphadenopathy. The location of
the lymphadenopathy allows you to form an initial
diferential diagnosis.
a. If the lymphadenopathy is generalized, the most
likely etiologies can be remembered with the
mnemonic, "SHE HAS CUTE LAN."
349
350
Chapter 62
Causes of Generalized Lymphadenopathy
("SHE HAS CUTE LN")
Syphi l i s
Hepatitis
Epstein-Barr virus infection
Histoplasmosis
AIDS/HIV i nfection
Serum sickness
Cytomegalovirus (CMV) infection
Unusual drugs (e_g_, hydantoi n derivatives,
anti-thyroid medications, anti-leprosy med
ications, isoniazid)
Toxoplasmosis
Erythrophagocytic Iymphohistiacytasis
Leishmaniasis
Arthritis (rheumatoid)
Neoplasm: leukemia and lymphoma
b. If the lymphadenopathy is localized, refer to Ta
ble 62-L
2. "IV status must always be considered whenever a
patient has regional or generalized lymphadenopa
thy. Typically, in HI V-infected patients, generalized
lymphadenopathy occurs early in the course of the
HIY. The lymphadenopathy can be caused either by
the HIV itself or other systemic diseases that are
common in HIV-infected patients.
3. Clinical scenario. Considering the patient's age and
associated fndings can help narrow the differential
diagnosis.
a Patient age. Lymphadenopathy in patients
younger than 30 years of age is most often benign
(and caused by an infection), whereas in patients
older than 30 years, the possibility of malignancy
becomes much more worrisome.
b. Signs and symptoms. Symptoms of fever, chills,
night sweats, and weight loss should always be
sought and, if present, usually imply a serious
systemic infection or malignancy. Symptoms or
signs of a local infection (e.g., pharyngitis, con
junctivitis, otitis, skin infection or trauma) usu
ally imply an infectious etiology.
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Lymphadenopathy 351
TABLE 62 1 : Major Causes of Localized Lymphadenopthy
Afected
Lymph Nodes Causes of Lymphadenopathy
Cervical
Supraclavicular
Head and neck malignancy or infection,
mononucleosis, tuberculosis, lymphoma
Lung, breast, or gastrointestinal mal ignancy,
lymphoma
Axillary Hand or arm infections, trauma or bites, cat
scratch disease, lymphoma, brucellosis,
breast cancer
Epitrochlear Uni lateral : hand infections, lymphoma, tula
remia
Inguinal
Bilateral: sarcoidosis, syphilis
Hilar / mediastinal
Leg or foot infections, plvic malignancy,
lymphoma, sexually transmitted disease
Sarcoidosis, tuberculosis, lymphoma, fungal
infections, lung cancer
Abdominal
4.
Lymphoma, tuberculosis, Mycobacterium
Qvium complex infection, metastatic mal ig
nancy
c. Historical data. Pertinent historical data should
be ascertained (e_g., cigarette use. history of a
cat scratch).
Characteristics of the lymphadenopathy on palpa
tion. The physical attributes of the lymphadenopa
thy can help a little, hut may be misleading; there
fore, these fndings alone should not dissuade
further evaluation. In general, the following tend
to be true:
a Infections tend to cause tender lymphadenopa
thy because of rapid growth of the node and
subsequent capsular stretching. The nodes tend
to be asymmetric with erythematous skin overly
ing the node.
b. Lymphoma classically leads to large. fr. rub
hery, nontender lymphadenopathy.
c. Metastatic cancer usually results in very fr
(sometimes "rock hard"). nontender nodes that
are immobile (i.e., fixed to the underlying tissue).
352
Chapter 62
C. Evaluation
1. If lymphoma or metastatic malignancy is strongly
considered, proceed to fne-needle aspiration, which
is quite sensitive for metastatic malignancies (and
infections), but not for lymphomas. If lymphoma is
a strong possibility, excisional biopsy is usually re
quired.
2. If bacterial infection is the most likely diagnosis, a
period of observation (2-3 weeks, with or without
antibiotics) is reasonable. If there is no evidence of
resolution. fne-needle aspiration. excisional biopsy,
or both is usually required.
3. If the etiology of the lymphadenopathy is unclear,
close follow-up is essential because a small but sig
nifcant percentage of these patients develop
lymphoma within 1 year.
TREATMENT varies considerably and depends on the under
lying cause.
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63. Lymphoma
@

INTRODUCTION
A. Defnition. Lymphoma is a malignant disorder of the
Iymphoreticular system.
B. Classifcation. There are two groups of lymphomas (Ta
ble 63-1). The distinction is based on the presence or
absence of multinucleated giant cells called Reed-Stern
berg cells.
1. Hodgkin's disease. Reed-Sternberg cells are usu
ally present.
2. Non-Hodgkin's lymphoma (NL). Reed-Sternberg
cells are absent.
HODGIN'S DISEASE
A. Epidemiology
1. Incidence. There are fewer than 10.000 cases re
ported per year.
2 Patient profle
a Age. Hodgkin's disease has a bimodal age distri
butiou. The incidence peaks in patients aged
2-2 years and again in patients older than 55
years. In young patients, Hodgkin's disease is
associated with high socioeconomic status and
small family size.
b. Gender. Except for the nodular sclerosis subtype,
Hodgkin's disease is more common in men
than women.
c. Race. Hodgkin's disease is more common in Cau
casians than African-Americans.
B. Pathogenesis of Hodgkin's disease. Disease progression
is orderly. I nitially. the malignancy spreads to anatomi
cally adjacent lymph tissues. Hematogenous spread to
the liver, bone marrow, and other viscera occurs only in
advanced disease.
C. Clinical manifestations of Hodgkin's disease
1. Painless, superficial adenopathy (usually involving
the neck or supraclavicular areas)
353
354
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lymphama 355
HOT
KE Y
Same patients report pain in lymphoid tissue following
the ingestion af alcohol.
2 Constitutional ("8") symptoms (i.e., fever, night
sweats, weight loss)
3. Severe pruritus (often confned to the lower extrem
ities)
4. Spinal cord compression or superior vena cava syn
drome (rare)
5. Immunologic dysfunction, which may develop simul
taneously with the onset of the lymphoma and predis
pose the patient to infection
6. Characteristic laboratory fndings include:
a Anemia
b. Leukocytosis (initially), thrombocytosis
c. Eosinophilia
d. Elevated erythrocyte sedimentation rate (ESR)
e. Elevated alkaline phosphatase level
1. Diagnosis. The finding of Reed-Sternberg cells on
lymph tissue biopsy is characteristic of Hodgkin's
disease.
a Diferential diagnoses. Reed-Sternberg cells are
also seen with phenytoin-induced lymphoid hy
perplasia, some NHLs or solid tumors, and
mononucleosis.
b. Subtypes. There are four main histologic sub
types of Hodgkin's disease, which are distin
guished by the relative number of lymphocytes
and Reed-Sternberg cells and the amount of fi
brous tissue (Table 63-2).
2. Staging. Survival is affected more by the clinical and
pathological stage than by the histopathologic
SUbtype.
a Staging evaluation
(1) Chest radiograph. A chest radiograph should
be performed to evaluate mediastinal in
volvement.
356 Chapter 63
TABLE 63-2: Histopathologic Subtypes of Hodgkin's Disease
Histologic Subtyp Comments
Lymphocyte-predominant Best pronosis; usually presents in
an earlier stage
Mixed cellularity Intermediate prognosis; patients are
older
Lymphocyte-depleted Warst prognosis; patients are older
Nodular sclerosis Female predomi nance; patients are
younger; usually involves lower
cervical, supraclavicular and medi
astinal nodes
(2) Computed tomography (CT)_ Abdominal
and pelvic c scans are routinely done to
assess nodes in these areas.
(3) Other studies. Some patients also undergo
lymphangiography, bilateral bone marrow
biopsies, and staging laparotomy with sple
nectomy.
b. Staging classifcation. The staging system for
Hodgkin's diseases is based on the Ann Arbor
classifcation system. Like most oncologic staging
systems, prognosis is best for stage I patients and
worst for stage IV patients. Table 63-3 presents
a simplifed staging scheme based on the extent
of lymph node involvement. Within these stages
are substages that affect treatment and prognosis.
(1) If patients have no "B" symptoms, the letter
"A" is added to the stage.
(2) If weight loss (in excess of 10% of body
weight), unexplained fever, or night sweats
is present, the letter "B" is added. In general,
those with symptoms have a poorer prog
nosis.
E. Treatment. In general, Hodgkin's disease should be
thought of as a curable cancer.
1. Treatment depends on the stage. General ap
proaches follow; an oncology reference can provide
detailed information regarding regimens.
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Lymphoma 357
M
a. Low-stage disease (e.g., stage I and IIa) is usually
treated with radiation.
b. High-stage disease (e.g., stage IIIb and IV) is
usually treated with combination chemotherapy
and radiation to bulky nodes.
c. Intermediate-stage disease. The optimal treat
ment for stage lIb and IlIa disease is contro
versial.
2. Long-term complications of treatment
a. Chemotherapy increases the risk for acute leuke
mia; this risk peaks 5 years after initiation of
therapy and decreases after 10 years. The devel
opment of acute leukemia as a result of chemo
therapy for Hodgkin's disease is much more com
mon in older patients.
b. Radiation therapy leads to an increased inci
dence of solid tumors (e.g., breast, stomach, or
thyroid tumors); this risk, unlike that of leuke
mia, continues to increase with time.
NHL is the name given to a heterogeneous group of malig
nancies involving both B and T cells.
A. Epidemiology
1. Incidence. The incidence is four times greater than
that of Hodgkin's disease. In addition, the HIV epi
demic has, in part, led to an increase in the incidence
of NHL over the last several years.
2. Patient profle
a Age. The median age at the time of diagnosis is
50 years.
b. Gender. NHL is more common in men than
women.
TABLE 63-3: Staging System for Patients with Hodgkin's Disease
Stage Definition
I
II
I I I
IV
limited to one area
Two or more areas but l i mited to one side of the dia
phragm
Two or more areas on both sides of the diaphragm
Involvement of extralymphatic tissue (i . e. , dissemi nated
di sease)
358 Chapter 63
c. Race. It is more common in Caucasians than
African-Americans.
d. Other factors
(1) NHL is more common in patients with al
tered immunity (e.g., HIV-positive patients,
those on immunosuppressive therapy. and
those with congenital immunodefciencies or
autoimmune disease).
(2) Some subtypes are associated with chromo
somal abnormalities.
B. Pathogenesis of NL. The spread of disease is not con
tiguous.
C. Clinical manifestations of NL. Presentations depend
on the site and subtype of tumor.
1. Common complaints include:
a. Asymptomatic superfcial lymphadenopathy
b. "B" symptoms (much less common than II
Hodgkin's disease)
c. Abdominal complaints
d. Bone pain or pathologic fracture
e. Symptoms related to pancytopenia
f. Acute emergencies (e.g .. superior vena cava syn
drome, spinal cord compression, airway com
pression)
2. Characteristic laboratory 6ndings include:
a Complete blood count (CBC) ranging from nor
mal to a decrease in all cell lines (i.e., pancyto
penia)
b. Elevated uric acid and lactate dehydrogenase
(LDH) levels
c. Elevated alkaline phosphatase levels
1. Diagnosis. Biopsy of tissue allows a defnitive diagno
sis to be made. The many subtypes of NHL can be
grouped into three categories based on the histologic
grade of the tumor: low-grade, intermediate-grade,
and high-grade.
2. Staging
a. Staging evaluation. Bone marrow biopsy, chest
radiographs, and abdominal and pelvic C scans
are often performed, and some patients require
lumbar puncture or a bone scan. Staging laparot
omy and lymphangiography are not usually indi
cated.
b. Staging c1assi6cation. The Ann Arbor staging
system for Hodgkin's disease (see Table 63-3) is
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Lymphoma
Stages I and I I
t
Radiation
Stages I and 1 1
t
Chemotherapy
and radiation
Stages I and 1 1

359
Stages 111 and IV
t
Chemotherapy with radiation to bulky nodes
Stages 1 1 1 and IV
t
Chemotherapy with intrathecal methotrexate
Stages 1 1 1 and IV
/
Chemotherapy with intrathecal methotrexate
Figure 63- 1 . General therapeutic measures for patients with nan-Hodg
kin's lymphoma (NHL).
360 Chapter 63
also used to stage NHLs; however, in NHL. the
histologic type is the single best predictor of prog
nosis. Therefore, the Ann Arbor staging system
is less useful for these patients.
E. Treatment depends primarily on histology, the extent of
disease, and patient characteristics. Treatment options
are diagrammed in Figure 63-1.
HOT
There exists a curious irony to NHL: tumors that confer
a favorable prognosis are the least likely to be cured
because low-grade tumors are less responsive to che
motherapy. Patients with high-grade lymphomas gen
erally have a poor prognosis, but the chance of cure
is increased.
KE Y
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64. Myeloprol iferative versus

Myelodysplastic Syndromes
@
INTRODUCTION. Myeloproliferative and myelodysplastic
disorders are often confused, but paying attention to the
names will remind you of how different these diseases re
ally are.
A. Myeloproliferative disorders are a group of diseases
where early cells in the bone marrow replicate uncomrol
lably; generally, an increase in white blood cells (WBCs),
red blood cells (RBCs), platelets, or a combination of
these is noted (myelofbrosis is often an exception).
E. Myelodysplastic disorders involve ineffective hemato
poiesis, causing a hypercellular, normocellular, or hypo
cellular bone marrow. Generally, a decrease in WBCs,
RBCs, platelets, or a combination of these is noted.
5
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MYELOPROLIFERATIVE DISORDERS
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A. Intoduction
1. Types of disorders. There are four myeloproliferative
disorders. All of them involve clonal proliferation of
the hematopoietic stem cell, leading to both qualita
tive and quantitative changes in all cell lines. The
type of disorder is therefore based on the predomi
nant cell line that is affected.
a. Chronic myelogenous leukemia (CML) is char
acterized by prominent proliferation of the
WBC line.
b. Polycythemia vera is characterized by prominent
proliferation of the RBC line.
c. Essential thrombocytosis is characterized by
prominent proliferation of platelets.
d. Myelofbrosis is characterized by prominent pro
liferation of fbroblasts.
2. General approach to the patient. A myeloprolifera
tive disorder is usually suspected when typical abnor
malities are found on the complete blood count
(CBC).
a. Primary abnormality
(1) [f the WEC is markedly elevated, CML is a
361
362
Chapter 64
possibility and the diferential diagnosis is
that of leukocytosis (see Chapter 58).
(2) If the RBC count is markedly elevated, poly
cythemia (see Chapter 57) is diagnosed and
polycythemia vera should be considered.
(3) If the platelets are markedly elevated, con
sider the differential diagnoses for thrombo
cytosis (see Chapter 55), including essential
thrombocytosis.
b. Multiple abnormalities. More than one abnor
mality (e.g., an increased hematocrit and platelet
count) is helpful in that it implies a myeloprolifer
ative disorder; however. more than one myelo
proliferative disorder may need to be considered.
The following features can help you diagnose a
specifc myeloproliferative disorder:
(1) Massive splenomegaly (see Chapter 29) im
plies either CML or mvelofbrosis.
(2) A decreased leukocyte
-
alkaline phosphatase
(LAP) score is noted in CML.
(3) Nucleated RBCs, early WBCs, and abnormal
RBC morphology (i.e., teardrop cells) are
characteristic of a leukoerythroblastic smear
and are seen in myelofbrosis.
(4) An increased hematocrit is only seen in poly
cythemia vera.
(5) Increased platelets out of proportion to the
WBC elevation and an increased LAP score
allow differentiation of essential thrombocy
topenia from CML.
HOT
KEY
B. CML
A bone marrow biopsy is usually not necessory to
diagnose a myeloproliferative disorder, with the possi
ble exception of myelofi brosis.
1. Approach to the patient
a. Patient histor
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Myeloproliferative versus Myelodysplastic Syndromes 363
(1) Common complaints include fevers, sweats,
fatigue, and abdominal fllness (from spleno
megaly).
(2) Marked leukocytosis (e.g., a WBC count
> 300,000 cells/ Jl) may cause leukostasis in
approximately 1% of patients with CML.
Symptoms of leukostasis include blurred vi
sion, respiratory distress, and priapism.
b. Physical examination. Marked splenomegaly is
a common fnding.
c Laboratory studies
(1) WBC count. The WBC count is markedly
elevated (e.g., 150.000 cells/ Jl).
(2) Peripheral blood smear. Typically, myeloid
forms in varying degees of maturation are
seen.
(3) Vitamin B12 and uric acid levels may be in
creased as a result of increased transco
balamin secretion and high cell turnover, re
spectively.
d. Bone marrow biopsy. If performed, a hypercellu
lar marrow with left-shifted WBCs is usually
seen. When the disease progresses to the acceler
ated (blast) phase, the bone marrow has more
than 30% blasts.
e. Cytogenetic studies. Almost all patients with
CML have a translocation between chromo
somes 9 and 22 (i.e., the Philadelphia chromo
some) that may be detected by karyotype testing
or by molecular testing.
2. Treatment
a. Plasmapheresis is used if the patient has symp
toms of leukostasis. which is a medical emer
gency.
(1) Hydroxyurea is usually used to lower the
WBC count to 5000-10,000 cells/il.
(2) Interferon-a (IFN-a) may offer palliation by
suppressing the Philadelphia chromosome.
c Bone marrow transplantation offers the only pos
sibility for cure. Patients should generally be
younger than 55 years and have a human leuko
cyte antigen (HLA)-matched sibling.
3. Prognosis. The average survival from diagosis is
3-4 years. The disease eventually progresses to an
364 Chapter 64
accelerated (blast) phase that results in progressive
anemia and thrombocytopenia; at this point, the sur
vival time usually decreases to a few months.
C. Polycythemia vera
HOT
K EY
a. Patient history
(1) Symptoms of hyperviscosity are common
(e.g., headaches, dizziness, blurred vision).
(2) Both thrombosis and bleeding may result
from abnormalities in platelet function.
(3) Increased basophils may result in increased
histamine release and account for the high
incidence of hoth pruritus and peptic ulcer.
Think of polycythemia vera when a patient is admitted
with a bleeding peptic ulcer but continues to have a
normal or elevated hematocrit.
b. Physical examination. Splenomegaly is com
monly found on exam. but is not as marked as
in CML and myelofbrosis.
c. Laboratory studies
(1) Hematocrit. A hematocrit consistently
greater than 60% in men and 55% in women
is usually due to polycythemia vera.
(2) Mean corpuscular volume (MCV). In ap
proximately 25% of patients, there is an asso
ciated iron defciency that causes a low MCV.
Gastrointestinal bleeding from engorged ves
sels or peptic ulcer disease and increased de
mand fom the elevated RBC mass are poten
tial etiologies of the iron defciency.
(3) Vitamin BIZ and uric acid levels are fre
quently elevated, as in CML.
(4) Erythropoietin level. The erythropoietin
level is usually low ( less than 20 mU!ml).
d. Marrow progenitor cell culture. This may be the
most sensitive test for polycythemia vera. Spon
taneous cell growth in the absence of exogenous
erythropoietin is diagnostic.
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e. Bone marrow biopsy. Although not necessary
for diagnosis, a bone marrow biopsy will show
panhyperplasia and, notably, increased megakar
yocytes. Iron stores may be decreased.
2. Treatment
a Phlebotomy may be performed weekly until the
hematocrit has been lowered to less than 45%;
thereafter, maintenance phlebotomy may be per
formed as needed.
b. Pharmacologic therpy
(1) Hydroxyurea is sometimes given to patients
with marked thrombocytosis (e.g., a platelet
count > 700,00 cells! fLI) with the goal of de
creasing the risk of thrombosis. Hydroxyurea
is also fequently administered to patients
with intractable pruritus or a high phlebot
omy requirement.
(2) Aspirin in low doses (e.g., 325 mg per day) is
sometimes given to patients who experience
recurrent thromboses, despite phlebotomy or
hydroxyurea therapy.
(3) Alkylating agents and radiophosphorus can
be leukemogenic and are increasingly
avoided.
3. Prognosis. The average survival is 10-15 years. Poly
cythemia vera can convert to CML, myelofbrosis,
and, rarely, acute myelogenous leukemia (AML).
C. Essential thrombocytosis
a Patient history
(1) Abnormalities in platelet function can lead
to both thromboses and bleeding. Erythro
melalgia (i.e., intense, burning pain in depen
dent extremities often accompanied by skin
warmth and mottling) results from microvas
cular occlusion. Although it can occur in all
myeloproliferative disorders, erythromelal
gia is especially common in patients with es
sential thrombocytosis.
(2) Many patients (particularly young women)
are asymptomatic.
b. Physical examination. Splenomegaly occurs in
two thirds of patients, but is not as marked as in
CML and myelofbrosis.
c. Laboratory studies
(1) Platelet count. The platelet count is invari-
366 Chapter 64
ably greater than 400,000 cells/Il, and often
exceeds 1 ,000,000 cells/ILl.
(2) Peripheral blood smear. The platelet mor
phology is frequently abnormal, with many
large, hypogranular forms.
(3) Bleeding times and aggregation studies may
show abnormalities in platelet function.
d. Bone marrow biopsy. If performed, bone marrow
biopsy reveals an increased number of large. hy
perploid megakaryocytes. This fnding contrasts
that of reactive thrombocytosis, where the mega
karyocytes are small and of lower ploidy.
e. Marrow progenitor cell culture. Cells can be
shown to grow without the usual exteral stimuli.
2. Treatment
a. Hydroxyurea is often used for patients with
symptomatic thromboses or platelet counts
greater than 700,000 cellS/ILl.
b. Aspirin. Small daily doses (e.g .q 325 mg per day)
may be indicated for patients with recurrent
thromboses despite adequate control of the
platelet count with hydroxyurea.
c. Alkylating agents and radiophosphorus are in
creasingly avoided.
3. Prognosis. Essential thrombocytosis is an indolent
disease. The average survival is usually at least
10-15 years.
D. Myelofbrosis
a. Patient history. Symptoms refect anemia (f
tigue, dyspnea), thrombocytopenia (easy bruisa
bility), and marked splenomegaly (abdominal
fullness).
b. Physical examination. Splenomegaly is usually
marked and hepatomegaly may also be present.
c Laboratory studies
(1) Hematocrit. Anemia is almost always
present.
(2) Peripheral blood smear. The combination of
teardrop cells, a leukoerythroblastic smear
(nucleated RBCs and left-shifted WBCs),
and large, abnormal platelets is virtually diag
nostic of myelofbrosis.
d. Bone marrow biopsy is diagnostic and reveals
increased reticulin fbers in the early stages of
disease and more severe fbrosis later on.
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2. Treatment
a Supportive measures include blood and platelet
transfusions as needed. Erythropoietin and an
drogens may be given in an attempt to decrease
transfusion requirements.
b. Splenectomy may be indicated for patients with
refractory anemia or thrombocytopenia or in pa
tients with recurrent pain from splenic en
largement.
c IFN-a may beneft some patients.
3. Prognosis. The illness usually results in bleeding from
thrombocytopenia and progressive liver failure from
extramedullary hematopoiesis: the average survival
is 5 years.
MYELODYSPSTC SYNDROMES have ineffective hema
topoiesis as their shared pathophysiologic disorder. The bone
marrow is often hypercellular while cytopenias are noted on
the peripheral smear.
A. Classifcation. The current classifcation scheme is far
from perfect. It includes chronic myelomonocytic leuke
mia (CMML), which is more like a myeloproliferative
disorder in its proliferation of the monocyte line. It is
also impossible to predict which patients will progress
to AML and which will follow a more benign course
using the current classifcation scheme.
B.
1. Refractory anemia (RA)
2. Refractory anemia with ringed sideroblasts (RARS)
3. Refractory anemia with excess blasts (RAEB); 5%-
1 9% blasts
4. RAEB in transformation (RAEB-t); 20%-29%
blasts
5. CMML
Approach to the patient
1. Patient history. Patients are frequently asymptom
atic at diagnosis. If symptoms and signs are present,
they result from one of the cytopenias and therefore
include fatigue, infection, and bleeding.
2. Physical examination. Splenomegaly may be present,
but often is not.
3. Laboratory studies. Abnormalities in two or three
of the following cell lines are usually present.
a. RBC line: anemia, an increased MCV, macro
ovalocytes, and a decreased reticulocyte count
b. WBC line: neutropenia, hypogranular neutro-
368
Chapter 64
phils, and the Pelger-Huet anomaly (bilobed
nuclei)
c Platelets: thrombocytopenia and hypo ganular
platelets.
4. Bone marrow biopsy is necessary to diagnose the
myelodysplastic syndromes. When there are more
than 30% blasts, an acute leukemia is diagnosed.
C. Treatment
1. Supportive therapy. Blood and platelet transfusions
are given as needed, but may eventually be compli
cated by alloantibody formation, which decreases
RBC and platelet survival.
2. Pharmacologic therapy
a. Growth factors
(1) Erythropoietin may decrease the transfusion
requirement in some patients.
(2) Granulocyte colony-stimulating factor
(G-CSF) or granulocyte-macrophage colony
stimulating fctor (GM-CSF) usually in
crease neutrophil counts and decrease the
incidence of associated minor infections, but
no signifcant survival beneft has been dem
onstrated.
b. Intensive chemotherapy (with regmens similar
to those for leukemia) has had mixed results.
3. Bone marrow transplantation offers the only possi
bility of cure for the small group of eligible patients.
Patients must be younger than 55 years and have an
HA-matched sibling donor.
D. Prognosis
1. RA and RARS. Patients have a low risk for leuke
mia, and can survive many years.
2. RAEB, RAEB-t, and CMML. Patients have an in
creased risk of conversion to acute leukemia (20%-
50%), and survival is often shorter (i.e., approxi
mately 2 years).
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65. Acute Leukemia
@
INtODUCTION
Q
A. Leukemia results from the clonal proliferation of white
blood cells (WBCs). Leukemias are classifed according
to the cell line involved (lymphocytic or myelogenous)
and the maturity of the malignant cell. Because chronic
myelogenous leukemia (CML) involves clonal prolifera
tion of stem cells, it is better thought of as a myeloprolif
erative disorder and is discussed in Chapter 64.
B. Patients with acute leukemia are commonly hospitalized
for chemotherapy or for complications associated with
the leukemia itself or its treatment.
ACUTE LEUKEMIA results from a hematopoietic progenitor
cell losing its ability to differentiate, while replicating uncon
trollably.
A. Classifcation
1. Acute lymphoblastic leukemia (ALL). The progeni
tor cell is a lymphocyte precursor. ALL can be classi
fed according to:
a. Morphology
(1) L1 small lymphoblastic
(2) L2 large lymphoblastic
(3) L3 = undifferentiated
b. Immune subtype
(1) Pre-B cell
(2) B cell
(3) T cell
2. Acute myelogenous leukemia (AML), also known
as acute nonlymphocytic leukemia, is diagnosed
when the progenitor cell is a myelocyte precursor.
AML can be classifed according to which cell in the
myelogenous lineage underwent clonal expansion
(Table 65-1).
B. Epidemiology
L ALL represents 80% of childhood cases of acute
leukemia (peak age: 3-7 years), and approximately
1 0%-20% of adult cases. The Ll morphology, which
usually occurs in children, and the pre-B cell immune
subtype carry a more favorable prognosis.
2. AML represents the majority of adult cases (approxi-
369
370
Chapter 65
TABLE 65- 1 : Classification of Acute Myelogenous Leukemia (AML)
Type Name of Leukemia'
M 1 Myeloblastic
M2 Myeloblastic with differentiation
M3 Promyelocytic
M4 Myelomonocytic
M5 Monocytic
M6 Erythroleukemia
M7 Thromboleukemia
General progression is from early to mature cell types.
mately 60%-70%); the average age at onset is 50
years.
3. Biphenotypic leukemia. In another 10%-20% of
adult cases. the leukemia has features of both ALL
and AML.
C. Risk factors for acute leukemia include prior radiation
or chemotherapy, chemical exposures (e.g .. benzene).
myelodysplasia, myeloproliferative disorders, aplastic
anemia, and congenital chromosomal disorders (e.g.,
Down's syndrome, Turner's syndrome, Klinefelter's syn
drome). In most cases, no obvious predisposing condition
is found.
D. Clinical manifestations of acute leukemia. Patients usu
ally seek medical attention within days or weeks of the
start of their illness. The pathologcal processes outlined
below (particularly pancytopenia), give rise to the most
common fndings on presentation.
1. Pancytopenia may result in petechiae, fatigue and
pallor, or clinically apparent infections (e.g., celluli
tis, pneumonia).
2. Blast cell proliferation and invasion
a. ALL. Bone pain, arthralgias, lymphadenopathy,
and hepatosplenomegaly are common with ALL.
b. AML. AML type M5 is associated with gingival,
skin, and central nervous system (CNS)
involvement.
3. Leukostasis [i.e., vaso-occlusion by white blood cells
(WBCs)] may occur with a leukocyte count greater
than 200,000 cells! f.1. CNS disorders (headaches,
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Acute leukemia
371
strokes) and pulmonary fndings (dyspnea, hypoxia)
are common manifestations of leukostasis.
4. Disseminated intravascular coagulation (DIC) may
occur with AML types M3 and M5, and usually re
sults in excessive bleeding, rather than clotting.
HOT
M3 causes ole.
K E Y
E. Approach to the patient
a. Complete blood count (CBC). Pancytopenia is
usually present, but also may be found in a variety
of other disorders (see Chapter 53).
b. Peripheral blood smear
(1) Blasts are usually, but not universally, found
on the peripheral blood smear.
(2) Auer rods, eosinophilic rods that may be seen
in the cytoplasm of blasts, are pathogno
monic for AML.
c. Coagulation tests. If DIC is present, a prolonged
prothrombin time (PT), decreased fbrinogen
level. and elevated levels of fbrin degadation
products may be seen.
d. Electrolyte panel. Metabolic abnormalities may
result from spontaneous tumor lysis syndrome
or, more commonly, with therapy-induced tumor
lysis. High cell turnover can result in hyperuri
cemia, hyperkalemia, hyperphosphatemia, hypo
calcemia, and!or acidosis.
e. Cerebrospinal fuid (CSF) analysis may show ab
normalities in patients with carcinomatous men
ingitis, which is most often associated with ALL
and AML type MS.
2. Radiography. A chest radiograph may show an ante
rior mediastinal mass in patients with ALL (espe
cially the T cell variety).
3. Bone marrow biopsy. The diagnosis of acute leuke-
372 Chapter 65
mia relies on the presence of more than 30% blasts in
the bone marrow. Morphology, histochemical stains
[i.e., peroxidase, periodic acid-Schiff (PAS)], surface
markers [i.e., terminal deoxynucleotidal transferase
(TdT)], and cytogenetics can all help determine
whether the leukemia is ALL or AML.
a ALL. Remember that you "ALL PAST
('passed')" the test by using this mnemonic:
Differentiating ALL from AML IALL PASr)
A is assoiated with a psitive PAS stain and
a positive TdT enzymology (TdT is positive in
95% of ALL cases) .
b. AML is associated with a positive peroxidase
stain. (Peroxidase stains the myeloid ganules.)
F. Treatment
1. Types of therapy
a. Induction chemotherapy is high-dose, usually
kills more than 99.9% of leukemic cells, and is
meant to induce a complete remission (CR). A
patient is in CR if there are fewer than 5% blasts
in the bone marrow, no blasts in the peripheral
blood. no evidence of extramedullary invasion,
and normalization of the blood counts.
b. Consolidation (early intensifcation) therapy is
usually needed to prevent relapse.
c. Maintenance therapy, which entails lower doses,
may be indicated and is often continued for sev
eral years.
2. General approaches to therapy
a ALL
(1) Chemotherapy
(a) Induction chemotherapy (often with
daunorubicin, vincristine, and predni
sone) can induce a CR in most patients
with ALL.
(b) CNS prophylaxis with cranial irradiation
and intrathecal methotrexate is usually
administered after remission because leu-
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Acute Leukemia 373
kemic meningitis is the site of relapse in
up to two thirds of patients who do not
receive prophylactic therapy.
(c) Maintenance therapy (or consolidation
therapy for high-risk patients) is often
given for 2-3 years.
(2) Bone marrow transplantation. With standard
chemotherapy, approximately two thirds of
children and one half of adults will be cured.
Because these rates are comparable to those
observed with allogenic transplantation dur
ing the frst remission, bone marrow trans
plantation is usually reserved for relapsed
patients who achieve a second remission.
b. AML
(1) Chemotherapy
(a) Indnction chemotherapy (usually with
daunorubicin and cytarabine) produces a
CR in approximately two thirds of pa
tients but less than one half are cured.
(b) CNS
'
prophylaxis. Patients with symp
toms suggestive of leukemic meningitis
and asymptomatic patients with M4 or
M5 AML usually undergo a CSF evalua
tion to rule out leukemic meningitis dur
ing remission.
(c) Consolidation therapy i usually gven,
often with the same induction agents or
cytarabine alone. In contrast with the
management of ALL, maintenance ther
apy is not indicated.
(2) Bone marrow transplantation may be prefer
able following the frst remission in patients
with AML because cure rates may be in
creased.
@
COMPICAnONS ASOCIATED WITH ACUTE LEUKEMIA
A. Leukostasis with symptoms is more common in pati
.
ents
with AML than those with ALL and may neceSSItate
emergent plasmapheresis.
B. Tumor lysis syndrome may occur de novo (most com
monly with M3 or M5 AML) or with the initiation of
therapy. Preventative and therapeutic measures usu
lly
include vigorous hydration, allopurinol therapy, clcIUm
replacement, and sodium bicarbonate administration (to
374
Chapter 65
treat acidosis and hyperkalemia and facilitate the excre
tion of uric acid).
C. Anemia and thrombocytopenia should be managed as
described in Chapter 53 V B 2 and Chapter 54, respec
tively. Menstruation should be suppressed to prevent
excessive bleeding.
D. DIC frequently accompanies treatment for M3 AML.
Low-dose heparin therapy may be used as prophylaxis.
E. Fever and neutropenia. The risks associated with neutro
penia are highest when the absolute neutrophil count is
less than 50 cells! p.l. Neutropenic precautions should
be taken (see Chapter 53 V A 3). Patients should be
thoroughly evaluated for the source of their fever (see
Chapter 43), and broad-spectrum antibiotics should be
instituted as soon as blood cultures are drawn.
F. Complications associated with bone marrow transplant
1. Graft versus host disease (GVHD) may accompany
allogenic bone marrow transplant.
a. Acute GVHD may manifest with a rash, diar
rh
a, a
d liver abnormalities. lmmunoprophy

laxls With methotrexate and cyclosporine may
be benefcial.
b. Chronic GVHD usually manifests with skin
changes similar to sclerodenna, and is often
treated with prolonged immunosuppression.
2. Pneumocystis carinii pneumonia (PCP) is usually
treated with trimethoprim/sulfamethoxazole (TMPI
SX). One d
uble- strength tablet (160 mg/800 mg)

dally or three tImes per week is effective prophylaxis.
3. ytomegal
.
ovirus (CMV) pneumonia must be recog
OIzed and IS often treated with ganciclovir.
4. Herpes virus infections, including herpes simplex vi
rus and varicella-zoster virus reactivations, may be
prevented and treated with acyclovir.
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66. Plasma Cell Dscrasias
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INTRODUCTION
A. Defnition. Plasma cell dyscrasias ( " monoclonal gam
mopathies paraproteinemias) are malignancies of the
B lymphocyte system. Common plasma cell dysplasias
include multiple myeloma and Waldenstrom's macro
globulinemia.
B. Clinical manifestations of plasma cell dyscrasias
I. The clinical manifestations of all plasma cell dyscra
sias result from:
a. Proliferation of the neoplastic cells and invasion
of various organs
b. Secretion of cell products (either immunoglobu
lins or subunits)
c. The host's response to the tumor
2. Patients with plasma cell dyscrasias often have M
(monoclonal) components in their serum.
a. The M component represents the immunoglobu
lin (or light or heavy chain) that is being secreted
and can be quantitated by performing serum pro
tein electrophoresis. Qualitative assessment is
made using immunoelectrophoresis.
b. M components are not specifc to plasma cell
dyscrasias. They are also seen in leukemia,
lymphoma, sarcoidosis, rheumatoid arthritis.
monoclonal gammopathy of uncertain sigif
cance (MGUS), and other diseases.
Q
MULPLE MYELOM
A. Epidemiology. Myeloma accounts for 1 % of all maligant
disease and more than 1 0% of hematologic malignancies
in the United States.
1. It is a disease of older people; the median age at
diagnosis is 61 years.
2. The incidence in African-Americans is twice that
in Caucasians.
B. Clinical manifestations of multiple myeloma. The most
common presenting symptoms are related to anemia,
bone pain, and infection. The important clinical manifes
tations of multiple myeloma can be remembered using
the mnemonic, "PLASMA":
375
376 Chapter 66
Important Clinical Manifestations of Multiple
Myeloma ("PLASMA")
Proteinuria/renal i nsufficiency
Lytic bone lesions and hypercalcemia
Anemia and Abnormal bleeding
Sepsis and infections
Marrow i nvolvement
Amyloidosis
1. Proteinuria/renal insuffciency is multifactorial in eti
ology, with causes including light-chain proteinuria,
hypercalcemia, hyperuricemia, amyloidosis, and py
elonephritis.
2. Lytic bone lesions and hypercalcemia. Bone pain
occurs in 70% of patients, usually involving the back
and ribs. Because the lesions are lytic, plain radio
graphs are better than bone scans.
3. Anemia and abnormal bleeding. The majority of pa
tients will have anemia (usually normocytic) due to
various causes. Paraproteinemias may cause platelet
dysfunction, leading to abnormal bleeding.
4. Sepsis and infections. Seventy-fve percent of
.
pa
tients will have a serious infection at some tIme,
primarily either pneumonia (due to Streptococcus
pneumoniae, Staphylococcus aureus. Haemophilus
infuenzae, or Klebsiella pneumoniae) or pyelone
phritis (due to Escherichia cl or other gram-nega
tive rods).
5. Marrow involvement. The bone marrow is infltrated
by plasma cells, which initially causes anemia and
may lead to bone marrow failure. The extent of mar
row plasmacytosis ranges from 5%-100%.
6. Amyloidosis develops in a minority of patients and
may lead to carpal tunnel syndrome, congestive heart
failure (CHF), or liver disease.
C. Laboratory fndings
1. Proteinuria may be evident on urinalysis, bur the
dipstick is often negative because it tests for albumin,
not globulin.
2. Anemia is usually normocytic and normochromic,
and rouleau formation may be noted on the periph
eral smear.
3. Narrow anion gap. Because globulin is cationic, the
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Plasma Cell Dyscrasias
377
increased unmeasured cations decrease the anion
gap.
4. Low serum bicarbonate. A type 2 renal tubular acido
sis may result from proximal tubular damage as a
result of fltered light chains.
5. Pseudohyponatremia may result from increased
paraprotein, which can cause laboratory errors.
6. Hyperalcemia may occur from increased osteo
clast activity.
7. Elevated erythrocyte sedimentation rate (ESR). The
ESR is frequently elevated, but this is a nonspe
cifc fnding.
1. Protein electrophoresis on serum and urine i usually
ordered based on suspicious symptoms, sigs, or lab
oratory test results.
a. Procedure. Albumin and a, {, and l globulin
are separated by differing mobilities in an elec
tric feld. In myeloma, increased paraprotein
causes an abnormal spike (usually in the ( or
1 region).
b. Results. When used together, serum and urine
protein electrophoresis will miss approximately
1 % of myeloma patients (those that are minimal
or nonsecretors). However, of patients who have
a variant of myeloma (solitary bone plasmacy
toma or extramedullary plasmacytoma), fewer
than 30% will have a positive protein electropho
resis.
(1) Serum protein electrophoresis will confrm
the diagnosis of myeloma in 80%-90% of pa
tients. Approximately two-thirds of patients
with positive serum protein electrophoresis
results will also test positive on urine protein
electrophoresis.
(2) Urine protein electrophoresis. In the re
maining patients, only the light chain is se
creted. The light chain can only be detected
using urine protein electrophoresis.
378 Chapter 66
HOT
The diagnosis of myeloma is usually established by
the following triad:
K E Y

Marrow plasmacyosis > 1 0%

Lytic bone lesions

M component i n serum (usually > 3 g/dl) or urine
IgG (50% of patients)
IgA (25% of patients)
Light chains only (20% of patients)
IgD ( l % of patients)
3. Immunoelectrophoresis is then perfonned to deter
mine if the abnonnal spike is polyclonal or mono
clonal.
HOT
K E Y
a. A polyclonal spike is seen in reactive conditions
(e.g., infection, malignancy, collagen vascular
disease).
b. A monoclonal (M component) spike often signi
fes myeloma, but may also be found in many
other conditions (e.g., chronic lymphocytic leu
kemia, lymphoma, sarcoidosis). Therefore, this
test should not be used to screen asymptomatic
patients because the clinical setting is critical to
interpreting the test correctly.
An IgG spike > 3. 5 g/dl or an IgA spike > 2 g/dl
almost always represents myeloma (ond will therefore
be monoclonal when tested by immunoelectropho.
resis).
4. Diferential diagnosis. The main disorder to distin
guish from myeloma is MGUS. Characteristics of
MGUS usually include:
a. M component usually < 2 g/dl
b. Absence of Bence Jones proteinuria
c. Marrow plasmacytosis < 5%
d. Absence of anemia, renal disease, hypercalce
mia, and bone lesions
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Plasma Cell Dyscrasias 379
HOT
I n approximately 1 0%-25% of patients, MGUS prog
resses to multiple myeloma (over many years or de
cades) .
K E Y
M
E. Treatment. Unless the patient undergoes bone marrow
transplant, the goal is primarily palliation.
L Chemotherapy. Various chemotherapeutic regimens
are available for patients with symptomatic my
eloma.
2. Radiation is also used for bone lesions.
F. Prognosis. Median survival without treatment i 6
months; with treatment, survival is extended to 3 years.
Tumor burden is an important predictor of survival.
1. Patients with a low tumor burden (i.e., IgG spike <
5 gldl, no more than one lytic lesion, and absence of
severe anemia, renal failure, or hypercalcemia) have
a median survival of approximately 5 years.
2. Those with a high tumor burden (IgG spike > 7 g/dl,
serum calcium > 12 mg/dl, more than three lytic
lesions, or a hematocrit < 25%) have a median sur
vival of approximately 1 year.
WALDENSTROM'S MACROGLOBULINEMIA. In Walden
strom's macroglobulinemia, the abnonnal cells are a hybrid
between lymphocytes and plasma cells.
A. Clinical manifestations of Waldenstrom's macroglobu
linemia. The hybrid cells secrete IgM, which accounts
for most of the clinical manifestations. The clinical mani
festations are similar to those of myeloma; however,
there are important diferences.
1. Hyperviscosity is much more common in Walden
strom's macroglobulinemia than in multiple my
eloma. Symptoms may include altered mental status,
visual disturbances, and mucosal bleeding.
2. Hepatomegaly, adenopathy, and splenomegaly are
commonly seen in Waldenstrom's macroglobulin
emia, but not in myeloma.
380 Chapter 66
3. Hypercalcemia. bony lesions, and renal insuffciency
are much less common in Waldenstrom's macroglob
ulinemia.
4. A simple way to remember the features that may
distinguish Waldenstrom's macroglobulinemia from
multiple myeloma is to use the mnemonic, "Uncle
Waldo loves HAMS. "
Characteristics of Walden strom' s Macroglobu
linemia ("Uncle Waldo loves HAMS")
Hyperviscosity
Adenopathy
IgM
Splenomegaly
B. Treatment is similar to that for myeloma_ however. plas
mapheresis may be needed more often because of the
increased incidence of hyperviscosity.
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67. Metastatic Neoplasms
@
Q
INTRODUCTION
A. Detection of malignancies. Malignancies are usually de
tected in one of three main ways:
1. Screening (e.g., as with breast, cervical, prostate, co
lorectal cancer)
2. As a result of local symptoms or fndings (e.g., pain,
a change in bowel habits, hematuria, lump)
3. As a result of systemic symptoms or fndings (e.g.,
metastatic disease, paraneoplastic syndromes)
B. Common sites of metastasis. This chapter will help you
remember the malignancies that commonly metastasize
to the bone, brain, liver, and lung.
e. Common malignancies capable of metastasis. Although
there are many malignancies capable of metastasizing to
different areas, there is a core group that can usually go
anywherethyroid cancer, lung cancer, breast cancer,
gastrointestinal malignancies, renal cell carcinoma, sar
coma, prostate cancer, and melanoma.
METASTASIS TO BONE
A. Common malignancies capable of metastasizing to bone
are depicted in Figure 67-l.
1. Melanoma is not included in the diagam, but be
cause melanoma can go anywhere, it should always
be considered when a patient has a metastatic malig
nancy to any organ.
2. Thyroid cancer
3. Lung cancer
4. Breast cancer
5. Gastrointestinal tract malignancies (usually only the
mucinous subtype goes to bone)
6. Renal cell carcinoma
7. Sarcoma'
8. Prostate cancer
* Multiple myeloma is not included on the diagram because i i
.
s a cancer
that arises within the skeletal system, rather than metastaslzmg to the
skeletal system. Nevertheless, if you want to include myeloma on the
"benzene ring" diagram, just place sarcoma next to myeloma (myeloma
commonly affects the iliac crest).
381
382 Chapter 67
Thyroid
Lung Breast
Kidney Sarcoma
Prostate
Figure 671. Despite the long lists of malignancies capable of metasta
sis contained in conventional textbooks, the most common cancers that in
valve the bone, brain, liver, and lungs can practically all be contained in
an easy-to-remembr "benzene ring" diagram. The bnzene ring repre
sents the human bdy; the cancers are placed at their approximate ana
tomical position rsarcoma can arise anywhere). Even though this dia
gram is set up t help you remembr those cancers that metastasize to
bone, the same diagram (with same slight modifications) can be used to
recall the cancers that go to the brain, liver, and lung.
B. Sites of metstasis. The bones most commonly involved
are the vertebrae, femur, pelvis, ribs, and sterum (in
that order).
C. Signs of bone cancer. Cancers that involve the skeletal
system can be asymptomatic or produce pain. deformity,
pathologic fractures, and hypercalcemia.
II
METASTASIS TO THE BRAIN
A. Common malignancies capable of metastasizing to the
brain. This list is the same as the one for cancers that
metastasize to bone, with one exception: prostate cancer
tends not to go to the brain (or lung).
1. Thyroid cncer
2. Lung cancer (most common)
3. Breast cancer
4. Gastrointestinal tract malignancies
6. Sarcoma
B. Sites of metstasis. Most metastases are supratentorial
and are often multiple.
C. Signs of brain cancer include evidence of increased
intracranial pressure or brain disturbances (focal or
diffuse).
METASTASIS TO THE lVER. Metastatic involvement of
the liver is very common and can involve virtually any cancer
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Metastatic Neoplasms 383
(except primary brain cancer). In the United States, the
incidence of metastatic cancer to the liver is much more
common than primary hepatocellular carcinoma. Only cir
rhosis causes more cases of fatal liver disease.
A. Common malignancies capable of metastasizing to the
liver. Again, this list is very similar to that for cancers
that metastasize to the bone. The major difference is
that pancreatic cancer commonly goes to the liver (which
is not surprising, given the proximity of the two organs),
whereas renal cell carcinoma. prostate cancer, and sarco
mas involve the liver to a lesser extent (but still can).
1. Thyroid cancer
2. Lung cancer
3. Breast cncer
5. Pancreatic malignancy
7. Sarcoma
8. Prostate cncer
B. Signs ofliver cncer. Often the frst (and sometimes only)
serum abnormality seen is an elevated alkaline phos
phatase.
HOT
KEY
In patients with isolated elevatians of alkaline phospha
tase, always cansider metastatic involvement of the
liver as a cause.
I METASTASIS TO THE LUNG
A. Common maligancies capable of metastasizing to the
lung. Although almost any malignancy can involve the
lung, the most common include:
1. Thyroid cancer
2. Breast cancer
4. Renal cell crcinoma
5. Testicular cancer (instead of prostate cancer)
B. Sites of metastsis. Classically, lung metastases tend to
384 Chaptr 67
be multiple and involve the peripheral areas of the lung
parenchyma; lesions are most common in the lower
lobes. Endobronchial metastases are very unusual.
C. Signs of lung cncer. Metastases are often detected by
imagng studies.
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PART VIII
.......................................................................................
Rheumatology
delete this me immediately!
EECnlATHOrO pacnpoCTpaHeHHR
MCA 3T pOHT.py
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68.Monorticular Arthritis
a
INTRODUCTION. When a patient presents with joint com
plaints, the list of possible causes seems enormous. However,
the number of possibilities can be lowered considerably by
answering the following questions:
A. [s the arthritis mono articular or polyarticular?
B- Which joints are involved? For example:
1. Distal interphalangeal (DIP) joint involvement is al
most always due to degenerative joint disease (OJO)
or psoriatic arthritis.
HOT
The first and last letters of DIP are the first letters af
the two diseases that most commonly affect the joint,
Degenerative joint disease and Psoriatic arthritis.
KEY
II
2. Wrist involvement is often due to rheumatoid ar
thritis.
3. First metatarsophalangeal (MTP) joint infammation
is usually due to gout or OJO.
CAUSES OF MONOARTCULR ARTHRITIS. It is very im
portant to diagnose a monoarticular arthritis quickly in order
to prevent permanent joint damage and, in some cases, sep
sis. With this caveat in mind. the mnemonic "If I Make The
Diagnosis, No More Harm" will help you recall the common
causes of monoarticular arthritis.
387
388
Chapter 68
Causes of Monoarticular Arthritis ("If I Make
The Diagnosis, No More Harm")
Infectious disease
Inflammatory disease
Metabolic disorders
Trauma
DJD
Neoplasm
Miscellaneous (foreign body synovitis, avascu
lar necrosis)
Hemarthrosis
A. Infection must be considered frst because it is potentially
life- threatening. Common joint infections include staph
ylococcal, streptococcl, and gonorrheal infections,
and tuberculosis.
B. Infammatory disorders (e.g., psoriatic arthritis, rheuma
toid arthritis, Reiter's syndrome, and other collagen vas
cular diseases). Although these diseases usually are poly
articular, they may begin as a mono articular swelling and
thus have to be considered when the other causes are
ruled out.
C. Metabolic disorders [e.g., gout, pseudogout (calcium py
rophosphate deposition disease, CPDD)]. Often diffcult
to distinguish purely on clinical grounds, pseudogout
tends to be accompanied by chondrocalcinosis that is
visible radiographically. These patients usually have nor
mal uric acid levels. Light microscopic examination of
synovial fuid is very helpful, in that gouty crystals are
seen as yellow crystals when parallel to the condenser
(i.e., negative birefringence) and of course, gout is
treated by allopurinol. Another way to remember the
birefringence patter is to remember that pseudogout
crystals are positive.
D. Trauma to a joint (e.g., torn Iigamtnt, bone fracture)
can lead to hemarthrosis or internal joint derangement.
The patient should always be asked specifcally about a
history of trauma to the affected joint.
E. DID, a very common disorder (especially in elderly pa
tients), can also cause polyarthritis (see Chapter 69).
E. Neoplasm is a rare cause of monoarticular swelling but
should be considered. Examples include osteoid osteoma
and pigmented villonodular synovitis.
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Monoarticular Arthritis
389
F. icellaneous. This category includes foreig body syno
VitiS and avascular necrosis (e.g., due to trauma, steroid
use, or alcohol).
G. Hemarthrosis. Bleeding into a joint, when not related to
r
.
auma, i

usuall

seen in patients with clotting abnormal
ItIes (patIents WIth hemophilia or other clotting defects
or those on anticoagulants).
'
II
APOACH T THE PAnENT
A. Patient history
1. A chro
ic history of joint complaints may imply a

crystal-mduced or other noninfectious etiology.
2. Sexual risk factors are very important, especially in
young patients.
B. Physical examination. The physical examination is use
ful for:
1. Determining what joints are involved
2. Ex
ding periarti
.
cular processes that may mimic ar
thntIs (e.g., cellulItis, bursitis, tendinitis)
3. Di
.
scer
ing signs that suggest specifc causes (e. g.,

skm eVidence of psoriasis)
C. Other diagnostic modalities
1. Plain radiographs of the affected joint are sometimes
helpful (e.g., when DJD, pseudogout, or fracture is
the cause of the joint pain), but often are not useful.
2. Artrocen!esis and joint fuid analysis is the mainstay
of diagnosIs and should be performed in almost all
patients, especially if infection is a consideration.
a As little as 1-2 ml of fuid are needed for the
necessary studies [White blood cell (WBC) count
with differential, Gram stain and culture, and
crystal examination].
b. B
.
ased on the results of the joint fuid analysis, the
?Isorder can be categorized as noninfammatory,
mfammatory, or septic (Table 68-1).
WBCs/mm3
%PMN
Possible causes
<200
<25%
200-10,000
<25%
DjD, trauma, asep
tic necrosis
10,000-100,000
50%-90%
Collagen-vascular diseases,
crystal-induced disease,
TB, mycotic infections
>100,000
50%-100%
Pyogenic bacterial
infections
DjD = degenerative joint disease; PMNs = polymorphonuclear neutrophils, TB = tuberculosis; WBCs = white blood cells.
* Results in different diseases may be variable.
W
-
o
(

a
"

0
0
Monoorticular Arthritis 391
HOT
KEY
Always consider infection, regardless of the joint fluid
analysis results.
3. Synovial biopsy and arthrosopy should be consid
ered if the diagnosis is still unclear.
69. Polyarticular Arthritis
a
II
INTODUCTION. Because polyarticular arthritis may have
many causes, clinical, laboratory, and radiogaphic features
are used to establish a diagnosis.
CAUSES OF POLYARTCULR ARTHRmS. In order to or
ganize the many causes, classify them as belonging to one
of three main categories: classic seropositive, classic seroneg
ative, and miscellaneous (Table 69-1).
A. Classic seropositive polyarthritis. These disorders are
characterized by symmetric swelling and the presence of
autoantibodies.
1. Rheumatoid arthritis is a chronic systemic infamma
tory disease primarily involving the synovial mem
branes of multiple joints.
a. Epidemiology. The disease affects women twice
as often as men, and the usual age at the time
of onset is 20-40 years.
b. Clinicl manifestations. The onset is insidious.
Major symptoms include malaise, fever, morning
stiffness, and progressive symmetric small joint
swelling. Extra-articular manifestations may in
clude subcutaneous nodules, polyserositis,
lymphadenopathy, and splenomegaly. The clas
sic radiographic fndings include periarticular os
teoporosis, joint erosions, and, occasionaIly, sub
luxation of the upper cervical spine. Eighty-fve
percent of patients are rheumatoid factor
(RF)-positive.
2. Systemic lupus erythematosus (SLE) is a multisystem
autoimmune disorder.
a. Epidemiology. Eighty-fve percent of all patients
are women 20-40 years of age.
b. Clinical manifestations. The criteria for diagnosis
are helpful to remember because they include
the major clinical manifestations of the disease.
The presence of 4 of the 11 criteria makes the
diagnosis. In our medical school, in order to pass,
we needed to know the 11 criteria for SLE; there
fore, we were all in "P-MOAD" -7 Ps and M
o A D. The frst two Ps are positive lab tests;
392
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Polyarticulor Arthritis 393
TABLE 69-1: Common Causes of Polyarticular Arthritis
Classic seropositive polyarthritis
Rheumatoid arthritis
Systemic lupus erythematosus (SLE)
Systemic sclerosis
Polymyositis
Overlap syndrome
Classic seronegative spondyloarthropathy
Ankylosing spondylitis
Psoriotic arthritis
Reiter's syndrome
Arthritis related to enteric disorders
Miscellaneous
I Gonorrheol-disseminated gonococcal inFection
2 Spirochetal-Lyme diseose, secondary syphilis
3 Viral-HIV, hepatitis B, parvovirus
4 Other-inFiltrative diseases, Still's disease, rheumatic fe
ver, vasculitis
the next fve Ps are arranged from head to toe.
Let
'
s go through it:
Criteria for the Diagnosis of SLE ("P-MOAD")
Positive antineutrophil antibody (ANA): seen
in 95% of patients
Positive other immunologic test [antibody (Ab)
to double-stranded DNA, Ab to Smith, LE cell
preparation, or false-positive syphilis serology]
Psychosis, seizures, or other neurologic abnor
malities
Photosensitivity rash
Polyserositis (pleuritis, pricarditis, or perito
nitis)
Proteinuria or renal involvement
Pancytopenia or single-celiline "penia" (ane
mia, thrombocytopenia, leukopenia)
Malar rash
Oral ulcers
Arthritis
Discoid rash
394 Chapter 69
3. Systemic sclerosis (scleroderma) is characteri
ed by
fbrosis of the skin and internal organs leadmg to
dysphagia, pulmonary fbrosis, and cardiac and re
nal disease.
a. Clinicl manifestations. Raynaud's phenomenon
(YO% of patients) and arthralgias are usually
early symptoms.
b. There are two forms of systemic sclerosis: difuse
(affecting 20% of patients) and limited (CREST
syndrome). CREST syndrome is the syndrome of
calcinosis, Raynaud's phenomenon, esophage
l
motility dysfunction; sclerodactyly, and telang
ectasia. Those with CREST syndrome have a
decreased risk of renal involvement, a higher risk
of pulmonary hypertension, increased incidence
of anticentromere antibodies, and a better prog
nosis.
B. Classic seronegative spondyloarthropathy. All of the
seronegative spondyloarthropathies are characterized by
an asymmetric polyarthritis affecting either the spine or
large peripheral joints, a strong association with HLA
B27, early onset of disease (usually before age 4), and
an absence of autoantibodies (hence the term "seroneg
ative").
1. Ankylosing spondylitis
2. Psoriatic arthritis
3. Reiter's syndrome, classically characterized by the
clinical triad of conjunctvitis, urethritis, and arthri
tis-the patient cannot "see, pee, or bend at the
knees"
4. Arthritis related to enteric disorders [e.g., infamma
tory bowel disease (lBD), Whipple's disease, en
teric infection]
C. Miscellaneous cuses. There are many other causes of
polyarthritis. Most can easily be remembered in the fol
lowing manner: one gonorrheal, to spirochetal, three
viral, and four others.
1. Gonorrheal. Disseminated gonococcal infecton (as
a result of NeLseria gonorrhoeae infection) may re
sult in migatory polyarthralgias of the large joints,
tenosynovitis, fever, and/or a pustular rash.
2. Spirochetal
a Lyme disease (caused by Borrelia burgdorferi
infection) is characterized by fu-like symptoms,
erythema migrans, neurological problems (e. g.,
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Polyarticular Arthritis
395
seventh nerve palsy, meningitis), cardiac disease,
and/or a chronic or recurrent large joint arthritis.
b. Secondar syphilis can involve almost any part
of the body, including the joints.
3. Viral The three common viral etiologies include
HIV, hepatitis B virus, and parvovirus.
4. Other
HOT
KEY
a Infhrative diseases include sarcoidosis, amy
loidosis, and tophaceous gout; biopsy is usually
necessary to make the diagnosis.
b. Still's disease i a form of juvenile rheumatoid
arthritis that affects adults. It is characterized
by spiking fevers, arthritis, and an evanescent,
salmon-colored rash.
e Rheumatic fever is discussed in Chapter 47.
d Vasculitis is discussed in Chapter 70.
Degenerative jaint disease (DJDI is a chronic, progres
sive noninflammatory arthropathy that primarily in
valves the articular cartilages. Although it may be the
most common cause af polyrticular arthritis, it is gener
ally nat acutely life-threatening.
70. Vasculitis
a
II
INTRODUCTION. The vasculitides are a heterogenous group
of disorders that have infammation of the vessels as a fnal
common pathway. Histologcally. the term leukocytoclastic
vasculitis is used to describe the leukocyte infltration and
polymorphonuclear neutrophil (PMN) fragentation seen
in the walls of affected vessels.
CUNICAL MANIFESTATONS OF VASCUUTlS. The vascu
litides can present with any combination of the following:
A. Constitutional symptoms (e.g., fever, fatigue, anorexia,
weigt loss)
B. Arthralgias
C. Symptoms of organ ischemia (e.g., abdominal pain from
mesenteric ischemia)
D. Peripheral neuropathy from small vessel involvement
E. Skin fndings (e.g., palpable purpura, livedo reticularis,
necrotic lesions, infarcts of the tips of digts)
HOT
Palpable purpura is pathognomonic of a vasculitis.
Inflammation of the vessel allows extravasation of
blood and RUid into the extravascular spce, resulting
in palpable edema. Because the blood is no longer
intravascular, the lesion is purpuric (nonblanchable),
rather than erythematous (blanchable).
KEY
II
CAUSES OF V ASCUUTIS. Because of the overwhelming
number of causes of vasculitis and the often nonspecifc
symptoms, vasculitis may be challengng to diagnose. Re
membering a few facts about each primary vasculitis and the
mnemonic provided for the secondary vasculitides distills
this overwhelming subject into one that is manageable.
A_ Primary vasculitides. Systemic symptoms may occur in
all, but differences in epidemiology or vessel involvement
help distinguish each disorder.
396
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Vasculitis 397
1. Takayasu's aortitis
a. Epidemiology. Takayasu's aortitis is rare. Young
Asian women are most commonly affected.
b. Clinical manifestations. The aortic arch and its
?ranch
s are involved, often leading to transient

IschemiC attacks (TIAs). "Pulselessness" on ex
amination of the arms is frequently noted.
c Diagnosis. Although often suspected on clinical
grounds, diagnosis requires angography or bi
opsy of the affected artery.
2_ Giant cell (temporal) arteritis
a. Epidemiology. Giant cell arteritis is rare in
patients younger than 50 years and African
Americans. Women are affected more often
than men.
b. Clinical manifestations
(1) Headache is the most common symptom (as
a result oftemporal artery involvement). Jaw
claudication and ocular symptoms (inclUding
blindness) may also occur.
(2) There is a close association with polymyalgia
rheu
atic (PMR), which is characterized by

proximal muscle pain and stiffness.
c. Diagnosis. Giant cell arteritis should be sus
pected in a patient older than 50 years who com
plains of a headache and has an erythrocyte sedi
mentation rate (ESR) greater than 50 mmlhour.
A temporal arter biopsy is needed for defnitive
?iagnosis. Because there is often segmental
mvolvement, multiple biopsy sites may be nec
essary.
3. Polyarteritis nodosa (PAN)
a. Epidemiology. The average age at the time of
onset is approximately 45 years. Men are affected
more often than women. In 30% of patients, PAN
is associated with hepatitis B antigenemia.
(1) Multiple organ system involvement. The kid
ney (renal artery and glomerulus), heart.
liver,
astrointestinal tract, nervous system,

and skill are most frequently involved.
(2) Hypertension, renal failure, myocrdial in
farctio
, con
estive heart failure (CHF),

bowel mfarctlOn, and stroke are potential
complications.
c. Diagnosis. Defnitive diagnosis is made by biopsy
398 Chapter 70
of involved organs or by visceral angiography,
which may reveal aneurysms, areas of stenosis,
or obliteration of vessels.
4. Churg-Strauss syndrome (allergic angiitis and granu
lomatosis)
a. Epidemiology. Churg-Strauss syndrome occurs
in patients with asthma.
b. Clinical manifestations. Although Churg-Strauss
syndrome may resemble PAN, the two can usu
ally be distinguished by the following features:
(1) In Churg-Strauss syndrome, pulmonary
involvement (with asthma and, occasionally,
feetng pulmonary infltrates) is most com
mon, whereas renal involvement is less com
mon and less severe.
(2) Peripheral eosinophilia is much more promi
nent in patients with Churg-Strauss syn
drome.
c. Diagnosis. Biopsy (usually of lung tissue) shows
small-vessel vasculitis, extravascular ganulomas,
and eosinophil infltration.
S. Wegener's granulomatosis
a. Epidemiology. Wegener's ganulomatosis is
most common in middle-aged men and is rare in
African-Americans.
(1) Pulmonary involvement with cough, dysp
nea, hemoptysis, or asymptomatic infiltrates
occurs in approximately 95% of patients. The
upper and lower respiratory tract are in
volved, resulting in ulcerations of the nasal
mucosa, saddle nose deformity (secondary
to perforation of the nasal septum), chronic
sinusitis, serous ottis, or pulmonary infil
trates or cavities.
(2) Renal involvement. The kidney is involved
in approximately 85% of patients, leading to
hematuria, proteinuria, and/or glomerulone
phritis. Progressive renal failure can develop
rapidly unless treatment is initiated.
(3) Other organs. The gastrointestinal tract,
heart, and peripheral nerves may also be af
fected.
c. Diagnosis. A positive antineutrophil cytoplasmic
autoantibody (ANCA) assay supports the diag
nosis.
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Vasculitis 399
B. Secondary (hypersensitivity) vasculitides. The mne
monic "VASCULITIS" can help you remember the
causes of secondary vasculitis.
Causes of Secondary Vasculitis ("VASCU
LITIS")
Various drugs
Autoimmune disorders
Serum sickness
Cryoglobulinemia
Ulcerative colitis
Low complement (hypocomplementemic urti
carial vasculitis)
Infections
Tumors
IgA nephropathy (Henach-Schonlein purpura)
Smoking-related (thromboangiitis obliterans)
1. Various drugs. Penicillins, sulfa drugs, and propylthi
ouracil are just a few of the many drugs that can
cause a hypersensitivity vasculitis.
2. Autoimmune disorders. Systemic lupus erythemato
sus (SLE) and rheumatoid arthritis may cause a vas
culitis.
3. Serum sickness occurs 7-10 days after a primary
exposure to an antigen (e.g., penicillin), or 2-4 days
after a secondary exposure.
4. Cryoglobulinemia is characterized by immunoglobu
lins that precipitate in cold temperatures.
a. Type I cryoglobulins are monoclonal and usually
associated with multiple myeloma, Walden
strom's macroglobulinemia, or other lymphopro
liferative disorders.
b. Type II cryoglobulins, which have one mono
clonal component and one poly clonal compo
nent, and type III cryoglobulins, which have two
polyclonal components, are both considered
mixed cryoglobulins. They are often associated
with infections (e.g., hepatitis), connective tissue
diseases, or Iymphoproliferative disorders. Es
sential mixed cryoglobulinemia may be diag
nosed when no precipitating condition can be
elicited.
400
Chapter 70
5. Ulcerative colitis is occasionally associated with a
secondary vasculitis.
6. Low complement. Hypocomplementemic urticarial
vasculitis occurs predominantly in young women.
Urticarial lesions. most commonly found on the
trunk and extremities, are the most notable feature.
Like Henoch-Schonlein purpura, hypocomplemen
temic urticarial vasculitis can be associated with fe
ver, arthritis, abdominal pain, and renal involvement.
All serum complement levels are low.
7. Infections should be considered frst because they
may be life-threatening.
a. Bacterial. Neisseria species, Staphylococcus
aureus, Streptococcus species, and Pseudomonas
aeruginosa infections are most commonly associ
ated with vasculitis. Syphilis and Lyme disease
should also be remembered.
b. Viral. The most commonly implicated viruses are
hepatitis B and C virus, Epstein-Barr virus, and
cytomegalovirus (CMV).
c. Rickettsial. Rocky Mountain spotted fever may
be associated with vasculitis. The characteristic
rash usually appears on the extremities 2-6 days
after the onset of fever.
8. Tumors. Lymphoma and multiple myeloma are the
malignancies most often associated with vasculitis.
9. IgA nephropathy (Henoch-Schonlein purpura) usu
ally occurs in children or young adults. Classically,
palpable purpura appears over the lower extremities,
followed by abdominal pain, arthritis, and renal
involvement. IgA deposits can be found in the skin
and kidney.
HOT
KEY
leukocytoclastic changes are indicative of vasculitis
but do not indicate the specific cause. However, IgA
deposits may be found an skin biopsy in patients with
Henoch-Schonlein purpura, making this the only vascu
litis that can be diagnosed by simple skin biopsy.
9. Smoking-related. Thromboangiitis obliterans (Buer
ger's disease) occurs predominantly in men younger
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Vasculitis
401
than 40 years who are heavy smokers. It involves
arteries and veins, leading to impaired arterial blood
supply, Raynaud's phenomenon, thrombophlebitis,
or deep venous thrombosis. Smoking cessation is the
mainstay of therapy.
A. Patient hst0
9
. A tr
vel history and medication history

?
ay
rovide mSlght mto the cause of the vasculitis (e.g.,

mfectIon, drug therapy).
B. Laboratory stUdies. Many abnormal laboratory test re
ults (e.g., an elevated ESR) are nonspecifc but may

mcrease or decrease clinical suspicion for a vasculitis
(e.g., a no
mal ESR would decrease your suspicion).

The followmg studies may be useful depending on the
clinical setting:
1. Com
lete blood count (CBC). Look for leukocytosis,

anemIa, or thrombocytosis.
2. Renal panel. Look for elevated creatinine levels.
3. Urinalysis. Look for hematuria or proteinuria.
4. ESR (usually elevated)
5. ANA and rheumatoid factor (RF) levels
6. Croglobulins
7. Complement levels
8. Blood cultures (especially to rule out endocarditis)
9. Cultures for gonococcal infection (e.g., oral, anal,
cervical, urethral)
11. Serologies for hepatitis Band C virus, Epstein-Barr
virus, CMV, Treponema palldum, or Borelia bur
doieri
TREATMENT. A rheumatology consult is often useful when
treating a patient with vasculitis.
A. Primar vasculitides are ofen treated with glucocorti
coids (e.g., prednisone, 1 mg/kg per day). The addi
tion of a cytotoxic agent (usually cyclophosphamide, 2
mg/kg p
r
.
day) may also be necessary. In general, tempo
ral artentIs responds to steroids alone, whereas addi
tional immunosuppression may be required for patients
ih PAN, Churg-Strauss syndrome, or Takayasu's aor

titIs.
B. Secondar vasculitides
1. The underlying condition must be treated. Empiric
402 Chapter 70
antibiotics may be given if an infection (e.g., menin
goocemia, endocarditis, Rocky Mountain spotted
fever) is suspected.
2. In certain cases, steroids with or without the addition
of a cytotoxic agent may be used, following consulta
tion with a rheumatologist.
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PART IX
Endocrinology
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1. PYCCKJX nOnb30BaTeneJ-
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IECnJATHOrO pacnpoCTpaHeHJR
MCAH; 3T 40HT. Py
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71.Hyercalcemia
a
INTRODUCTION
A. Defnition. Hypercalcemia is an elevated level of ionized
calcium in the blood. Hypercalcemia is a common prob
lem in both inpatients and outpatients. [n the former,
the hypercalcemia is usually secondary to malignancy,
whereas in the latter, hyperparathyroidism is a more
common cause of the hypercalcemia.
B. Because albumin binds calcium, it is important to make
sure that the hypercalcemia is real and not just a refec
tion of hyperalbuminemia.
HOT
KEY
For every 1-mg increase in albumin (the narmal albu
min level is 4 mg/dl), you must decrease the colcium
level by 0.8 mg/ dl. The converse is true for hypoalbum
inemio. Far example, if the serum colcium is 1 1 mg/dl
and the albumin is 5 mg/dl, the corrected calcium is
1 0.2 mg/dl (and the patient is not hypercalcemic).
II
CUNICAL MANIFESTA10NS OF HYPERCALCEMIA
A. Symptoms are usually nonspecifc and tend to occur
when the serum calcium level exceeds 12 mg/dl. The
severity of symptoms is partially dependent on the rapid
ity of the calcium elevation. "Abdominal moan, psychiat
ric groan, kidney stone, and urination zone (i.e.. the
bathroom)," is a way to recall common symptoms.
1. Gastrointestinal symptoms include constipation,
nausea, vomiting, and anorexia. Patients may de
velop acute pancreatitis.
2. Central nervous system (CNS) symptoms include
confusion, lethargy, and weakness. Progression to
coma and death are the most feared manifestations.
3. Renal symptoms include nephrolithiasis, renal fail
ure. and polyuria. Hypercalcemia interferes with an
tidiuretic hormone (ADH) action, leading to fre
quent urination.
405
406
II
Chapter 71
B. Signs of hypercalcemia include hypertension, hypotonia,
decreased deep tendon refexes, and a shortened QT
interval on the electrocardiogram (EKG).
CAUSES OF HYPERCALCEMIA. There are many causes of
hypercalcemia, the mnemonic "MISHAP+F" will help you
remember the most important ones.
Causes of Hypercalcemia ("MISHAP+F")
Malignancy
Intoxication (vitamin D)
Sarcoidosis (and other granulomatous dis
eases)
Hyperparathyroidism
Addison's disease and milk-lkali syndrome
Paget's disease
+
Familial hypocalciuric hypercalcemia (FHH)
A. Malignancy. Hypercalcemia occurs secondary to local
osteolysis (seen with extensive bone involvement by the
tumor) or humoral infuences [induced by parathyroid
hormone (PTH)-related peptide].
B. Intoxication with vitamin D. Some patients take large
amounts of vitamin D for unclear reasons; serum 25-
hydroxycholecalciferol levels help confrm this diagnosis.
C. Sarcoid and other granulomatous disases (e.g., tubercu
losis, berylliosis). Hypercalcemia results from increased
formation of 1,25-dihydroxyvitamin D in granuloma
tous tissues.
D. Hyperarathyroidism. Primary hyperparathyroidism is
caused by solitary adenomas (85% of patients), four
gland hyperplasia (10% of patients), or carcinoma (less
than 5% of patients). Patients are usually asymptomatic
at the time of diagnosis. Serum phosphate is often low.
E. Addison's disease. Adrenal insuffciency is an uncom
mon cause of hypercalcemia.
F. Alkali ingestion. Hypercalcemia occurs secondary to ex
cess calcium carbonate ingestion (usually seen in patients
with peptic ulcers).
G. Paget's diseas, a nonmetabolic bone disease of u
known etiology, is characterized by excessive bone de
struction and unorganized repair that leads to skeletal
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Hypercalcemia 407
deformities (e.g., kyphosis, bowing of the tibias, and en
largement of the skull). Hypercalcemia occurs in the
setting of prolonged immobilization.
H. Familial hypocalciuric hypercalcemia (FUH) is a benign,
autosomal dominant genetic disease characterized by hy
percalcemia, hypocalciuria ( < 50 mg/24 hours), and oca
sional hypermagnesemia. The serum PTH level is often
slightly increased. which can lead to a mistaken diagnosis
of hyperparathyroidism.
TREATMENT is warranted if symptoms are present or if se
rum calcium exceeds 12 mg/dl.
A. Initial therapy entails fuids, fuids, and more fuids, fol
lowed by diuretics when fuid overload develops. Other
therapies include biphosphonates, calcitonin, plicamycin,
and corticosteroids.
B. Defnitive treatment will, of course, depend on the un
derlying cause.
72. Hypocalcemia
a
INTRODUCTION
A. Defnition. Hypoalcemia is defned as a decreased ion
ized calcium level. Hypocalcemia is a common occur
rence in very ill, hospitalized patients.
B. Because albumin binds calcium, it is important to make
sure that the hypocalcemia is real and not just a refection
of hypoalbuminemia.
HOT
For every I-mg decrease in albumin (the normal albu
min level is 4 mg/dl), you must increase the calcium
by 0.8 mg/di. For example, if the serum calcium is 7.5
mg/dl and the albumin is 2 mg/dl, then the corrected
serum calcium is 9. 1 mg/ dl (and the patient is not hypo
calcemic).
KEY
II
C. In patients with respiratory alkalosis, the total serum
calcium is normal but the ionized calcium is low' there
fore, the patient may have signs and symptoms of hypo
calcemia.
CUNICAL MANIFESTATIONS OF HYPOALCEMIA. Because
hypocalcemia leads to enhanced excitation of the nervous
ystem and muscle cells, the symptoms and signs primarily

mvolve the neuromuscular and cardiovascular systems.
A. Symptoms include muscular cramps (which can progress
to tetany), inspiratory wheezing (stridor due to laryngo
spasm), and paresthesias of the lips and extremities.
B. Signs include hypotension, Chvostek's sign (tapping the
facial nerve leads to contraction of the facial muscles),
and Trousseau's sign (oclusion of the brachial artery
with a blod pressure cuff leads to carpal spasm). The
electrocardiogram (EKG) may show a prolonged QT
interval or atrioventricular (A V) block.
408
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Hypocalcemia 409
II
CAUSES OF HYPOCALCEMIA. There are many causes of
hypocalcemia; the mnemonic "HIPOCAL" will help you
remember the most important ones.
Causes of Hypocalcemia (HHIPOCAlH)
Hypoparathyroidism
Infection
Pancreatitis
Overload states
Chronic renal failure
Absorption abnormalities
Loop diuretics
A. Hypoparathyroidism. Causes of hypoparathyroidism in
clude thyroidectomy, autoimmune destruction of the
parathyroid, DiGeorge's syndrome, and damage to the
p
ara
hy
!
oid as a result of infection, heavy metals, or
IrradIatlOn. Functional hypoparathyroidism [i.e., de
creased secretion of parathyroid hormone (PTH)] may
occur secondary to magnesium defciency.
B. Infection. Up to 20% of patients with gram-negative
sepsis are hypocalcemic due to acquired defects i the
parathyroid-vit
min 0 axis. This hypocalcemia may

cause hypotenslOn that is responsive to calcium re
placement.
C. Pancreatitis. Serum calcium below 8 mg/dl is one of Ran
son's criteria; the calcium level may correlate with the
severity of acute pancreatitis.
D. Overload states. Occasionally, hypocalcemia may be
seen in cases of rapid intravascular volume expansion.
E. Chronic renal failure. Vitamin D is metabolized in the
normal kidney to 1,25-dihydroxyvitamin 0, which pro
motes intestinal calcium absorption. With renal failure
intestinal calcium absorption decreases and the patient
becomes hypocalcemic.
F. Absortion abnormalities. Patients with malabsorption
(due to any cause) of calcium, magnesium, or vitamin 0
will often have hypocalcemia.
G. Loop diuretics. Unlike thiazide diuretics (which can
ause hypercalcemia). furosemide and other loop diuret

ICS lead to enhanced renal excretion of calcium.
410
Chapter 72
I TREATMENT
A. If the patient has tetany, arrhythmias, or seizures, imme
diate therapy with intravenous calcium gluconate is indi
cated.
B. If the patient has asymptomatic hypocalcemia, oral cal
cium and vitamin D are usually suffcient.
C. If the patient has hypomagnesemia, replacement of mag
nesium is required to correct the hypocalcemia.
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73. Diabetic Ketoacidosis (DK)
D
INTRODUCTION
A. Defnition. Diabetic ketoacidosis (DKA) is a life-threat
ening complication of diabetes mellitus caused by a rela
tive or absolute defciency of insulin as compared with
the "stress hormones" (i.e., glucagon, epinephrine, and
cortisol). This imbalance results in impaired cellular up
take of glucose. gluconeogenesis, lipolysis, and ketogene
sis. Patients present with hyperglycemia, marked dehy
dration from a glucose-induced osmotic diuresis, and
acidosis from ketone production.
B. Causes. Infection, surgery, myocardial infarction (MI),
or noncompliance with insulin therapy may all lead to
DKA in those with diabetes.
II
(UNICAL MANIFESTATIONS OF DK
A. Signs and symptoms. DKA may present with any of the
following signs and symptoms.
1. Hypotension and tachycardia often refect volume
depletion, but sepsis should always be considered.
2. Tachypnea is common, and often refects the hyper
ventilation needed to compensate for the meta
bolic acidosis.
3. Mild hypothermia is usually present. Even mild tem
perature elevations may indicate an underlying in
fection.
4. Neurologic abnormalities, including seizures and al
tered mental status, may be present.
5. Abdominal pain assoiated with nausea o vomiting
may occur as a result of the ketoacidosis itself, or as
a result of intra-abdominal pathology.
6. Polyuria and polydipsia often precede other symp
toms by 1-2 days and refect the osmotic diuresis
generated by the glycosuria. The diferential diagno
sis for polyuria can be remembered as the 6 Ds:
411
41 2
Chapter 73
Differential Diagnoses for Polyuria ("6 Ds")
Diabetes mellitus
Diabetes insipidus
Diuretics
Diuretic phose of acute tubular necrosis (ATN)
Drinking too much
Damn! To much calcium
B. Laboratory fndings
1. Blood glucose levels greater than 300 mg/dl are usu-
ally found in conjunction with 4+ glycosuria.
2. Ketonemia and ketonuria are present.
3. Anion gap acidosis with a pH less than 7.3 is typical.
4. Hyponatremia usually results from the hyperglyce
mia, which exerts an osmotic pull of water into the
intravascular space, thereby decreasing the sodium
concentration. Vomiting with fuid losses accompa
nied by free water replacement may also cause hypo
natremia. Marked hyperlipidemia may accompany
DKA, resulting in pseudohyponatremia (see Chap
ter 41).
5. Potassium, magnesium, and phosphate depletion are
usually found. The acidosis results in a compensatory
movement of hydrogen ions intracellularly and po
tassium ions extracellularly; this may normalize or
even elevate the serum potassium despite marked
total body depletion.
6. An elevated blood urea nitrogen (BUN) and creati
nine level usually results from prerenal azotemia.
7. An elevated white blood cell (WBC) count with a
left shift can occur even without infection.
8. An increased amylase level is common, but refects
both salivary and pancreatic sources and is therefore
not a good marker for pancreatitis.
II
ApPROACH TO THE PATIEN
A. Diagnose DKA. The diagnosis of DKA is made by the
association of acidosis, hyperglycemia, and serum ke
tonemia.
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Diabetic Ketoacidosis (DKA) 413
Because immediate serum ketone determinations are
not always available, understanding the implications
HOT
of urine ketone and serum electrolyte determinations
KEY
is extremely useful:

Urine ketone. Ketones are concentrated in the
urine, so the absence of ketnuria usually rule
out D. Urine ketones are, however, nonspecific;
therefore, a diagnosis of DKA requires other clini
cal criteria (i.e., acidosis, hyperglycemia).

Serum electolyts. The absence of an anion gap
acidosis usually rl out D.
B. Rule out infections. The possibility of an underlying in
fection should be investigated. even if the patient does
not have a fever.
1. A chest radiograph. urinalysis, and urine and blood
cultures are usually obtained; other evaluation de
pends on the clinical presentation.
2. Whether to image the abdomen in patients with
DKA and abdominal pain is an extremely diffcult
decision that must be based on associated fndings
(e.g., fever, marked leukocytosis, liver test abnormal
ities) and clinical judgment.
TREATMENT
A. Fluid replacement. Aggressive intravenous fuid replace
ment is the frst line of action, to help correct both the
volume depletion (5-6 liters on average) and the hyper
glycemia.
L How much? The most common mistake is not giving
enough fuids. At least 1 L should be given in the
frst hour, often followed by 0.5-1 Llhr intravenously
thereafter. Patients with cardiac dysfunction should
have frequent lung exams and oxygen saturation
measurements to assess the possibility of pulmo
nary edema.
2. What kind? A useful way of deciding beteen nor
mal saline and half normal saline is to determine the
corrected sodium concentration, which corrects for
the dilution caused by hyperglycemia. For every
extra 100 mg/dl of glucose over normal (e.g., 100
mg/dl), the serum sodium concentration needs to be
increased by approximately 1.5 mg/dl:
414 Chapter 73
C t d So
(Serum Glucose - 100)
rrec e mm =
100
X 1.5 + Serum Sodium
a. Nonnal saline is often used if the corrected so
dium is less than or equal to 142 mg/dl.
b. Half normal saline may be a better choice for
patients with a corrected serum sodium that is
greater than 1 42 mg/dl. In these patients, normal
saline would keep the sodium high and contribute
to persistent hyperosmolarity, which is correlated
with por outcome.
B. Insulin. Because patients with DKA are markedly vol
ume depleted, insulin is best given following or during
aggressive fuid replacement. Giving insulin frst may
precipitate marked hypotension by increasing the cellu
lar uptake of glucose and water from the intravascular
space.
1. Insulin bolus. Regular insulin in a dose of 0.1-0.3
U/kg should be administered intravenously. A dose
of 10 U avoids overdosage, and is usually adequate.
2. Insulin drip
HOT
KEY
a. Initiation. A dose of 0.1 U/kg/hr is effective, and
can be titrated to keep the glucose level at 200-
300 mg/dl.
b. Continuation. The insulin drip needs to be con
tinued until the anion gap is back to normal and
the glucose level is less than 300 mg/dl. Once the
glucose level is below 250 mg/dl, change the fuids
to 5% dextrose in normal saline solution or 5%
dextrose in half normal saline solution and con
tinue the insulin drip (adjust to keep the glucose
level at 200-30 mg/dl).
Changing ta subutaneous insulin prematurely will reo
suit in a rebound af the ketoacidasis.
c. Tennination. The half-life of insulin is only 8
minutes, so subcutaneous insulin should be ad
ministered before the insulin drip is stopped.
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Diabetic Ketoacidosis (DKA) 415
TABLE 73 1 : Subcutaneous Insulin Doses in the Treatment of
Diabetic Ketoacidosis (DKA)
Glucose Level (mg/ dl)* Dose (Regular Insulin)
<150
> 150 but <250
>250 but <350
>350 but <450
>450
o units
3 units
5 units
7 units
9 units; call house afficer
* If the glucase level is greater than 60 mg/dl but less than 100 mg/dl,
the patient may be given 1 cup af orange juice. If the glucose level is less
than 60 mg/ dl, administer 0.5 ampule af 50% dextrose (D50) and call the
hause officer.
3. Subcutaneous insulin. The patient's glucose level is
checked every 4-6 hours initially and every 6-8
hours thereafter. Subcutaneous insulin is adminis
tered on a sliding scale; the approximate doses are
given in Table 73-l.
C. Electrolyte replacement
1. Potassium repletion is essential to prevent hypoka
lemia and potentially life-threatening arrhythmias.
The potassium level universally falls during the treat
ment of DKA as a result of fuid replacement and
correction of the acidosis.
a A potassium level below 4.5 mEqI is usually
the trigger for initiating replacement therapy. A
potassium level below 4 mEq/ should alert you
to aggressively replete potassium because the
level is likely to continue falling with therapy.
b. A potassium level of 4-5 mEqI is the goal.
(1) Often, 20-40 mEq of potassium are given in
each liter of intravenous fuid. Extra po
tassium can be given to keep the potassium
level in the desired range.
416 Chapter 73
HOT
KEY
Generally, each 1 0 mEq of potassium given will raise
the ptassium level approximately 0. 1 mEq/l (assum
ing normal renal function and no major change in
volume or acid-bose status).
(2) Patients with renal insuffciency, hypoten
sion, or signifcant volume depletion require
careful potassium repletion to avoid causing
hyperkalemia. Hypotensive or markedly vol
ume depleted patients should probably not
have a standing potassium dose given in their
intravenous fuids because they may inadver
tently receive an excessive amount of po
tassium with large volume replacement.
2. Magnesium replacement is frequ
ntly n
cessary
.
, and
will also help correct hypokalemia that IS assoClated
with hypomagnesemia. If the magnesium level is be
low 1.6 mEqI intravenous magnesium sulfate may
be given and repeated as needed. Magnesium reple
tion also needs to be titrated carefully in the presence
of renal failure.
3. Phosphate replacement is often not required, but a
level below 1 mgldl may be an indication for replace
ment with potassium phosphate (usually 9-15 mmols
given at a maximal rate of 3 mmollhr, repeated as
needed).
. . .
D. pH Regulation. Patients with a symptomatic aCidOSIS
(e.g., cardiac pump dysfunction) or a seve
e asympt
I
?
atic acidosis (pH less than 7.0) are sometImes admmls

tered sodium bicarbonate to keep the pH greater than
7.0. but in general, sodium bicarbonate is contraindic
ted
because it increases hypokalemia, shifts the oxygen diSSO
ciation curve to the left (increasing tissue hypoxia), in
creases intracellular acidosis. and has not been associated
with any survival advantage.
. .
E. Frequent monitoring is the key to treatmg patients
with DKA.
1. An arterial line is often useful because frequent arte
rial blood gas and electrolyte measurements are
needed.
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Diabetic Ketoacidosis (DKA)
417
a. pR The pH may be checked multiple times in
the frst hour (especially if it is markedly low),
and hourly thereafter until a steady upward trend
is noted. At this point, less fequent evaluation
should be instituted (e.g., every 2-4 hours).
b. Electrolytes (including glncose) are usually
checked each hour initially, and may be followed
by checks every 2-4 hours after improvement
is noted.
2. Following the electrolytes and the anion gap is more
useful than following the serum ketones because se
rum ketone measurements may not include f-hy
droxybutyrate.
a. In patients with DKA and concomitant tissue
hypoxia or circulatory collapse (e.g., sepsis), 1-
hydroxybutyrate is produced preferentially, so
serum ketones may look falsely low when the
patient is very sick.
b. With therapy, f-hydroxybutyrate may be con
verted to acetoacetate; thus, serum ketone mea
surements may increase despite clinical im
provement.
74. Thyoid Disease
D
II
APPROACH TO THE PATIENT. Because thyroid hormone
affects virtually all body functions, abnormal thyroid func
tion has protean manifestations. The simplest approach is to:
A. Decide whether the patient is hypo- or hyperthyroid on
the basis of clinical manifestations and the results of
thyroid function tests.
B. List the possible causes of the abnormal thyroid function
and begin the process of elimination, using the clinical
scenario, laboratory data, and the results of a thyroid
scan as a basis.
HYPOTHYROIDSM
A. Causes
1. Primar hypothyroidism results from a thyroid ab
normality. Common causes include:
a. Hashimoto'S disease (the most common cause)
b. Thyroiditis (subacute, postpartum)
c. Drugs (sulfonamides, amiodarone, iodide,
lithium)
d. Surgical excision or radiation of the thyroid gland
2. Secondary hypothyroidism results from pituitary dis
orders.
3. Tertiary hypothyroidism has a hypothalamic basis.
B. Clinical manifestations of hypothyroidism
1. Symptoms
a. Weakness, fatigue, and lethargy
b. Arthralgias or myalgias
c. Cold intolerance
HOT
Remember: hypothyroidism gives cold intolerance.
KEY
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Thyroid Disease 41 9
C.
d. Skin dryness or edema
e. Slow speech or hoarseness
L Menstrual irregularities or galactorrhea
g. Weight gain or loss
h. Constipation
i. Decreased sense of taste, smell, and hearing
j. Peripheral neuropathy and carpal tunnel syn
drome
2. Signs
a. Thin, brittle nails or thin, coarse hair
b. Delayed return phase of deep tendon refexes
c. Puffness of the face and eyelids or thickened
tongue
d. Pitting edema
e. Effusions (anywhere)
f. Hypothermia, bradycardia, or hypotension (but
usually the blood pressure is normal)
g. True obesity is rare.
h. Goiter. a term that refers only to thyroid enlarge
ment and is not necessarily assoiated with ab
normal thyroid function, is variably present.
a. Elevated levels of thyroid-stimulating hormone
(TSH) and decreased levels of thyroxine (T4) are
diagnostic of primary hypothyroidism; both pa
rameters are low with secondary or tertiary hypo
thyroidism.
b. Serum levels of cholesterol, creatine kinase, pro-
lactin, and liver enzymes may be increased.
c. Anemia, usually normo- or macroytic
d. Hypoglycemia and hyponatremia
e. Positive antithyroid antibody (i.e., antimicro
somal and antithyroglobulin) titers in patients
with Hashimoto's disease
f. Sinus bradycardia, low-voltage QRS complexes,
and nonspecifc T-wave abnormalities
Treatment
1. Primary hypothyroidism. Replacement therapy with
L.thyroxine is the treatment of choice in almost all
cases of primary hypothyroidism.
a. Start with a low dose and increase it slowly (every
4 weeks) until the maintenance dose level is
achieved (e.g., 1.5 Jg/kg/day).
b. TSH levels should be monitored every 4-6 weeks
until the patient is euthyroid. Thereafter, moni
toring can take place on an as-needed basis.
420 Chapter 74
2. Secondary or tertiary hypothyroidism. L-Thyroxine
should be administered only after adrenal insuff
ciency has been excluded or treated.
D. Myxedema coma is a life-threatening manifestation of
hypothyroidism; usually patients are stuporous, hypo
thermic, bradycardic, hypotensive, hypoxemic, and
hypercapnic.
1. Approach to the patient. Always search for a precipi
tating cause (e.g., infection, ischemia, inadequate
thyroid hormone replacement) and treat the precipi
tating cause aggressively.
2. Treatment. Patients often require ventilatory sup
port and should be admitted to the intensive care
unit (ICU). Intravenous L-thyroxine should be ad
ministered after adrenal insuffciency has been ex
cluded or treated.
IIHYPERTHYROIDISM
A. Causes of hyperthyroidism. There are many causes of
"thyrotoxicosis" (a term that simply implies increased
circulating thyroid hormone); the causes can be subdi
vided into those that are attributable to thyroid hyper
functioning and those that are not. A radioactive thy
roid scan will reveal the functional status of the gland.
1. Hyperfunctioning thyroid. The scan will reveal high
radioactive iodine uptake (i.e .. it will be "tagged").
a. TSH-screting tumor. This pituitary tumor is rare
and should be considered in thyrotoxic patients
with normal (or elevated) TSH levels.
b. Autonomous toxic adenoma(s). Hyperthyroid
ism may be caused by a single adenoma or
by a toxic multinodular goiter. There are no
assoiated eye fndings, antithyroid antibodies,
or thyroid-stimulating immunoglobulins (TSls),
which helps to distinguish this disorder from
Graves' disease.
c. Graves' disease, an autoimmune disorder that
causes diffuse thyroid enlargement, is the most
common cause of hyperthyroidism. Women
20-40 years of age are most commonly afected.
Graves' disease may be associated with an infl
trative ophthalmopathy, dermopathy, or sys
temic autoimmune disorders, and is usually asso
ciated with elevated TSI (and other antithyroid
antibody) levels.
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Thyroid Disease
421
Causes of Hyperthyroidism-Hyperfunc
tioning Gland ("TAG")
TSH-secreting tumor
Autonomous toxic adenoma
Groves' disease
2. Normal-fnctioning thyroid. The thyroid scan will
reveal low radioactive iodine uptake (i.e., a "fst"
obscures the view).
a. actitious thyrotoxicosis results from the inges
tIon of large amounts of exogenous thyroid
hormone.
b. Iodine-induced hyperthyroidism (Jodbasedow
disease) occurs when a patient with a multinodu
lar
oiter
eceives a large iodine load (e.g., fol

lowmg radIOgraphic contrast studies or amiodar
one therapy).
c. Struma ovarii. A small percentage of ovarian der
moid tumors and teratomas contain thyroid tis
sue, which may autonomously secrete thyroid
hormone.
d. Thyroiditis s characterized by an enlarged,
tende
.
r hyrOId that frst causes transient hyper
thyrOIdIsm (due to release of pre-formed thyroid
h
one), but may eventually lead to hypothy

rOIdIsm.
Causes of Hyperthyroidism-Normal Gland
Function ("FIST")
Factitious thyrotoxicosis
Iodine-induced hyperthyroidism
Struma avarii
Thyroiditis
422 Chapler 74
B. Clinical manifestations of hyperthyroidism
1. Symptoms
a. Nervousness, emotional lability, and restlessness
b. Heat intolerance and increased sweating
c. Fatigue, weakness, and muscle cramps
d. Palpitations and angina
e. Weight los (despite increased appetite) and di
arrhea
2. Signs
a. Agitation
b. Warm, moist palms
c Stare. lid lag, and infrequent blinking
d. Fie tremor and hyperrefexia
e. Irregularly irregular pulse (a sign of atrial fbril
lation), widened pulse pressure, and, occasion
ally, evidence of heart failure
3. Laborator studies
a. Serum T4 is usually increased and serum TSH is
usually decreased (except when a TSH-secreting
tumor is responsible for the hyperthyroidism).
b. Hypercalcemia, anemia, and increased alkaline
phosphatase levels may accompany the hyperthy
roidism.
C. Treatment. There are many potential ways to treat thyro
toxic patients-the best way depends on the cause and
clinical setting.
1. Symptomatic relief is provided by f blockers (e.g.,
propranolol). { blockers do not decrease thyroid
hormone secretion.
2 Reduction of thyroid hormone secretion can be ac
complished using thiourea drugs (e.g., methimazole,
propylthiouracil), iodinated agents, radioactive io
dine, or thyroid surger.
3. Thyroiditis. Patients with thyroiditis are best treated
symptomatically until the condition resolves sponta
neously. These patients will then usually require
treatment for hypothyroidism.
D. Tyroid storm is a life-threatening exacerbation ofthyro
toxicosis.
1. Approach to the patient. Always look for a precipi
tating cause (e.g., myocardial infarction, infection,
surgery, excessive thyroid replacement).
2 Clinical manifestations include the usual features of
hyperthyroidism and the precpitating event, plus fe
ver, psychosis, nausea, vomiting. and seizures.
3. Treatment goals include suppression of the effects
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Thyroid Disease 423
of thyroid hormone and rapid reduction of circulating
thyroid hormone levels.
a These goals are usually accomplished by intrave
nous administration of a { bloker, a thiourea,
an iodide, and corticosteroids.
b. Defnitive treatment occurs once the patient is
rendered euthyroid.
75. Adrenocortical Insuficiency
a
INTRODUCTION
A. Defnitions. Adrenal insuffcienc is defned as inade
quate production of glucocorticoids. mineralocorticoids.
or both.
1. Adrenocortical insufciency occurs when glucocorti
coid production is defcient but mineralocorticoid
production is intact. Many people use the term "ad
!
e
nal insuffciency" when they are actually referng
to adrenocortical insuffciency. Adrenocortical insuf
fcency is the focus of this chapter.
2 Hypoaldosteronism occurs when mi
eralocorticoi
production is impaired. It can occur with adrenocortI
cal insuffcency (as in Addison's disease) or as an
isolated finding; when hypoaldosteronism occurs as
an isolated fnding, it is usually the result of defective
renin secretion.
II CAUSES OF ADRENOCOROCAL INSUFFICIENCY
A. Primar adrenocortical insufciency (Addison's disas
)
results from destruction of the adrenal gands and IS
accompanied by hypoaldoteronism. One way to remem
ber the common causes of primary adrenocortical insuf
fcienc is to use the mnemonic "ADDISON'S":
Causes of Addison's Disease (" ADDISON'S")
Amyloidosis
Destruction (autoimmune)
Drugs (anticoagulants leading to bilateral adre
nal hemorrhage)
InFections [tuberculosis, disseminated fungal in
Fections, cytomegalovirus (CMV) in AIDS pa
tients, syphilitic gummas]
Sarcoidosis
Overload of iron (hemochromatosis)
Neoplasm (metostatic disease, usually from
the lung)
Surgical (hemorrhage during open-heart sur
gery or follOWing bilateral adrenalectomy)
424
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Adrenocortical Insufficiency
TABLE 75-1: Causes of Secondary Adrenol Insufficiency
Cotegory SpeciFic Cause
Congenital
Hematologic
Pregnancy-related
Drugs
Metabolic/endocrine
Infectious
Iatrogenic
Idiopathic
Neoplasm
Surgical
Familial hypopituitarism
Pituitary apoplexy (hemorrhage)
Sheehan's syndrome
Withdrawal of chronic exogenous
corticosteroids
Chronic renal Failure, diabetes
mellitus, hemochromatosis
Tuberculosis, syphilis, fungal
disease
Irradiation of the pituitary gland
Empty sella syndrome, sarcoidosis
Pituitary tumors
Surgical destruction
425
B. Secondar a . enocortical insufciency is caused by pitu
itary dysfunction. There are many causes of secondary
adrenocortical insufciency, but the mot important are
summarized in Table 75-1. All of these causes affect the
pituitary gland and lead to hypopituita.ism; the most
common diso . de . s are adrenocorticotropic hormone
(ACTH) suppression due to withdrawal of chronic exog
enous corticosteroids or pituitary tumo . s.
C. Tertiary adrenocortical insufciency occurs with hypo
thalamic diso . de . s, pituitar stalk destruction, and cer
tain central nervous system (CNS) disases.
I CUNICAL MANIFESTATIONS OF ADREAL
INSUFFICIENCY
A. p . imary adrenocortical insufciency. The clinical mani
festations vary depending on the time course of adre
nal destruction.
1. Chronic insufciency. Most patients (75%) present
with chronic insufficiency due to gradual destruction
of the adrenal gland. More than 90% of the gland
must be destroyed before symptoms occur; therefore,
426
Chapter 75
TABLE 75-2: Clinical Manifestations of Chronic Adrenal
Insufficiency ("WWHHOOO")
Clinical Manifestation Incidence
Weakness
Weight loss
Hyperpigmentation
Hypotension
Common
Common
Common
Variable
Variable Obstipation and other gastrointestinal symptoms
(nausea, vomiting, diarrhea, pain)
Orthostasis
Other (hyponatremia, hyperkalemia, nonanion
gap metabolic acidosis, hypoglycemia, eosin
ophilia)
Variable
Variable
HOT
KEY
symptoms occur over a period of many months, and,
in some cases, years. Table 75-2 can be used to deter
mine "WWHHOOO" has chronic insuffciency.
Hyperpigmentation may precede other manifestations.
It tends to be generalized but is accentuated in sun
exposed areas, pressure points (e.g., knees and knuck
les). and on the nail beds, nipples, and palmar creases.
In dark-skinned patients, the only signs of hyperpig
mentation may b on the tongue and in the perilimbal
region of the eyes.
2 Acute insufciency (adrenal crisis)_ Only 25% of pa
tients with adrenocortical insuffcency will present
acutely, but when it occurs, it can be life-threatening.
Adrenal crisis is usually seen in a patient with adrenal
insuffciency (known or not) who experiences a sig
nifcant stress (e.g., infection, cardiac ischemia, sur
gery). It may also be seen in a previously healthy
patient if acute adrenal destruction occurs (e.g., adre
nal hemorrhage due to sepsis or anticoagulation
therapy).
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Adrenocortical Insufficiency
427
a. Signs and symptoms
(1) Profound anorexia, nausea, and vomiting
may be seen.
(2) Abdominal pain may be mistaken for a "sur
gical abdomen."
(3) Hypotension may be severe and minimally
responsive to saline hydration.
(4) Fever may occur, even in the absence of an
initiating infection.
(5) Hyperpigentation may occur, but is not a
common as in chronic insuffcienc.
b. Laborator fndings are similar to the fndings in
chronic insuffciency.
B. Secondary adrenocortical insufciency. The develop
ment of signs and symptoms can be chronic or acute.
The clinical manifestations are the same as in primary
adrenocortical insufciency, with the following excep
tions:
1. Patients may have other evidence of pituitary dys
function (e.g., hypothyroidism, diabetes insipidus,
gonadotropin defciency).
2 Hyperkalemia and a non-anion gap metabolic acdo
sis are usually not present (because aldosterone i
sill secreted appropriately).
3. Hyperpigmentation usually does not ocur.
I APPROACH TO THE PATENT
A. The most diffcult aspect of diagnosing adrenocortical
insufciency is considering the diagnosis. The pattern of
clinical manifestations and lab fndings should alert you
to the possibility of adrenal insuffcency. When a patient
B.
presents with hypotension, weakness, abdominal pain,
or nonspecfc fndings, consider Addison's disease.
Confrmation of the diagnosis is straightforward.
1. Plasma cortisol assay. If the plasma cortisol level is
greater than 20 Jg/dl, adrenocortical insuffciency is
very unlikely.
2. Rapid ACTH stimulation test. If the plasma cortisol
level is Less than 20 Jg/dl, perform a rapid ACTH
stimulation test. A normal response rules out primary
(but not secondary) adrenocortical insuffciency.
3. Plasma ACTH level. Measure the plasma ACTH if
secondary adrenocortical insuffcienc is still a con
sideration. A plasma ACTH level below 20 pg/ml
usually confrms the diagnosis.
428 Chapter 75
I
TRTMENT
A. Acute insufciency (adrenal crisis). If there is strong
clinical suspicon for adrenal crisis, appropriate treat-
ment should not be delayed until diagnostic testing is
completed. Dexamethasone does not interfere with the
plasma cortisol assay and can be used initially.
1. Intravenous gIucocorticoids. High doses of glucocor-
ticoids (e.g., hydrocortisone, 100 mg every 8 hours)
are administered initially; mineralocorticoids may
also be used but are not routinely gven until the
cortisol dose has been tapered to lower levels.
2 Supportive treatment (e.g., intravenous fuids, oxy-
gen) should also be instituted in a monitored setting.
3. Precipitating causes should be treated.
B. Chronic insufciency
1. Primar adrenocortical insufciency. Both glucocor-
ticoids and mineralocorticoids are administered.
a. Doses vary, but a rough estimate for a mainte-
nance dose is 20-30 mg of cortisol daily and
0.1-0.2 mg of fudrocortisone daily.
b. Patients should be counseled that treatment is
lifelong and that doses should be increased dur-
ing times of stress.
2. Secondar or tertiary insuffciency. Usually only gluco-
corticoids are needed.
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PART X
........................................................................................
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76.Altered Mental Sttus
a
II
INTRODUCTION. Altered mental status is a disorder of cog
nitive fnction that is broadly classifed as a disturbance in
either the level or content of conscousness.
A. A disturbance in the level of consciousness usually repre
sents an abrupt change in awareness that spans the spec
trum from alertness, through mild confusional states,
frank delirium and, fnally, coma.
B. A disturbance in the content of consciousness usually
presents as a slow deterioration or change in any or all
of the following: memory, judgment, abstract thinking,
recognition, language skills, or personality. A global
change in the content of consciousness represents c
mentia.
CAUSES Of ALTERED MENTAL STATUS. The mnemonic
"MOVE, STPID" is a useful memory aid for this
lengthy differential.
Causes of Altered Menial Stalus ("MOVE,
STUPID")
Metabolic derangements
Oxygen deficiency to the brain
Vascular disorders
Electrolyle derangemenls or Endocrine dis
orders
Seizures, Srcoidosis, or Structural disorders
Tumors, Trauma, or Temperature derange
ments
Uremic or hepatic encephalopalhy
Psychiatric disorders or Porphyria
Infections
Drugs or Degenerative disease
A. Metabolic derangements that can cause altered mental
status include Wilson's disase, thiamin defciency (Wer-
431
432
II
B.
C.
D.
E.
F.
G.
H.
I.
J.
Chapler 76
nicke-Korsakof syndrome), vitamin B\2 defciency, and
niacin defciency (pellagra).
.
Oxygen defciency to the brain may resul

from I
suff-
cient oxygen in the blood (i.e., hypoxemia), an made-
quate number of red blood cells (RBCs) to carry
.
the
oxygen (i.e., anemia), or insufcient forward fow (I.e.,
decreased cardiac output). Elevated levels of other gass
(e.g., carbon monoxide, carbon dioxide) may also lead
to altered mental status.
Vascular disorders
L
2
3.
4.
5.
Ischemic infarcts (from emboli, thromboses, or vas-
culitis)
. .
Bleeds (epidural, subdural, subarachnOId, or mtrace-
rebral)
Hypertensive encephalopathy
Thrombotic thrombocytopenic purpura (TIP) or
dissminated intravasular coagulation (DIC)
Hyperviscosity syndrome [seen with plasma cell dys-
crasias o markedly elevated white blod cell
(WBC) counts]
Electrolyte derangements (e.g., disorders of sodium, glu-
cose or calcium) or endocrine disorders (increased or
decrased levels of glucose, cortisol, or thyroid hormone)
Seizures (active or the postictal state), sarcoidosis, or
structural causes (e.g., hydrocephalus)
Tumors, trauma, or temperature derangements (i.e.,
hypo- or hyperthermia)
Uremic or hepatic encephalopathy
Psychiatric caues or porphyria
Infection [central nervous system (CNS) or systemic]
Drugs (ingestions or withdrawals) or gene
,
rati
e dis-
eases (e.g., Alzheimer's disease, Parkmson s dIsease,
Huntington's chorea)
APROACH TO THE PATENT.
Given the overlap in the
differential diagnoses for mild confusional states, delirium,
coma, and dementia and the potential consequences of an
incorrect or delayed diagnosis, you should evaluate all pa-
tients with altered mental status in a thorough and system-
atic manner.
A. Perform the ABCs.
1. Airway. Consider intubation.
2 Breathing. Consider intubation.
3. Circulation. Check the vital signs.
B. Assess the need for intravenous access and fuids, oxy-
gen, and electrocardiogaphic monitoring.
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Altered Mental Status 433
C. Rule out easily reversible conditions.
1. Thiamin (100 mg intravenously) is usually given.
2. 50% dextrose (D50) is usually given empirically
when a fngerstick test for glucose is not readily avail
able.
3. Naloxone hydrochloride should be administered if
an opiate overdose is suspected.
D. Rule out common, immediately life-threatening condi
tions. Check the pupils, oculocephalic refex, motor re
sponse, meningeal signs, and vital signs, looking for evi
dence of any of the following disorders:
L Mass efect (e.g., tumor, infarct, bleed, or abscess).
If mass effect is suspected, make arrangements for
emergent neuroimaging and an emergent neurosur
gical consult. Mannitol, steroids, or intubation with
hyperventilation may be indicated.
2. Meningitis. Initial measures include blood cultures
and early empiric antibacterial therapy followed by
a lumbar puncture. Steroids are usually administered
as welL especially in patients with altered mental
status.
3. Status epilepticus. Lorazepam, phenytoin, and, if
necessary. phenobarbital are administered.
4. Hypertensive encephalopathy. Nitroprusside is of
ten administered.
5. Hyperthermia. Coolig measures should be initiated.
E. Continue the worup if the cause of the altered mental
status is stilI not apparent.
L Patient history and physical examination. Perform a
thorough examination, with particular focus on the
neurologcal exam.
2 Laborator studies. The following studies are often
useful:
a. Complete blood count (CBC)
b. Electrolyte panel (including glucose and cal-
cium)
c. BUN and creatinine levels
d. Liver tests
e. Prothrombin time (P) and partial thromboplas
tin time (PIT)
g. Arterial blood gases (possibly including carboxy
hemoglobin)
h. Toxicology screen
i. Urinalysis
3. Other studies. An electrocardiogram (EKG), chest
radiograph, lumbar puncture (with an opening pres-
434
Chapter 76
sure), and head computed tomography (CT) or mag
netic resonance imaging (MRI) scan may be appro-
.
4. Neurology consult. Consultation with a ne
rolog
st
may be necessary if you still cannot fnd the dIagnosIs.
F. Initiate treatment according to the cause.
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77. Peripheral Neuropathy
...............................................................................................................
a
II
II
INTRooucoN
A Clinical syndromes. Peripheral neuropathies can be di
vided into three clinical syndromes:
1. Polyneuropathies present with symmetrical abnor
malities in sensation, motor strength, or both.
2 Mononeuritis multiplex is an initi
ally asymmetric ab
normality in more than one nerve trunk occurring
either simultaneously or over days to years.
3. Mononeuropathies imply focal involvement of a sin
gle nerve (e.g., carpal tunnel syndrome) and usually
result from local nerve compression o stretch.
B. Because polyneuropathy is the most Common peripheral
neuropathy and poses the greatest difculty in differen
tial diagnosis, it is the focus of this c
hapter.
CUNlCAL MANIFESTATIONS OF POLYNEUROPATHY
A. Sensory abnormalities in the feet are usually the frst
symptom of a polyneuropathy.
1. Hypesthesia (decreased sensation), anesthesia (ab
sent sensation), paresthesia ("pins and needles" sen
sation without any stimuli), dyssthesia (burning sen
sation with or without stimuli), and hyperpathia
(exaggerated pain perception) may all be noted. Ini
tially, subjective complaints may be unaccompanied
by objective fndings.
2 Later, a pansensory loss in the feet may occur and
progress centrally. Finger involvement often occurs
once the shins are affected; eventually, the classic
"stocking-ove" pattern may be seen.
B. Motor abnormalities may also occur. The extensors are
usually more involved than the fexors (i.e., weakness of
dorsifexion of the toes is a common fnding). The ankle
refex is often diminished early in the course of the dis
ease, and a diminished knee refex and foot drop are
seen with progression.
CAUSES OF POLYNEUROPATY. Polyneuropathies may
result from a variety of disorders, many of which are also
causes of altered mental status. The mnemonic for the causes
435
436
Chapter 77
of altered mental status, "MOVE, STUPID," can be used
once again, with some modifcations (e.g., this mnemonic for
polyneuropathy has 4 Ps).
Causes of Polyneuropathy ("MOVE, STUPID")
Metabolic disorders (diabetes mellitus)
Other (rare heredofamilial disorders)
Vasculitis or Vitamin deficiency (vitamin B
12
,
thiamine, pyridoxine, folate)
Endocrine disorders (hypothyroidism)
Syphilis or Sarcoid
Tumarrelated (i.e., paraneoplastic syndrome)
Uremia or liver disease
Paraproteinemia/amyloidosis, * Porphyria,
Primary biliary cirrhosis, or Polycythemia vera
lnfectionst or Idiopathic causes [e.g., Guillain
Barre syndrome, chronic inflammatory demye.
linating polyneuropathy (CiDPIl
Drugs or toxins (including alcohol)
APPROACH TO THE PATIENT. Many of the disorders that
can cause polyneuropathies are potentially life-threatening
if not appropriately diagnosed and treated. Because the dif
ferential is extensive and the etiology may or may not be
obvious, your evaluation needs to be tailored to the situation.
If the diagnosis is not initially apparent, a four-step process
may be used to cover most of the possibilities.
A. Take a thorough patient histor.
1. Make sure to ask about recent events that may pro
vide a clue to the diagnosis. Specifcally, inquire
about recent viral illnesses (which may suggest Guil
lain-Bar syndrome), the presence of similar symp
toms in family members or coworkers (which may
suggest a toxic exposure), and systemic symptoms
* Amyloidosis may cause peripheral neuropathy without an accompanying
paraproteinemia, but is listed with paraproteinemia because these disorders
are often thought of together.
t Peripheral neuropathy can be associated with infection (e.g., Lyme dis
ease, leprosy, or AIDS). Patients with AIDS may develop polyradiculopa
thy with abnormalities on cerebrospinal fuid (CSF) analysis that may be
secondary to cytomegalovirus (CMV) infection.
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437
(e.g., weight loss. which may raise suspicion for an
occult malignancy).
2. Obtain a medication histor. Some drugs that may be
responsible for a polyneuropathy include phenytoin,
isoniazid, hydralazine, dapsone, amiodarone, metro
nidazole. nitrofurantoin, vincistine, and high doses
of pyridoxine.
3. Inquire about toxin exposures. The most common
toxins include heavy metals (e.g., arsenic, thallium,
lead, mercury), industrial agents, and pesticides (e.g.,
organophosphates); diphtheria toxin should also be
considered but is quite rare.
HOT
Remember, common things are common. If diabetes
or uremia is present or the patient is a longtime alco
holic, you may not need to look any further.
KEY
B. Assss the time course. Only a few disorders commonly
result in an acute polyneuropathy (i.e., one that occurs
over a few days). Furthermore, unlike subacute or
chronic polyneuropathies, acute disorders usually pro
duce predictable patterns on electrodiagnostic evalua
tion (i.e., electromyography, nerve conduction studies).
1. Acute axonal polyneuropathies have relatively pre
served nerve conduction and are usually caused by
porphyria or intoxications (e.g., arsenic).
c.
2. Acute demyelinating polyneuropathies display a
marked decrease in nerve conduction and are essen
tially synonymous with Guillain-Barre syndrome; al
though diphtheria and toxic berr (buckthorn) inges
tion may rarely produce the same clinical picture.
Perform appropriate laborator studies if the diagnosis
is still not evident. Review the list of possible causes
and obtain the laboratory tests that will help you shorten
the list. Tests that may be requested include:
1. Complete blood count (CBC)
2. Erythrocyte sedimentation rate (ESR)
3. Renal panel with electrolytes
4. Fasting glucose level
438 Chapter 77
5. Vitamin BIz level
6. Thyroid function tests
7. Liver tests
8. Venereal Disease Research Laboratory (VORL) test
for syphilis
.
9. Serum and urine protein electrophoresIS
D. Consider occult disorders. The simple laboratory tests
outlined in IV C may not rule out some of the more
occult processes (e.g
.
, tumor, vasculitis, sarcoid
?
sis),
.
but
they may provide evidence for o against
p
osslbl diag
nosis (e.g., a normal ESR makes
ascuht
s le
s
.
hkely).
The following tests may be useful m certam chllIcal set-
tings:
.
1. Antinuclear antibody (ANA), rheumatOid factor
(RF), and serum croglobulin assesments
.
ay be
used in the evaluation of a suspected vascuhtIs.
2. Radiography
. '
a. Chest radiographs may show eVidence of sarcOId-
osis or an occult tumor.
b. A computed tomography (C) scan may be ob
tained if an intra-abdominal malignancy is sus
pected.
3. Urinary heavy metal and porphobilinogen levels can
be used to evaluate the possibility of toxic metal
exposures and acute intermittent porphyria, respec-
tively.
. . .
4. Lyme titers are only useful in te
ppropnate chmcal
setting because they lack speCIfcIty.
5. CSF evaluation
a Finding include hig protein levels and a normal
cell count in patients with Guillain-Barre syn
drome or ClOP.
b. In AIDS patients with CMV polyradiculopathy,
fndings include neutrophilic pleoctosis, high
protein levels, and low glucose levels.
.
6. Electrodiagnostic studies may be performed (If they
have not been already) to help categorize whether
there is primarily axonal degene
ation or de
ye
.
lin
ation. These studies may be especially helpful II diag
nosing CIDP.
7. Sural nerve biopsy. The ankle is the easiest place to
obtain a cutaneous nerve biopsy.
a. Nerve biopsy is of low yield in symmetric poly
neuropathies, but should be considered in pa
tients with suspected mononeuritis multiplex be
cause a vasculitis may be more likely. The yield of
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Peripheral Neuropathy
439
biopsy is also increased in patients with suspected
vasculitis, amyloidosis, sarcoidosis, or leprosy,
and in those with palpably thickened nerves.
b. Because heredofamilial disorders often present
at an early age and have a characteristic histopa
thology, a sural nerve biopsy should also be con
sidered in children.
TREATMENT is generally aimed at the underlying disorder.
Some general measures and specifc therapies are dis
cussed here.
A. General measures. Relief of neuropathic pain is usually
not easily accomplished. Tricyclic antidepressants (e.g.,
desipramine, amitriptyline) or anticonvulsants (e.g., phe
nytoin, carbamazepine, clonazepam) are often tried.
Topical capsaicin may also be helpful.
B. Specifc therapies
L Guillain-Barre syndrome
a. Most patients require hospitalization for obser
vation and supportive care (e.g., intubation for
respiratory failure).
b. Plasmaphereis is benefcial (especially within
the frst 2 weeks of illness). Steroids are not usu
ally effective.
c. Approximately 85% of patients will recover com
pletely or have only mild residual defects. The
mortality rate is approximately 3%-4%.
2. CIDP may be treated with steroids, immunosuppres
sants, and plasmapheresis if ambulation is threat
ened.
3. Isoniazid overdose can be treated with intravenous
pyridoxine (1 g for each gram of isoniazid ingested).
4. Acute intermittent porphyria
a Awte treatment. Intravenous gucose and hema
tin may be needed for acute attacks.
b. Chronic treatment entails avoiding precipitating
factors (e.g., sulfa drugs) and adhering to a high
carbohydrate diet.
78. Vergo
O.
a
INTRODUTION
II
A. Defnitions
1. Dizziness is a term used to describe an unusual head
sensation or gait unsteadiness. Faintness and vertigo
are forms of dizziness.
2 Faintness is usually described as a sense of light
headedness and is usually caused by an insuffcient
supply of oxygen. blood, or glucose to the brain.
Faintness often occurs with hyperventilation, hypo
glycemia, or just before a syncopal event.
3. Vertigo, the topic of this chapter, is the illusion of
movement (usually spinning). The patient may de
scribe the environment as moving while she remains
stationary, or vice versa.
B. Clinical manifestations of vertigo
1. Nausea and vomiting usually accompany the vertigo.
2. Gait unsteadiness and ataxia are common.
3. The vertigo worsens with head movement.
C. Etiology. Vertigo most commonly results fom a defect
in the vestibular system, but defects in the visual system
or the somatosensory system can cause vertigo as well.
TYES OF VERTIGO. Prognostically, it is important to dis
tinguish central vertigo from peripheral vertigo.
A. Central vertigo often has a poorer prognosis than periph
eral vertigo.
1. Clinical manifestations of central vertigo
a. Central vertigo is usually accompanied by other
brain stem, cerebellar, (and occasionally even ce
rebral hemispheric) signs (e.g., headache, limb
ataxia, true weakness. paresthesias. dysarthria.
diplopia). Nystagmus may b present and can
take any form: horizontal, vertical, or multidirec
tional.
b. Central vertigo is usually not accompanied by
tinnitus or hearing loss.
2. Causs of central vertigo. The most common causes
of central vertigo can be remembered with the mne
monic, "MAIM." (Often, patients with central ver
tigo are "maimed" because of their poor prognosis.)
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Causes of Centrol Vert igo ("MAIM")
Multiple sclerosis
Acoustic neuromo
441
Ischemia or centrol nervous system (CNS)
lesions [especially basilar transient ischemic
attack (TIAII
Migraine (especially basilar)
B. Peripheral vertigo
L Clinical manifestations of peripheral vertigo tend to
cause more patient distress than those of central ver
tigo; however, the episodes are briefer because the
CNS tends to adapt.
a. Tinnitus and hearing loss are common.
b. Nystagmus, which is usually present, occurs uni
directionally and is horizontal. The fast compo
nent is toward the side of the unafected ear.
Unlike the nystagmus of central vertigo, the nys
tagmus of peripheral vertigo is inhibited by visual
fxation. Otherwise, the neurologic examination
is completely normal.
2 Causes of peripheral vertigo. Peripheral vertigo is
usually a result of processes that involve the labyrinth
(inner ear) or eighth cranial nerve. Causes include:
a. Acoustic neuroma (also causes central vertigo)
b. Meniere's disease (vertigo. hearing loss, and tin
nitus)
c. Benig paroxysmal positional vertigo (BPPV),
very brief (e.g., less than 1 minute) episodes of
vertigo, usually brought on by head movement
and often following ear trauma or infection
d. Labyrinthitis leads to acute, severe vertigo, nau
sea, and vomiting in patients who have had a
recent viral syndrome.
e. Inner ear infections
f. Head trauma (recent)
g. Psychogenic causes (considered in patients with
a normal neurologic examination and lacking
nystagmus during an episode of vertigo)
h. Aminoglycoside antibiotics and other drugs
i. Endocrine disorders (e.g., hypothyroidism, dia
betes)
442 Chapter 78
Common Causes of Peripheral Vertigo
("AMPLITUDE")
Acoustic neuroma
Meniere's diseose
Positional (BPPV)
Labyrinthitis
Infection of the inner ear
Trauma (head)
'chogenic causes
Drugs
Endocrine disorders
II
A. Patient history. In many patients. the cause of the vertigo
can be determined from the history alone.
B. Physical examination. Te exam should fous on the
ears, eyes, and nervous system.
1. The presence or absence of an ear infection, nystag
mus, and neurologic defcits should be ascertained.
2. The Nylen-Barany maneuver is important in the as
sessment of BPPV. The seated patient turns her head
to one side while quickly lying down so that her
head hangs over the edge of the table. If vertigo is
reproduced (along with nystagmus), the patient is
likely to have BPPV.
C. Special tests should be ordered in the following situa
tions:
1. If hearing loss or tinnitus is a major component, an
audiogram is useful to evaluate for Meniere's disease
or acoustic neuroma.
2. If thyroid disease or diabetes mellitus is suspected,
blood work is useful.
a Thyroid-stimulating hormone (TSH) levels may
be useful i thyroid disease is suspected.
b. Serum glucose values may prove useful if diabe
tes is suspected.
3. If peripheral causes seem unlikely or if the patient
has neurologic abnormalities, brain magnetc reso
nance imaging (MRI) is indicated.
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I TREATMENT
A. Central vertigo. The treatment depends on the cause. In
patients suspected of having vertebrobasilar TIAs, a trial
of an antiplatelet agent is useful.
B. Peripheral vertigo. For acute peripheral vertigo of almost
any cause, the patient should be put to bed rest and
given antihistamines, anticholinergics, and/or benzodiaz
epines.
1. Medications may prevent eNS adaptation to periph
eral vertigo and, therefore, should not be used for
an extended period of time.
2. A mild exercise program can expedite the adapta
tion proess.
79. Singultus
a
II
II
INTODUCTION. A hiccough is an inspiratory sound
caused by the abrupt closure of the glottis in the setting of
rhythmic spasm of the diaphragm and respiratory muscles.
Hiccoughs can occur at any age and can last for years
(but usually only last for a few minutes). There is a strong
male predominance.
CAUSES OF SINGULTUS. Singultus may be caused by a
wide variety of conditions that have one thing in common
they involve the refex arc shown in Figure 79-1. Causes
can be classifed as peripheral (i.e . involving the vagus or
phrenic nerves or structures adjacent to the diaphragm)
or central.
Common Causes of Singultus ("SINGULTUS")
Surgery (following obdominal, thoracic, or
neck surgery)
Infction of structures adjocent to the diD
phragm (e.g., lower lobe pneumonia,
subphrenic abscess, peritonitis)
Nervous system disorders (e.g., stroke, menin
gitis, brain tumor, multiple sclerosis)
Gastric distention (a very common cause)
Uremia
Low srum calcium, sodium, or potassium
Tumor of the poncreas
'Ichiatric disorders
Steroids and other drugs (e.g., alcohol, benzo
diazepines, borbiturotes)
TREATMENT. Treating the underlying disorder is the best
course of action.
A. Several benign strategies to relieve hiccoughs have been
anecdotally successful. These include (in no particular
order):
444
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Singultus
445
Stimulation of
vagus nerve
Stimulation of
brain stem
Stimulation of
phrenic nerve
(Peripheral cause) (Central cause) (Peripheral cause)
Figure 79-1. The many causes of singultus involve this reflex are in
some way.
1. Having the patient swallow a tablespoon of granu
lated sugar
2. Massaging the sof palate or applying traction to
the tongue
3. Placing a nasogastric tube or a nasopharyngeal
catheter
4. The age-old scare tactic
B. Pharmacologic therapy (e.g., with chlorpromazine o
metolopramide) may be instituted if the benign strate
gies fail.
80. Stroke
a
INTRODUCTION
A Defnitions. A stroke is an acute focal neurologic defcit
produced by a disturbance in cerebral circulation that
results in ischemic infarction, hemorrhage, or both. If
the defcit resolves within 24 hours, the incident is a
transient ischemic attack (TIA).
B. Epidemiology. Stroke is the third leading cause of death
and a leading cause of disability in the United States.
Mortality from stroke has fallen by over 50% in the last
30 years, probably owing to better control of hyperten
sion and other risk factors.
II
CAUSES OF STROKE
A. Ischemic infarction
1. Distribution. Cerebral infarcts can be classifed ac
cording to the type of vessel involved.
a. Small vessel. Chronic stress to vessels produces
lipohyalinosis, leading to stenosis and occlusion.
b. Large vessel. Embolism from a vessel. valve, or
cardiac chamber, or thrombosis (often caused
by a ruptured atherosclerotic plaque) leads to
stenosis and inadequate perfusion. Affected ar
teries include the:
(1) Middle cerebral artery
(2) Anterior cerebral artery
(3) Carotid artery
(4) Posterior cerebral arter
(5) Vertebrobasilar circulation
c. Watershed infarctions may occur at the junction
of the anterior and middle cerebral arteries or
the junction of the psterior and middle cerebral
arteries during systemic hypotension.
I Venous. Thrombosis occurring in the superior
sagttal sinus or other large cerebral veins may
also result in cerebral infarction.
2. Source. Small vessel, large vessel, watershed, and
venous infarctions may be produced by loal pro
cesses or disease in the systemic circulation. It is
helpful to remember the sources of infarcts by begin-
446
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Strke 447
ning in the arterioles of the brain, working backward
to the heart, and then through the venous system to
the brain again (Table 80-1).
B. Hemorrhage
1. Intraparenchymal hemorrhage is usually caused by
hypertension; an underlying vascular malformation
or tumor may also result in intraparenchymal hemor
rhage.
2. Subarachnoid hemorrhage is usually caused by rup
tured cerebral aneurysms. A sudden onset of head
ache and neck stiffness is characteristic.
3. Subdural hematoma often occurs without a history
of preceding trauma.
4. Epidural hematoma is almost always sudden and
post-traumatic.
5. Hemorrhagic transformation. Bleeding occurs into
an ischemic infarct.
II
A. Consider diferental diagnoses.
1. Migraine
2 Postictal state*
3. Hypoglycemia
4. Hypertensive encephalopathy
B. Brain imaging
1. Infarction. In the frst 6 hours after ischemic in
far
tion, head computed tomography (CT) and mag

netIc resonance imaging (MRI) may be unrevealing;
therefore, the patient history and physical examina
tion fndings are particularly important. Localization
of the lesion helps to identify the infarction as large
es
1. small
.
vessel.
.
watershed, or venous, thereby
hmltmg the dIfferentIal diagnosis and directing treat
ment. Table 80-2 summarizes the clinical manifesta
tions and fndings on imaging studies for each type
of cerebral infarct.
2 Hemorrhages will usually be apparent immediately
using c or MRI, although lumbar puncture may
be
.
reqUlred to rule out subarachnoid hemorrhage,
whIch may not be seen on imaging.
* Focal weakness following a seizure (i.e., Todd's paralysis) is occasion
ally seen.
Small arteries Small vessel Hypertensian, diabetes mellitus Glucose, Hg-A 1 C
large and medium large vessel Diabetes mellitus, elevated cholesterol, vascu- Glucose, Hg-A 1 C, cholesterol panel, ESR,
arteries litis, Asian decent, syphilis, dissection toxicology screen, MHATP, MRA or angi-
ography
Carotid stenosis large vessel Diabetes mellitus, elevated cholesterol Glucose, Hg-A 1 C, cholesterol panel; MRA,
Elevated cholesteral, caronary artery disease
Doppler ultrasound, or angiography
Aortic arch large vessel Transesaphageal echocardiogram
left ventricle large vessel History of anterior myocardial infarction, EKG, cardiac monitoring, echocardiogram
ejection fraction <30%
Heart valves large vessel Abnormal or prosthetic valves, endocardiHs Echocardiogram, ESR, blood cultures
Left atrium Large vessel Atrial fibriliaHon, left atrial enlargement EKG, echocardiogram
Hypotension Watershed Coronary arte' disease, arrhythmia, shock EKG, cardiac monitoring, CBC
Hematologic Venous; large or Polycythemia, t rombocytasis, leukocytosis, CBC, PT, PI, anticardiolipin antibody, Rus-
small vessel hypercoagulable states, sickle cell anemia sell viper venom test, protein C and S, anti-
Deep venous thrombosis with patent faramen
thrombin III, IgM, viscosit studies
Systemic veins large vessel Echocardiogram with contrast, lower extrem-
ovale or atrial septol defect it Doppler ultrasound
Cerebral veins or Venous Dehydration, hypercoagulable stote, otitis, si- Magnetic resonance venogram, conventional
sinuses nusitis venogram
CBC = complete blood count; EKG = electrocardiogram; ESR = erythrocyte sedimentation rate; Hg-A 1 C = glycosyloted hemoglobin;
MHA-TP = microhemagglutination- Treponema pallidum; MRA = magnetic resonance angiogram; PT = prothrombin time; PIT = partial
thromboplastin time_
:.
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Small vessel
Large vessel
Middle cerebrol ortery
Anterior cerebral artery
Corotid artery
Posterior cerebrol artery
Vertebrobosilar circulation
Watershed
Venous
Lacunar syndrome (e.g., pure motor hemi
paresis, ataxic hemiparesis, pure sensory
deficit, clumsy hand dysorthria)
Hemiparesis and hemisensory deficit (face
= arm> leg)
Same as for middle cerebral artery in
farction except leg> arm, sporing face
Signs of middle cerebral ortery infarct plus
or minus signs of anterior cerebral artery
infarct or amourosis fugax
Visual field cut
Cranial nere palsies, ataxia, coma
"Man in the barrel" with proximal arm and
leg weakness and numbness
Variable; headache often present; legs of
ten affected
Small, often round, lesions in the white mot
ter, deep gray matter, and brain stem
Infarction in wedge of cortex ond underly
ing white matter
Infarction in cortex and underlying white
matter in a line from the eyes to the oc
ciput
Infarction and hemorrhage near the supe
rior sagital sinus or in the temporol lobe
* Specific neurologic deficits in a given patient are often more complex and depend on the exact location of the infarct.
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450 Chapter 80
TABLE 80-3: Standard Work-Up for the Evaluation
of Stroke Patients
Tests Purpose
CBC, P, PTI
ESR, MHA-TP
EKG
Rule out hematoloic problem
Rule out vcsculitis, syphilis
Rule out arrhythmia, myoccrdial infarction
Rule out non-stroke, differentiate ischemic in- Head CT ar
MRI scan farction from hemorrhage *
CBC = complete blod count; CT = computed tomogrcphy; EKG = electro
ccrdioram; ESR = erythrocyte sedimentction rate; MHA-TP = microhemag
glutination-Treponema palidum; MRI = mcgnetic resononce imaging; PT =
prothrombin time; PTI = partial thromboplastin time.
* Head CT may not show evidence of ischemic infarction until 6 hours
postinfarclion, but is relatively sensitive for hemorrhcge immedictely. Con
trast is rarely helpful. MRI is more sensitive for ischemic infarct, especially
in the brcin stem and cerebellum where bone obscures the CT view, but is
more expensive and time consuming.
C. Search for an underlying cause.
1. Almost all patients should undergo the studies sum
marized in Table 80-3.
2. The following studies are indicated in certain circum
stances.
a. Carotid Doppler ultrasound may be indicated
following a TIA or stroke when endarterectomy
o stent is being considered.
b. Cardiac echocardiography may be indicated fol
lowing a TIA or stroke in patients with an abnor
mal electroardiogram (EKG) or cardiac exami
nation.
c. Magnetic resonance angiography. A magnetic
resonance angiogam (MRA) of the head is indi
cated for patients with possible intracranial large
vessel disease. MRA of the neck can confrm
abnormal carotid Doppler ultrasound fndings.
d. Angiography may be appropriate if carotid end
arterectomy is being considered or when vasculi
tis, aortic dissection, or subarachnoid hemor
rhage is suspected.
e. Transcranial Doppler ultrasound is often indi
cated for patients with possible intracranial large
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451
vessel disease or vasospasm following subarach
noid hemorrhage.
f. Lumbar puncture is indicated if subarachnoid
hemorrhage is a possibility.
g. Hypercoagulability studies (see Chapter 61 IV
B) are appropriate in young patients with no
other risk factors for stroke.
h Toxicology screen. A toxicology screen is ofen
performed in young patients with stroke to rule
out coaine use.
I TREATMENT
A. Isch
mic infarction. Treatment has been primarily sup

portive and foused on secondary prevention, but thera
pies directed at dissolving clots and protecting the patient
from cerebral ischemia have been evolving rapidly.
1. Generally accepted therapies
a. Pharmacologic therapy
(1) Heparin followed by warfarin reduces the
risk of a recurrent event by approximately
65% for patients with cardiac sources of em
bolus. The timing and level of treatment
are debated.
(2) Aspirin is usually indicated for stroke pro
phylaxis in patients who are not receiving
anticoagulants. Aspirin reduces the recur
rence rate by approximately 2%.
(3) Ticlopidine is indicated for patients who have
intolerable side effects with aspirin therapy
or a recurrence of stroke in spite of aspirin
therapy.
b. Supportive measures
(1) Hold antihypertensive agents and consider
intravenous hydration to increase blood fow
to the ischemic area around the infarct
(2) Watch for aspiration, deep venous thrombo
sis, and other complications.
c. Specifc treatment that addresses the cause of the
stroke (e.g., carotid endarterectomy) should be
carried out if possible.
d Physical, occupational. and speech therapy are
necessary.
2. Evolving therapies
a. Anticoagulation. Administration of low molecu
lar weight heparin and warfarin for all infarcts
452 Chapter 80
when the risk of hemorrhagic conversion is small
is under study.
b. Thrombolysis
(1) Tissue plasminogen actvator. Intravenous
administration of tissue plasminogen activa
tor may be benefcial for cerebral infarct pa
tients who can be treated within 3 hours of
symptom onset.
(2) Urokinase may be benefcial if administered
intra-arterially during cerebral angogram
within 6 hours of infarct onset.
c. Neuroprotection. Administration of excitatory
amino acid antagonists, calcium channel block
ers, and free radical scavengers is being investi
gated as a way of minimizing ischemic damage.
B. Hemorrhage
1. Hemorrhagic transformation. Te treatment is the
same as that for ischemic infarction, except heparin
and aspirin are withheld.
2. Intraparenchymal hemorrhage. Surgical evacuation
may be possible, depending on the size and location
of the hemorrhage.
3. Subarachnoid hemorrhage
a. Consultation with a neurosurgeon or interven
tional radiologist is indicated to explore the possi
bility of early aneurysm clipping or coiling.
b. Nimodipine therapy and hydration are indicated.
4. Snbdural and epidural hemorrhages. Consultation
with a neurosurgeon to investigate the possibility of
evacuation is appropriate.
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81. Meningitis
a
INTRODUCTION. Meningitis may result fom infection, ma
lignancy (i.e., carcinomatous meningitis), or systemic illness
(e.g., lupus, sarcoidosis). Infectious etiologies (particularly
acute bacterial meningitis) are common, life-threatening
causes of meningitis, and will be the major focus of this
chapter. Infectious meningitis can be classifed as easy as
"A,B,C":
Classification of Infectious Meningitis
("A,B,C")
Aseptic meningitis
Bacterial meningitis (acute)
Chronic meningitis
II
CAUSES OF INFECTIOUS MENINGITIS
A. Aseptic meningitis
B.
1. Viral infections, including mumps, herpes simplex
virus 1, coxsackievirus, Epstein-Barr virus, and cyto
megalovirus (CMV), are common causes of aseptic
meningitis.
2. Spirochetal infections. Secondary syphilis, Lyme dis
ease, and leptospirosis may also cause aseptic menin
gitis.
Acute bacterial meningitis
1. Streptococcus pneumoniae is the most common
cause of meningitis in adults.
2. Neisseria meningitidis infection may be epidemic or
sporadic and is rare in adults older than 50 years.
3. Haemophilus injuenzae infection is most common
in children younger than 6 years.
4. Listeria monoctogenes infection is most often seen
in infants, the elderly, the debilitated, alcoholics, and
patients on steroids or immunosuppressants.
453
454
Chapter 81
5. Staphylococcus aureus Staphylococcs epider
midis, and gram-negative bacilli. Infections with
these organisms may ocur following neurosurgical
proedures, head trauma, or shunt infections. Left
sided endocarditis should always be considered when
the infecting organism is S. aureus.
C. Chronic meningitis
1. Fungal infections, including Coccidioides immitis and
Crptococcus neoformans infections, are especially
common causes of chronic meningitis.
2. Mycobacterial infections. Mycobacterium tuberculo
sis is the most common mycobacterial cause of
chronic meningtis.
3. Spirochetal infections. Treponema paLlidum and Bor
relia burgdorfer, the causes of syphilis and Lyme
disease, respectively, may cause aseptic or chronic
meningitis.
II
CUNICAl MANIFESTATIONS Of INFECTIOUS MENINGITIS
A. Fever and headache should always raise the suspicion
of meningitis.
B. Neck stifness, positive Kernig's and Brudzinski's signs,
and photosensitivity are also common fndings, but are
less likely with certain infections (e.g., cryptooccal men
ingitis).
C. Altered mental status (rare in aseptic meningitis), focal
neurological abnormalities, seizures, and evidence of in
creased intracerebral pressure (e.g., papilledema) may
all be seen.
D. Signs related to the causative organism may be present.
For example, a petechial or purpuric rash caused by
meningooccus infection is present in approximately 50%
of patients with meningococal meningitis.
HOT
KEY
Infants, the elderly, and immunosuppressed patients
may not generate a high fever or signs of meningismus.
The sensitivities of neck stiffness and the other findings
are not high enough to rule out meningitis clinicolly;
therefore, all patients with 0 fever and altered mental
status, ond many patients with 0 fever and 0 headache,
require further evaluation.
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Meningitis 455
A. Patient history. The time course of the patient's illness
may provide a clue as to the type of meningitis: however,
a lumbar puncture is always necessary.
1. Aseptic meningitis ofen presents acutely after a "fu
like" prodrome. Over 90% of patients are younger
than 30 years.
2 Acute bacterial meningitis presents acutely (usually
within hours to days) and typically with symptoms
that are more severe than in patients with aseptic
meningitis.
3. Chronic meningitis usually is more indolent; symp
toms may not appear for days to weeks.
B. Blood cultures and empiric therapy. If acute meningitis
is suspected, draw two sets of blood cultures and start
empiric therapy with antibiotics (and possibly steroids)
immediately (see V): the yield on Gram stain and
culture of the cerebrospinal fuid (CSF) will probably
not change within 4 hours of starting therapy. Blood
cultures are positive in approximately 50% of patients
with bacterial meningitis, and should always be obtained
because they may be diagnostic in patients with a
negative CSF culture.
C. Lumbar puncture and CSF fuid analysis. Acute bacterial
meningitis often cannot be distinguished fom more be
nign proesses (e.g., aseptic meningitis, common viral
syndromes) on the basis of clinical criteria alone; there
fore, a lumbar puncture should be performed whenever
meningtis is a consideration.
1. Lumbar puncture
a. Contraindications. A lumbar puncture can usu
ally be done safely in the presence of a nonfocal
neurological exam with no evidence of increased
intracerebral pressure (e.g., papilledema). If
there is evidence of a focal neurologic examina
tion or increased intracerebral pressure, empiric
therapy should be initiated and a computed to
mography (C) scan obtained prior to the lum
bar puncture.
b. Procedure
(1) Premedicate the patient. Premedicating with
low doses of a benzodiazepine (e.g., lora
zepam; 0.5-2 mg intravenously) and mor
phine sulfate (e.g., 2-4 mg) often lessens the
456 Chapter 81
pain and anxiety associated with a lumbar
puncture. These agents should b avoided in
patients with altered mental status.
(2) Measure the opening pressure. Opening
pressure elevations are nonspecifc, but
marked elevations are common with acute
bacterial meningitis and normal or minimal
elevations predominate in aseptic meningitis.
(3) Draw four samples. You will usually have
four tubes.
(a) A cell count i usually performed on the
CSF sample in tubes 1 and 4. If the last
tube has a markedly decreased number
of red blood cells (RBCs) in comparison
to the frst tube, a traumatic tap may be
more likely than a true disease process
(e.g., subarachnoid hemorrhage, herpes
encephalitis).
(b) Protein and glucose levels are ofen ob
tained from the sample sent in tube 1 or
tube 4.
(c) Gram staining and culture. The CSFsam
pIe in tube 2 is usually used for Gram
staining and culture. Only a small amount
of CSF (e.g., 1 ml) is required.
(d) Crptococcal antigen (CRAG) titer, an
India ink preparation, and fungal culture
can also be performed on the tube 2 sam
ple in HIV-positive patients; however, a
serum CRAG is more sensitive than a
CSF CRAG.
(e) Other studies may be needed. Tube 3 i
often flled and refrigerated pending the
results of the standard tests.
2. CSF analysis
a. Cell count. The normal cell count is 0-5 lympho
cytes! pJ. If pleoytosis is found, the predominant
cell type helps to prioritize the diferential diag
noses.
(1) Neutrophilic [polymorhonuclear neutro
phil (PMN)] pleocytosis
(a) The patient should be considered to have
acute bacterial meningitis until proven
otherwise.
(b) Early viral infections can also be neutro-
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Meningitis 457
phil predominant, but you should always
assume the worst frst.
(c) PMN counts greater than 50,000 cells/pJ
should alert you to a possible brain ab
scess with rupture into a ventricle.
(2) Lymphocytic pleocytosis. An elevated lym
phocyte count can occur with all three catego
ries of infections meningitis (i.e., the ABCs)
as well as with other processes.
(a) ARCs. Aseptic and chronic meningitis
typically have a lymphoytic predomi
nance. Certain types of bacterial infec
tions (e.g., early or partially treated bac
terial meningitis, brain abscesses,
parameningeal infections) may also cause
a lymphocytic pleoytosis.
(b) Other causes. These patients will proba
bly need "2 ICE" cubes to help their
headaches.
Other Causes of lymphocytic Meningitis ("2
ICE")
Infections (malaria, toxoplasmosis, fresh water
amebiasis, cyst icercosis, Rocky Mountain spot
ted fver)
Intoxications (salicylates, barbiturates, heavy
metals)
Cancer (carcinomatous meningitis)
Collagen vascular disease [systemic lupus ery
thematosus (SLE)]
Endocrine disorder (pheochromocytoma)
Endocarditis
b. Protein level. The normal protein level is 15-45
mgl dl. Approximately 90% of patients with acute
bacterial meningitis have an elevated CSF pro
tein level, whereas patients with aseptic mening
tis often have a normal or minimally elevated
protein level.
c, Glucose level. The normal glucose level is 45-85
mg/dl. The CSF glucose may vary with the se
rum glucose.
(1) The ratio of CSF to serum glucose is less than
458 Chapter 8 1
0.4 (assuming that the serum glucose level is
less than 250 mg/dl) in most patients with
acute bacterial meningitis, but is normal
(greater than 0.4) in patients with aseptic
meningitis.
(2) Carcinomatous, fungal, and tuberculous
meningitis are other common causes of a de
pressed CSF glucose.
d. Gram stain and culture
(1) Gram stain. The Gram stain is positive in the
majority of cases of untreated acute bacterial
meningitis. (L. monocytogenes, however, is
notorious for not being identifed.)
(2) Culture. The CSF culture is positive in most
cases of bacterial meningitis.
D. Ancillary tests
1. Patients with neutrophilic pleocytosis (i.e., a high
probability of bacterial meningitis)
a. Latex agglntination tests for bacterial antigen can
be done on patients who may have a partially
treated culture-negative bacterial meningitis.
b. Head CT scan or magnetic resonance imaging
(MRI). Acute bacterial meningitis may be caused
by direct extension from sinusitis, otitis, or mas
toiditis. An imaging study is necessary if exten
sion is suspected.
2. Patients with lymphocytic pleocytosis. By consider
ing the possible causes of a lymphoytic pleoytosis
(i.e., the ABCs and the 2 ICE cubes) and the clinical
setting, you can determine which diagnostic tests may
be useful.
a. ABCs
(1) Aseptic meningitis. Mumps virus, herpes sim
plex virus, varicella-zoster virus, and CMV
can be recovered from the CSF, and a Mono
spot test can be done for Epstein-Barr virus,
but in most cases, the viral agent is not recov
ered. A Venereal Disease Research Labora
tory (VORL) test should always be sent and
Lyme titers are also a consideration in cases
of suspected aseptic meningitis.
(2) Bacterial meningitis. Acute bacterial infec
tion resulting fom a parameningeal fous is
a possibility and, depending on the presenta
tion, a CT scan or MRI may be considered.
(3) Chronic meningitis. M. tuberculosis infection
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459
or fungal infection are possible etiologies.
Commonly ordered tests include a purifed
protein derivative (PPD) test, a CSF acid
fast bacillus stain and culture, CSF and serum
CRAG titers, and Coccidioides serology
(other fungal serologies and cultures may
also be ordered).
(a) Multiple CSF samples increase the yield
on acid-fast bacillus staining and culture,
but the culture may still be negative in
up to 25% of patients with tuberculous
meningitis.
(b) A history of tuberculosis, active tubercu
losis, or a basilar meningitis on MRI may
support the diagnosis of tuberculous
meningitis.
b. Other causes. CSF cytology is frequently sent
when carcinomatous meningtis is a consider
ation. Multiple CSF samples are needed to in
crease the yield.
TREATMENT. Medication doses are given for adults with
normal renal function.
A. Empiric antibacterial therapy for acute bacterial menin
gitis is critical.
1. No penicillin allergy
a. Ceftriaxone (ofen 2 g intravenously every 12
hours) or cefotaxime (2 g intravenously every 4
hours) is the best choice because these drugs
cover gram-negative organisms (including H in
Juenzae) as well as the emergng penicillin-resis
tant S. pneumoniae.
b. Ampicillin (12-18 g/day in divided doses) or pen
icillin G (18-24 million units intravenously/day
divided or with continuous therapy) should be
added in patients with epidemiologic risk factors
for L. monocytogenes.
2. Penicillin allergy
a. In patients who are allergic to penicillin and have
a history of anaphylaxis, chloramphenicol may
be used. Chloramphenicol is also efective
against Listeria.
b. If the patient is allergc to penicillin but has no
history of anaphylaxis, cefriaxone or cefotaxime
may be tried. Trimethoprimlsulfamethoxazole
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Chopter 81
(TMP/SMX) can be added if Listeri infection
is a possibility.
B. Steroids are often given in the following situations:
1. To decrease the incidence of deafness in children
with H. injunzc infedion
2. To decrease the CSF infammatory response in adults
with acute bacterial meningitis
3. When the patient has altered mental status or signs
of incrased intracerebral pressur
4. When the patient has tuberculous meningitis
PEVENTION. Rifampin prophylaxis (600 mg orally twice
dally for 2 days for adults) is appropriate for close contacts
of a patient with meningococal meningitis. Household and
daycare center contacts and hospital workers with intense
exposure should all be given prophylaxis.
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82. Spinal Cord Compression
D
II
INTRODCTION. Spinal cord compression is a true medical
emergency that requires prompt intervention. The clinical
diagnosis of cord compression may be difficult because early
symptoms are often attributed to more common processes.
Furthermore, the characteristic symptoms often ocur to
late to prevent irreversible damage. Clinical suspicion is
therefore paramount.
CAUSES OF SPINAL CORD COMPRESSION
A. Malignancy, most often from metastatic disease, is by
far the most common cause of spinal cord compression.
Consistent with the number of each type of vertebrae,
the thoracic vertebrae are most ofen involved, followed
by approximately equal involvement of the cervical and
lumbosacral vertebrae.
1. If you remember the cancers that involve the bone
breast, lung, thyroid, kidney, prostate, and multiple
myeloma-you will remember the most common
causes of spinal cord compression (see also Chapter
67). Breast, lung, and prostate cancer account for
most cases of cord compression.
2 Lymphomas, primary spinal tumors (i.e., meningio
mas, neurofibromas), and many other malignancies
can also cause spinal cord compression.
B. Infedions. Epidural abscesses and osteomyelitis (e.g.,
from bacteria or tuberculosis) occasionally lead to
cord compression.
C. Herniated discs that are large and central in loation
occasionally result in cord compression. Clinically sig
nifcant cord compression fom heriated discs occurs
almost exclusively in the lumbar region (usually in the
L4-LS and LS-Sl regions).
D. Epidural hemorrhage may ocur spontaneously or result
from arteriovenous malformations, trauma, anticoagula
tion therapy, or underlying tumors, resulting in cord com
pression.
E. Rheumatologic disorders. Rheumatoid arthritis with cer
vical involvement can result in cord compression from
relatively minor trauma (e.g., whiplash or intubation).
461
462 Chapter 82
Ankylosing spondylitis may result in lumbar cord com
pression.
II
CUNICAL MANIFESTATONS OF SPINAL CORD
COMPESSION
A. Back pain is the most common symptom and is present
in at least 80% of patients. The quality of the pain is
variable and nonspecifc, and does not usually allow spi
nal cord compression to be distinguished from more be
nig disorders. Point tenderess over the involved verte
brae is common in spinal cord compression and should
raise a red fag.
B. Neurological fndings are infequent initially, but become
more prominent with time.
1. Decreased sensation and/or weakness in the lower
extremities, a sensor level, saddle anesthesia, and
hyperrefexia may all be found.
2. Bladder and bowel dysfnction may occur late in the
course of disease. Urinary retention with overfow
incontinence and constipation are often seen.
APROACH TO THE PATIENT. Diagnosis depends on im
aging studies.
A. Modalities
1. Magnetic resonance imaging (MRI) is extremely sen
sitive and noninvasive, and is therefore the frst
choice. The entire cord needs to be evaluated be
cause multiple skip lesions are often present.
2. Computed tomogaphy (CT) with a myelogram can
be used when MRI is not available or contraindi
cated.
3. Radiographs and bone sans are of little value in the
diagnosis of cord compression. Radiogaphs are not
sensitive enough to detect vertebral metastases, and
neither test evaluates the spinal cord itself.
B. Indications
1. Absolute indications. The following patients usually
require testing:
a. All patients with a known cancer accompanied by
symptoms or signs of possible cord compression
(e.g., back pain)
b. Patients with acute radiculopathy accompanied
by urinary retention, saddle anesthesia, or bilat
eral neurological fndings
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2. Risk stratifcation. In the remaining patients who
present with back pain, you can perform a simple
risk stratifcation to assess the likelihood of possible
cord compression and the appropriateness of im
aging studies.
HOT
KEY
a. Simple back pain. Patients with back pain who
are younger than SO years, without a history of
cancer or weight loss, and with no evidence of
sciatica have musculoskeletal pain approximately
9% of the time. Usually, no tests are performed,
and conservative therapy is recommended.
b. Back pain with risk factors. These patients have
a higher incidence of an underlying malignancy,
and are often initially evaluated with plain radio
graphs and an erythrocyte sedimentation rate
(ESR). If these tests are abnormal, or if conserva
tive therapy has failed, additional diagostic test
ing to rule out cord compression is usually indi
cated.
If spinal cord compression is a possibil ity, then imaging
studies need to be performed immediately. Patients
with stable symptoms may be eval uated on a less
acute basis.
I
TRETMENT
A. Steroids. High-dose dexamethasone (often 10-100 mg
via an intravenous bolus) followed by 46 mg every 6
hours (intravenously or orally) is often administered. [f
cord compression is suspected, do not wait for the MRI
results before initiating treatment. There is little harm
in one dose of steroids if your clinical diagosis proves
incorrect, and much to be lost by not giving the dose if
cord compression is present.
B. Radiation therapy should be initiated once the diagnosis
is made. Early steroid treatment is also useful in decreas
ing the swelling associated with radiation therapy.
C. Ketoconazole administered intravenously can reduce
maligant prostatic metastases acutely, and is therefore
464 Chapter 82
sometimes used in patients who have known prostate
cancer associated with cord compression.
D. Chemotherapy alone is sometime effective in patients
with extremely chemosensitive tumors (e.g., small cell
lung cancer, lymphoma).
E. Emergency srgery for cord compression is usually indi
cated:
1. With rapidly progessive neurological defcits
2 When radiation therapy is failing
3. For radio-insensitive tumors
4. When the etiology is unclear
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PART XI
Dermatology
83. Exanthems
a
INTODUCTION
A. A vascular lesion is caused by congestion within the
blood vessel and therefore, usually blanches with pres
sure. The term erythematous implies that the lesion
blanches.
HOT
The best way to determine blanchability is to place a
glass microscope slide onto the lesion while applying
pressure. You will be able to quickly tell whether the
lesion blanches or not.
KEY
II
B. A pururic lesion, on the other hand, is caused by the
escape of blood into the perivascular tissue. Purpuric
lesions do not blanch with pressure. Pururic lesions may
be more worrisome than erythematous ones because the
diseases that can cause purpura are occasionally life
threatening (e.g., meningococcemia).
1. There are two types of purpuric lesions:
a Petechiae are small purpuric lesions.
b. Ecchymoses are large purpuric lesions.
2. When purpuric lesions become raised, they are con
sidered "palpable purura" and represent a vascu
litis.
C. An exanthem is an acute, generalized rash. Exanthemas
are common in hospitalized patients and in those visiting
the emergency department. Most of these eruptions are
benign; however, life-threatening disorders can also
cause exanthemas and must be considered. Exanthemas
can be morbilliform or scarlatiniform eruptions. Both
morbilliform and scarlatiniform eruptions blanch and are
therefore caused by vascular congestion.
MORBILLIFORM RSH. A morbilliform rash is an erythe
matous macular/papular, nonconfuent eruption that usually
467
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Chapter 83
involves the torso. Morbilliform eruptions are much more
common that scarlatiniform ones.
A. Causes
1. Drug reactions. Any drug can cause a morbilliform
rash; however, penicillins and sulf-containing com
pounds are the most common culprits. The skin reac
tion is usually symmetric and involves the torso more
than the appendages. In previously exposed patients,
the rash appears within 3 days; in previously unex
posed patients, the eruption appears 7-9 days into
the course of treatment. Clinical manifestations such
as fever, pruritis, lymphadenopathy, and eosinophilia
are sometimes present.
2 Infections
a. Viral infections [e.g., rubeola (measles), rubella,
Ebstein-Barr virus, echovirus, coxsackievirus
adenovirus, and early HIV] are the most commo
infectious causes of morbilliform rashes.
HOT
KEY
Viral exanthemas are usually preceded by fever and
constitutional symptoms.
b. Bacterial causes include typhoid fever and sec
ondar
yphiHs. arly rickettsial and meningo

coccal disease-diseases usually associated with
purpuric lesions-can initially present as morbil
liform reactions and must b considered, given
the mortality associated with each. If you suspect
rickettsial or meningococcal disease, begin em
piric antibiotics while awaiting the defnitive di
agnosis.
3. Acute graft versus host disease (GVHD) is seen in
Iogeneic bone marrow transplant recipients when
Immunocompetent donor lymphocytes and macro
phages are transplanted and attack the new host.
B. Diagosis. If the diagosis is unclear, skin biopsy (a safe,
easy procedure) should be considered.
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IIScARLTINIF RH. A scarlatiniform eruption is a
generalized, confuent, blanching erythema. It may be diff
cult to distinguish a scarlatiniform rash from a morbilliform
rash, which can begin to coalesce; however, scarlatiniform
eruptions are usually confluent at the outset.
A. Scarlet fever. Patients with a f-hemolytic streptococcal
(group A) pharyngtis or tonsillitis can develop a charac
teristic rash caused by an erythrogenic toxin. The rash,
which is confuent, papular, and sandpaper-like in tex
ture, begins on the neck and upper chest and then spreads
over the extremities and abdomen. Circumoral pallor
and a strawberry tongue are characteristic; desquamation
of most of the involved areas occurs in 5 days.
B. Kawasaki disease is a m ultisystemic disorder of unknown
etiology that mainly affects children.
1. Clinical manifestations. Kawasaki disease is charac
terized by fever, conjunctivitis, mucous membrane
involvement, edema, cervical lymphadenopathy, and
a scarlatiniform (or sometimes a morbilliform) rash
that is most prominent on the trunk.
2. Treatment is usually with intravenous immune glob
ulin (IVIG) and aspirin.
3. Complications. Patients are at risk for coronary ar
tery aneurysms and myocardial infarctions.
HOT
KEY
Kawasaki disease rarely affecs adults, but may occa
sionally occur in epidemic fashion. One theory of
pathogenesis proposes that staphylococcal toxin acts
as a "superantigen" that interacts with T cells.
C. Toxic shock syndrome is a life-threatening disorder
caused by toxins elaborated by Staphylococcus aureus
or group A streptococci.
1. Toxic shock syndrome is most commonly seen in
tampon-using menstruating women, post-surgical pa
tients, and in those with a site of toxin-producing
staphylococcal or streptococcal infection (e.g., a ab
scess). However. whenever a patient has a scarlatini
form rash, always consider toxic shock syndrome.
2 Clinical manifestations. Toxic shock syndrome is
470
HOT
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Chapter 83
characterized by fever, hypotension, and multi
organ involvement:
a. Gastrointestinal-nausea. vomiting, diarrhea, ele-
vated liver enzymes
b. Musculoskeletal-myalgias, arthralgias, myositis
c. Renal-acute renal failure
d. ucous membranes-nonexudative conjunctivi
tIS, strawberry tongue
e. Plmonary-Acute respiratory distress syn
drome CARDS)
f. Cutaneous-diffse erythematous rash that
blanches very easily; desquamation occurs after
1-2 weeks
The rash of toxic shock syndrome is often accentuated
in the Aexural folds.
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84. Pruritus
a
II
INTRODUCTION. Itching can be caused by a variety of der
matologic and non-dermatologic disorders.
A. Dermatologic disorders. Itching is the most common
symptom of dermatologic disorders. Skin lesions are usu
ally present when a dermatologic disorder is the cause
of the itching.
8. Systemic disorder. When no lesions are present, the
itching is often caused by a systemic disorder. Fifteen
percent of patients with itching but without skin lesions
have a systemic disorder diagnosed at initial presen
tation.
CAUSES OF PRURITUS
A. Dermatologic disorders
1. Xerosis (dr skin) is a very common cause.
2 Parasitic infestation (e.g., scabies, pediculosis) and
insect bites cause pruritus.
3. Other causes include urticaria, atopic or contact der
matitis, superfcial fungal infections, drug reactions,
sunburn, dermatitis herpetifonis, fberglass dena
titis, lichen planus, and folliculitis.
8. Systemic disorders
1. Uremia is the most common cause of pruritus when
lesions are not present.
2. Primar biliary cirrhosis, extrahepatic biliary ob
struction, and cholestatic drugs cause total bilirubin
elevation, bile salt retention, and pruritus.
3. Cancer. Neoplasms that cause pruritus include
lymphoma (especially Hodgkin's disease) and breast,
lung, and stomach cancer.
4. Hematologic disorders. Polycythemia vera (and the
other myeloproliferative disorders) and iron def
ciency anemia can cause pruritus.
5. Endocrine disorders (e.g., diabetes mellitus, hyper
and hypothyroidism, carcinoid syndrome) can
cause pruritus.
471
472
Causes of Pruritus ("ITHED")
Infestation (e.g., scabies)
Chapter 84
Total bilirubin elevation (e.g., primary biliary
cirrhosis)
Chronic renal failure (uremia) or Cancer
Hematologic disorders
Endocrine disorders
Dermatologic disorders
IIApPROACH TO THE PATIENT
A. Patient histor. A detailed history focusing on medica
tions, other medical conditions, travel, hobbies, occupa
tion, and the presence of constitutional symptoms (e.g.,
weight loss, fever) is very useful.
1. The itching associated with Hodgkin's disease is of
ten described as a "burning" sensation, especially on
the lower extremities.
2. Patients with scabies usually describe worsening of
their pruritus at night.
3. Polycthemia vera is often associated with a
"prickly" itch that usually occurs as the patient cools
off afer bathing.
4. Xerosis is common in the elderly, especially when
the heater is turned on during the winter months.
B. Physical examination. A thorough dermatologic exami
nation, focusing on the presence of burrows (due to sca
bies), plate-like scaling (due to xerosis), and other lesions
that will aid in the diagnosis should be performed. If no
obvious skin cause is found, examination of the abdomen
(to look for hepatosplenomegaly) and the peripheral
lymph nodes is necessary.
C. Diagnostic tests. If physical examination and patient
history fail to reveal the cause of the patient's pruritus,
a 2-week course of emollients and the use of a mild
soap may be prescribed. If treatment for xerosis provides
no relief, then blood tests [e.g., a complete blood count
(CBC) with platelets, alkaline phosphatase, thyroid
stimulating hormone (TSH), and creatinine levels] and
a chest radiograph should be considered. If these studies
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are unrevealing, a more extensive work-up is rarely
worthwhile and should be done only in selected patients.
TREATMENT. Treatment of the specifc cause is always pref
erable. However, when no clear etiology exists, symptomatic
treatment with antihistamines may be useful.
85. Clubbing
a
II
INTRODUcON. A curious relationship exists between cer
tain systemic disorders and the shape of the fngertips: some
diseases cause the tips of the phalanges to become enlarged,
or "clubbed."
A. Clubbing is a bulbous enlargement of the connective
tissue in the distal phalanges of the fngers and toes.
B. Hypertrophic osteoarthropathy is a more advanced stage
of clubbing that is characterized by:
1. Periosteal new bone formation (especially of the
long bones)
2 Symmetric arthritis-like changes in various joints
3. Neurovascular changes of the hands and feet (e.g.,
paresthesias, erythema, sweating)
CLINICAL MANIFESTATIONS OF CLUBBING
A. The thumb and index fnger are typically affected frst.
B. Clubbing is usually symmetrical; however, it may be uni
lateral in certain vascular disorders (e.g.. aortic arch
anomalies, subclavian artery aneurysms, patent ductus
arteriosus).
C. Clubbing is usually a gradual, painless process; however,
some patients will complain of a dull aching in the fnger
tips. In general, there are three stages to clubbing:
1. During the initial stage, the most diffcult stage to
appreciate, the nail bed becomes spongy.
HOT
KEY
The best way to assess whether a patient's nail bed is
spongy is t compare it with your own nail of the
sme finger.
2 During the next stage, the angle made by the nail
and the dorsum of the distal phalanx increases (when
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Clubbing 475
viewed from the side). Normally, this angle is less
than 180, but in patients with clubbed fngers, the
angle exceeds 180. Schamroth's sign can be helpful
in confrming this increased angie. In patients without
clubbing, when the dorsal surfaces of distal digts of
similar fngers are placed together, a diamond
shaped opening appears at the bases of the nails.
Schamroth noticed that in patients who have mild
clubbing, this opening is obliterated.
3. During the fnal stage, the overall shape of the digit
is visibly altered.
IICOMMON CAUSES OF CLUBBING
A. Acquired
1. Pulmonar disease. Seventy-fve percent of patients
with acquired clubbing have pulmonary disease.
a. Abscess
b. Bronchiectasis
c. Cancer (usually primary)
2. Cardiac disease. Ten percent of patients with ac
quired clubbing have cardiac disease.
a. Congenital cyanotic heart disease
b. Subacute bacterial endocarditis
3. Gastrointestinal disease. Ten percent of patients with
acquired clubbing have gastrointestinal disease.
a. Infammator bowel disease
b. Cirrhosis
c. Colon or esophageal cancer
4 Miscellaneous causes
a. Hyperthyroidism
b. Hemoglobinopathies
c. Local vascular diseases (leading to unilateral
clubbing)
B. Hereditary. Clubbing due to heredity is indistinguishable
morphologically from clubbing caused by acquired dis
ease. However, hereditary clubbing generally develops
during childhood and persists for life. There is usually a
family history of clubbing.
ApPOACH TO THE PATIENT. For patients with acquired
clubbing, an exhaustive search for the underlying causes is
unnecessary; however, looking for potentially treatable and
reversible diseases is worthwhile. If the patient gives a history
compatible with hereditary clubbing, no further evaluation
is usually necessary.
476 Chapter 85
A. Patient histor. The history should focus on eliciting
information about pulmonary symptoms, constitutional
symptoms (e.g., fever, weight loss, night sweats), signs
(e.g., bloody diarrhea, jaundice, nervousness or tremu
lousness), alcohol and tobacco use, and the family
history.
B. Physical examination. The exam should be focused on
fnding evidence of pulmonary, cardiac, gastrointestinal.
or thyroid disease.
L. Diagnostic tests. A complete blood count (eBC), a chest
radiograph, an electrocardiogram (EKG), blood gas
analysis, serum thyroid-stimulating hormone (TSH) lev
els, and stool samples (to search for occult blood) may
be useful. Additional tests may also be necessary.
TREATMEN usually entails treatment of the underlying
cause and pain relief with nonsteroidal anti-infammatory
medications if necessary.
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PART XII
.......................................................................................
Toxicology
86.Alcohol Intoxication
and Withdrawal
a
II
INTODUCTION. Alcohol abuse is an important consider
ation in hospitalized patients for many reasons:
A. Many medical conditions are associated with chronic
alcohol abuse.
B. Alcohol withdrawal may present with protean symptoms.
C. Patients with delirium tremens are at a signifcant risk
of dying not treated properly.
ALCOHOL INTOXICATION. Tolerance occurs with chronic
alcohol consumption. Thus, higher serum alcohol levels are
needed to cause intoxication in a long-time, heavy drinker
as compared with a frst-time drinker.
A. Clinical manifestations of alcohol intoxication. Alcohol
is a central nervous system (CNS) depressant. Alcohol
intoxication is characterized by one or more of the fol
lowing: euphoria, ataxia, reduced inhibitions, nausea, or
altered mental status.
1. A serum osmolality greater than or equal to 340
mOsmll is usually necessary to produce altered men
tal status. Lower levels in a patient with altered men
tal status shOUld therefore prompt further evaluation
(see Chapter 76).
Z A toxic alcohol ingestion (e.g., methanol, ethylene
glycol) shOUld always be considered if an anion gap
acidosis (see Chapter 40) is accompanied by an osmo
lar gap.
3. Patients with alcohol intoxication usually do not re
quire admission to the hospital unless they have a
comorbid condition.
IIALCOHOL WITHDRWAL
A. Pathogenesis. Alcoholics drink continually in order to
avoid the uncomfortable symptoms of alcohol with
drawal. As tolerance develops, more alcohol is needed
to avoid withdrawal. When something occurs to keep
the alcoholic from drinking, such as an infection, gastritis,
or lack of money, alcohol withdrawal may develop.
479
480 Chapter 86
B. Clinical manifestations of alcohol withdrawal. As the
blood alcohol level decreases, symptoms and signs de
velop that are generally opposite in nature to the primary
CNS depressant effect of the drug (i.e., generalized CNS
arousal and hyperactivity). There are four alcohol with
drawal syndromes that may have differing time courses
and clinical manifestations; however, substantial overlap
may occur.
1. "The shakes." Symptoms may appear within 0-1
hours of the patient's last drink and may arise before
the blood alcohol level has returned to zero.
a. Early symptoms include jitters or shakes, an in
tense craving for alcohol, anxiety, weakness, dia
phoresis, and myalgias.
b. The patient is often agitated, irritable, and hyper
vigilant. Common sigs also include tachycardia,
hypertension, and a coarse tremor of the hands
or tongue.
2. Hallucinations. The hallucinations are typically vi
sual (e.g., bugs crawling on the wall) but may be
auditory. Patients may become fearful or paranoid,
but their mental status is otherwise clear. These hal
lucinations typically occur in the frst 3 days after the
last drink.
3. Seizures. Withdrawal seizures are typically general
ized motor seizures that almost always occur within
48 hours of the patient's last drink. Look for other
causes, especially if the patient is febrile, has head
trauma, has prolonged seizure activity, or if the sei
zures begn more than 48 hours after the last drink.
4. Delirium tremens is characterized by altered mental
status and autonomic lability. Typically, delirium tre
mens begn 2-7 days after the patient's last drink
(but may begin a late as l4days after the last drink).
Hypertension, tachycardia, fever, diaphoresis, and
volume depletion are commonly seen (due to ele
vated catecholamine levels).
C. Approach to the patient
. Alleviate withdrawal smptoms.
a. Supportive measures. Keep the patient in a quiet
rom. Restraining the patient may increase her
paranoia and agitation; therefore, restraints
should be used only when necessary. The pa
tient's status should be monitored frequently.
b. Pharmacologc therapy
(1) Benzodiazepines are the drug of choice be-
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Alcohol Inloxication and Withdrawal
481
cause they act at the same receptor as alcohol,
the l'-aminobutyric acid (GABA) receptor,
to sedate the patient.
(a) Diazepam (5-10 mg intravenously every
10- 20 minutes) is administered until the
patient is awake but calm. The dose
should be reduced as the patient re
covers.
(b) In elderly patients or those with impaired
liver function, lorazepam (1-2 mg intra
venously) is preferred because of its
shorter half-life.
(2) Phenytoin. Only those seizures not entirely
attributed to alcohol withdrawal are treated
with phenytoin.
(3) P blockers. A f blocker should be considered
in addition to benzodiazepines if severe hy
pertension and tachycardia are present.
2. Correct metabolic defciencies.
a. Thiamin and vitamins should be administered
before infusing glucose in order to prevent the
development of Wernicke's encephalopathy.
b. Estimate the fuid defct and administer intrave
nous fuids.
c. Replace potassium, magnesium, and phosphorus
if serum levels are low.
d. Vitamin K is administered if the prothrombin
time (PT) is prolonged.
3. Manage associated medical conditions. Perform a
complete history and physical examination to look
for associated medical conditions and to rule out
other causes of altered mental status. A head com
puted tomography (CT) scan and lumbar puncture
are often necessary in patients with fever, altered
mental status, seizures, or an abnormal neurologi
cal exam.
4. Attempt rehabilitation. The patient should be e
ferred to an alcohol rehabilitation center, AlcoholIcs
Anonymous, or an outpatient mental health center.
87. Toxicologic Emergencies
a
INTRODUCTIO. Drug overdose is commonly encountered
in medical practice and if not managed in an expedient and
appropriate fashion, can be lethal.
II
GENERAL APPROACH TO THE OERDOSE PATIENT
A. ARCs. Initial attention should focus on airway, breath
ing, and circulatory system management. Intravenous
catheterization, supplemental oxygen, and cardiac moni
toring are usually required.
R. Patient history. The patient history is of critical impor
tance and should be obtained from the patient, fiends,
caregivers, or paramedics. Pill counts and attention to
empty bottles found at the site are useful.
C. Physical examination. The physical examination may be
helpful. Areas of fous include the patient's vital signs,
mental status, pupils, and bowel sounds. Table b-1sum
marizes physical examination fndings for four of the
major types of overdoses.
D. Data
1. Electrocardiography. An electrocardiogram (EKG)
is indicated for patients with ingestion to rule out
any potential cardiac effect of ingested drugs.
2. Drug levels and toxicologic screen. Urine and serum
analysis may be useful in the management of inges
tion patients.
3. A chest radiograph, complete blood count (CRC),
and renal panel are useful for evaluating possible
concomitant disease.
E. Gatric lavag and mMcharcoal. Limiting gastric absorp
tion of many acute ingestions can be accomplished by a
combination of gastric lavage and oral charcoal adminis
tration.
IISPECIFIC TOXIC SYNDROES e'TOXIDROES11)
A. Opioid recptor agonists include morphine and related
illicit substances (e.g., heroin). Acute toxicity can result
from clinical overdose in the hospitalized patient being
treated with narcotic agents, or from accidental overdose
in the injection drug user.
482
Opioid t RR Varies from euphoria Constricted Decreased
t BP to obtundation
a-Adrenergic i HR, i RR, i BP Hyperigilance Dilated Variable
agonist
Cholinergic t HR Agitation Constricted Increased
agonist
Cholinergic t HR, t temperature Irritability, delusions Dilated Decreased
antagonist*
BP = blood pressure; HR = heart rate; RR = respiratory rate
* In patients with clinical manifestations of on anticholinergic syndrome, tricyclic overdose should be considered,

F
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c
w
484 Chapter 87
1. Clinical manifestations of opioid overdose. These pa
tients are typically stuporous and clammy, and have
miosis. A memory aid for the opioid toxidrome may
be derived from the street term for heroin, "DOPE":
Clinical Manifestations of Opioid Agonist
Overdose ("DOPE")
Decreased respiratory drive
Obtundation
Pinpoint pupils
Euphoria
2. Major concers
a. Respiratory depression is of major clinical con
cern and may lead to hypoventilation, hypox
emia, and death.
(1) The establishment of a patent airway and
adequate ventilation are critical frst steps.
(2) If hypoxemia is persistent, noncardiogenic
pulmonary edema must be considered.
b. Hypotension, which is mediated at histaminic re
ceptors, may complicate opioid overdose.
3. Treatment. Opioid antagonists (e.g., naloxone) may
produce dramatic reversal of some of the acute symp
toms of opioid overdose (e.g., respiratory depres
sion), but will not reverse the histamine-mediated hy
potension.
B. a-Adrenergic agonists include coaine and methamphet
amine.
1. Clinical manifestations of a-adrenergic agonist over
dose. The clinical syndrome results primarily from
stimulation of al receptors, leading to tachypnea,
tachycardia, vasoconstriction, and psychostimulation
(including hyperactivity).
2. Major concers include tachycardia and vasospasm
of the epicardial coronar arteries.
3. Treatment in the acute setting is primarily support
ive. Benzodiazepines have been shown to be useful
in the treatment of cardiac symptoms. Of note, f
blokers should be avoided in the setting of coaine
induced ischemia.
C. Cholinergic agonists. Organophosphate insecticides in-
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T oxicolog ic Emergencies 485
D.
hibit acetylcholinesterase and are a common cause of a
pure cholinergc syndrome. This toxidrome is primarily
seen in farm workers and in victims of chemical warfare.
. Clinical manifestations of cholinergic agonist toxic
ity. Sustained stimulation of acetylcholine (ACh) re
ceptors causes tremor, nausea, urinary and fecal in
continence, generalized hypersecretion, and coma.
Many of the important features can be remembered
using the mnemonic "SLUDGE."
Clinical Manifestations of Cholinergic Agonist
Toxicity ("SLUDGE")
Salivation
Lacrimation
Urination
Defecation
Grimacing
Eretion
2. Major concers include respiratory muscle paralysis,
hypotension, and hypoxemia.
3. Treatment
a. Supportive measures. Respiration and blood
pressure should be maintained. Contaminated
clothing should be removed.
b. Atropine is administered to block the action of
ACh at the receptor.
C Pralidoxime (2-PAM) may also be administered.
Cholinergic antagonists include atropine and the bella
donna alkaloids, which antagonize the activity of ACh
at the muscarinic receptor. Many other drugs (including
phenothiazines and tricyclic antidepressants) can pro
duce the anticholinergic toxidrome. Exposure to Atropa
beladonna, Jimson weed, or stinkweed plants may also
cause toxicity.
1. Clinical maniestations of cholinergic antagonist tox
icity include the following:
a. Restlessness, irritability, and delusions ("mad as
a hatter")
b. Dilation of cutaneous blood vessels ("red as a
beet")
c. Decreased aporine and salivary gland secretion
("dry as a bone")
0 Mydriasis and cycloplegia ("blind as a bat")
486 Chapter 87
e. Tachycardia ("fast as a rabbit")
f. Decreased gastrointestinal motility with de
creased bowel sounds ("slow as a mule")
g. Increased bladder sphincter tone ("tight as a
drum")
2. Treatment
a. Supportive treatment. Respiratory and circula
tory support may be necessary.
b. Physostigmine may be used.
Tricyclic antidepressants
1 Pharmacologic efects. Tricyclic antidepressants
have several important and complex pharmaco
logic effects:
a. Blockade of central dopamine and norepineph-
rine uptake
b. Anticholineric activity
c. Peripheral Q receptor blockade
d. Class Ia antiarrhythmic effects
Z CHnicl manifestations of tricycHc antidepressant
overdose are often dose-dependent.
a. At lower doses, the anticholinergic properties
usually predominate.
b. At higher doses, seizures, coma, cardiac dys
rhythmia (primarily ventricular tachyarrhyth
mia), and hypotension may occur.
3. Approach to the patient. Rapid diagnosis is impera
tive and is made on the basis of the patient history,
physical examination fndings, and EKG fndings
(e.g., prolongation of the QRS interval).
4. Treatment
a. Supportive measurs include supporting respira
tion and circulation as needed.
(1) Sodium bicarbonate should be administered
immediately for QRS prolongation.
(2) Diazepam may be administered for the acute
control of seizures.
F. Phenothiazines
1. Pharmacologic efects. Like tricyclic antidepressants,
phenothiazines have multiple pharmacologic effects:
a. Antagonism of dopaminergic receptors
b. Blockade of norepinephrine and 5-hydroxytryp
tamine reuptake in the central nervous system
(CNS)
c Peripheral Q receptor blockade
d. Anticholinergc activity
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Toxicologic Emergencies
487
e. Lowering of the seizure threshold
f. Class Ia antiarrhythmic effects
Z Clinical manifestation of phenothiazine overdose.
The clinical syndrome can be similar to that of tricy
clic antidepressant overdose. with the following ex
ceptions:
a. The anticholinergic state tends to be less predom-
inant.
e. Neuroleptic malignant syndrome (NMS) may oc
cur. NMS is an idiosyncratic (i.e., dose-indepen
dent) reaction to phenothiazines characterized
by:
(1) Autonomic instability
(2) Hyperthermia
(3) Alterd mental status
(4) Extrapyramidal symptoms, including rigidity
and posturing
3. Treatment. Dantrolene and bromocriptine are usu
ally used in the management of NMS.
Summar of Mnemonics
PART I: GENERAL APPROACH TO
MEDICAL PROBLEMS
Potential Etiologies ("CHOPPED MINTS") ................ Chapter 1
Congenital
Hematologc or vascular
Organ disease
Psychiatric or Psychogenic
Pregnancy-related
Environmental
Drugs (prescription, over-the-counter, herbal, illicit)
Metabolic or endocrine
Infectious, Infam atory, Iatrogenic, or Idiopathic
Neoplasm-related (and paraneoplastic syndromes)
Trauma
Surgical or procedure-related
PART II: CARDIOLOGY
Causes of Syncope ("SYNCOPE") ................................. Chapter 5
Situational
Vasovagal (the "V" looks like a "Y")
Neurogenic
Cardiac
Orthostatic hypotension
Psychiatric
Everything else
Causes of Atrial Fibrillation
("SWAMP CHILD") ........................................................ Chapter 7
Sick sinus syndrome, Stress
Wolff-Parkinson-White syndrome
Alcohol (intoxication, withdrawal, "holiday heart")
Myoarditis, Metabolic abnormality
Pericardia disease, Pulmonary disease
CHF, Coronary artery disease, Congenital heart disease
Hypertension, Hyperthyroidism, Hypertrophic cardiomyopathy
Infltrative disease, Infection
Lone (idiopathic)
Dilated cardiomyopathy, Drugs
489
490 Summar of Mnemonics
Risk Factors for Stroke in Patients with Atrial Fibrillation
("CHASE") ........................................................................ Chapter
CHF (within months)
Hypertension
Atrial size > 5 cm
Stroke in past
Ejection faction reduced
Common Causes of Dilated Cardiomyopathy
("PIPED") ......................................................................... Chapter 11
Postmyoarditis
Idiopathic
Peripartum
Ethanol
Drugs (cocaine and heroin)
Factors that Can Exacerbate CHF
("FAILURE") .................................................................. Chapter 11
Forgot meds
Arrhythmia or Anemia
Infections, Ischemia, or Infarction
Lifestyle (e.g., increased sodium intake, stress)
Upregulators (e.g., thyroid disease, pregnancy)
Rheumatic valve or worsening of other valvular diseases
Embolism (pulmonary)
Treatment of Acute Pulmonary Edema
("MOIST 'N DAMP") .................................................... Chapter 11
Morphine (2-4 mg intravenously as long a the blood pressure
is adequate)
Oxygen (as much as necessary to raise the oxygen saturation
over 90%)
Intubation, if necessary (pulmonary edema is rapidly reversible,
but if the patient is tiring, intubation can be lifesaving)
Sit 'em up (to reduce preload)
Tourniquet (rotating touriquets to decrease preload were once
used)
Nitrates (to acutely decrease preload)
Diuretics (20-40 mg furosemide intravenously to frst decrease
preload and then induce a diuresis)
Albuterol (may help bronchospastic patients)
More morphine, more nitrates, and more diuretics as needed
Phlebotomy (was once used to reduce preload)
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Summar of Mnemonics 491
The Causes of Shock ("SHOCK") ................................ Chapter 12
Sepsis
Hypovolemia
Obstruction to Flow
Cardiac
Kooky disorders
"Kooky" Disorders Leading to Shock
("DEAN") ........................................................................ Chapter 12
Drug toxicity (primarily vasodilating drugs)
Endocrine disorders (adrenal insuffciency or myxedema)
Anaphylaxis
Neurogenic (especially after spinal cord injury)
Vasopressors ("PND EDI?
,
') ......................................... Chapter 12
Phenylephrine
Norepinephrine
Dopamine
Epinephrine
Dobutamine
Isoproterenol
PART III: PULONARY AND CRITICAL CARE
Causes of Hemoptysis ("BATLE CAMP") .............. Chapter 14
Bronchiectasis or Bronchitis
Aspergilloma
Tumor
Tuberculosis
Lung abscess
Emboli
Coagulopathy
Arteriovenous malformation, Arteritis, or Alveolar hemorrhage
Mitral stenosis
Pneumonia
Other Causes of Wheezing ("CARES") ...................... Chapter 1b
Cardiac asthma (i.e., CHF) or Churg-Strauss syndrome
Refux esophagitis
Exposures (irritants, medications), Embolism (pulmonary)
Sinusitis, Strongyloids infection
Agents Used to Treat Exacerbations of Asthma or COPD
("ASTHMA") ................................................................ .. Chapter 18
Albuterol or ipratropium (Atrovent)
Steroids (oral or intravenous)
Theophylline
Humidifed oxygen
Magnesium
Antibiotics
Causes of Restrictive Ventilatory Defects
("PAINT") ........................................................................ Chapter 19
Pleural (fbrosis, effusions, empyema, pneumothoax)
Alveolar (edema, hemorrhage, infammation)
Interstitial lung disease
Neuromuscular (myasthenia, phrenic nerve dysfunction,
myopathy)
Thoracic or extrathoracic (kyphoscoliosis, obesity, ascites,
pregnancy)
Causes of Interstitial Lung Disease
("HITS FACED") ........................................................... Chapter 19
Histioytes 7or Hypersensitivity pneumonitis
Idiopathic pulmonary fbrosis
Tuberculosis or Tumors
Sarcoidosis
Fungal infection
Alveolar proteinosis
Collagen vascular disease
Environmental or Eosinophilia-associated
Drugs
Criteria for Hospital Admission of Patients with Community-
Acquired Pneumonia ("ADMIT NOW") .................... Chapter 20
Age> 65 years
Decreased immunity (e.g., cancer, diabetes, AIDS, splenectomy)
Mental status changes
Increased A-a gadient
Two or more lobes involved
No home (i.e .. homeless patients)
Organ system failure (increased creatinine, bone marrow
suppression, severe hypotension, liver failure)
WBC count greater than 30,OOO/mm3 or less than 400/mm3
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Summar of Mnemonics
493
Most Important Weaning Criteria
("WEANS NOW") .......................................................... Chapter 24
Wake (patient must be awake!)
.
Electrolytes OK (i.e., no hypomagneserua or
hypophosphatemia)
Acidosis (metabolic) or Alkalosis (metabolic) abs
.
ent
.
Neuromuscularly intact (beware of prolonged arunoglycoslde or
steroid use or neuromuscular blockade)
Suctioning and Secretion controlled
Nutritionally intact
Obstruction of the airways reduced
Weaning parameters
MIF ~ -20 cm H20
VT > 300 ml
VE ~ 10 L
Respiratory rate/VT ~ 100 breaths/L
PART IV: GASTROENTEROLOGY
Metabolic and Systemic Causes of Abdominal Pain
("Puking My BAD LUNCH") ...................................... Chapter 25
Porphyria
Mediterranean fever
Black widow spider bite
Addison's disease or Angoedema
Diabetic ketoacidosis
Lead poisoning
Uremia .
Neurogenic (impingement of spinal nerves or roots, diabetes,
syphilis)
Herpes zoster
Causes of Markedly Increased ( > 100 U/L) AST and ALT
Levels ("Tainted Mushrooms Can Cause Bad Hepatitis,
So Watch Out!") .............................................................. Chapter 26
Tylenol or Tetracycline toxicity
Mushrooms (Amanita phalloids)
Carbon tetrachloride toxicity (rare)
Congestive hepatopathy
Budd-Chiari syndrome
Hepatitis (viral)
Shock liver (due to hypotension of any cause)
Wilson's disease (subtype associated with fulminant hepatic
necrosis)
Other toxins (e.g., halothane, valproic acid, vitamin A)
Selected Causes of Diarrhea ("MESSY CACA") ...... Chapter 27
Medical disease
Escherichia coli
Shigella
Salmonella
Yersinia entercolitica
Campylobacter
Aeromonas
Clostridium difcile
Amoeba
Gastrointestinal Bleeding-Upper Gastrointestinal Sources
("GUM BLEEDING") ................................................... Chapter 28
Gastritis (secondary to NSAIDs, alcohol, or stress)
Ulcers (often caused by Helicobacter pylori or NSAIs)
Mallory-Weiss tear (often secondary to excessive vomiting)
Biliary (hemobilia, usually secondary to trauma)
Large varices (seen in patients with portal hypertension)
Esophagitis or Esophageal ulcer
Enteroaortic fstula (usually seen in patients with aortic grafts)
Duodenitis or Dieulafoy's lesion (an ectatic artery in the
stomach)
Infammatory bowel disease (upper tract Crohn's disease)
Neovascularization (arteriovenous malformation)
Gastric cancer
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Gastrointestinal Bleeding-Lower Gastrointestinal Sources
("DRAIN") ....................................................................... Chapter 28
Diverticulosis
Radiation colitis
Arteriovenous malformation (angodysplasia)
Ischemia, Infammation, or Infection
Neoplasm
Criteria for Admittance to ICU with a Gastrointestinal Bleed
("VISA") ........................................................................... Chapter 28
Variceal bleeding (suspected or confrmed)
Instability of vital signs
Serious comorbid conditions (e.g., coronary artery disease,
COPD)
Active gastrointestinal bleeding
Clinical Manifestations of Serum Sickness
("SALT") .......................................................................... Chapter 29
Skin rash (morbilliform, urticarial, or palpable purpura)
Arthralgias or Arthritis
Lymphadenopathy
Temperature increase
Causes of Massive Splenomegaly ("Hopefully, My Medical
Students Can Learn Gastroenterology") ...................... Chapter 29
Hairy cell leukemia (uncommon, resembles chronic lymphocytic
leukemia)
Malaria
Myeloid metaplasia with myelofbrosis (one of four
myeloproliferative disorders)
Sarcoidosis
Chronic myelogenous leukemia (another myeloproliferative
disorder)
Lymphoma (primarily splenic lymphoma)
Gaucher's disease
Common Causes of Acute Pancreatitis
("BAD HITS") ................................................................ Chapter 31
Biliary stones
Alcohol abuse
Drugs
Hyperlipidemia or Hypercalcemia
Idiopathic or Infectious
Trauma
Surgery (post-ERCP) or Scorpion sting
Ranson's Criteria at Admission ("WAGLS") ............. Chapter 31
White blood cell (WBC) count > 16,OOO/mm3
Age > 55 years
Glucose> 200 mg/dl
Lactate dehydrogenase (LDH) > 350 U/L
SGOT > 250 U/L
Ranson's Criteria During the Initial 48 Hours
("BaC wasn't an SOB") .............................................. Chapter 31
Base defcit > 4 mEq/L
Calcium ~ 8 mgt U
Hematocrit decrease > 10%
Sequestration of fuid> 6 L
Oxygen ~ 60 m Hg
Blood urea nitrogen (BUN) increase of > 5 mg/dl
PART V: RENAL/ACID-BASE
Chronic Diseases that Lead to Enlarged Kidneys
("SHAPE") ....................................................................... Chapter 35
Scleroderma
HIV nephropathy
Amyloidosis
Polycystic kidney disease
Endocrinopathy (diabetes)
Indications for Acute Dialysis ("AEIOU") ................ Chapter 35
Acidosis
Electrolytes (e.g., hyperkalemia)
Intoxication
Overload
Uremia
Characteristics of the Nephrotic Syndrome
("PALE") .......................................................................... Chapter 36
Proteinuria ( > 3.5 grams/24 hours)
Albumin (low)
Lipids (elevated)
Edema
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Secondary Causes of Nephrotic Syndrome
("TIS LAD HAS nephrotic syndrome") .................. Chapter 36
Tumors
Heroin, Heavy metals, and toxins
Infection
Hepatitis B and C
AIDS
Subacute bacterial endocarditis, Syphilis, Schistosomiasis
Systemic disorders
Lupus
Amyloid
Diabetes
Causes of Hypocomplementemic Acute Nephritic Syndrome
("She Saw Sally Cook Poisoned Macaroni") .............. Chapter 37
SLE
Subacute bacterial endocarditis
Shunt nephritis
Cryoglobulinemia
Poststreptococcal glomerulonephritis
MPGN
Irritative Symptoms Suggestive of UTI
("FUND") ......................................................................... Chapter 39
Frequency
Urgency
Nocturia
Dysuria
Causes of Anion Gap Acidosis ("MUD PLIERS") .... Chapter 40
Methanol intoxication (through conversion into formic acid)
Uremia (urea is an anion)
Diabetic or alcoholic ketoacidosis
Paraldehyde (a medicine no longer in use)
Lactate (usually from anaerobic metabolism during shok or
extensive tissue injury)
Isoniazid or Iron overdose
Ethylene glycol intoxication (antifreeze ingestion)
Rhabdomyolysis
Salicylate intoxication
Common Causes of Chloride-Unresponsive Metabolic Alkalosis
("ABCD") ......................................................................... Chapter 40
Aldosteronism (primary)
Bartter's syndrome
Cushing's syndrome
Depletion of magnesium
Causes of Secondary Hypertension ............................... Chapter 42
One anatomic cause
Two renal causes
Three adrenal canses
Four CENTs
Ethanol abuse or Estrogen use
Neurologic disease
Thyrotoxicosis
PART VI: INFECTIOUS DISEASE
Gram-Positive Rods
("CLumsy BActeria NOrmally ACt LIke ERror-prone
COrnballs") ....................................................................... Chapter 44
Clostridium
Bacilus
Nocardia
Actinomycosis
Listeria monocytogenes
Ersipelothri
Corynebacterium
Seven Killer Causes of Fever and Rash
("SMARTT") ................................................................. Chapter 45
Sepsis
Meningococcemia
Acute endocarditis
Rocky Mountain spotted fever
Toxic erythemas
Toxic epidermal necrolysis (TEN)
Travel-related infections
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Drugs That Commonly Cause TEN
("SNAP") .......................................................................... Chapter 45
Sulfonamides
Nonsteroidal anti-infammatory drugs (NSAIDs)
Allopurinol
Phenytoin
Diferential Diagnoses for Vesicles and Bullae Accompanied by
Fever
("VESICLES") ................................................................. Chapter 45
Viral infections (e.g .. varicella-zoster. herpes simplex. coxsackie)
Erythema multiforme
SSSS
Impetigo (bullous)
Contact dermatitis
LESs likely etiologes (e.g., porphyria cutanea tarda. bullous
pemphigoid, pemphigus vulgaris, dermatitis herpetiformis)
Differential Diagnoses for Pustules Accompanied by Fever
("Very Full of PUS") ...................................................... Chapter 45
Viral infections (e.g., varicella-zoster, herpes simplex)
Fungal infections (e.g., candidiasis)
Pustular psoriasis
Urethritis-related (i.e., DGI)
Syphilis
Major Jones Criteria
("J\NES") ....................................................................... Chapter 47
Joints (arthritis)
\ Involvement
Nodules
Erythema marginatum
Sydenham's chorea
PART VII: HEMATOLOGY/ONCOLOY
Common Causes of Pancytopenia
("PANCYTO") ................................................................ Chapter 53
Aplastic anemia
Consumption
Vitamin defciencies (the "V" looks like a "Y")
Toxins, drug, and radiation therapy
Causes of Decreased Platelet Production
("PANYTO") ................................................................... Chapter 54
Aplasia
Vitamin defciencies (the "V" looks like a "Y")
Causes of DIC
("MOIST") ........................................................................ Chapter 56
Maligancy
Obstetric complications
Infection
Shock
Trauma
Causes of Absolute Polycythemia
("Hypoxia Can Cause Polycythemia Every Time") ... Chapter 57
Hypoxia (chronic)
Carboxyhemoglobinemia
Cushing's syndrome or Corticosteroids
Polycythemia vera
Erythropoietin-secreting Tumors
Causes of Eosinophilia
("PHILlA CAN ACT FAST") ..................................... Chapter 59
Pulmonary disease
Helminthic infections
Filariasis
Ascariasis
Schistosomiasis or Strongyloide infection
Trichinosis
Infections, other
Coccidioidomycosis
Tuberculosis (especiaUy chronic)
L-Tryptophan
Immunologic disorders
Addison's disease
Cutaneous disorders
Allergic disorders
Neoplasms
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Causes of Hypercoagulable States
("DAN TROMBUS") .............................................. Chapter 61
Defciencies or alterations in coagulation factors (e.g., protein C,
protein S, antithrombin III, factor V, fbrinogen,
plasminogen)
Antiphospholipid antibody syndrome
Malignancy (e.g., Trousseau's syndrome)
Nephrotic syndrome (because of urinary loss of protein C
and S)
Trauma
Homocystinuria or Heparin-induced thrombocytopenia and
thrombois (HIT) o Hemoglobinuria [i.e., paroxysmal
nocturnal hemoglobinuria (PNH)]
Rheumatologic causes (i.e., vasculitis)
Oral contraceptives
Myeloproliferative disorders
Baby-carriers (i.e., pregnancy)
Unknown
Surgery or postoperative states (particularly neurosurgical and
orthopedic)
Causes of Generalized Lymphadenopathy
("SHE HAS CUTE LAN") ........................................... Chapter 62
Syphilis
Hepatitis
Histoplasmosis
AIDS/HIV infection
Serum sickness
Cytomegalovirus (CMV) infection
Unusual drugs (e.g., hydantoin derivatives, anti-thyroid
medications, anti-leprosy medications, isoniazid)
Toxoplasmosis
Erythrophagoytic lymphohistiocytosis
Leishmaniasis
Arthritis (rheumatoid)
Neoplasm: leukemia and lymphoma
Diferentiating ALL from AML
("ALL PAST") ................................................................ Chapter 65
ALL is associated with a positive
PAS stain and a positive TdT enzymology (TdT is positive in
95% of ALL cases).
Important Clinical Manifestations of Multiple Myeloma
("PLASMA") ................................................................... Chapter 66
Proteinurialrenal insufciency
Lytic bone lesions and hypercalcemia
Anemia and Abnormal bleeding
Sepsis and infections
Marrow involvement
Amyloidosis
Characteristics of Waldenstrom's Macroglobulinemia
("Uncle Waldo loves HAMS") ...................................... Chapter 66
Hyperviscosity
Adenopathy
IgM
Splenomegaly
PART VIII: RHEUMATOLOGY
Causes of Monoarticular Arthritis
("If I Make The Diagnosis, No More Ha") ........... Chapter 68
Infectious disease
Infammatory disease
Metabolic disorders
Trauma
DJD
Neoplasm
Miscellaneous (foreign body synovitis. avascular necrosis)
Hemarthrosis
Criteria for the Diagnosis of SLE
("P-MOAD") .................................................................... Chapter 69
Positive antineutrophil antibody (ANA): seen in 95% of patients
Positive other immunologic test [antibody (Ab) to double-
stranded DNA, Ab to Smith, LE cell preparation, or false
positive syphilis serology]
Psychosis, seizures, or other neurologic abnormalities
Photosensitivity rash
Polyserositis (pleuritis, pericarditis, or peritonitis)
Proteinuria or renal involvement
Pancytopenia or singIe-celi line "penia" (anemia,
thrombocytopenia, leukopenia)
Malar rash
Oral ulcers
Arthritis
Discoid rash
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Summar OMnemonics 503
Causes of Secondary Vasculitis
("VASCULITIS") ............................................................ Chapter 70
Various drugs
Autoimmune disorders
Serum sickness
Cryoglobulinemia
Ulcerative colitis
Low complement (hypocomplementemic urticarial vasculitis)
Infections
Tumors
IgA nephropathy (Henoch-Schonlein purpura)
Smoking-related (thromboangiitis obliterans)
PART IX: ENDOCRINOLOGY
Causes of Hypercalcemia
("MISHAP+ F") ............................................................... Chapter 71
Malignancy
Intoxication (vitamin D)
Sarcoidosis (and other granulomatous diseases)
Hyperparathyroidism
Addison's disease and milk-Alkali syndrome
Paget's disease
+
Familial hypocalciuric hypercalcemia (FHH)
Causes of Hypocalcemia ("HIPOCAL") ..................... Chapter 72
Hypoparathyroidism
Infection
Pancreatitis
Overload states
Chronic renal failure
Absorption abnormalities
Loop diuretics
Differential Diagnoses for Polyuria
("6 Ds") ............................................................................. Chapter 73
Diabetes mellitus
Diabetes insipidus
Diuretics
Diuretic phase of acute tubular necrosis (AT)
Drinking too much
Damn! Too much calcium
504
Summar of Mnemonics
Causes of Hyperthyroidism-Hyperfunctioning Gland
("TAG") ............................................................................ Chapter 74
TSH-secreting tumor
Autonomous toxic adenoma
Graves'disease
Causes of Hyperthyroidism-Normal Gland Function
("FIST") ............................................................................ Chapter 74
Factitious thyrotoxicosis
Iodine-induced hyperthyroidism
Struma ovarii
Thyroiditis
Causes of Addison's Disease ("ADDISON'S") ......... Chapter 75
Amyloidosis
Destruction (autoimmune)
Drugs
.
(anticoagulants
.
leaing t

bilateral adrenal hemorrhage)
InfectIOns [tuberculosIs, dissemInated fungal infections,
cyom
galovirus (CMV) in AIDS patients, syphilitic gummas]

SarcOIdosIs
Overload of iron (hemochromatosis)
Neoplasm (metastatic disease, usually frm the lung)
Surgical (hemorrhage during open-heart surgery or following
bilateral adrenalectomy)
Clinical Manifestations of Chronic Adrenal Insuffciency
("WWHHOOO") ............................................................. Chapter 75
Weakness
Weight loss
Hyperpigmentation
Hypotension
Obstipation and other gastrointestinal symptoms
Orthost
Othe

(h
pohatremia, hyperkalemia, nonanion gap metabolic

aCdOSIS, hypoglycemia, eosinophilia)
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PART X: NEUROLOGY
Causes of Altered Mental Status
("MOVE, STUPID") ...................................................... Chapter 76
Metabolic derangements
Oxygen defciency to the brain
Vascular disorders
Electrolyte derangements or Endocrine disorders
Seizures, Sarcoidosis, or Structural disorders
Tumors, Trauma, or Temperature derangements
Uremic or hepatic encephalopathy
Psychiatric disorders or Porphyria
Infections
Drugs or Degenerative disease
Causes of Polyneuropathy
("MOVE, STUPID") ...................................................... Chapter 77
Metabolic disorders (diabetes mellitus)
Other (rare heredofamilial disorders)
Vasculitis or Vitamin defciency (vitamin B12, thiamine,
pyridoxane, folate)
Endocrine disorders (hypothyroidism)
Syphilis or Sarcoid
Tumor-related (i.e., paraneoplastic syndrome)
Uremia or liver disease
Paraproteinemia! amyloidosis, Porphyria, Primary biliary
cirrhosis, or Polycythemia vera
Infections or Idiopathic causes [e.g., Guillain-Barre syndrome,
chronic infammatory demyelinating polyneuropathy (CIDP)]
Drugs or toxins (including alcohol)
Causes of Central Vertigo ("MAIM") ....................... .. Chapter 78
Multiple sclerosis
Acoustic neuroma
Ischemia or central nervous system (CNS) lesions [especially
basilar transient ischemic attack (TIA)]
Migaine (especially basilar)
Common Causes of Peripheral Vertigo
("AMPLITlDE") ........................................................... Chapter 78
Acoustic neuroma
Meniere's disease
Positional (BPPV)
Labyrinthitis
Infection of the inner ear
Trauma (head)
Wchogenic causes
Drugs
Endocrine disorders
Common Causes of Singultus
("SINGULTUS") ............................................................. Chapter 79
Surgery (following abdominal, thoracic, or neck surgery)
Infection of structures adjacent to the diaphragm (e.g., lower
lobe pneumonia, subphrenic abscess, peritonitis)
Nervou

system disorders (e.g., stroke, meningitis, brain tumor,
multIple sclerosis)
Gastric distention (a very common cause)
Uremia
Low serum calcium, sodium, or potassium
Tumor of the pancreas
Wchiatric disorders
Steroid

and other drugs (e.g., alcohol, benzodiazepines,
barbIturates)
Classifcation of Infectious Meningtis
("A,B,C") .......................................................................... Chapter 81
Asptic meningitis
Bacterial meningitis (acute)
Chronic meningitis
Other Causes of Lymphocytic Meningitis
("2 ICE") ........................................................................... Chapter 81
Infections (malaria, toxoplasmosis, fresh water amebiasis,
cysticercosis, Rocky Mountain spotted fever)
Intoxications (salicylates, barbiturates, heavy metals)
Cancer (carcinomatous meningitis)
Collagen vascular disease [systemic lupus erythematosus (SLE)]
Endocrine disorder (pheochromocytoma)
Endocarditis
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Summar of Mnemonics
507
PART XI: DERMATOLOGY
Causes of Pruritus ("ITCHED") ................................... Chapter h
Infestation (e.g., scabies)
Total bilirubin elevation (e.g., primary biliary cirrhosis)
Chronic renal failure (uremia) or Cancer
Hematologic disorders
Endocrine disorders
Dermatologic disorders
PART XII: TOXICOLOGY
Clinical Manifestations of Opioid Agonist Overdose
("DOPE") ......................................................................... Chapter o
Decreased respiratory drive
Obtundation
Pinpoint pupils
Euphoria
Clinical Manifestations of Cholinergic Agonist
Toxicity ("SLUDGE") .................................................... Chapter o
Salivation
Lacrimation
Urination
Defecation
Grimacing
Erection
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Index
Note: Page numbers in italic denote illustrations; those followed by t
denote tables.
Abdominal computed tomogra
phy. (See alo Computed
tomography)
m diagnoing abdominal pain,
160
in diagnosing ascites, 184
Abdominal pain
approach to patient. 159
diagnostic tests for, 158-160
guidelines for management
of, 160-161
history of, 156, 157t, 158, 158t
physical examination in, 158
causes of, 155
in diabetic ketoacidosis (DKA),
411
metabolic and systemic causes
of, 493
Abdominal ultrasound in assessing
abdominal pain, 159-160
Abnormal bleeding in multiple my
eloma,376
Absorption abnormalities as cause
of hypocalcemia, 409
Acetaminophen overdose, 194,
197
Acid-base disorders
compensation, 240-241
differential diagnoses, 235-240
steps in evaluation of, 233-235
Acidemia, 233, 234
Acid-fast bacillus stain in diagnos
ing ascites, 184
Acidosis, 215
classifcation of, 224, 225t, 226,
22
defnition of, 224
metabolic, 233
respiratory, 233, 240
Acoustic neuroma. 441
Acute bacterial meningitis, 455
Acute cor pulmonale, 25
Acute dyspnea
approach to patient, 102-103
causes of, 101-102
treatment of, 103-104
Acute glomerulonephritis. (See
Nephrotc syndrome)
Acute graft versus host disease
(GVHD),468
Acute intermittent porphyria, 439
Acute interstitial nephritis, 209,
215
Acute leukemia
classifcation of, 369
clinical manifestations of,
370-371
complications assoated with,
373-374
epidemiology of, 369-370
risk factors in, 370
Acute lymphoblastic leukemia
(PLL), 369, 370, 372-373
differen tiating, 501
Acute mitral regurgitation, 17
Acute myelogenous leukemia
(AML), 369, 370, 372, 373
differentiating, 501
Acute pancratitis, common
causes of, 495
Acute pulmonary edema. 88-89
treatment of, 49
Acute tubular necrosis (A T),
207-208
Addison's disase, 331, 406,
424-425
causes of, 504
Adenosine for arrhythmias, 41, 46
Adrenal insuffciency, clinical man
ifestations of, 504
509
I
I
5 1 0
1
51 1
Index Index
:
a-Adrenergic agonist overdoe,
0.
tachyarrhythmias, 3, 35t
Alveolar hemorrhage a cause of Angiography
clinical manifestations of, 484 hemoptysis, 106
F
in diagnosing acute gastrointesti-
treatment of, 41-43
7
Adrenocortical insuffciency Alveolar proteinosis, 125 0
nal bleeding, 174
wide, irregular tachyarrhythmias
approach to patient, 427 Alveolar-to-arterial (A-a) gradi- 0. in searching for cause of stroke.
differential diagnosis of,
causes of, 424-425, 425t ent, 1 13-114
450
46-48
clinical manifestations of, 425- Ambulatory EKG monitoring, 32 F Angiotensin-converting enzyme
treatment of, 48-49
427, 426t Amebiasis, fever of unknown ori-
O
(ACE) inhibitors for myocar-
wide, regular tachyarrhythmias
defnition of, 424 gin (FUO) in, 270
F
dial infarction, 81
differential diagnosis of,
treatment of, 428 Aminoglycoside antibiotics, 441 J Anion gap, 236-238
45-46
Adult respiratory distress syn- Amiodarone for atrial fbrillation,
C
Anion gap acidosis, causes of, 497
mechanism, 44-45
L
drome (ARDS) as cause of 55 Ankylosing spondylitis, 394
treatment of, 46
dyspnea, 102 Amphotericin for fungal esophagi-
Ann Arbor classifcation system,
Arterial blood gases in diagnosing
Aerobic gram-negative rods as tis, 291
356, 359, 360

pulmonary emboli, 140
cuse of pneumonia, 129 Ampicillin for meningitis, 459 : Antibiotics
Arterial oxygen tension (Pa<),
Albumin in assessing liver func- Amyloidosis, 436
O
for acute diarrhea, 168 113-114
0.
tion, 162 in multiple myeloma, 376 O for asthma, 122
Arteriovenous fstulae, 20
Albuterol Androgens for aplastic anemia,
II
for chronic obstructive pulmo-
Arteriovenous malformation
for asthma, 122 307
7
nary disease, 122
as cause of acute gastrointesti-
0
for chronic obstructive pulmo- Anemia of chronic disease (ACD) x Anticoagulation for pulmonary
nal bleeding, 171
nary disease, 122 versus iron defciency,
I
emboli, 142-143
Arteritis as cause of hemoptysis,
=
Alcohol abuse in panceatitis, 186 318-319
Antidromic conduction, 39 106

Alcohol intoxication. 479 Anemias. 374
M Antimotility agents for acute diar- Arthritis
approach to patient, 480-481 as cause of dyspnea, 102
rhea, 168
monoarticular, 387
O
clinical manifestations of, 480 macrocytic, 319-32 F Antiphospholipid antibody syn-
approach to patient, 389,
Alcohol withdrawal. 479-481 megaloblastic, 319
:
drome, 346
39Ot, 391
approach to patient, 480-481 microangiopathic hemolytic, Antipyretic therapy for fever, 258
causes of, 387-389, 502
clinical manifestations of, 480 207, 311 7 Antithymocyte globulin (ATG)
polyarticular, 392
Alcoholic hepatitis. 189, 191 microctic, 317-319
M
for aplastic anemia, 307
causs of, 392-395, 393t
x
Alcoholic liver disease, 18 approach to patient, 318-319 O Anxiety as cause of dyspnea, 102
rheumatoid, 176, 388
approach to patient, 189 causes of. 317-318 Aortic coarctation in hyperten-
clinical manifestations of, 392
clinical manifestations of, 189, in multiple myeloma, 376
V
sion, 246
epidemiology of. 392
190t normoytic, 320, 32J, 322 I Aortic dissection. 62-63, 111
Arthroentesis i n diagosing
treatment of, 191 in pancytopenia, 303
I
Aortic insufciency, 18
monoarticular arthritis, 389
Alcoholism. 195 sideroblastic, 317 Aortic sclerosis, 17
Arthroscopy in diagnosing
in macrocytc anemia, 320 Anesthesia, 435 Aortic stenosis, 17
Alkalemia, 233, 234
Aneurysm. left ventricular, 83 Apical pneumothoraces. III
Ascariasis i n eosinophilia, 330
Alkali ingestion, 406 Angina I Aplastic anemia, 310 Ascites
Alkalosis approach to patient, 65-67
I
as cause of panctopenia, 304
approach to patient, 180-181,
metabolic, 233, 238-239 classifcation of, 64
1
182t, 183-184
respiratory. 233, 240
clinical manifestations of coro- Arrhythmias, 31, 81-8
causes of, 179-180
Alkylating agents
nary artery disease, 64-65
:
bradyarrhythmias, 34
treatment of, 184
for esential thrombocytosis, defnition, m as cause of dyspnea, 102

Ascitic fuid cytology in diago-
366
risk factors for coronary artery
M
monitoring, 84
ing asctes, 184
0
for polycythemia vera, 365 disease, 64
0.
narrow, irregular tacyar-
Aseptic meningitis, 455, 458
Allergic bronchopulmonary asper- stable. 64. 67 t: rhythmias
Aspergilloma as cause of hemopty-
gillosis in eosinophilia, 331 treatment of, 67-72
differential diagnosis of, sis, 106

AL T levels, causes of markedly in- unstable, 64, 67, 70-71
43-44
Aspiration as cause of dyspnea,
creased, 494 Angiodysplasia
M
treatment of, 44 101
Altered mental status
as cause of acute gastrointesti-
O
narrow, regular tachyarrhyth- Aspirin
approach to patient, 432-434 nal bleeding, 171 7 mias, differential diagnosis for angina, 68, 72
causs of, 431-432, 505
as cause of hemoptysis, 106 of, 34-41
for atrial fbrillation, 55
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5 1 2
Index
1
Index
5 1 3
:
Aspirin (continued)
Benzodiazepines for alcohol with-
0
Blood urea nitrogen:creatinine
Bullae, differential diagnoses for,
for essential thrombocytosis,
drawal, 480-481
F
(BUN:Cr) ratio in diagnosing
accompanied by fever, 499
7
366
Bernard-Soulier syndrome, 339
0
renal failure, 211
Bundle branch blok, 26
for myocardial infarction, 81
Bilateral bone marrow biopsies in 0 Blue bloaters, 121
for polycythemia vera, 3
diagnosing Hodgkin's disease,
Bone, malignancies of, 381-382,

Calcium channel blockers
for stroke, 451
356
F 32
for angina, 69, 71-72
AST levels, causes of markedly in-
Biliary stones in pancreatitis, 186
O
Bone marrow biopsy
creased, 494
Biopsy
F
in diagnosing acute leukemia,
Cancer
Asterixis in liver failure. 192
bone marrow J 371
breast, 381, 382
Asthma, 121
in diagnosing acute leukemia,
C
in diagnosing chronic myeloge-
kidney, 381, 382
agents usd to treat exacerba-
371
L
nous leukemia, 363
lung, 381, 382
tions of, 492
in diagnosing chronic myelog- 2 in diagnosing essential thrombo-
prostate, 381
Atelectasis, 139
enous leukemia, 363
cytosis, 366
thyroid, 381, 382
Atherosclerosis as complication of
in diagnosing essential throm- : in diagnosing fever of unknown
Candidiasis, 285
nephrotic syndrome, 219
bocytosis, 366
O
origin (FUO), 274
fever of unknown origin (FUO)
Atrial fibrillation, 43, 44
in diagnosing fever of un-
I
in diagnosing myelofbrosis, 366.
in, 270
(
with aberrancy, 47
known origin (FUO), 274
I
368
Carboxyhemogiobinemia as cause
approach to patient, 52
in diagnosing myelofbrois,
7
in diagnosing pancytopnia, 306
of polycythemia, 324
0
causes of, 51-52, 489
366, 368 x in diagnosing polycythemia
Cardiac echoardiography in
clinical manifestations of, 50-51
in diagnOSing pancytopenia,
I
vera, 365
searcing for cause of stroke,
complications. 52-53
306
=
Bone marrow transplantation
450
risk factors for stroke in pa-

in diagnosing polycythemia II for acute leukemia, 373
Cardiac enzyme studies, 75
tients with, 49
vera, 365
complications assoiated with,

Cardiac examination
treatment of
open lung, 128
(
374
auscultation
F
acute, 53-54
peritoneal, in diagnosing ascites, for myelodysplastic syndromes.
fndings, 15-19
chronic, 54-55
184
:
368
technique, 15, 15t
Atrial futter, 40-41, 41, 42, 43
renal 7 in treating aplastic anemia, 308
neck vein, 13
with variable blok, 43, 44
in diagnosing glomerulone-
II
Bone pain in fever of unknown or-
anatomy, 13-14
Atrioventricular nodal blocking
x
fndings, 14
phritis, 223
O
igin (FUO), 272
agents, 49, 54
in diagnosing renal failure, Bordetella pertussis, 262
patient positioning, 13
Atrioventricular nodal reentrant
213
V
Bradyarrhythmias, 34, 81-82
precordial palpation, 14
tachycardia (A VNRT), 35-39 stereotactic brain, 2f7 I Bradycardia, 21
Cardiac murmurs in fever of un-
Auscltation
synovia in diagnosing monoartic-
I
Brain, malignancies capable of me-
known orign (FUO), 272
fndings, 15-19
ular althritis, 391 tastasizing to, 382
Cardiac tamponade, 82
technique, 15, 15t
temporal aTtery, in diagnosing Breast cancer, 381, 382
Cardiogenic shock, 76, 92
Autoimmune disorders, 399
giant cell (temporal) arteTi- Bronchiectasis as cause of hemop-
Cardiomegaly, III
Autoimmune hepatitis, 196, 197
tis, 3f7
I tysis, 106
Cardiomyopathy, common causes
Autonomic insuffciency, 30
transbronchial, 128
I
Bronchitis
of dilated, 490
Autonomous toxic adenomas, 420
Biphenotypic leukemia, 370
1
as cause of hemoptysis, 106
Cardiovascular disorders, 51
Bismuth subsalicylate for acute di- chronic, 121
Cardiovascular signs, 192-193
Bacillary angiomatosis, 285
arrhea, 168
:
Bronchoscopy, 127-128
Carotid arteries, 13-14
Bacteremias, fever of unknown ori-
Carotid Doppler ultrasound in

Bleeding disorders
II
Bronchospasm as cause of dys-
gin (FUO) in, 270
approach to patient, 333, 334, M
pnea, 101
searching for cause of stroke,
Bacterial infection, 284
335
0
Brucelln, 262
450
0
Bacterial meningitis, 458
clinical manifestations of. 333 | BTUdzinski's signs in infectious
Carotid sinus massage, 41
Bacteriuria, asymptomatic,
meningitis, 454
CD4 counts, differential diagnoses
230-231
-Blockers
|
Brugada criteria, 45
according to, 284-285
Bartter's syndrome, 239
for alcohol withdrawal, 481 M Budd-Chiari syndrome, 179, 195
Ceftriaxone fOT meningitis, 459
Benign paroxysmal positional ver-
for angina, 68-69, 71
(
as cause of ascites, 180
Cell count in diagnosing asctes,
tigo (BPPV), 441
for myocardial infarction, 81 7 Buerger's disease, 400-401
183
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5 1 5
5 1 4
Index Index
:
0.
CSF fuid analysis in diagnosing
Central venous pressure (CVP),
Chronic meningtis, 455, 458-459
Community-acquired pneumonia
14
Chronic myelogenous leukemia
F
approach to patient, 130 meningitis, 455-458
7
Central vertigo
(CML)
0 criteria for hospital admis- Cullen's sign, 185
causes of, 440
0.
sion, 130-131 Culture-negative organisms as
prognosis, 363-364
diagnostic tests for, 130 cause of infective endocardi-

treatment of, 443
teatment of, 363 F
causes of, 129-130 tis, 278-279
Cephalosporin for meningitis, 459
types of disorders in myelopro-
O
classifcation of, 129 Cushing's syndrome, 239, 247
Cerebrospinal fuid (CSF) analysis
liferative disorders, 361 F clinical manifestations of, 129 as cause of polycythemia, 324
in diagnosing acute leukemia.
Chronic non bacterial prostatitis,
J
epidemiology of, 129 refex in liver failure, 192
371
treatment of, 131 Cystitis 231
L
Chamber enlargement, 111
Chronic obstructive pulmonary dis-

Complete blood count (CBC) in recurrent, 230, 232
Chemotherapy
ease (COPD), 24, 121 diagnosing acute leukemia, uncomplicated, 230, 231
for acute leukemia, 372-373,
agents used to treat exacerba- 371 Cytogenetic studies in diagnosing
373
tions of, 492
:
Computed tomography. (See also chronic myelogenous leuke-
as caus of dysuria. 228 O
Abdominal computed tomog- mia, 363 asthma
0.
for Hodgkin's disease, 357
O raphy) Cytomegalovirus (CMV), 285
for multiple myeloma, 379 II
in diagnosing fever, 257 in esophagitis, 292
120-121
7
for myelodysplastic syndromes.
diagnosis of, 121 0 in diagnosing Hodgkin's dis- in fever of unknown origin
368
x
ease, 356 (FUO) in. 270
for spinal cord compression, 464
I
Congenital heart disease, 24 m pneumonia and bone marrow
diagnosis of, 121
=
Chest pain
Congestive heart failure, 111 transplants, 374
treatment of, 137
M
approach to patient, 88 Cytopenias in fever of unknown
causes of, 56
Chronic renal failure as cause of
as cause of dyspnea, 102 origin (FUO), 272

hypoalcemia, 409
O
Chest radiograph, 93, 127
F classifcation of. 85-87
in diagnosing Hodgkin's dis-
Churg-Strauss syndrome
ease, 355
clinical manifestations of, 398 :
factors that can exacerbate, 490 Danazol in treating idiopathic
in diagnosing pulmonary embo-
diagnosis of, 398
7
incidence, 85 thromboytopenic purpura,
lism, 139-140
epidemiology of, 398
M
mortality rates, 85 314
Chvostek's sign in hypocalcemia.
outside-in approach, 110-112

O
treatment of, 88-89 Deep venous thrombosis as cause
preliminary considerations,
408
Connective tissue disorders, fever of pulmonary embolism, 138
109-110
CIDP, 439
V of unknown origin (FUO) in, Degenerative joint disease (DJD)
Chlamydia pneumoniae (TWAR)
Cirrhosis. 189. 191
I
271 as cause of polyarticular ar-
as cause of pneumonia. 130
as cause of ascites, 180 I
Constrictive pericarditis as cause thritis, 395
Chlamydiae, 262 Classic seronegative spondy-
of ascites, 180 Dehydration as cause of polycythe-
Chloramphenicol for meningitis, loarthropathy, 394
Contaminated L-tryptophan, 331 mia, 324
459 Clubbing
Continuous murmurs, 19-20 Desmopressin for bleeding disor-
Chloride-unresponsive metabolic approach to patient. 475-76
I
Coronary artery disease der, 341-342
alkalosis, common causes of, causes of, 475 I
clinical manifestations of, 64-65 Dexamethasone for spinal cord
498 clinical manifestations of,
1
risk factors for, 64 compression, 463
Cholestatic pattern in assessing 474-475
Coronary artery obstruction, 19 Diabetes, control of, 67
liver function, 163 treatment of. 476 :
Coronary catheterization. 67 Diabtic ketoacidosis (DKA), 237
Cholinergic agonist Coagulation tests in diagosing

m
Corticoteroid therapy as cause of approach to patient, 412-413
toxicity acute leukemia, 371 M
polycythemia, 324 causes of, 411
clinical manifestations of, Coagulopathy as cause of hemop-
0
Creatine kinase in diagnosing re- clinical manifestations of, 0.
485-486, 507 tysis, 106 t:
nal failure, 212 411-412
Chronic bacterial prostatitis, 231 Coarctation of aorta, 20
Cryoglobulinemia, 39 defnition of, 411

Chronic bronchitis, 121
Coccidioidomycosis, 125
as cause of acute nephritic syn- treatment of, 413-417, 415t
Chronic hepatitis B, 197
in eosinophilia, 331 M
drome, 220 Diagnosis
Chronic hepatitis C, 197
Colitis, ulcerative, 400
O Cryoprecipitate for bleeding disor- differential, 3-4
Chronic liver disease in macro-
Collagen vascular diseases, 125, 7
ders, 342 unifying, 3
cytic anemia, 320
388
Cryptococcus infection, 285 Dialysis, indications for acute, 496
V
I
I
51 6
Diarrhea
acute
approach to patient, 166, 167
causes of, 166
treatment of, 166, 168
causes of, 494
Diastolic murmurs, 18-19
Diazepam for alcohol withdrawal,
481
Diet for congestive heart failure,
8
Differential diagnosis, systematic
approach, 3-4
Diffusion capacity (Dd, 117
Diffusion defects, 115-116
Digoxin
for congestive heart failure,
88-89
Dilators for congestive heart fail
ure, 88-89
Diltiazem
for angina, 69
Dipyridamole for angina, 66
Disseminated gonococal infection
as cause of polyarticular ar-
thritis, 394
Disseminated intravascular coagu
lation (DlC), 371, 374
causes of, 500
Diuretics for congestive heart fail
ure, 88-89
Diverticulosis as cause of acute
gastrointestinal bleeding, 171
Dobutamine
for angina, 66
Doks murmur, 19
Double-density sign. 111
Dysesthesia, 435
Dyspnea, 51
Dysuria, 227-m
differential diagnoSis for, 228
Early systolic murmurs, 17
Ecchymoses, 467
Echocardiography, 32
Edema in nephrotic syndrome,
220
Index
Electrocardiogram (EKG), 93
in diagnosing abdominal pain,
160
in diagnoing pulmonary em
boli, 140
exercise, 65-66
interpretation, 21
axis
causes of deviation, 22,
24-25
determining, 22, 23
normal, 22
hypertrophy, 27-28
intervals, 25-27
Q waves, 28-29
rate, 21
rhythm, 21
STf wave changes, 29
resting, 65
right-sided, 75
Elecrolyte
panel m diagnosing acute leuke
mia, 371
replacement in treating diabetic
ketoacidosis, 415-416
Electrophysiologic testing, 32-33
Emboli as cause of hemoptysis,
106
Emergency surgery for spinal cord
compression, 464
Emphysema ("pink puffers"), 121
Empiric antibiotic therapy
for fever, 258
for pneumonia, 131
Encephalopathy, 297-298
hypertensive, 248
Endoarditis
acute, 264-265
infective, 278
causes of, 278-279
clinical manifestations of. 279
complications of, 280
follow-up, 282-283
Endocrine disorders, 441
Endoscopy in diagnosing fever of
unknown origin (FUO), 274
Enterococcal infecions, 282
jV
, I
1
V
1
1
Index
Enterocolitis
causes of, 292
treatment of, 293
Environmental exposures, 126
Eosinophilia, causes of. 330-331,
500
Eosinophilic pneumonias, 126
Epidural hematoma, 447
Epidural hemorrhage, 452, 461
cytomegalovirus, 194
fever of unknown origin in, 270
Erythema marginatum, 276
Erythema nodosum, 269
Erythrocyte sedimentation rate
(ESR) in multiple myeloma,
377
Erythromelalgia, 365
Erythropoietin
in diagnosing myelodysplastic
syndromes, 368
level in diagnosing polycythe
mia vera, 3
for myelodysplastic syndromes,
368
Erythropoietin-seceting tumors,
325
as cause of polycythemia. 324
Escherichia coli, 261
accounts in urinary tract infec
tions, 227
Esmolol for atrial fbrillation, 54
Esophagitis
causes of, 291
Essential thromboctosis
prognosis, 366
treatment of, 366
Evaporative cooling for fever, 258
Exanthemas
morbilliform rash, 467-468
scarlatiniform rash, 469-470
Excitation loop, 36, 38
Exercise radionuclide angiography
or echocardiography, 66
Exercis treadmill testing, 32
Exiratory fow rate, 117
517
External jugular veins, 13
Extrapulmonary tuberculosis, 284
Factitious thyrotoxicosis. 421
Familial hypocalciuric hypercalce-
mia (FH), 407
Fanconi's anemia as cause of pan-
cytopenia, 304
Fatty liver, 189, 191
Felty's syndrome, 176
Fever
causes of, 253, 498
diferential diagnoses
for pustules accompanied by,
499
for vesicles and bullae accom
panied by, 499
normal body temperature, 253
and rash
approach to patient, 266-269,
267t
causes of, 264-266
treatment of. 257-258
Fever of unknown origin (FUO)
causes of, 270t, 270-271
Filariasis in eosinophilia, 330
First-degree A V nodal block, 25
Flow murmurs, 17
Fluconazole
for esophagtis, 2'1
for fungal esophagitis, 291
Fluids
\
for fever, 258
replacement in treating diabetic
ketoacidosis (DKA),
413-414
Fluoroquinolones for urinary tract
infections (UTIs), 231
Forced vital capacity (FVC), 117
Francisella (Pasteurella) /uiarensis,
262
Fungal esophagitis, treatment of,
291-292
Fungal infections, 125
and chronic meningitis, 454
Fungi
as cause of infective endocardi
tis, 279
as cause of pneumonia, 130
I
I
1
5 1 8 Index
: Index 5 1 9
0
Furosemide Hashimoto's disease, 418
F Hep!titis D, 194 peripheral neuropathy,
for liver failure, 198 Head trauma, 441
7
Hepatitis E, 194 298-29
0
for renal failure, 214 Heart sounds. 61
0
Hepatobiliary disease space-occupying lesions,
Hean-Iung transplantation for pul- + approach to patient, 294 296--2f7
Gastrointestinal bleeding monary hypnension, 136
F
causes of, 293-294 Humidifed oxygen
acute Hemarthrosis, 389
O treatment of, 294 for asthma, 122
approach to patient, 171-174 Hematemesis, 169
F
Hepatocellular patter in as- for chronic obstructive pulmo-
causes of, 170-171 Hematochezia, 169
J
sessing liver function, nary disease, 122
classifcation of, 169 Hematocrit in diagnosing polycy-
G 163-164 Hydration for polycythemia, 326
defnitions, 169 themia vera, 364
L
Hepatopulmonary syndrome, 193 Hydroxyurea for essential throm-
:
criteria for admittance to ICU Hematologic signs, 192
Hepatorenal syndrome, 193, 19, boctosis, 366

with, 495 Hematoma
207 Hyperaldosteronism, primary, 239,
lower gastrointestinal sources epidural, 447
Herniated discs, 461 247

:
of, 495 subdural, 447 O Herpes simplex virus (HSV) Hypercalcemia
upper gastrointestinal sources Hematuria 0
esophagitis, 292 causes of, 406-40, 503
of, 494 in fever of unknown origin
<l
Herpes virus infections and bone clinical manifestations of,
II
Gastrointestinal tract malignan- (FUa), 272 7
marrow transplants, 374 405-406
cies, 381. 382 in nephrotic syndrome, 220
0
Hiccough. [See Singultus (hic- defnition of, 405
x
Giant cell (temporal) arteritis Hemohromatosis, 195, If7
I cough)] in multiple myeloma, 376, 377
clinical manifestations of, 3f7 Hemodynamic status, 75-78 =
. High resolution computed tomog- treatment of, 407
diagnosis of, 3f7 Hemolytic-uremic syndrome
raphy (HRCT), 127 Hypercapnia in respiratory failure,

II
epidemiology of, 3f7 (HUS)/thrombotic thrombocy- r High-output states, 17 144, 145
Glanzmann's thrombasthenia, 339 topenic purpura (l), 322
<l
Histoplasmosis, 125 Hypercatecholamine states, 34
Glomerulonephritis, 207, 209, 214 Hemoptysis
F
fever of unknown origin (FUa) Hypercholesterolemia, control of,
Glucose levels in assessing liver causes of, 491 :
in, 270 67
function, 163 in fever of unknown origin
7
HIT, 346 Hypercoagulability studies in
Goodpasture's syndrme, 221 (FUa), 272 II HIV-infected patients, pulmonary searching for cause of stroke,
Gout, 388 Hemorrhage
disease in, 287, 28& 451

Graft versus disease and bone epidural, 452, 461
O
Pneumocystis carinii pneumo- Hypercoagulable states
marrow transplants, 374 intraparenchyrl, 447, 452
V
nia, 287-289, 2V0 approach to patient, 346-347
Graham Steell murmur, 19 subarachnoid, 447, 452
I
Hodgkin's disease, 353, 471 causes of, 345-346, 501
Gram-negative bacteria as cause subdural, 452 I approach to patient, 355-356 clinical manifestations of, 345
of infective endoarditis, 278 Hemorrhagic fevers, 266
clinical manifestations of, 353, treatment of, 347-348
Gram-positive rods, 498 Hemorrhagic infarction, 452
355 Hyperfunctioning thyroid, 420
Granulocyte colony-stimulating Hemorrhagic transformation, 447
epidemiology of, 353 Hyperkalemia, 24, 215
factor (G-CSF) for myelodys- Henoch-Schonlein purpura, 400
I
itching assoiated with, 472 Hyperlipidemia in panceatitis,
plastic syndromes, M Heparin
I pathogenesis of, 353 186
Granuloyte-macrophage colony- for angina, { 1
treatment of, 356-357 Hyperparathyroidism, 406
stimulating factor (GM-CSF) for myocardial infarction, 81
Holosystolic murmurs, 16-17 Hyperpathia, 435
for myelodysplastic syn- for pulmonary emboli, 142-143 : Human immunodefciency virus Hyperpigmentation, 427
dromes, 368 for stroke, 451
r
(HIV) disease Hypersensitivity pneumonitis, 124
Graves' disease, 420 Hepatic encephalopathy, 199

M gastrointestinal manifestations Hypersensitivity vasculitis, 221
Group A streptococci, 259 Hepatic vein obstruction, 195 0
of, 291 Hypersplenism, 175
Group B streptococci, 259 Hepatic veno-occlusive disease as
0
enterocolitis, 292-293 as cause of pancytopenia, 305
t:
Guillain-Barre syndrome, treat- cause of ascites, 180
esophagitis, 291-292 Hypertension
ment of, 439 Hepatitis
hepatobiliary disease, 293-294 causes of secondary, 246-248,

|
alcoholic, 189, 191
M
neurologic manifestations of, 498
Haemophilus infuenzae, 262 autoimmune, If7
295 control of, 67
as cause of meningitis, 453 Hepatitis A, 194
<l
encephalopathy, 297-298 hypertensive crises, 248-249
as cause of pneumonia, 129 Hepatitis B, 194
7
meningtis, 295-296 in nephrotic syndrome, 220
Hampton's hump, 139 Hepatitis C, 194
V
myelopathy, 298 Hypertensive crises, 248-249
I
I
I
I
1
520 Index
Index 52 1
0
Hypertensive encephalopathy, Hypotonic hyponatremia, 242, F
Intra-abdominal abscesses, fever Klebsiella species, 261
248, 433 243/, 243-244, 2441
7
of unknown origin (FUO) in, in urinary tract infections, 227
0
Hypelthermia, 433 Hypoventilation, 116
0 270
Hyperthyroidism
Hypovolemia
Intraparenchymal hemorrhage,
causes of, 420-421, 504
as cause of shok, 91
F 447, 452 Labyrinthitis, 441
cinical manifestations of, 422
as complication of nephrotic syn- O
Intravenous gammaglobulin in Laparoscoy in diagnosing ascites,
treatment of, 422
drome, 219
F
treating idiopathic thrombocy- 184
Hypertonic hyponatremia, 242
Hypoxemia
J topenic purpura, 314 Laparotomy in diagnosing fever of
Hypertrophic cardiomyopathy, 18
clinical values, 113-114
Intravenous magnesium unknown origin (FUO), 274
L
Hypertrophic osteoarthropathy,
mechanisms of, 114-116
2
for asthma, 122 Late systolic murmurs, 18
474
in respiratory failure, 145
for chronic obstructive pulmo- Left atrial abnormality, 28
Hypertrphy, 27-28
Hypoxia, 34, 209
nary disease, 122 Left bundle branch block, 26

Hypesthesia, 435
as cause of polycythemia, 324
: Iodine-induced hyperthyroidism, Left ventricular aneurysm, 83
Hypoaldosteronism, 424
in respiratory failure, 144 O
421 Left ventricular hypertrophy, 14,
Hypocalcemia 0
Iron defciency, 317 27 (
causes of, 4, 503
Idiopathic pulmonary fbrosis, 124 II
versus anemia of chronic dis- LegioneUa species
Idiopathic thromboytopnic pur-
7
ease, 318-319 as cause of pneumonia, 129, 131
defnition of, 408 0
pura (ITP), treatments for,
as cause of anemia, 317, 471 Leptospirosis, fever of unknown
treatment of, 410
314 I
versus thalassemia, 318 origin (FUO) in, 271
Hypocomplementemic acute ne-
IgA nephropathy (Berger's dis-
=
Irregular rhythm, 21 Leukocytosis
phritic syndrome, 220-221
ease), 221-222, 400 II

Ischemia, 74-75 lymphocytosis, 328, 329t
causes of, 497
Immune-mediated destruction as
Ischemic colitis as cause of acute monocytosis, 328-329, 329t
Hypocomplementemic urticarial
cause of pancytoenia, 305
(
gastrointestinal bleeding, 171 neutrophilia, 327-328, 328
vasculitis, 400
F
Immunolectrophoresis in multi-
Ischemic disorders, 31 Leukostasis, 370-371, 373
Hypoglycemia, 193, 19
pIe myeloma, 378
:
Isoniazid overdose, 439 Lidocaine for arrhythmias, 46
Hypokalemia, 193, 19
Immunosuppressive agents in
7 Isotonic hyponatremia (pseudohy- Likelihood ratio, 6-8
Hyponatremia, 193, 199
treating idiopathic thrombocy-
II
ponatremia), 242 Listeria monocytogenes as cause
action of antidiuretic hormone
(ADH), 242
topenic purpura, 314
O Ive flter for pulmonary emboli, of meningitis, 453
Indomethacin for fever, 258
143 Liver, malignancies capable of me-
Infarct, 74-75
V
tastasizing to, 382-383
defnition, 242
Infection as cause of hypocal-
I Liver biopsies in diagnosing fever
cemia, 409 I
of unknown origin (FUO), hypertonic, 242
Infectious colitis as cause of acute
Janeway lesions in infective endo-
274 hypotonic, 242, 243/, 243-244,
gastrointestinal bleeding, 171
carditis, 279
Liver disease, alcoholic, 189-191, 2441
Jodbasedow disease, 421
isotonic, 242
Infectious meningitis, classifcation
Joint fuid analysis in diagnosing
1901
syndrome of inappropriate anti-
of, 506
I Liver failure
Inferior vena cava, 195 I
acute, 192, 197 diuretic hormone secetion,
Infammatory bowel disease as
1 Jugular venous pressure, 61
approach to patient, 196-197 244-245
Hypoparathyroidism as cause of
cause of acute gastrointestinal
causes of, 193-196
hypocalcemia, 409
bleeding, 171 :
chronic, 19/, 192, 193, 197
Hypotension, 209, 484 Inner ear infections, 441

II Kaposi's sarcoma, 285 clinical manifestations of,
in diabetic ketoacidosis (DKA), Insulin in treating diabetic ketoaci- M
Kawasaki's syndrome, 469 192-193
411 dosis (DKA), 414-415
0
Kernig's signs in infectious men in- treatment of, 197-200
0
Hypothermia in diabetic ketoaci- Internal jugular veins, 13
t: gitis, 454 Liver function tests, 162-164
dosis (DKA), 411 Interstitial cystitis as cause of dys-
Ketoonazole abnormalities in. 164, 165t

Hypothyroidism uria, 228
|
for esophagitis, 291 Loop diuretics as cause of hypoal-
as cause of ascites, 180 Interstitial lung disease, causes of, M
for fungal esophagitis, 291 cemia, 409
in macocytic anemia, 320 492
(
for spinal cord compression, Lorazepam for alcohol with-
primary, 419 Interstitial nephritis, acute, 208
7 463-464 drawal, 48]
secondary, 418, 420 Interventricular conduction delay,
Kidneys, chronic diseases that Low inspired oxygen tension, 116
tertiary, 420 26
V
lead to enlarged, 496 Low stroke volume states, 34
I
I
I
I
1
522 Index :
Index 523
0.
Methicillin-sensitive Staphyloccus Morxella catarrhalis a cuof
Lumbar puncture Massive hemoptysis F
aureus (MSSA), 2 pneumonia, 130
7
in diagnosing meningitis, approach to patient, 1(-108
0 Microangiopathic hemolytic ane- Morbilliform rash. 467-468
455-456 causes of, lO5-10 0.
mia (MAHA), 2m, 311 Multifocal atrial tachycardia,
in searching for cause of stroke, Mean corpuscular volume (MeV)
Microbiology 43-44
451 in diagnosing polycythemia
F anaerobes, 262 Multiple myeloma, 381, 400
Lung, malignancies capable of me- vera, 364 O
antimicrobial therapy, 263 approach to patient, 377-378
tastasizing to, 383-384 Mechanical ventilation
F approach to patient, 263 clinical manifestations of,
Lung cancer, 381, 382 defnition, 147
J
gram-negative cocci 375-376
Lung disease initial ventilator settings, 149, C
Moraxell (Branhamella) ca- epidemiology of, 375
L
obstructive, 120-122 150t
2
tarrhalis, 261 laboratory fndings, 376-377
versus restrictive, 117-118 modes of positive-pressure venti-
Neisseria, 261 prognosis, 379
restrictive, 123-128 lation, 147-149
Neisseria meningitUis, 261 treatment of, 379
Lung volumes, 117 phases of ventilatory support.
: gram-negative rods, 261-262 Murmurs, 16-17, 61
Lyme disease, 268, 394-395 147 O
gram-positive c Mushrom poisoning, 197
0.
Lymphadenopathy, 112 ventilator emergencies, 151-152
Q Enterococcus, 259 Mycobacterial infections and
approach to patient. 349-352. weaning, 149. 151 II
Staphylococcus, 259 chronic meningitis, 454
7
351t Medical decision making, qualita-
0
STreptococcus, 259 Mycobacterium avium complex in-
causes of generalized, 501 tive assessment, 5
gram-positive rods fections, 285
in fever of unknown origin Medical problems, general ap- I
Actinomyces, 260 fever of unknown origin in, 270
=
(FUO), 272 proach to, 489
Bacillus, 260 Mycobacterium tuberculosis as
treatment of, 352 Megaloblastic anemias, 319 II
Clostridium: 259 cause of pneumonia, 130
Lymphangiography in diagnosing Megaloblastosis. 305
Corynebacterium, 260 Mycoplasma pneumoniae, 262
Q
Hodgkin's disease, 356 Melanoma, 381
F Corynebacterium diphtheriae, as cause of pneumonia, 130
Lymphatic obstruction as cause of Melena, 169
:
260 Myelocyte precursor, 369
ascites, 180 Membranoproliferative glomerulo-
Corynebacterium jeikeium, Myelodysplasia in macrocytic ane-
Lymphocytic meningitis, causes of, nephritis (MPGN) as cause of
7
260 mia, 320
506 acute nephritic syndrome, 221
II
diphtheroids, 260 Myelodysplastic syndromes
Lymphoytic pleocytosis, 458-459 Meniere's disease, 441

O Erysipelothrix. 260 approach to patient, 367-368
Lymphocytosis, 328, 329t Meningitis, 433
Listeria monocytogenes, 260 clasifcation of, 367
Lymphoma, 284, 400 approach to patient, 295-296,
V
Nocardia, 260 prognosis, 368
classifcation of. 353, 354t 455-459
I
miscellaneous organisms, 262 treatment of, 368
defned, 353 causes of, 295, 453-454
I
Microcytic anemia, 317-319 Myelofbrosis
Lytic bone lesions in multiple my- clinical manifestations of, 454
approach to patient, 318-319 approach to patient, 366
eloma, 376 prevention. 460
causes of, 317-318 prognosis, 367
treatment of, 459
Mid-diastolic murmurs, 19 treatment of, 367
Macrocytic anemia, 319-320 Meningococcemia, 264
I
Mid-systolic murmurs, 17 types of myeloproliferative dis-
Magnesium, depletion of, 239 Metabolic acidosis, 233, 235-238 I
Mitral regurgitation. 17. 18 orders. 361
Magnetic resonance angiography as cause of dyspnea, 10
1
Mitral stenosis, 19 Myeloma, important clinical mani-
in searching for cause of Metabolic alkalosis, 233, 238-239
as cause of hemoptysis, 10 festations of mUltiple, 502
stroke, 450 Metastatic neoplasms
:
Monoarticular arthritis. 387 Myelopathy
Major Jones criteria, 499 to bone, 381-382, 32

m approach to patient, 389, 39 approach to patient, 298
Malaria, fever of unknown origin to brain, 382 M
391 causes of, 298
(FUO) in, 270 to liver, 382-383
0
causes of, 387-389 Myeloproliferative disorders
0.
Malignancy, 406 to lung, 383-384 t:
Monocytosis, 328-329, 329t approach to patient, 361-362
Mannitol for renal failure, 215 Methanol or ethylene glycol intoxi-
Monomorphic ventricular tachycar- types of, 361

Marrow involvement in multiple cation, 237
| dia, 48 Myocardial infarction. 62, 73
myeloma, 376 Methemoglobinemia as cause of M
Mononeuritis multiplex, 435, anterior, 29
Marrow progenitor cell culture in polycythemia, 324
Q 438-439 approach to patient, 75-81
diagnosing polycythemia vera, Methicillin-resistant Staphylococ-
7
Mononeuropathies, 435 as cause of dyspnea, 102
364 cus au reus (MRSA), 282
V
I
I
I
I
1
524
Index
:
Index 525
0
Myocardial infarction (continued) Neutrophilia, 327-328, 328
F
Orthostatic hypotension, 31 Patent ductus arteriosus, 17, 20
clinical manifestations of, 73 Nifedipine for angina, 69
:
Osler's nodes in infective endocar- Pathologic Q waves, 28
complications Nitrates O ditis, 279 Pelvic irradiation as cause of dys-
arrhythmias, 81-82 for angina, 68, 70-71
0
Osteomyelitis, fever of unknown uria, 228
mechanical. 82-83 for myocardial infarction, 81 origin (FUO) in, 270 Penicillin for meningitis, 459
pump dysfunction, 82 Nitroglycerin for chest pain, 61
F
Overload states as cause of hypo- Percutaneous transluminal coro-
recurrent ischemia, 82 Non-Hodgkin's lymphoma (NHL),
O
calcemia. 409
nary angioplasty (PTCA) for
right ventricular infarction. 82 353 F Oxygen (02) saturation, 113
myocardial infarction, 78
diagnosis of, 73-75 approach to patient, 358-359
J
Oxygen therapy
Pericardial knock, 16
electrocardiography, 74-75 clinical manifestations of, 358

L
Pericardial tamponade as cause of
patient history and physical epidemiology of. 357-358 for polycythemia, 326
dyspnea, 10
examination in. 74 pathogenesis of, 358
for pulmonary hypertension,

Pericarditis, 34
inferior wall, 24, 28 treatment of, 359, 30 t 136
Peripheral blood smear in diagnos-
pathophysiology of. 73 Noninfectious esophagitis, 292
S
O
ing acute leukemia, 371
posterior wall, 28 Noninvasive lower extremity test-
0 Peripheral neuropathy, 298-299
risk reduction, 83-84 ing in diagnosing pulmonary ( Paget's disease, 40-407
approach to patient, 299,
Myocardial ischemia emboli. 141-142
II
Pain. (See alo Abdominal pain;
: 436-439
as cause of dyspnea, 102 Noninvasive positive-pressure ven- O Chest pain)
causes of, 299, 435-436
Myocardial perfusion scintigraphy, tilation (NPPV), 148-149
x
bone, in fever of unknown ori-
66 Nonpalpable purpura, 269
I
gin (FUO), 272
= treatment of, 439
Myocarditis, 34 Nonproliferative normocytic ane- Palpable purpura, 269
Peripheral vertigo
Myxedema mia, 322
II
Pancreatic abscess, 187
causes of, 441
as cause of ascites, IS Non-Q wave myocardial infarc-
(
Pancreatic ascites as cause of asci-
clinical manifestations of. 441
coma, 420 tions, 75 F tes, IS
common causes of, 50
Nonspecifc interventricular bun-
S
Pancreatic pseudocyst; 188
treatment of, 443
Nafcillin plus gentamicin, 281 die branch block. 26 Pancreatitis
Neisseria meningitidis as cause of Nonsteroidal anti-infammatory
:
acute, 185
Peritoneal biopsy in diagnosing as-
II cites, 184
meningitis, 453 drugs (NSAIDS), 207
x
Neoplasms, 304 Normal Q waves, 28 O causes of, 185-186
Persistent headaches in fever of
as cause of acute gastrointesti- Normal sinus rhythm, 21 clinical manifestations of, 185
unknown origin (FUO), 272
nal bleeding, 171 Normoctic anemia, 320, 32J, 322 V complications, 187-188
Petechiae, 467
fever of unknown origin (FUO) Nylen-Barany maneuver. 442
I
treatment of, 187
pH regulation in treating diabetic
in, 271 Nystagmus, 441
I
as cause of ascites, IS
ketoacidosis (DKA), 416
Nephrology, renal syndromes, 203, as cause of hypocalcemia, 409
Pharmacologic therapy for pulmo-
204t Obstructive disorders, 31 chronic, 185
nary hypertension, 136
Nephrotic syndrome Obstructive drug disease Pancytopenia, 370, 371
Phenothiazines
approach to patient, 218-219, clinical manifestations of
I
222-223 asthma, 120-121
I
causes of, 304-305
pharmacologic efects, 486-487
1
causes of, 217-218, 220-222 clinical manifestations of clinical manifestations of, 303
treatment of, 487
characteristics of, 496 chronic obstructive pulmo-
S
common causes of, 499
Phenytoin for alcohol withdrawal,
clinical manifestations of, 220 nary disease, 120-121

481
complications, 219 diagnosis of asthma, 121 II Paracentesis
Pheochromocytoma, 247
secondary causes of, 497 diagnosis of chronic obstructive
1
in diagnosing abdominal pain,
Phlebotomy, 136-137
O
treatment of, 219, 223 pulmonary disease. 121 0 160 for polycythemia, 326
Neuroleptic malignant syndrome treatment of, 121-122
t:
for liver failure, 198-199 for polycythemia vera, 365
(NMS). 487 Open lung biopsy, 128
t
Parasitic infestation, 471 for pulmonary hypertension,
Neurologic abnormalities in dia- Opioid agonist overdose, clinical I Paresthesia, 435 136-137
betic ketoacidosis (DKA), manifestations of, 507
1
Paroxysmal nocturnal hemoglobin- Plasma cell dyscrasias
411 Opioid overdose, clinical manifes- ( uria (PNH), 310 clinical manifestations of, 375
Neutropenia, 374 tations of, 484
:
as cause of panctopenia, 304 defnition, 375
in panctopenia, 303 Orthodromic conduction, 38-39 treatment for, 307 Plasmapheresis, 439
V
I
I
I
I
1
526 Index Index 527
:
0
Platelet production, causes of de- Polyuria
F
Prostatodynia, 231, 232 Purified protein derivative (PPD)
creased, 500 in diabetic ketoacidosis (DKA),
:
Prothrombin time (PT) in as- test in diagnosing ascites, 184
Platelet transfusions in treating 411 0 sessing liver function. 162 Purpuric lesion. 467
thromboytopenia, 313-314 diferential diagnoses for, 503
0
Pruritus Pustules, diferential diagnoses
Pneumocystis carinii pneumonia Positive-pressure ventilation,
approach to patient, 472-473 for, accompanied by fever,

(PCP), 130, 285, 287-289, 2V0 modes of, 147-149 F causes of, 471, 507 499
and bone marrow transplants, Post-anion gap acidosis, 236
O
treatment of, 473 Pyelonephritis, uncomplicated,
374 Postcapillary pulmonary hyperten-
F
Pseudoaneurysms, 83 230, 231-232
Pneumonia. (See also Community- sion. treatment of, 137
J
Pseudogout, 388
acquired pneumonia) Post-hyperventilation, 236

L
Pseudohyponatremia in multiple Q waves, 28-29, 75
as cause of dyspnea, 102 Poststreptococcal glomerulonephri- myeloma, 377 myocardial infarctions, 75
as cause of hemoptysis, 106 ts as cause of acute nephritic
Pseudomona 261 QRS interval, 26

criteria for hospital admission syndrome, 220-221 t
Psoriatic arthritis, 388, 394 QT interval, 26-27
of patients with commu- Posttest probability, 8 S Psychogenic causes, 441 Qualitative assesment, 5
nity-acquired, 492 Postvoid residual (PVR) in diag-
O
Pulmonary angiography Quantitative assessment, 5-6
0
eosinophilic, 126 nosing renal failure, 210 ( in diagnosing pulmonary em- Quinidine for atrial fibrillation, 55
Pneumonitis, hypersensitivity, 124 PR interval, 25
II
boli, 142
:
Pneumothorax, 25 Precapillary/capillary pulmonary
0
in diagnosing pulmonary hyper- Radiation colitis as cause of acute
as cause of dyspnea, 101 hypertension, treatment of, x tension, 136 gastrointestinal bleeding, 171
Point of maximal impulse (PMI), 137
I
Pulmonary disease in HIV-in- Radiation therapy
=
14 Precordial palpation fected patients, 287, 288t for Hodgkin's disease, 357
Polyarteritis nodosa (PAN), 221 fndings, 15-19
II
Pneumocystis carini; pneumo- for multiple myeloma, 379
clinical manifestations of, 397 technique, 15, 15t

(
nia, 287-289, 2V0 for spinal cord compression, 463
diagnosis of, 397-398 Pregnancy-related liver failure, F Pulmonary embolism, 62 Radiography
epidemiology of, 397 197
S
approach to patient, 139-142 in diagnosing abdominal pain,
Polyarticular arthritis, 392 Pretest probability, 5-6, 8 as cause of dyspnea, 101 159
causes of, 392-395, 393t Primary adrenocortical insuffi-
:
causes of, 138 in diagnosing acute leukemia,
II
Polycythemia ciency, 428
x
approach to patient, 324-325 Primary biliary cirrhosis, 195 O 138-139 in diagnoing monoarticular ar-
causes of, 323-324 Primary CNS lymphoma, 285 treatment of, 142-143 thritis, 389
causes of absolute, 500 Primary hyperaldosteronism, 247
V
Pulmonary embolus, 24 Radiophosphorus
clinical manifestations of. 323 Primary hypothyroidism, 419-420
I
Pulmonary fibrosis, idiopathic, 124 for essential thrombocytosis,
treatment of, 326 Primary vasculitides, 396
I
Pulmonary function tests 366
Polycythemia vera, 325, 471, 472 treatment of, 401 interpretation of, 118-119 for polycythemia vera, 365
approach to patient, 364-365 Procainamide obstructive versus restrictive Ranson's criteria
as cause of polycythemia, 324 for arrhythmias, 46, 48 lung disease, 117-118 at admission, 496
prognosis, 365 for atrial fbrillation, 55 I Pulmonary histioytosis X (eosino- during initial 48 hours, 496
treatment of, 365 Proliferative normocytic anemia,
I
philic granuloma), 124 Rapidly progressive glomerulone-
1
types of myeloproliferative dis- 320, 322 Pulmonary hypertension, 111 phritis (RPGN) as cause of
orders, 361 Propranolol
S
approach to patient acute nephritic syndrome, 222
Polydipsia in diabetic ketoacidosis for angina, 68-69
confrmation. 135-136 Rash

(DKA), 411 for liver failure, 198 II preliminary evaluation, causes of, 498
Polymicrobial aspiration, 130 Prostate cancer, 381
1
134-135 morbilliform, 467-468
0
Polymorphic ventricular tachycar- Prostate syndromes. 228. 231. 232
0
causes of. 133-134 scarlatiniform, 469-470
dia, 48 Prostatic secretion analysis in diag-
t:
clinical manifestations of, Red blood cell (RBC) in ne-
Polymyalgia rheumatica (PMR) in nosing urinary tract infections
t
132-133 phrotic syndrome, 220
diagnosing giant cell (tempo- (UTIs), 229 I treatment of, 136-137 Reed-Sternberg cells, 353, 355
ral) arteritis, 397 Prostatitis
1
Pulmonary tuberculosis, 284 Refactory anemia (RA), 366
Polyneuropathies, 435 chronic bacterial, 231
(
Pulmonic insufciency, 19 Refractory anemia with excss
causes of, 505 chronic nonbacterial, 231 : Pulmonic stenosis, 18 blasts (RAEB), 366
V
I
I
I
I
1
528
Index
Index 529
:
0
Refactory anemia with excess Revascularization, 69-70
F
Scorpion stings. 186 Sodium nitropruside for myocar-
blasts (RAEB) in transform a- Reye's syndrome, 195
7 Secondary adrenocortical insuffi- dial infarction, 77
tion (RAEB-t), 366
Rheumatic arthritis, 125-126 0
cienc, 427 Specifcity, 6
Refactory anemia with ringed sid- Rheumatic fever
0
Secondary biliary cirrhosis, 196 Spinal cord compression
eroblasts (RARS), 366 acute, 275

Secondary hypothyroidism, 418, approach to patient, 462-463
Regular rhythm, 21
diagnosis of, 275-276 F
420 causes of, 461-462
Reiter's syndrome, 388, 394 treatment of, 276-277
O
Secondary insufciency, 428 clinical manifestations of, 462
Renal artery stenosis, 207, 247 as cause of polyarticular arthri-
F
Secondary syphilis, 268 treatment of, 463-464
Renal biopsy tis, 395 J
as cause of polyarticular arthri- Spiral computed tomography (Cf)
G
in diagnosing glomerulonephri-
Rheumatoid arthritis, 176, 388
L tis, 395 scanning in diagnosing pulmo-
tis, 223
fever of unknown origin (FUO) nary emboli, 142
in diagnosing renal failure, 213 epidemiology of, 392
in, 271 Spirochetal infections

Renal failure, 235
Rheumatologic disorders, 461-462
Secondary vasculitides, 399-401 and chronic meningitis, 454

acute Rickettsia, 262 S
treatment of 401 fever of unknown origin (FUO)
O
approach to patient, 208-213 as cause of infective endoardi-
0 Second-degree A V nodal block, in, 271
causes of, 205-208, 20 tis, 279 (
25 Spironolactone for liver failure,
clinical manifestations of, 205 Rickettsial infections, fever of un-
II
Sensitivity, 6 198 7
epidemiology of, 205 known origin (FUO) in, 271
0
Sepsis, 207, 264 Splenectomy
treatment of, 213-216 Right atrial enlargement, Z x
as cause of dyspnea, 102 for myelofbrosis, 366
I
as complication in pancreatitis, Right axis deviation (RAD), 25
= as cause of shock, 91 in treating idiopathic thrombocy-
188 Right bundle branch block, 26
Serum protein electrophoresis in topenic purpura, 314

Renal syndromes, 20, 204t Right ventricular hypertrophy, 25,
II
multiple myeloma, 377 Splenic infarct, 176
r
Renal tubular acidosis, 235 28
( Serum sickness (SALT), 399 Splenic rupture, 175
Renal tubular defects, acidosis Right-heart catheterization in diag- F
clinical manifestations of, 495 Splenomegaly
classification of, 224, 225t, 226, nosing pulmonary hyperten-
S Serum-ascites albumin gradient in approach to patient, 178
22 sion, 136
diagnosing ascites, 183 causes of, 176-178
definition of, 224 Right-sided electroardiography, 7
Shock causes of massive, 495
II
Renal ultrasound, 212 75
approach to patient, 92-93, 94t clinical manifestations of,
in diagosing urinary tract infec- Right-sided heart failure as cause O
cardiogenic, 92 175-176
tions (UTIs), 229-230 of ascites, 180
causes of, 91-92, 491 Sputum analysis in diagnosing
Reptilase time, 341 Right-to-Ieft shunting, 114-115
V
clinical manifestations of, 91 pneumonia, 130
Residual volume (RV), 117 Rocky Mountain spotted fever, I
defnition, 91 Staging laparotomy with splenec-
I
Respiratory acidosis, 233, 240 265
"kooky" disorders leading to. 491 tomy in diagnosing Hodgkin's
Respiratory alkalosis, 233, 240
Roth spots in infective endoardi-
treatment of, 95, 96t, 97t disease, 356
Respiratory depression, 484 tis, 279
Shunt nephritis as cause of acute Staphylococcal infections, 282
Respiratory failure Russell's viper venom time, 341
nephritic syndrome, 220 Staphylococcus aureus, 259
I
Sideroblastic anemias, 317 as cause of infective endocardi-
I
causes of, 144-145
1 Signal-averaged EKG (SAEKG), tis, 278
as complication in pancreatitis, Salicylate overdose, 237
33 as cause of pneumonia, 129
188 Salmonela, 262
S
Singultus (hiccough) Staphylococcus epidermidis, 259
treatment of, 146 Sarcoidosis, 125
r common causes of, 444, 44J, as cause of infective endocardi-
Restrictive cardiomyopathy, 87 Sarcoma, 381, 382
50 tis, 278
M
Restrictive lung disease Scabies, 472
0 treatment of, 444-445 Staphylococcus saprophyticus, 259
approach to patient, 127-128 Scarlatiniform rash, 93, 469-470
0
Sinus bradycardia, 21 in urinary tract infections
causes of, 123-127 Scarlet fever, 265, 469 t:
Sinus rhythm. 36, 38 (UTIs), 227
defnition, 123 Shamroth's sign, 475
Sinus tachycardia, 34-35, 41, 42, Status epilepticus, 433
etiology, 123 Schistosomiasis in eosinophilia, |
43 Stereotactic brain biopsy. 297
Restrictive ventilatory defects, 330
M
Sleep apnea, treatment of, 137 Steroids
causes of, 492 Schonlein-Henoch purpura, 221
(
Small ventricular septal defects, 17 for asthma, \Z
Reticulocytosis in macroctic ane- Scleroderma, 126 7
Smoking cessation for polycythe- for chronic obstructive pulmo-
mia, 320 Sclerosing cholangitis, 293
mia, 326 nary disease, 122
V
I
I
I
I
1
530 Index
:
Index 53 1
0
Steroids (continued) Sydenham's chorea, 276
F
Teniary insuffciency, 428 Tilt table test, 33
for meningitis, 46 Synchronized intermittent manda- 7
Thalassmia Tinnitus, 44]
for spinal cord compression, 463 tory ventilation (SIMV), 147
0 as cause of anemia, 317 Tissue plasminogen activator (t-
in treating idiopathic thrombocy- Syncope
0
versus iron defciency, 318 PA), 79-N, 452
+
topenic purpura, 314 approach to patient Theophylline Total bilirubin levels, 162-163
Still's disease as cause of polyartic- electrocardiogram (EKG), 32
F
for asthma, 122 Total lung capacity (TLC), 117,
ular arthritis. 395 history and physical examina-
O
for chronic obstructive pulmo- 123
Storage pool disease, 339 tion in, 31-32 F nary disease. 122 Toxic epidermal necrolysis (TN),
Streptooccal viridans infections, risk assessment, 32-33
J
Thiamin defcency, 431 265-266
C
282 causes of, 30-31, 489 L
Third-degree A V nodal block, 25 drugs that commonly cause, 499
as cause of infective endocardi- prevention, 33
Thoracentesis in diagnosing pneu- Toxic erythemas, 265, 267-268

tis, 278 treatment of, 33
<
monia, 13O Toxic shock syndrome (TSS), 265,
Streptococcus prumoniae, 259 Syndrome of inappropriate antidi- Thrombin time, 341 469-470
as cause of meningitis, 453 uretic hormone secretion
S
Thromboangiitis obliterans, Toxicologic emergences
O
as cause of pneumonia, 129 (SIADH), 244-245 0
400-401 general approach to overdoe
Streptokinase for myocardial in- Synovial biopsy in diagnosing
(
Thrombocytopenia, 374 patient, 482, 483t
II
farction, N monoarticular arthritis, 391
7
approach to patient, 311-312 specifc toxic syndromes, 482,
Stress erythrocytosis (Gaisbock's Systemic lupus erythematosus 0 causes of, 309-311, 3J0 484-487
polycythemia) as cause of (SLE), 126. 268, 399
clinical manifestations of, 309 Toxicology screen in searching for

I
polycythemia, 324 as cause of acute nephritic syn-
=
in pancytopenia, 303 caus of stroke, 451
Stress testing, 84 drome, 220
treatment of, 313-314 Toxoplasmosis, fever of unknown
Stroke as cause of splenomegaly, 177
M
Thromboctosis origin (FUO) in, 270
approach to patient, 447-449t clinical manifestations of, 392 ( approach to patient, 315-316 Transbronchial biopsy, 128
causes of, 446-447, 448t, criteria for diagnosis of, 50
F
causes of, 315 Transcranial Doppler ultrasound
450-451 epidemiology of, 392
S
clinical manifestations of, 315 in searching for cause of
defnition of, 446 Systemic sclerosis (scleroderma),
7
treatment of, 316 stroke, 450-451
epidemiology of, 446 394
0
Thromboembolic disease, treat- Transesophageal echocardiogra-
risk factors for, in patients with Systolic murmurs, 16-17 ment of, 137 phy (TEE) in diagnosing in-
atrial fbrillation, 490
O
Thrombolysis for myocardial infective endocarditis, 281
treatment of, 451-452 Tachyarrhythmias, 34, 35t, 81 farction, 78-79 Transformation, hemorrhagic, 447
Strongyloides infection in eosino- Tachycardia, 21 V Thrombolytic agents for pulmo- Transient ischemic attacks (TIAs),
philia, 330 in diabetic ketoacidosis (DKA),
I
nary emboli, 143 30, 446
I
Struma ovarii, 421 411 Thrombosis as complication of ne- Transthoracic echocardiography
STff wave changes, 29 in pulmonary embolism, 138 phrotic syndrome, 219 (TE) in diagnosing infective
Subacute bacterial endocarditis as Tachypnea Thyroid disease endocarditis, 281
cuse of acute nephritic syn- in diabetic ketoacidosis (DKA), approach to patient, 418 Tricuspid regurgitation, 17
drome, 220 411
I
clinical manifestations of, 422 Tricuspid stenosis, 19
I
Subarachnoid hemorrhage, 447, in pulmonary embolism, 138 1
treatment of, 422-423 Tricyclic antidepressants
452 Takayasu's aortitis hyperthyroidism, causes of, approach to patient, 486
Subdural hematoma, 447 clinical manifestations of, 397
S
420-421 clinical manifestations of. 486
Supraventricular arrhythmias with diagnosis of, 397
hypothyroidism overdose of, 25
aberrancy, 46 epidemiology of, 397
M
causes of, 418 pharmacologic effects, 486
M
Supraventricular tachycardia, 35 Technetium-99 ('f')-labeled red
0
clinical manifestations of, treatment of, 486
Suspected prosthetic valve endo- blood cell scan in diagnosing 0 418-419 TrimethoprimJsulfamethoxazole
carditis. 281-282 acute gastrointestinal bleed-
t:
treatment of, 419-420 (TMP/SMX)
Suspected subacute endocarditis, ing, 174 Thyroid storm, 422-423 for meningitis, 459-460
281 Temporal artery biopsy in diagnos-
| Thyroiditis, 418, 421, 422 for urinary tract infections
Sustained left ventricular impulse, ing giant cell (temporal) arte-
M
Thyrotoxicosis, 248 (UTIs), 231
14 ritis, 397 ( factitious, 421 Trousseau's sign in hypocalcemia,
Sweet's syndrome, 269 Tertiary hypothyroidism, 420
7
Ticlopidine for stroke, 451 408
V
I
I
532
TSH-secreting tumor, 420
Tuberculosis, 124-125
as cause of hemoptysis, 106
in eosinophilia. 331
fever of unknown origin (FUO)
in, 270
Tumor, 125
Tumor lysis syndrome, 373-374
Turner's sign, 185
Typhoid fever, 268
Ulcerative colitis, 400
Ultrasound
in assessing abdominal pain,
159-160
in diagnosing fever, 257
in diagnosing renal failure, 210
renal, 212
in searching for cause of stroke,
450
Unifying diagnoses, 3
Unresponsive viral esophagitis,
292
Upper airway obstruction as cause
of dyspnea, 102
Uremia, 216, 237, 471
Ureteral obstruction, 207
Urethritis, 228
as cause of dysuria, 228
Uric acid levels in diagnosing poly
cythemia vera, 3
Urinalysis in diagnosing renal fail
ure, 211
Urinary tract infections (UTls)
227-228
differential diagnoses for dys
uria, 228
irritative symptoms suggestive
of, 497
laboratory studies. 229-230
Urine
culture mdiagnosing urinary
tract infections, 229
dipstick in diagnosing urinary
tract infections, 229
electrolytes in diagnosing renal
failure, 211
Index
microscopic analysis in diagnos
ing urinary tract infections.
229
pregancy test in diagnosing uri
nary tract infections, 229
Urine protein electrophoresis in
multiple myeloma, 377
Vaginitis as cause of dysuria, 228
Vancomycin plus gentamicin, 281
Vasculitis syndrome, 208, 209, 215,
221
approach to patient. 401
as cause of polyarticular arthri-
tis, 395
causes of, 396-401
causes of secondary, 503
Vasopresors, 491
Vasovagal syncope, 30
Veno-occlusive disease. 179, 195
Venous hum of childhood, 19
Ventilation-perfusion (V 10)
lung scanning in diagnosing pul
monary hypertension, 136
mismatch, 114
scanning, 140-141
Ventricular septal defect, 17,
82-83
Ventricular tachycardia. 4, 4
Verapamil
for angina, 69
for atrial fbrillation. 54
Vertigo
defnition of, 4
etiology, 440
treatment of, 443
types of, 440-441
Vesicles, differential diagnoses
for, accompanied by fever,
499
Viridans streptococci, 259
Vital capacity (VC), 117, 123
Vitamin Utz
defciency, 432
in diagnosing polycythemia
vera, 364
V
I
I
I
I
1
V
I
I
Index
Vitamin D, intoxication with, as
cause of hypercalcemia, 406
Vitamin defciencies as cause of
pancytopenia, 305
von Willebrand's disease (vWD),
338-339
Waldenstrim's macroglobulin
emia, 375
characteristics of, 502
379-380
treatment of, 380
Warfarin
for atrial fibrillation, 55
for pulmonary emboli, 143
Wasting as complication of ne
phrotic syndrome, 219
Watershed infarctions, 446
Waveforms, 14
533
Weaning criteria, 493
Wegener's granulomatosis, 221
diagnosis of, 398
epidemiology of, 398
Wernicke-Korsakof syndrome,
432
Westermark's sign, 139
Wheezing, causes of, 491
Wilson's diseas, 195, 197, 431
Wolff-Parkinson-White syndrome,
54
Xerosis, 471
Yersinia petis, 262
Zidovudine in treating idiopathic
thrombocytopenic purpura,
314
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ODUCTION. Diagnoses tend to exist on the following

terior fasccle is blocked, the muscle that It

impulse is conducted down the faster bundle and

a Cardioversion should be undertaken only after

INTRODUCTION. Acute dyspnea is a common cause of

INTRODUCTION. Hemoptysis, defned as the expectoration

INTRODUCTION. It is often necessary to rely on your own

INTRODUCTION. Restrictive lung disease is an uncommon

tilatory failure has occurred, necessitating mechanical ventI

Presence of fecal PMNs,

A. The amount of alcohol required to produce liver disease

3. Acute interstitial nephritis affects the interstitium.

Determi ne whether the pH is greater than or less

look at the Pac02

Calculate the anion gap

Calculate the corrected serum bicarbonate

3. Treatment usually involves a combination of fuid

HYPERTENSIVE CRISES: URGENCIES AND EMERGENCIES

Patients who are elderly, i mmunocompromised, or

The degree of fever is of little predictive value in

Hypothermia often signals the presence of an over

ANTIMICROBIAL THERAPY. The best wa

gestive laboratory abnormaht

over weeks; therefore, ask the laboratory to save

rompt an echocardiogram to evaluate pos

ble myocardIal abscess formation (TEE is more sensi

pulmonary tuberculosis is much more common In

Treat for PCP

Treat for PCP

Treat specific disease

oCYSfS corm" pneumonia (PCP. A- gradient alveolar-to-arterial

cite is an important consideration in patients ex

e phospatase levels. When symptoms occur, they

, ketoconazole, and fuconazole, can cause hepa

ed for patIents WIth a

INTRODUCTION. Pancytopenia is defined as a decrease in

helming infections. Sepsis, tuberculosis, or fungal

ytopenia. from the infection itself, superim

ding a heparinized specimen will confrm your sus

ased destruction or sequestration is the mech

tinue medications that may cause thrombocy

topenia and. paradoxically, sys

ist. Increasing the heparin

lOns shoul be avoded

e is just like thrombin time, except it

d PT is from vitamin K defciency,

64. Myeloprol iferative versus

d liver abnormalities. lmmunoprophy

uble- strength tablet (160 mg/800 mg)

ic history of joint complaints may imply a

ing signs that suggest specifc causes (e. g.,

s are involved, often leading to transient

atic (PMR), which is characterized by

astrointestinal tract, nervous system,

estive heart failure (CHF),

vel history and medication history

rovide mSlght mto the cause of the vasculitis (e.g.,

ults (e.g., an elevated ESR) are nonspecifc but may

mal ESR would decrease your suspicion).

lete blood count (CBC). Look for leukocytosis,

ih PAN, Churg-Strauss syndrome, or Takayasu's aor

ystem and muscle cells, the symptoms and signs primarily