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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.
Chief Medical Resident, 1996-97
University of Califoria, San Francisco
San Francisco, Califoria
Williams & Wilkins
A WAVRY COMPA
BALTIMORE' PHILADELPHIA' LOJDON PARIS' BANGKOK
BUENOS AIRES' HONG KONG' MUNICH' SYDNEY, TOKYO' WROCLAW
Editor: Elizabeth Nieginski
Managing Editor: Alethea Elkins
Develoment Editor: Melanie Cann
Production Coordinator: Danielle Hagan
Designer: Sandra Janniche, Ashley Pound Design
Cover Desiger: Ashley Pound Design
Typesetter: Bi-Comp, Inc.
Pri nter: Por City Press
Binder: Port City Press
Copyright L 1997 Williams & Wilkins
351 West Camden Street
Baltimre, Maryland 21201-2436 USA
Rose Tree Corporate Center
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Building II, Suite 5025
Media, Pennsylvania 1906 3-2043 USA
All rights reserved. This book is protected by copyright. No part of this book may be
reproduced in any form or by any means, including photocopying, or utilized by
any information storage and retrieval system without written permisSion from the
copyright owner.
Accurate indications, aderse reactions and dsage schedules for drugs are proided
in this book, but it is pssible that they may change. The reader is urged to review
the package information data of the manufacturers of the medications mentioned.
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
T publishers have made every effort to trace the copyright hoders for borrowed
material. If they have indvertently overloked any, they wil be pleased to make
the necessary arrangments at the fst opportunity.
To purchase additional copies of this book, call our customer service deparment at
(BOO) 638-0672 or fax orders to (BOO) 447-8438. For other book services. including
chapter reprints and large quanttty sales, ask for the Special Sales department.
Canadian customers should call (80) 268-4178, or fax (90S) 470-6780. For all other
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Visit Wiliams & Wilkins O the Intemet: http://ww.wilklns.com or cntact our
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tomer service representatives are available from 8:30 am to 6:00 pm. EST. Monday
through Friday, for telephone access.
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
this is for non-commercial usage by
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0.
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GUIDE TO
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INPATIENT
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MEDICINE
:
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Contents
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II
:
Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Xlii
0
: Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xv
I
Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . XVll
&
c
PART I: GENERAL APPROACH TO MEDICAL
O
PROBLEMS
I
:
l. APPROACH TO DIFFERENTIAL DIAGNOSIS 3
:
c
2. ApPROACH TO MEDICAL DECISION MAKING 5
:
0
PART II: CARDIOLOGY
v
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3. CARDIAC EXINATION 13
I
4. ELECTROARDIOGRA INTERPREATION 21
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5. SYNCOPE 30
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6. ARRYHMIAS 34
1
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7. ATRIAL FIBRILLDON 50
c
8. CHEST PAIN
56
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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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vii
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viii
Contents
1
Contents
ix
:
PART III: PULONARY AND CRITICAL CARE
0.
PART V: RENAL/ACID-BASE
.
8
13. AcU DYSPNEA 101
:
34. OERVIE OF NEPHROLOGY
0
203
0.
14. MASSIVE HEOPTYSIS 105
0
8
35. ACUTE RENAL FAILURE
205
15. ApPROACH TO THE CHEST RADIOGRAPH 109
C
I 36. NEPHROTIC SYNDROME 217
113
::
16. HYPOXEMIA
.
37. NEPHRITIC SYNDROME
220
u
:
17. PULONARY FUNCTION TESTS 117
n
38. RENAL TUBULR DEFECTS 224
18. OBSTRUCTIVE LUNG DISEAE 120
:
0
39. URINARY TRACT INFECTIONS 227 0.
19. RESTRlcnVE LUNG DISEASE 123
O
II
40. APPROACH TO ACID-BASE DISORDERS :
233
20. COMMUNITY-ACQUIRED PNEUMONIA 129
0
:
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41. HYPONATREMIA
242
21. PULONARY HYPERENSION 132
&
C
42. HYPERTENSION
246
22. PULONARY EMBOLISM 138
O
23. RESPIRATORY FAILURE 144
I
:
PART VI: INFECTIOUS DISEASE
24. MECHANICAL VENTILTION 147
:
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
1
48. INFEcnVE ENDARDITIS
278
29. SPLENOMEGALY 175
:
49. CD4 COUNTS AND COMPLICATIONS OF HI
C
I:
INFEcnON
284
30. ASCITES 179
0
0.
t:
50. PULONARY DISEASE IN HIV-INFECTED
31. ACUTE PANCREATITIS 185
n
PATIENTS
t: 287
32. ALCOHOLIC LIVER DISEASE 189
I:
O 51. GASTROINTESTINAL MANIFESTATIONS OF
33. LIVER FAILURE 192
:
HIV DISEASE
291
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x Contents
1
Contents xi
:
52. NEUROLOIC MANIFESTATIONS OF
0.
PART IX: ENDOCRINOLOGY
.
HIV DISEASE 295
8
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71. HYPERCALCEMIA 0
405
0.
PART VII: HEMATOLOGY/ONCOLOGY
0
8
72. HYPOCALCEMIA 408
53. PANCYTOPENIA 303
C
73. DIABETIC KETOACIDOSIS 411
I
54. THROMBOCYTOPENIA 309
::
74. THYROID DISEASE 418 .
u
55. THROMBOCYTOSIS 315
75. ADRENOCORTICAL INSUFFICIENCY 424
I
56. ANEMIA 317
:
PART X: NEUROLOGY
0
0.
76. ALTERED MENTAL STATUS
57. POLYCYHEMIA 323
O
431
II
:
77. PERIPHERAL NEUROPATHY
58. LEUKOCYTOSIS 327
0
435
:
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78. VERTIGO
59. EOSINOPHILIA 330
&
440
C
79. SINGULTUS
60. BLEEDING DISORDERS 333
444
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80. STROKE 446
61. HYPERCOAGULBLE STATES 345
:
: 81. MENINGmS 453
62. LYMPHADENOPATHY 349
C
:
82. SPINAL CORD COMPRESSION 0 461
63. LYMPHOMA 353
V
PART XI: DERMATOLOGY
64. MYELOPROLIFERATIVE VERSUS MYELODYSPLSTIC
I
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SYNDROMES 361
83. EXANHEMS 467
65. ACUTE LEUKEMIA 369
I
84. PRURITUS 471
66. PLSMA CELL DYSCRASIAS
I
85. CLUBBING
375
1
474
67. METASTATIC NEOPLSMS 381
:
PART XII: TOXICOLOGY
C
PART VIII: RHEUMATOLOGY
I:
86. ALCOHOL INOXICATION AND WITHDRAWAL 479 0
0.
t:
87. TOXICOLOIC EMERGENCIES 482
68. MONOARTICULR ARTHRms 387
I
t:
Summary of Mnemonics . . . . . . . . . . . . . . . . . . . . . . . 489
69. POLYARTICULR ARTHRITIS 392
I:
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 509
O
70. VASCULITIS 396
:
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Contributrs
Joshua S. Adler, M.D.
Chief Medical Resident, 1993-94
University of California, San Francisco
Chapter 13, Acute Dyspnea
Steve Bent, M.D.
Medical Resident, 1993-96
University of California, San Francisco
Chapter 5, Syncope
Chapter 7, Atrial Fibrillation
Chapter 18, Obstructive Lung Disease
Kent Dauterman. M.D.
Chief Medical Resident, 1997-98
University of California, San Francisco
Chapter 86, Alcohol Intoxication and Withdrawal
Mark D. Eisner, M.D.
Chief Medical Resident, 1995-96
University of California, San Francisco
Chapter 22, Pulmonary Embolism
Daniel Feikin, M.D.
Medical Resident, 1993-96
University of Califoria, San Francisco
Chapter 27. Acute Diarrhea
Scott A. Flanders, M.D.
Chief Medical Resident, 1996-97
University of California. San Francisco
Chapter 19, Restrictive Lung Disease
Chapter 2n, Liver Tests
Daniel J. Friedland, M.D.
Medical Resident, 1 992-95
University of California, San Francisco
Chapter 76, Altered Mental Status
xiii
xiv
Pushkal P. Garg, M.D.
Medical Resident, 1993-96
University of Califoria, San Francisco
Chapter 61, Hypercoagulable Stales
Alan S. Go, M.D.
Medical Resident, 1993-96
University of California, San Francisco
Chapter 20, Community-Acquired Pneumonia
Chris Goss, M.D.
Chief Medical Resident, 1996-97
University of California, San Francisco
Chapler 2, Re.piratory Failure
S. Claiborne Johnston, M.D.
Chief Resident in Neurology, 1995-96
University of California, San Francisco
Chapler 80, Stroke
M. Andrew Mirhej, M.D.
Medical Resident, 1992-95
University of Califoria, San Francisco
Chapter 28, Acute Gastrointestinal Bleeding
Somnath Saha, M.D.
Medical Resident, 1992-95
University of California, San Francisco
Chapter 14, Massive Hemoptysis
Peter Salzmann, M.D.
Medical Resident, 1993-96
University of Califora, San Francisco
Chapler 2, Approach Medical Decision Making
E. Rand Sutherland, M.D.
Chief Medical Resident, 1997-98
University of California, San Francisco
Chapter 87, Toxicologic Emergencies
Mary Whooley, M.D.
Chief Medical Resident, 1995-96
University of Califoria, San Francisco
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
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
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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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t
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1
()
:
I
V
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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.
I
I
I
I
1
I
o
0
J
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
I
I
Arrhythmias
/
/
/
I
I
1
I
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
I
v
I
I
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
I
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F
C
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3
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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
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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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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
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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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. 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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P
K
F
C
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F
F
0
3
X
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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
V
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V
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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 >-- --<
Phenylephrine
Norepinephrine
Dopamine*
Epinephrine
Dobutamine
Isoproterenol
al"Adrenergic
al"Adrenergic, .1"adrenergic
Dopaminergic
.1"Adrenergic
al"Adrenergic
al"Adrenergic, .r<drenergic,
.2-adrenergic
.1"Adrenergic, .2"adrenergic
.
1
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2
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Sepsis
Sepsis
Sepsis, hypotensive cardiogenic shock
Pulseless arrest, sepsis
Cardiogenic shock (but not by itself if patient is
hypotensive), congestive heart failure
Bradycardia
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PART III
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Pulmonary and Critical Care
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13.Acute Dyspnea
@
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
@
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.
ApPROACH TO THE PATIENT
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.
ApPROACH TO THE PATIENT
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
monary hypertension.
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
monary hypertension.
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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Pulmonary Embolism 1 39
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
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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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Mechanical Ventilation 1 5 1
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
Gastroenterology
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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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4
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.
ApPROACH TO THE PATIENT
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
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
ApPROACH TO THE PATIENT
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.
ApPROACH TO THE PATIENT
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.
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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
W
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
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Chapter 32
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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.
ApPROACH TO THE PATIENT
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
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34. Oeriew of Nephrology
@
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
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.
ApPROACH T THE PATIENT
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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225
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).
ApPROACH TO THE PATIENT
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
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
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.
ApPROACH TO THE PATIENT
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.
ApPROACH TO THE PATIENT
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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Fever and Rash
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-
V
I
I
I
I
1
V
I
I
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
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.
:
:
II
o
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
278
J
I
.
i
0.
-
|
:
{
Infective Endocarditis 279
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
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
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
Obsere
Negative
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
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.
B. Approach to the patient
.
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.
3. Laboratory studies
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
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
B. Approach to the patient
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.
2. Laboratory studies
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.
B. Approach to the patient
.
.
1. Imaging studies. MRI of the Involved area of spmal
cord helps to rule out spinal cord compression.
2. Laboratory studies
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
@
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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I
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
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")
Paroxysmal nocturnal hemoglobinuria (PNH)
Aplasia
Neoplasms and Near neoplasms
Vitamin deficiencies (the "V" looks like a "Y")
Toxins, drugs, and radiation therapy
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)].
APROACH TO THE PATIENT
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
3
C
p
y
I
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Thrombocytopenia
3 1 3
b. Increased megakaryocytes are found when in
cr
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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
APPROACH TO THE PATIENT
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
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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%.
I
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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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I
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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0
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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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.
B. Approach to the patient
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
Allergic bronchopulmonary aspergillosis
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
KE Y
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
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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
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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.
APPROACH TO THE PATIENT
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.
ApPROACH TO THE PATIENT
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
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Chapter 63
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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
D. Approach to the patient
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
D. Approach to the patient
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
I
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I
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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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.
b. Pharmacologic therapy
(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
1. Approach to the patient
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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Myeloproliferative versus Myelodysplastic Syndromes 365
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
1. Approach to the patient
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
1. Approach to the patient
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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Myeloproliferative versus Myelodysplastic Syndromes 367
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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
1. Laboratory studies
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
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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.
D. Approach to the patient
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
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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
5. Renal cell carcinoma
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
V
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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
4. Gastrointestinal tract malignancies
5. Pancreatic malignancy
6. Renal cell carcinoma
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
3. Gastrointestinal tract malignancies
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.
V
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PART VIII
.......................................................................................
Rheumatology
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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
ding periarti
.
cular processes that may mimic ar
thntIs (e.g., cellulItis, bursitis, tendinitis)
3. Di
.
scer
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
, con
r
.
day) may also be necessary. In general, tempo
ral artentIs responds to steroids alone, whereas addi
tional immunosuppression may be required for patients
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
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
?
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
41 8
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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.
3. Laboratory studies
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
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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Vertigo
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
ApPROACH TO THE PATIENT
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
ApPROACH TO THE PATIENT
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
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_
:.
:.
(
(
:
o
1
(
o
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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Stroke
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
.
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.
b. Pharmacologic therapy
(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
Allergic bronchopulmonary aspergillosis
Refux esophagitis
Exposures (irritants, medications), Embolism (pulmonary)
Sinusitis, Strongyloids infection
492 Summar of Mnemonics
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)
Calcium (hypercalcemia)
Herpes zoster
494 Summar of Mnemonics
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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Summar of Mnemonics 495
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
496 Summar of Mnemonics
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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Summar of Mnemonics 497
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
498 Summar of Mnemonics
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
Calcium (hypercalcemia)
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
Paroxysmal nocturnal hemoglobinuria (PNH)
Aplastic anemia
Neoplasms and Near neoplasms
Consumption
Vitamin defciencies (the "V" looks like a "Y")
Toxins, drug, and radiation therapy
Overwhelming infection
500 Summar of Mnemonics
Causes of Decreased Platelet Production
("PANYTO") ................................................................... Chapter 54
Paroxysmal nocturnal hemoglobinuria (PNH)
Aplasia
Neoplasms and Near neoplasms
Vitamin defciencies (the "V" looks like a "Y")
Toxins, drugs, and radiation therapy
Overwhelming infection
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
Allergic bronchopulmonary aspergillosis
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
Epstein-Barr virus infection
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).
502 Summar of Mnemonics
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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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
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
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
monoarticular arthritis, 391
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
treatment of, 307-308
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
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
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
V
I
I
I
I
1
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
approach to patient, 362-363
0.
sion, 130-131 Culture-negative organisms as
clinical manifestations of, 440
prognosis, 363-364
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
(ADH), 242
topenic purpura, 314
O Ive flter for pulmonary emboli, of meningitis, 453
approach to patient, 242
Indomethacin for fever, 258
143 Liver, malignancies capable of me-
clinical manifestations of, 242
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
monoarticular arthritis, 389
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
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
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
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 in- fective 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)
approach to patient, 230-231
clinical manifestations of,
227-228
differential diagnoses for dys
uria, 228
irritative symptoms suggestive
of, 497
laboratory studies. 229-230
treatment of, 231-232
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
clinical manifestations of, 396
treatment of, 401-402
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
approach to patient, 442
clinical manifestations of, 440
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
clinical manifestations of,
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
clinical manifestations of, 398
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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