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COMMON
MEDICAL
DIAGNOSES:
An Algorithmic Approach
Third Edition
Patrce M. Healey, M.D.
Edwin J. Jacobson, M.D.
Assisllwt Clinical Professor of Medicine

UCLA Sch I of Medicine
Los Angeles:, California
Clinical Professor of Medicine

UCLA School of Medicine
Los Angeles, California
W.B. SAUNDERS CO
PANY
A Harcourt Health ScienCes Company

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W.B. SAUNDERS COMPANY

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Independence Square West
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Ubrery of Congreaa Cataloglng-ln-Publlcatlon
Data
Healey, Patrice M.
Common medical diagnoses: an algcHithmic approach!
Patrice M. Healey, Edwin J. Jacobson.-3rd ed.
p.
em.
Includes bibliographicaJ references and index.

ISBN O-7216-n32-Q
1. Medical protocols. 2. Diagnosis, Differential.
I. Jacobson,
Edwin J.
U. lille.
[DNlM: 1. Diagnosis. 2. Algorithms.
3. Decision Support Techniques.
we 141 H434c 2000)
AC64.H432000
616.07'5--dc21
DNlM/DLC
99-37694
COMMON MEDICAL DIAGNOSES: An Algorithmic Approach
ISBN 0-7216-7732-0
Copyright C 2000, 1994, 1990 by w'B. Saunders Company.

All rights reserved. No part of this publication may be reproduced or transmitted in any fonn or by any means, electronic or mechanical, including photocopy, recording, or any infonnation
storage and retrieval system, without permission in writing from the publisher.
Printed in the United States of America.
La.st digit is the print number:
Foreword
According to William Osler, to study medicine without reading books is like navigating without maps;
however, trying to become a physician without seeing
patients is never to go to sea at all.
In the light of what they have read, thoughtfuJ
students and physicians learn from their patients, and
what they learn from patients in turn enhances what
it is po'isible for them to learn from reading. Access
10 the experience
of others and one's own experience
combine synergistically
in the acquisition of clinical
wisdom.
In pmctice. interpretation
of the history and physical examination
is often commingled
with the
weighing of other diagnostic clues from laboratories
and special procedures.
The diagnostician
may at
many stages in the analysis of a patient's illness shorten
the distance from complaint to diagnosis-and
render
the trip less expensive-by
finding out before ordering
it how helpful a particular test or procedure has generally proved to be. The doctor's bedside findings lead
to a fork in the road. At this point for this patient,
which pathway is better?
Burgeoning
techniques,
which when used wisely
greatly improve diagnostic accuracy, can also make the
choice of pathways more complicated or unnecessarily
expensive. Even to know where to look or whom to
consult ror help requires not only skillful gathering of
data but also logical use of them.
Doctors lIealey and Jacobson have approached the

diagnostic process by considering such (.'Olllmon clinical problems
as headache
and fever through algorithms. The word algOrithm, derived from the name
of a ninth century Arab mathematician,
means stepby-step, logical problem-solving.
Algorithms prepared in advance cannot infallibly be
applicable to all patients. who vary enormously. I n a
sense every patient requires step-by-step
logical problem-solving for his or her specific problem(s).
Algorithms can, however, help the physician to develop
logical steps in difTerential diagnosis by indicating in
stepwise fashion frequently encountered
bifurcations
in the reasoning process and how, generally, to choose
the best route.
An additional benefit of this work is that the algorithms arc cross-referenced
to two medical textbooks.
Thus this Ix>ok can enhance for students of all ages
the circle of learning that proceed'!: for a Iifctimf' from
patients to medical literature
and back to patients
again.
SI-IEHM"N M. MELLINKOFF,
M.D.
Professor of Medicine
UCL.A School of Medicine
Fonner Dean, UCLA School of
Medicine, 1962-1986
Los Angeles, California
Preface
The third edition of Common Medical Diagnoses:
An Algorithmic Approach remains in the same rannal
as the first two editions. For the third edition, we
undertook
an extensive review of the literature
to
update all of the algorithms, so that new diagnostic
tests and techniques have been incorporated
into the
algorithms.
As with the first two editions, we have rresented
an approach to the differential
diagnosis 0 multiple
medical presentations
common to daily medical practice. Problems are presented as signs, symptoms, and
laboratory abnormalities,
as would confront the practitioner. These problems are organized into chapters
by pertinent organ systems. The algorithms presume
that the practitioner,
whether house officer or longtime clinician, commands a basic knowledge of clinical
medicine and can make judicious choices in using an
algorithm to diagnose any given clinical problem. The
algorithms rely on the use of clinical examination and
diagnostic tests to break dOYffl the larger list of diagnoses for any given problem. Although many algorithms
suggest a diagnostic test as the first break point in the
decision tree, all algorithms presume
that the first
"test" performed
has been a thorough
history and
physical examination.
The purpose of this text has been to provide the

clinician with an overview of the differential diagnosis
of a medical presentation,
yet allow for an easy and
cost-effective
way to break down a large list quickly
into more manageable
lists of differential diagnoses.
The ability to narrow choices for diagnosis will most
often be cost-effective
and important
in this era of
managed care. This book of algorithms, however, suggests but one approach to the diagnosis for each problem presented.
It will be obvious to the reader that
any number of alternative approaches to cost-effective
diagnosis can be constructed
by simply seeing the "big
picture" presented in this book.
As with prior editions, treatment is never addressed
unless it is used as a further "test" for diagnosis.
Each algorithm is again cross-referenced
to the latest
editions of the major textbooks of medicine: Cecil
Textbook of Medicine and Hamson's
Principles of Internal Medicine.
The third edition of Common Medical Diagrwses:
An Algorithmic Approach should remain a useful tool
for the clinician.
Patrice M. Healey, M.D.
Edwin J. Jacobson, M.D.
Acknowledgments
Many people have contributed to the writing of this
book. The authors would like to thank Doctors Saleh
Saleh, Franklin Murphy, Allen Nissensan, Jan Tillisch,
Paul Betlamy, John Child, James Roach, Michael Hosave, Sheldon Jordan, Marvin Derezin, Edwin Amos,
Charles Frankel, Kenneth Kalunian, Gary La7.1.f, John
Glaspy, Richard P. Kaplan, Larry Ford, Inder Chopra,
Jaime Moriguchi, Gayle Randall, and Martin Pops for

their help in reviewing the manuscript. We thank Ray
Kersey for his patience and skill in guiding us lhrou~h
this second editioll.
PMII
EJI
NOTICE
Medicine is an ever-changing field. Standard safety precautions must be followed, but as
new research and clinical experience broaden our knowledge. changes in treatment and
drug therapy become necessary or appropriate. Readers are advised to check the product
infonnation currently provided by the manufacturer of each drug to be administered to
verify the recommended dose, the method and duration of administration, and the
contraindications. It is the responsibility of the treating physician, relying on experience
and knowledge of the patient, to determine dosages and the best treatment for the
patient. Neither the publisher nor the editor assumes any responsibility for any injury
anG'or damage to persons or property.
THE
PUBUSIIER
Contents
1
Generalized Disorders
Acute Diarrhea .
Chronic Diarrhea
SIGNS AND SYMPTOMS.
Fatigue
Fever of Unknown Origin .
Weight Loss ....................
Weight Gain ..........................
.
_
Respiratory Disorders
SIGNS AND SYMPTOMS.

Cough ...............................
Dyspnea
Hemoptysis
Cyanosis
.
LABS
Pleural Effusion
Hypercarbia
12
12
'
.
.,.
.
_._
_
Hypertension
LABS
Cardiomegaly
14
16
18
20
LABS
Transaminitis
Elevated Alkaline Phosphatase
22
3 Cardiovascular Disorders
.
.
24
SIGNS AND SYMPTOMS

Oliguria
58
60
62
64
66
70
.
.
24
24
Renal Disorders
72
72
74
76
76
76
26
28
30
32
36
36
4 Gastrointestinal
SIGNS AND SYMPTOMS
Constipation
Diarrhea
52
54
56
LABS
Hematuria
Proteinuria
78
78
80
34
Disorders
50
Right Upper Quadrant and Left Upper Quadrant

Abdominal Pain .
Epigastric Abdominal Pain
Generalized Abdominal Pain
Periumbilical Abdominal Pain
Right Lower Quadrant and Left Lower Quadrant
Abdominal Pain .
Pelvic Pain
Jaundice/Hyperbilirubinemia
Hepatomegaly
Ascites
20
SIGNS AND SYMPTOMS

Chest Pain
Hypotension
Syncope
,
Edema
.
Gastrointestinal
Bleeding
Dysphagia
Abdominal Pain .
12
Murmurs
2
2
4
8
10
40
42
44
48
38
'
.
38
38
40
Acid-Base and Electrolyte

Disorders
LABS.
Hyponatremia
Hypernatremia
Hypokalemia
Hyperkalemia
Hypocalcemia
Hypercalcemia
82
82
82
64
86
.
88
92
94
xi
Hypophosphatemia
Hyperphosphatemia
Hypomagnesemia
Hypermagnesemia
Acidosis
Alkalosis.
96
98
100
102
..............
.............
Vertigo
168
170
172
176
Dementia
Altered Mental Status
Seizure
104
106
9 Endocrine Disorders
Hematologic Disorders
108
108
112
114
LABS.
Anemia ..
Microcytic Anemia
Normocytic Anemia .
Hemo~ Anemia.
Immune Hemo~ Anemia
Aplastic Anemio
Macrocytic Anemia
...............
Vitamin 811 Deficiency .
Folic Add Defidency .
118
118
120
122
124
126
128
Mye/odysplastic
Syndromes
Polycythemia
Pancytopenia
Neutropenia.
Neutrophilia .
Monocytosis .
Lymphocytosis
Eosinophilia .
Thrombocytosis
............
Thrombocytopenia
Dysproteinemia
.
130
132
134
136
138
..............
140
142
144
148
150
152
156
158
162
Neurologic Disorders
SIGNS AND SYMPTOMS

Headache
xii Contents
108
SIGNS AND SYMPTOMS.

Bleeding.
Lymphadenopathy
Splenomegaly
180
SIGNS AND SYMPTOMS

Amenorrhea
.
Hirsutism.
Thyroid Nodule
Thyroid Enlargement
LABS.
Abnormal Thyroid Function Tests
Hyperlipidemia
Hypogtycemia
10
180
180
184
186
188
190
190
194
198
Skin Disorders
202
SIGNS AND SYMPTOMS.

Pruritus
Urticaria
Purpura
Alopecia.
202
202
204
206
208
11 Musculoskeletal
Disorders
212
SIGNS AND SYMPTOMS.

Arthralgias and Arthritis .
Muscle Weakness .
Low Back Pain.
212
Index
221
212
216
218
166
.
.
166
166
Common Medical Diagnoses
Signs and symptoms:
Fatigue
Fever of unknown origin
Weight Joss
Weight gain
SIGNS AND SYMPTOMS

FATIGUE
Fatigue is one of the most common physical
complaints. It is the chief complaint in as many
as 55% of visits to primary c:ue physicians.
Almost everyone feels fatigue at some time during his
or her life. The causes of the fatigue usually are stress,

overactivity. poor physical conditioning,
or inadequate
sleep. At times, however, fatigue may be severe. VYhen
fatigue lasts more that a few days, or when fatigue
affects the normal activities of daily life, a more serious
underlying disorder may he present, and a thorough
evaluation is necessary.
Drugs may cause fatigue as a direct elTect, or
as an indirect eITect by altering normal sleep
pattems or metabolism. Dmgs most commonly
associated with fatigue include sedatives and hypnotics,
tranquili ..ers, some antihistamines.
most analgesics, tetracyclines, colchicine, steroids, birth control pills, centrally acting antihypertensives,
many fl-blockers,
and
some of the nonsteroidal anti-inflammatory
drugs. Digitalis toxicity is a common cause of fatigue and should
be evaluated in any patient taking the drug. Many hypnotics, tranquilizers,
and antidepressants
may interfere
\.Vith nornlal rapid eye movement
(REM) sleep. The
resultant abnormal sleep pattern is a common cause of
fatigue even though the number of hours slept may
be normal.
II
The. medical history and physical examination

proVlde clues for many of the causes of fatigue.
Most often, fatigue of an organic etiology is
2 Generalized Disorders Fatigue
worse in the evenings and is partially relieved by sleep.

Psychogenic fatigue, on the other hand, usually has the
opposite
pattern.
Many times, however, no specific
cause can be determined
on examination. Further evaluation, including
the use of laboratory
tests, radiographic examinations,
various imaging techniques,
and
an extensive psychological profile, may be necessary to
determine the cause of the fatigue.
II
Fatigue
is o~te~ ass~cialed
with infections.
Acute bactenal mfectlons are usually obvious
from the medical history and physical examination. Diagnosing chronic infections may require a more
extensive evaluation. The evaluation may require cultures of blood, other body fluids and secretions
for
bacteria, fungus, and acid-fast organisms. Hadiographic
examinations
of the lungs and sites of bone pain may
be helpful. Stool examination
for parasites should be
performed
for patients with an appropriate
history or a
change in bowel habits. Other imaging techniques such
as bone scan, computed tomography (Cf), or magnetic
resonance imaging (MHO may also be useful in appropriate settings.
Fatigue is often a sign uf an advanced or endstage malignal1(;y. Abnormalities on the physical
examination
or historical clues, as well as a
statistical likelihood, should direct the evaluation
for
occult malignancy. Leukemias and lymphomas are the
malignancies
most often associated
with fatigue, although fatigue may accompany any cancer.
Any nutritional
deficiency may cause fatigue.
The most common deficiencies include protein,
calories, and certain vitamins. Although malnutrition is not thought of commonly
in industrialized
nations, fad diets, malabsorption
syndromes, and eating
disorders may all contribute
to significant nutritional
deficiencies.
Depression is probably the most common cause

of chronic fatigue. In classic depression, fatigue
is often accompanied
by mood changes, anorexia, and sleep disturbances.
Depression can present
in more subtle ways and should always be suspected
when no obvious cause for the fatigue can be found,
especially in elderly persons.
Chroni.c viral infections are controversial causes

of fatigue. After initial infection, many viruses
remain in latent states \vithin various tissues of
the body. The most common of these viruses are the
herpesvirus,
Epstein-Barr
virus, and cytomegalovirus.
Any of these viruses may become reactivated and cause
serious disease in the immunocompromised
host. Several of these vimses, most notably the Epstein-Barr
vims, have been implicated in patients with a variety of
systemic complaints,
including fatigue. There is little
firm evidence, however, linking chronic viral diseases
with fatigue in the immunocompetent
patient.
Chronic fatigue syndrome is the name given to

a symptom complex consisting of ehronic severe
fatigue, mild systemic complaints such as pharyngitis, and occasional myalgias. The illness usually affects women between 20 and 45 years of age. It is
frequently associated with an active, high-stress lifestyle.
Although chronic viml diseases have, in the past, been
thought to play a role in the illness, it now appears
that some combination
of stress, a fonn of chemieal
depression, and possibly allergy may be the cause of the
fatigue and many of its assodated symptoms.
ToxIC exposures
Drugs
Heavy metals
Carbon monoxide
Pesticides
SoIv
ants
Posl-concussion syndrome
Congestive hear1 failure
Severe psychological stress
Perlorm
Fatigue
history
Anemia
Uremia
Diabetes mellitus
Adrenal insufficiency
Hypokalemia
Hyponatremia
Hepatitis
physical
Viral prodrome
Chronic Infection
-1
Endocarditis
Osteomyelitis
Tuberculosis
Parasitic
Fungal
Nu1ritional deficiency
Cecil Chapter
452
Harrison Chapter
384
Chronic fatigue syndrome
GeneraJlnd
Dlsorden
Fatigue 3
FEVER OF UNKNOWN
ORIGIN
The body's temperature

regulation is an excellent indicator of general health. Although "normal" temperature
may vary from person to person, deviation from an individual's nonnal pattern is
usually an indication of disease. Heavy meals, strenuous
exercise, ovulation, and menstruation
may cause signifi.
cant increases in body temperature,
but these increases
are short-lived and fil a predictable pattern. In general,
an oral temperature
over ggoF or a rectal temperature
over lOO"F' is defined as fever. Fevers that last less than
1 week are virtually always associated with some fonn
of infection. Fevers that last longer than 1 week are
usually associated with serious disease. If fever lasts
more than 3 weeks with daily temperature
elevations to
greater than 101F and no diagnosis is readily apparent
from routine history and physical examination, the fever
is classified as fever of unknown origin (FUO). In 90%
of cases, FUOs are associated with serious infections,
malignancies, and eollagen-vascular
diseases. An extensive evaluation may be necessary to reach a diagnosis.
Many approaches have been devised to evaluate FUGs.
This algorithm represents only one such approach.
II
Culture of blood, bodily secretions, the throat,

or abnormal-appearing
areas of the lxxly are
the cornerstone
of the evaluation of FUO. In
addition to routine culture for bacteria, special methexls
for fungal and acid-fast culture should always be performed on appropriate
fluids or tissues. The selection
of the proper culture media and collection methexls is
essential. In most large series, 30% to 35% of FUOs
are due to previously undiagnosed infection.
4 GenenJI:r:edDisorders
Fever of Unknown Origin
II
Endocarditis should always be suspected in the

patient with FUO. Patients with underlying cardiac valvular abnormalities.
especially
those
who have recently undergone
procedures
associated
with bacteremia,
such as dental. abdominal,
gynecologic, or urinary tract surgery, are particularly susceptible to endocarditis.
Intravenous
dmg users are also
susceptible
to endocarditis,
many times with infection
involving the right side of the heart. The bacteremia
associated with endocarditis
may be intennittent,
and
several blood cultures may be necessary to detect the
organism. Most studies have shown that six sets of blood
cultures are necessary to detect 90% or more of patients
with endocarditis.
Fungal blood cultures should always
be performed in immunocompromised
patients and intravenous dmg users.
Tuberculosis is one the most common causes of
FUO, accounting
for 5% to 15% of all cases.
Prolonged fever is usually caused by extrapulmonary spread of the disease. Disseminated
tuberculosis is more common in blacks than in whites. The most
common extrapulmonary
sites of infection are the liver,
Ixme marrow, and kidney.
Lymj)homas arc the malignancies

most common y associated with fever. These tumors account for as many as 20% of FUOs. Non-Hodgkin's lymphomas are more likely to be associated with
fever. Other systemic symptoms usually accompany fever in these patients. These symptoms include weight
loss, anorexia, and night sweats. These systemic symptoms constitute the B category when grading or staging
various lymphomas.
B-type
with shorter survival.
symptoms
are associated
Several methods are available for detecting antibody to the human immunodeficiency
virus
(HIV) in blood. The most common method
is the enzyme-linked
immunosorbent
assay (ELISA).
Although the test is very sensitive, there is a 10% to
15% false-positive
rate. A test, most commonly
the
Western blot, should be perfonned to confinn exposure
to HIV. Detection of HIV antibody is only an indic.'1tion
of exposure to the virus, but it is thought that the
majority of persons exposed \vill progress to the fullblown acquired immunodeficiency
syndrome (AIDS).
Fever is a common fonn of aJlergic reaction to

many dmgs. The mechanism of the fever may
be related to the classic sennn sickness reaction
or may be an immune-mediated
form of vasculitis. Most
of the antibiotics can cause allergic-type
fever. Other
dmgs associated with drug fever include allopurinol,
captopril, heparin, hydralazine, hydantoins, methyldopa,
procainamide,
propylthiouracil,
quinine, and quinidine.
Endocarditis
Sepsis
UTI/pyelonephritis
Rheumatic fever
Sinusitis
Tuberculosis
1
Fsver of
unknown
origin
Cecil Chapter
311
Hamson
125
Chapter
(continued
on page 7)
Fever of Unknown
Origin 5
FEVER OF UNKNOWN
ORIGIN (Continued)
Metastatic
carcinoma
11
I
of the lung, pancreas,
and
stomach is frequently associated with fever.

Liver metastases aTe usually present before Fe
ver becomes
a prominent
feature
of the disease.
Cardiac myxomas are rare primary tumors of

the heart. Myxomas most commonly occur in
the left atrium. Myxomas occur most frequently
in women and usually present in the middle decades of
life. Fever, malaise, arthralgias, and an elevated sedimentation rate are frequently associated with myxomas,
and the presentation
can easily be confused with any
chronic infection. Clues to the diagnosis include paroxysmal positional congestive heart failure and systemic
or pulmonary emboliz.1.tion.
6 Generallz:ed Disorders
Fever Of Unknown Origin
Non lupus vasculitis is a common cause of
FUGs, accounting
for approximately
10% of
cases. This form of vasculitis is also associated
with other constitutional
symptoms, including intense
myalgias, arthralgias, and occasionally rashes. Some of
the highest fevers occur in patients with this syndrome.
II
Familial Mediterranean
fever is a rare inherited
disease. Persons of Middle Eastern and southern European
ancestry have the highest incidence of the disease. Familial Mediterranean
fever is
characterized
by recurrent episodes of fever, peritonitis,
arthralgias,
arthritis, elevated sedimentation
rate, and
occasionally pleuritis. The episooes are self-limited, but
amyloidosis is a frequent late complication.
II
Among the solid localized

tumors,
hypernephromas have the highest incidence of associated fever.
and the
proach
antibody
titer or
titers is
Viral cultures are often difficult, time-consuming, and expensive. The highest yield comes
from cultures of urine, pharyngeal secretions,
buffy coat of the blood. A more practical apis the measurement
of viral and Toxoplasf1U1
titers. The presence of elevated IgM antibody
a fourfold or greater increase in IgG antibody
presumptive
evidence of active infection.
III
As many as 10% of FUOs may go undiagnosed

after extensive evaluation. About half of these
will eventually be diagnosed, usually with some
form of malignancy. The remainder will continue undiagnosed, with fever in about half of this group remitting
spontaneously
and the other half responding to antipyretics and anti-inflammatory
drugs.
(cxmrinued
frompag8S)
Perform
abdominaV
paM<
CT scan
EpsteinBarr virus
Cytomegalovirus
Toxoplasmosis
Cecil Chapter
311
Hamson
125
Chapter
GeneraJized Disorders
Fever Of Unknown Origin
WEIGHT LOSS
Involuntary weight loss is one of the most omi-
nous signs in medicine. The weight loss i~usually a sign of a serious underlying physical or
psychological disorder. True weight Joss is usually defined as a 5% or greater reduction in the patient's wua!
weight over a period of 6 months or less. More rapid
weight loss, especially if it is accompanied
by other
systemic symptoms such as fatigue or fever, is usually
associated with more serious underlying
conditions.
Many patients do not complain of weight loss unless it
is extremely rapid. Most often the physician detects the
weight loss during routine examination.
The diagnosis
of true weight loss must be made on the basis of actual
weight measurements
rather than on historical data such
as a change in clothing size or fit.
Weight loss may be caused by a deficiency of
II
intake or absorption
of sufficient calories to
meet metabolic needs. Increased metabolic demands may also cause this caloric imbalance in spite of
normal food intake. There are numerous formulas that
allow for an accurate estimation of normal basal caloric
needs. These fonnulas may be modified to account for
any unusual expenditure
of el.\lories as a result of increased activity or increased metabolic needs. A reliable
rule states that a I-Ih weight reduction will occur for
each 35OO-kcal deficit. Keeping a careful dietary history,
including diet logs and fonnal calorie counts, is essential
to determine
whether the cause of the weight loss is
decreased intake of calories rather than decreased absorption or increased metabolic demands.
More than 50% of cases of inflammatory bowel
disease are associated with weight loss. Weight
loss is more common with Crohn's disease than
with ulcerative colitis because involvement of the small
bowel is usually more extensive. The weight loss may
be secondary to decreased absorption of calories as well
as to a rapid transit time of food in the intestine. Physical symptoms such as pain and early satiety may contribute to decreased intake of food and subsequent
weight
loss.
4~
Celiac disease (nontropical

sprue) is the result
of gluten-associated
inflammation of the epitheliUln of the small bowel. The inflammation
re-
8 GeneraJlzed Disorders Weight Loss
suits in malabsorption
of nutrients
and calories. The
disease occurs in approximately
0.5% of the general
population. There is a strong family history in 20% of
patients with celiac disease. The disease is associated
with weight loss, steatorrhea,
anemia, cramps, and diarrhea. Severe vitamin and calcium deficiencies may occur. A classic pattem
may be seen on small bowel
barium studies, but the definitive diagnosis is made by
small bowel biopsy. A gluten-free
diet will result in
resolution of the abnonnalities.
The abdominal cr scan may be useful in diagnosing obstruction of the lymphatic drainage of
the bowel and mesentery. Weight loss is caused
by decreased absorption of food owing to edema of the
intestinal wall. The etiology of the lymphatic obstruction, however, usually requires tissue samples and cultures obtained by laparotomy.
II
Several resins are used in the treatment of hyperlipidemia

and hyperkalemia,
including
cholestyramine
and sodium polystyrene sulfonate. These drugs may bind nutrients in the intestine if
taken immediately prior to or after meals.
Several drugs can cause weight loss as a result

of anorexia, nausea and vomiting, or changes in
absorption in the intestine. These drugs include
digitalis, anti-arrhythmics,
diuretics, opiates, some antibiotics, some nonsteroidal anti-inflammatory
drugs, hypoglycemiC agents, cytotoxics, sucralfate,
and several
antihistamines.
Anorexia and weight loss are common with severe chronic congestive heart failure. The anorexia is secondary to fatigue, depression,
and
dyspnea. Increased metabolism may also play a role in
the weight loss owing to the increased work of breathing. The actual weight loss may at times be masked by
fluid retention but will be uncovered when the patient
is made euvolemic during treatment.
.
II
Chronic infection is a common cause of weight
loss. Granulomatous
disease. deep fungal infections, intestinal and hepatic parasites, and subacute bacterial endocarditis are the most common infections associated with significant weight loss.
1m
Weight loss and anorexia may be prominent

components
of many of the collagen-vascular
diseases. The collagen-vascular
diseases most
commonly associated with weight loss include systemic
lupus erythematosus,
polyarteritis
nodosa, rheumatoid
arthritis, polymyositis, sclerodenna,
ankylosing spondylitis, polymyalgia rheumatica, and temporal arteritis.
II
As much as 15% to 20% of total body weight

may be lost during the {.'Ourse of A1DS. The
etiology of this weight loss is multifactorial. Infections involving the mouth, teeth, esophagus, and intestine are common. The most common organisms include Candida, herpes simplex virus, Cryptosporidillm,
Campylobacter, and Entamoeba histolytica. Kaposi's sarcoma and A1DS-related lymphoma may involve the gastrointestinal
tract. Decreased
appetite may also arise
from depression or as a part of AIDS encephalopathy.
II
Eating disorders are being diagnosed with increased frequency. Anorexia nervosa and bulimia are the most common of these disorders.
Although any severe psychological
illness can cause
weight loss, a greater than 25% weight loss secondary
to decreased intake alone is classified as anorcxia nervosa. The prevalence of this disorder may be as high
as 1 in 200 in the general population, with a female
predominance
of 30 to 1. The disease is more common
in Western society, where slimness is a cultural goal.
Other, more severe, underlying
psychological
factors
may play an important role in the etiology of the illness.
Bulimia, the syndrome of eating and purging for the
purpose of losing or maintaining weight, may be a separate disorder or can be associated with anorexia nervosa.
Both of these disorders can lead to endocrine abnormalities, especially amenorrhea,
and can ultimately lead to
serious physical complications
as a result of starvation
and electrolyte imbalances.
Social stresses, including poverty and physical

or mental infinnity, as well as inadequate knowledge of proper nutrition and inadequate access
to food, may lead to weight loss. This condition is
probably much more widespread,
even in developed
countries, than is commonly thought.
lnfta,nvnalO<y bowel
dtHaN
f'IoplieulcerdiN.N
Glturnors
E~J
~EsopI\a
..
"'.''''''''''
diInM[=~
Motl~disofden
-.-
Eallngdiaofder
Cecil Chapter
Harrison
Chapter
226
43
GeneraJlz:ed Disorders
Weight Loss 9
WEIGHT GAIN
The causes of weight gain may include physical.
psychological, and socioeconomic factors. Six

percent to 15% of children and adolescents are
overweight. Approximately 25% of men and 30% of
women are overweight. There is also an inverse relationship between socioeconomic status and the prevalence
of obesity. Genetic factors, such as fat type and distribution, may/lay important roles in the way weight is
gained an lost. By far. the most common cause of
weight gain is excessive caloric intake. Drug-induced
changes in appetite or metabolism are also common.
Only rarely can a physical cause such as an endocrine
imbalance be found.
II
Excessive caloric intake is the most common

cause of weight gain. Main patients may be
reluctant to discuss their dietary habits or may

not realize how the quantity and type of food they are
eating affect their weight. An effective tool for dietary
evaluation is a log kept by the patient and then analyzed
for total calories consumed. This calorie count, when
combined with an estimate or measurement of metabolic rate, can give a good assessment of the possible
contribution of diet to the patient's weight gain.
Several classes of drugs are associated with

weight gain. Their mechanisms are usually not
well understood, but these medications may af-
10 Generalized Disorders Weight Gain
feet both appetite and metabolism. TIle dosage and the

route of administration may also have an effect. Generally, the more sedating the drug, the greater the potential for weight gain.
II
The cessation of smoking is usually associated

with a modest weight gain, averaging 10 lb.
Stopping nicotine decreases the patient's resting
metabolic rate. There may also be a concomitant increase in caloric intake. This effect usually lasts no
longer than 2 months.
~
Psychiatric disorders must be considered in the

evaluation of weight gain. Many neuroses and
some fonns of depression may invplve overeating. Among the more severe disorders, bulimia nervosa
is most commonly associated with weight gain. This
disorder is associated with binge eating alternating with
caloric restriction. Bulimia nervosa should be distinguished from other variants, in which purging usually
feads to weight loss. Bulimia nervosa is more common
than previously thought; it may affect 10% of women
and 1% to 2% of men in the United States.
Routine blood chemistries may reveal clues to

several causes of weight gain. A high incidence
of rapid weight gain and obesity has been found
associated with the onset of non-insulin-dependent dia-
betes. Other abnonnalities in electrolytes such as potassium and total CO2 may be found in the pituitary cause
of Cushing's disease or the adrenal cause of Cushing's
syndrome. If either of these disorders is suspected, a
serum cortisol is the single most useful confirmatory
test. Should the serum cortisol be elevated, then a
dexamethasone suppression test may be used to further
define the disorder.
Although commonly suspected in weight gain,
hypothyroidism is rarely a cause. Even with the
severe deficiency in thyroid hormone seen in
myxedema, the majority of the weight gain is secondary
to fluid retention. Occasionally, weight gain may occur
when excess artificial hormone is withdrawn.
Bibliography
Goldman L, Bennett Je (eds): Cecil Textbook of Medicine. 21st ed. Philadelphia, WB Saunders, 2000.
Jacobson E: Chronic mononucleosis-it almost never
happens. Postgrad Med 83:56--65, 1988.
Louis AA (ed): Handbook of Difficult Diagnoses. New
York, Churchill Livingstone, 1990.
Norton J: Gastrointestinal Disorders. 2nd ed. St Louis,
Mosby-Year Book, 1981.
Sugarman JR: Evaluation of fatigue in family practice. J
Fam Pract 19:643--647, 1984.
Taylor HB: Difficult Diagnosis 2. Philadelphia, WB
Saunders, 1992.
.r
Genetic
Prader-Willi syndrome
L FrOhlich's syndrome
Laurence-Moon-Biedl
syndrome
ArItipSychOtics
Tricyclics
Estrogen
Valproic acid
Antihypertensives
AdrenaVanabolic
steroids
1
Weight
gain
Cushing's
disease/syndrome
Increased androgenic honnones
Surreptitious
Cecil Chapter
Hamson
eating
226
Chapter
Generallz:ed Disorders
Weight Gain 11
Signs and symptoms:
Cough
Dyspnea
Labs:
Pleural effusion
Hypercarbia
Hemoptysis
Cyanosis
SIGNS AND SYMPTOMS

COUGH
Cough is the most common respiratory symptom. Cough is normally a protective mechanism
for clearing the airway of secretions, foreign
material, or irritants. The cough is initiated by mechanical stimulation of the irritant receptors in the nose, ears,
esophagus, larynx, trachea, and larger bronchi, as well
as the pleura, pericardium, and diaphragm. The stimulation is carried via the afferent fibers of the vagus nerve
to the "cough center" in the lower medulla and the
upper pons. The reflex arc is completed via the efferent
fibers of the vagus nerve and the spinal nerves C2 and
C3 to the muscles of the diaphmgm, chest wall, and
abdomen. It is the contraction of these muscles followed

by the sudden opening of the glottis that creates the
cough. Airflows exceeding 500 mph have been documented during cough.
II
The forced expiratory volume in I second

(FEVl), the peak flow, and the vital capacity are
the most useful pulmonary function tests to
determine the presence of an obstnlctive pulmonary
defect. The most common causes of obstnlctive pulmonary function test abnormalities are intrinsic airway hyperreactivity as seen in asthma and extrinsic airway
12 Respiratory Disorders
Cough
obstruction secondary to compression from lymph

nodes, masses, or aneurysms. If initial spirometry is
nonnal and obstnlctive airway disease is still suspected,
a methacholine inhalation challenge test may be per
formed. A positive test is indicated by a 20% or more
decline in FEYl and is a clear indication of bronchial
hyperreactivity.
Cigarette smoking is the most common cause of
chronic cough. 11le cough does not necessarily
occur when the patient is actually smoking but
is usually more severe in the early morning. The cough
is usually not productive unless accompanied by bronchitis. Some studies have shown that complete cessation
of the cough may occur as soon as 1 month after smoking has been stopped.
Common air pollutants such as sulfur dioxide,

nitrogen dioxide, and ozone are frequent causes
of cough. Many industrial and agricultural e:qxr
sures can cause an acute or chronic cough. Symptoms
may appear minutes to years after the exposure. A
cough that initially begins after work or at night is a
clue to exposure to airway irritants.
Psychogenic cough is a diagnosis of exclusion.

The cough is most common in adolescents with
concomitant emotional disorders. Prior to this
diagnosis further evaluation with endoscopy of the pharynx and sinus, 24-hour pH monitoring of esophageal
pH, or the newer rapid spiral computed tomography
(cr) of the chest may be undertaken if indicated. The
cough does not produce sputum, usually does not occur
at night, and is not affected by commonJy used cough

suppressants.
Lung biofsies may be perfonned by the transbronchia or the transthoracic method depending on the location of the lesion or area to
be sampled. When the diagnosis is not evident or a large
amount of lung tissue is required. open lung biopsy may
be necessary.
Cough occurs more commonly with bronchogenic carcinoma than with metastatic disease.
Seventy percent to 90% of patients with bronchogenic carcinoma have cough as a prominent symptom. Isolated cough, even in the absence of radiographic
findings, may be the first symptom of bronchogenic
carcinoma in a patient at risk. Sputum cytology or brou
chial washings may be of help in making the diagnosis
in this setting.
Cough is common in patients with interstitial

lung disease. The cough is probably caused by
changes in the airways with activation of stretch
receptors as a result of the increase in fibrous tissue
within the lung. The cough in this setting is usually
increased by deep breathing.
Recurrent aspiration is usually seen in elderly

patients and patients with central nervous sys
tern or swallowing disorders. The cough may be
provoked by either solids or liquids or may occur during
sleep. Chronic aspiration with resulting lipoid pneumonitis is commonly seen in patients who use mineral oil
as a nighttime laxative.
Acute bronchitis
Obstructive
pulmonary -{
disease
1
Cough
4
Asthma
Extrinsic airway compression
Chronic bronchitis
Ahway irritants
----.!r
Smoking
-L Postvirat
Gastroesophageal reflux
Allergic postnasal drip
Vagus nerve stimulation
Irritation of pleura or diaphragm
5
Psychogenic
Angiotensin-converting enzyme
(ACE) inhibitors
Malignant disease
Nodular infiltrate 6
Fungal infection
-{
Primary
Metastatic
Benign nodules
Bacterial
Pneumonia
-1
Fungal
Mycobacterial
Viral
Parasitic
Diffuse Infiltrate
Cardiac failure
Sarcoidosis
Cecil Chapter
Interstitial fibrosis
72
9
Harrison Chapter
]]
Aspiration
Foreign body
Respiratory Disorders. Cough 13
DYSPNEA
II
Dyspnea is one of the most common symptoms

for which patients seek medical attention. The
various forms of dyspnea may provide important diagnostic clues. Orthopnea, or dyspnea in the
supine position, along with paroxysmal nocturnal dyspnea, is usually associated with pulmonary venous congestion. Platypnea, or dyspnea on sitting upright, is
usually associated with intracardiac or intrapulmonary
shunts and neuromuscular disorders of the chest wall
muscles. TreIX'pnea, or dyspnea in the lateral decubitus
IX>sition,is usually associated with congestive heart failure. Even if the patient does not or cannot complain of
the condition, dyspnea can be suspected when other
signs, such as gasping, intercostal muscle retraction,
audible wheezing, or Haring nostrils, are present.
II
Spirometry should include the FEV!, the maximum voluntary ventilation (MW), the forced
vital capacity (FVC), total lung capacity (TLC),
and the diffusion of carbon monoxide (Dee). An FEVI
and an MW of 25% to 40% of the predicted level are
associated with moderate to severe dyspnea. An FEV 1
and an MW of 15% or less are associated with dyspnea
at rest. FEV/FYC ratios of less than 70% are found
with obstructive airway diseases. If the FEV /FVC ratio
is greater than 70%, a restrictive defect should be
sought using additional tests such as the TLC and the
Dee. Pulmonary function testing may also be useful in
diagnosing dyspnea associated with some abnormal
chest radiographic findings.
Direct measurement of the oxygen saturation
by oximetry is necessary to determine the true
saturation of the hemoglobin. The value reported with most routine blood gas measurements is a
calculated value derived from the oxygen partial pressure (Po,J, the pH, and the body temperature. This
calculated value will not reflect the true saturation in the
presence of carbon monoxide or abnormal hemoglobins.
When the etiology of the dyspnea is not evident

after standard pulmonary function tests (PITs)
and the resting arterial P<>2(Pa<>t)
is normal,
exercise pulmonary function testing may be useful. The
object of the test is to determine the ability of the
Dyspnea
oxygen transport system (heart, lungs, and respiratory

muscles) to supply the necessary increase in oxygen
delivery to the tissues during exercise. The test may also
induce bronchospasm not evident at rest. Usually a
bicycle ergometer or a treadmiU is used to increase
physical activity in a controlled manner. Minute ventilation (VE), oxygen oonsumption (Vo,)/(Vco,), and carbon
dioxide production (Vc~), as well as the heart rate
(HR) and traditional spirometry, are measured during
the test.
Disorders that limit the heart from increasing
cardiac output when needed include certain valvular abnormalities, decreased myocardial mass
or contractility, and pericardial disease causing restriction of diastolic filing. The exercise PIT abnormalities
most commonly seen with fix~ cardiac output syndromes include failure of the V<>2to increase at the
start of exercise, or a low Vo,tH R. Both of these findings
are due to a decreased stroke volume.
II
Psychogenic dyspnea and hyperventilation are

often associated with various anxiety neuroses.
The dyspnea is intermittent, does not accompany all fonns of physical exertion, and usually occurs
in patients under 40 years of age. The dyspnea may
be accompanied by dizziness, giddiness, difficulty with
concentration, palpitations, and fatigue. Both standard
and exercise PITs are normal.
Although cardiac catheterization remains the

"gold standard" in diagnosing intracardiac
shunts and pulmonary hypertension, several less
invasive tests are available and may be helpful. These
tests include "bubble" echocardiography for the determination of intracardiac shunts and lung perfusion scans
with differential counting over the brain and kidney to
detect particles shunted through dilated pulmonary ves
sels.
Pulmonary hypertension may be a primary disorder of unclear etiology or the result of multiple pulmonary emboli. Other evidence of
rightsided cardiac failure may be present, including
accentuation of the second heart sound, fixed splitting
of the second heart sound, or a right ventricular heave.
The diagnosis is confinned by right-sided cardiac catheterization.

Large airway obstruction may be either internal
or external to the trachea or main stem bronchi.
The most common fOnTISof external compression come from neoplasms within the neck or mediastinum or large goiters. Internal obstruction may also be
caused by neoplasms, but foreign bodies must always
be considered.
1m
Respiratory muscle weakness may result from

dysfunction of the motor nerves, the neuromuscular junction, or the muscle cells themselves.
For a more complete explanation of respiratory muscle
weakness, refer to the hypercarbia algorithm (see page
23).
II
Pneumothorax may occur spontaneously or as a

result of trauma. Spontaneous pneumothorax
occurs most commonly in patients with cystic
fibrosis or in young adults idiopathic:t1ly,but it may also
occur with Staphylococcus aureus pneumonia, chronic
obstructive pulmonary disease, pulmonary tuberculosis.
asthma. interstitial lung disease (such as sarcoidosis),
malignancy, endometriosis, and Marfan's syndrome.
II
Interstitial lung disease presents as a diffuse

pulmonary parenchynlal process without airway
obstruction. Idiopathic pulmonary fibrosis,
rheumatoid lung disease, sarcoidosis, and various pneumoconioses are the most common interstitial lung diseases. Ellertional dyspnea is invariably present and usu
ally occurs before any changes on spirometry are noted.
Chest radiographic findings may initially be subtle, but
with time, radiographic changes in the parenchyma, as
well as volume loss, wiD become evident.
DJ
Progressive exertional dyspnea is a common

presentation of cardiovascular disease. The
echocardiogram and radiographic changes in
cardiac size and shape will help to define whether the
abnormality is valvular, myocardial, or pericardial in
origin. Cardiac catheterization may be necessary to confinn the diagnosis.
Anemia
Fixed cardiac output

Exercise-induced
Pulmonary embolus
6
Pulmonary hypertension
AighHo-left
1
DYlpne8
Cardiac
large
asthma
Deconditioning
Psychogenic dyspnea
Hypermetabolic
stales
cardiac shunt
myxomas
airway obstruction
Bronchospasm
Restrictive
10
disease
Respiratory
--[
muscle weakness
eNS lesion
Primary muscle weakness
Idiopathic dyspnea
Pneumothorax
Pulmonary edema
Interstitial lung disease
Pulmonary
vascular
disease
Emphysema
Chest wall deformity
Carcinoma of the lung
. -{
Va Ivu Isr a bnormality
Aortic stenosis
Mitral stenosis
No valvular abnormality -{
Cecil Chapter
72
Harrison Chapter
J2
Pericardial effusion
Cardiomyopathy
Dyspnea J 5
HEMOPTYSIS
Hemoptysis is the expectoration of blood arising
from the respiratory tract. The quantity of
blood may range from streaking of the sputum
to a massive hemorrhage. Hemoptysis of greater than
100 mV24 hr is considered potentially life-threatening.
Expectorated blood does not always arise from the respiratory tract. Hemoptysis must be distinguished from
epistaxis. oral or laryngeal bleeding. and hematemesis.
A careful head and neck examination is always necessary
as part of the evaluation of hemoptysis. The usually
bright-red color and alkaline pH of respiratory tract
bleeding may help distinguish hemoptysis from hema-
temesis .
The history and physical examination may be

useful in both the diagnosis and localization of
the bleeding. Trauma to the lungs or thorax is
a commoo cause of hemoptysis. The most common
traumatic causes of hemoptysis are pulmonary contusion
from blunt trauma, such as impact with a steering
wheel; rib fracture; and inhalation of toxic fumes. Even
when the history and physical examination fail to pinpoint the exact diagnosis, findings like fever, cough,
weight loss, cardiac murmurs, adenopathy, and clubbing
may give useful clues. Patients may often be able to
localize the site of the bleeding to one lung or the other
by feeling the sensation of fluid in the bronchi. The
physical finding of isolated rhonchi or wheezes may
further narrow the search for the site of the bleeding.
The chest radiograph is the most useful diagnostic test in the evaluation of hemoptysis. Primary diseases of the respiratory tract such as
infiltrates or nodules will be evident. Aids to the diagnosis of hemoptysis secondary to nonpulmonary organ
dysfunction may be found on the radiograph. Cardiomegaly, Kerley's lines, and hilar adenopathy may be
useful in detennining the cause of hemoptysis. It should
be noted, however, that an abnormality on the chest
radiograph does not always indicate the site of the
bleeding. Old inflammatory changes may coexist with a
radiologically undetectable tumor. Bleeding from any
area of the lung may spread throughout the pulmonary
tree, giving the false impression of diffuse disease on
radiography. In addition, some studies have shown that
Hemoptysis
up to 50% of patients with hemoptysis may initially have

normal chest radiographs.
Most primary lung neoplasms are malignant. In
smokers over the age of 40 years, 90% of these
lesions are bronchogenic carcinomas. Hemoptysis occurs in more than 50% of fatients with lung
cancer at some point in the course 0 their disease. The
hemoptysis is caused by erosion of the tumor into the
bronchus or by necrosis of bulky fungating tumors.
Benign tumors of the lung rarely cause hemoptysis;
therefore, if the mass is found to be benign, other
sources of bleeding should be sought.
Most metastatic tumors do not calise hemoptysis. However, osteogenic sarcoma and metastatic choriocarcinoma have been associated frequently with massive hemoptysis and should be
suspected in the appropriate clinical setting.
Infection is the most common cause of hemoptysis. Acute and chronic bronchitis are the most
common respiratory infections causing hemoptysis. Primary bacterial infections of the lungs causing
hemoptysis are most commonly due to Staphylococcus,
Klebsiella, and Pseudomonas species. Pneumococcal
pneumonia rarely presents with hemoptysis, although
the sputum can be rust-colored. Often the infectious
agent responsible for the bronchitis cannot be isolated
and empiric therapy must be begun.
Tuberculosis is a common cause of hemoptysis.

The bleeding arises from anastomoses between
the bronchial and pulmonary circulations within
the tuberculous cavity walls. These lesions are sometimes called Rasmussen's aneurysms. Because the bleeding is not related to the tuberculous infection itself,
massive hemoptysis may occur even when distinct cavities are no longer visible.
Most pulmonary fungal infections can cause hemoptysis, and bleeding is most commonly associated with a mycetoma or a fungal ball. A
mycetoma is usually caused by Aspergillus fumigatus
growing in an old tuberculous cavity. TIle bleeding may
be caused by the release of certain fungal enzymes and
by local irritation.
A wide variety of immunologically mediated diseases may cause hemoptysis. The diseases can
be broken down into two groups. The first is
characterized by antibody-mediated damage to the pulmonary capillary membranes. The capillary damage may
occur in an isolated fonn or in conjunction with renal
failure, as in Goodpasture's syndrome. In the second
and more common group, pulmonary damage is caused
by deposition of antibody or immune complexes in the
lung. Lupus pneumonitis, periarteritis nodosa, sarcoidosis, Beh~t 's syndrome, and Wegener's granulomatosis
are examples of this group of diseases.
1m
Hemoptysis is seen in 10% to 20% of patients

with mitral stenosis. The hemoptysis is most
common in young people and tends to occur
after exercise. The bleeding is due to the rupture of
pulmonary veins and capillaries caused by the markedly
elevated left atrial pressure.
III
Hemoptysis may occur in either viral or bacterial bronchitis. Because the inflammatory process is localized to the bronchial tree, the chest
radiograph will usually be negative. In addition to standard cultures, bronchial brushings and washings should
be performed specifically for fungal or opportunistic disease.
II
Twenty-five percent to 40% of patients with

pulmonary embolus and infarction present with
hemoptysis. The suspicion of embolus is increased when the other "classic" symptoms of dyspnea,
cough, and pleuritic pain are present. The diagnosis of
pulmonary embolus should, however, be considered in
any patient with a sudden onset of hemoptysis.
DJ
Even after thorough examination, 5% to 15%

of patients have no explanation for their hemoptysis. A significant number of these patients
eventually manifest an initially occult disease during
careful follow-up.
1
Hemoptysis
Bronchogenic cyst
Pulmonary Implant of endometriosis
6
5 Metastatic disease
Positive
Infectious
Bacterial
Parasitic
7
Mycobacterial
Fungal
Negative
Immunologicdisea~es
Cysticfibrosis
Congenital lesions
Pulmonary sequestration
Hemorrhagic telangiectasia
Congestive heart failure
Primary cardiac disease
1
10
Mitralstenosis
Pulmonic stenosis
Eisenmenger's
syndrome
Foreign body
Bronchial wall telangiectasla
Pulmonary
infarction
A-V fistula
Pulmonary
Cecil Chapter
72
Harrison
]]
Chapter
13
hypertension
Idiopathic
Respiratory Dlsorden
Hemoptysis 17
CYANOSIS
Cyanosis occurs when the level of unsaturated
hemoglobin
reaches 5 g/100 011 of capillary
blood. Cyanosis is difficult to delect clinically
when serum hemoglobin is less than 7 gllOO 011. Car
boxyhemoglobinemia
may be confused with cyanosis
owing to the reddish Rush seen in this setting. Changes
in skin pigmentation,
such as the blue coloration seen
with argyria or the brownish discoloration
in Addison's
disease or hemochromatosis,
Olay also be confused
with cyanosis.
II
Raynaud's phenomenon
is defined as episodes
of pallor and cyanosis of the hands and feet,
usually in resJX>nse to cold or stress. When the
disorder is primary. it is caJlOO Raynaud's d.isease. The
disease is more common in women, with a peak occurrence between 20 and 40 years of age. The etiology
is unknown but may involve increased activity of the
sympathetic nervous system. The disease has been described in sevcra.! families. The secondary form of the
disorder is seen in association with several groups of
diseases. These include (I) occlusive arterial disease
such as thromboangiitis
obliterans; (2) connective tissue
diseases. including systemic lupus erythematosus.
rheumatoid arthritis. and sclerodennll;
(3) rcpclllt.d minor
trauma to the digits; (4) neurogenic disorders, including
thoracic outlet syndrome; (5) chemically induced fonns
secondary to drugs like ergotamine,
j3,-blockers, and
mcthyscrgidc,
as well as chemicals such as polyvinyl
chloride; (6) intravascular coagulation of blood elements
as seen in cryoglobulinemia
and will. {.'old agglutinins;
and (7) primary pulmonary hypertension.
Cyanosis that is greater in the upper extremities
is usually associated with transposition
of the
great arteries and a preductal coan.1ation of the
aorta. The SC{:ondary pulmonary hypertension
causes a
18 Respil"atory Oisorden CY'dllOSis
reversal of blood now in the ductus, with a resultant

increased delivery of oxygenated blood 10 the legs.
TIle pulmonary hypertension
associated with a
patent ductus arteriosus may lead to iru..:reased
cyanosis and clubbing of the feet compared to
the left hand and the relatively nonnal right hand. The
MdifTerential cyanosis~ is due to the reversal of blood
Row through the ductus, which enters the aorta distal
to the left subclavian artery.
Oxygen saturation
must be measured directly
by oximetry. The saturation reported on routine
blood gas detenninations
is a calculated value
and would therefore not detect abnonnal hemoglobins
such as carboxyhemoglobin
or methemoglobin.
Acrocyanosis
is a benign condition
in which
cyanosis is caused by congenital diITerences in
capillary density or transient local changes in
capillary flow with resultant increased oxygen extraction
by the tissues. Placing a cyanotic extremity in warm
water will reverse the cyanosis. There may be some
difficulty distinguishing
acrocyanosis
from Raynaud's
disease.
111e findings on cardiac examination in (he setting of cyanotic heart disease will depend on
the site of the abnormality, associated lesions.
and the duration and severity of the anatomic lesion.
The most consistent abnormalities
are pathologic murmurs. The electrocardiogram
(EKe) and the configuration of the heart on chest radiograph
may, at times,
be normal.
8
arterial
Cyanotic heart disease requires a major rightto-left intracardiac

shunt. The shunt lIlay be
primary or secondary to increast..-d pulmonary
pressure, with reversal of Row through an intm-
cardiac abnonnality. The cyanotic heart diseases may be

classified by their anatomic location. The great arteries
may be involved in patent ductus arteriosus (see No.4),
aorticopulmonary
window, or transportation of the great
arteries. The atria may be involved via an atrial septal
defect, anomalous
pulmonary
venous drainage,
or a
patent foramen ovale. Ventricular lesions such as ven
tricular septal defects, Fallofs tetralogy, and single ventricle may be associated with {.yanotic heart disease.
Mismatched
perfusion defects seen on a venti
lation-perfusion
(VQ) SC~\J1 are specific for pulmonary embolus. The scan may, however. be
more difficult to interpret in the presence of other Illng
abnormalities
or when matched defects are seen. The
pulmonary arteriogr.un rem<lins the gold standard III the
diagnosis or exclusion of pulmonary embolus.
1m
The most common causes of cyanosis secondary

to abnormal hemoglobin
are methemoglobinemia and sulOlCmoglobinemia.
Methemoglohinemia may be congenital
or due to the ingestion of
sulfonamides,
nitrites, or aniline derivatives in susceptible individuals. SulOlemoglobinemia
may be the result
of ingestion of toxic doses of phenacetin or acetanilid
or exposure 10 la~e amounts of aromatic amino and
nitro compounds.
Excess hydrogen sulfide produced in
the intestine has also heen implicated in this disorder.
Unlike methemoglobinemia,
which is reversible whell
the cause is diseontinut."d. sulOlemoglobint'mia
may fX'rsist for weeks.
Peripheral
Raynaud's phenomenorv'disease
vasoconstricting
Localized --{
drugs
Arterial occlusion
..
Congenital heart disease ~
.5 Upper
4
extremity -
Lower extremity -
transposition of great arteries

patent ductus ar1eriosus
1
Cyanosis
Cyanotic
heart disease
Pulmonary embOlus
Abnormal hemoglobin
Interstitial panem
-f
Pneumonia
Pulmonary edema
Interstitiallibr05ls
Emphysema
Hypennllalion --{
Cecil Chapter
92
Harrison
]6
Chapter
Mass lesions
Bronchitis
Pulmonary A-V malformations
Respiratory Disorders Cyanosis
19
LABS
PLEURAL
EFFUSION
II
A pleural effusion is an abnormal accumulation

of fluid within the pleural space. The fluid may
be an ultrafiltrate of the plasma, an inflammatory exudate, chyle. or blood (see No.3).
Effusions of
more than 300 ml may be detected on physical examination as decreased fremitus and dullness to percussion.
Effusions of greater than 2000 ml may cause severe
dyspnea and mediastinal shift. On chest radiographic
examination,
effusions of less than 300 ml are usually
noted on the lateral flIm only. Effusions of less than
150 ml may be seen only on lateral decubitus films.
II
Pleural effusions will occur in more than half of

the patients who develop a pulmonary embolus.
Effusions rarely develop. however, unless pulmonary infarction has also occurred.
The effusion is
usually bloody and occasionally bilateral.
Most pleural effusions have traditionally

been
classified as transudates
or exudates based on
the protein concentration
of the fluid. Greater
than 3 gtlOO ml of protein denotes an exudate, whereas
less than 3 ylOO ml indicates a transudate.
Recent evidence has <lemonstrated
that the use of this criterion
alone leads to an inaccurdte classification in more than
10% of cases. A more accurate diagnosis of an exudate
may be made when three separate criteria are met: (1)
a pleural fluid protein-to-serum
protein ratio of 0.5 or
greater;
(2) a pleural
fluid lactate dehydrogenase
(LDH)-to-serum
LDH ratio and more than 0.6; (3) an
absolute pleural fluid LDH greater than 200 UIL. The
glucose concentration
or the absolute cell count of the
fluid is less specific. A glucose concentration
of less than
60 109/ell, however, is usually associated with an exudate.
4~
Meigs' syndrome is the triad of ascites, ovarian

tumor, and large pleural effusion. 1be tumor
may be malignant or may be a benign fibroma.
Pleural Effusion
The effusion is serosanguineous

and usually resolves
after the removal of the tumor. The mechanism of the
effusion is not understood,
but Meigs' syndrome should
be considered when the source of the effusion is obscure and there is evidence of pelvic disease.
Pleural fluid pH is of value in the further differ
entiation of exudative effusions. With the exception of direct rupture of gastric contents into
the pleural space, the pleural fluid pH is detennined
by
both fixed acids and CO2 content.
Damaged
pleura
decreases CO2 efflux from the pleural space, causing
pH to fall. An exception is the alkaline pH of the pleural
fluid at times associated with congestive heart failure
and empyema owing to Proteus mirabilis infection.
Empyema is defined as pus in the pleural space.

The empyema develops as a result of infection
in the pleural space, or as a complication
of
pneumonia with spread of the infection into the pleural
space. Common
pathogens
include
Staphylococcus
aureus, Streptococcus pneumoniae, and gram-negative
and anaerobic organisms. The empyema usually contains a white blood cell count of greater than 1O,()()(V
mm:l, A parapneumonic
effusion, on the other hand, is
an effusion that resembles a true empyema but develops
as a result of local inflammation
near the site of a
pneumonia
without direct extension of the infection
into the pleural space.
Rheumatoid pleuritis develops in approximately

5% of patients with rheumatoid
arthritis. The
effusion usually occurs in the absence of rheumatoid lung disease. The pH and glucose are low, and
rheumatoid
factor is usually present. The effusion may
~rsist for weeks following successful treatment of the
direase.
8:
Pleural Auid cytology is positive in 50% to 75%

of patients with malignant processes involving
the pleura, False-negative
resuJts may be due
to the chronicity of the effusion or degeneration

of the
malignant cells during processing of the sample. A pleu-
ral biopsy may be necessary if cytology is negative and

there is a strong sllspicion of malignancy. Needle biopsy
of the pleura and open thora<.'otomy are the most commonly employed
techniques
for determining
malignancy, but the endoscopic procedure of pleuroscopy in
well-trained hands may be useful as well, In the absence
of direct pleural involvement,
malignancy may cause
pleural effusion through lymphatic obstruction,
endobronchial obstruction
with postobstructive
pneumonia,
or atelectasis. Under these conditions, pleural Auid cy_
tology will be negative.
Metastatic disease, most frequently from carcinoma of the oolon or breast. is the most common fonn of pleural malignancy. However, malignancies arising from virtually any other tissue may
involve the pleura. Primary malignancies of the pleura
are rare. Mesotheliomas
arc the most common primary
pleural tumors. In older age groups, 30% to 40% of
pleural effusions are malignant.
1m
Tuberculous
effusions may be found even in
the absence of other radiographic
findings of
active tuberculosis. The effusion may represent
a pleural reaction to the tuberculous
protein. For this
reason, smears and cultures of the pleural Auid for acidfast organisms are rarely positive. Culture of pleural
tissue obtained
at biopsy, however, yields a positive
result in 55% to 80% of cases. Because of the ubiquitous
nature of this disease, all specimens of pleural Auid or
tissue should be cultured for tuberculosis.
II
Several drugs have been associated with pleurd.l

effusions with or without pleural disease. These
include nitrofurantoin,
dantrolene,
methysergide, bromocriptine,
procarbazine,
and amiodarone.
Pleural effusions are usually associated with an eosinophil count of greater than 10%,

Thoracic duel trauma
Granulomatous disease
2
Pulmonary infarction
Malignancy
1
Pleurtll
effusion
Trauma
Resolving congestive heart failure
Cirrhosis
Nephrotic syndrome
Hypoalbuminemia
Acute atelectasis
Meigs' syndrome
Churg-Strauss syndrome
6"[
Empyema or parapneumonic effusion
Rheumatoid pleuritis
Drug reaction
Cecil Chapter
Harrison
Chapter
Trauma
86
Uremia
Pericardial disease
262
pleural Effusion 21
HYPERCARBIA
Hypercarbia,
or the increase of CO2 in the
blood, is measured by an increase in the partial
pressure
of CO2 (PC02). Hypercarbia
occurs
when the lungs are unable to excrete the normal 13,000

to 15,000 mmol of CO, produced by the body daily.
Because there is rarely an increase in bodily CO2 production, hypercarbia almost always represents decreased
alveolar ventilation (hypoventiJation).
Hypoventilation
is
produced by a decrease in the minute ventilation (the
amount of air exchanged by the lungs in 1 minute) or a
ventilation-perfusion
mismatch.
II
The equation
CO2
+ Hz()....+H COr-JoH ~ + HC0

2
3-
tary control of respiration.

Spinal cord lesions at the
CI-C2 level may produce dysfunction of both voluntary
and autonomic pathways. Lesions at the C3-C5 cord
level produce dysfunction
of the phrenic nerve and
diaphragmatic
paralysis, leaving only the accessory muscles of respiration functional. Lesions in the lower cervical and thoracic cord may impair expiratory and intercostal muscle function. Polio and amyotrophic
lateral
sclerosis (ALS) damage the anterior horn cell of the
cord, whereas
primary
myopathies
affect
muscle
strength
directly. Many of these lesions may cause
nearly total respiratory
paralysis requiring ventilator
support, and all are associated with the acid-base abnormalities of chronic hypoventilation.
Malnutrition
may
contribute significantly to neuromuscular
weakness.
defines how an increase in the CO2 will increase H +

concentration,
leading to respiratory acidosis. The H ~ is
then buffered by non bicarbonate buffers such as plasma
proteins and hemoglobin, causing an increase in HC03as Peo2 rises (see No.4).
Chronic obstructive pulmonary disease (COPD)

is the most common cause of chronic hypercnrbia, The hypoventilation
results from a combination of ventilation-perfusion
mismatch
and an increase in dead space. Hypoxemia is frequently present
and is due to the same mechanism.
II
II
Because none of the body's buffering systems

can overcompensate
for a respiratory acidosis,
a pH greater than 7.40 represents
a primary
metabolic alkalosis with the hypercarbia as a compensatory mechanism.
When the Peo2 rises acutely, the H" liberated

is rapidly buffered by i.nte.rcellula~ b~ffers (see
No.2). nle small but SIgnificant nse III HCOJpartially buffers the expected fall in pH, This buffering
occurs within the first 10 to 15 minutes. Usually serum
HC03 - rises 1 mEqIL for each 10 mm Hg rise in Peo2,.
Over the course of several days, renal buffering mechanisms come into play and the HC03 - rises further. The
increased H C03 - is the result of increased renal H"
excretion in the form of NH . with consequent
HCOJgeneration. Under chronic conditions, the HCOJ - may
rise by 3.5 mEqlL for each 10 mm Hg rise in Peo2'
Therefore, the HCO] - concentration
is a useful tool in
differentiating
between acute and chronic respiratory
acidosis.
Respiratory neuromuscular
weakness may result
from dysfunction of the motor nelVes, the neuromuscular junction, or the muscle cells themselves. Lesions in the central nelVous system manifest
themselves according to the site of the lesion. Lesions
in the motor cortex or pyramidal system produce weakness of the voluntary muscles of respiration, Lesions in
the medullary reticular formation disrupt the involun-
22 Respirator")' Oisorden
Hypercarbia
The severity of the hypoventilation

seen with
kyphoscoliosis is related to the degree of deformity of the spine and rib cage. The deformity
causes changes in the relation and Icngth of the diaphragm and the intercostal muscles. Ventilatory volumes
fall in proportion to the degree of deformity, leading to
the development
of chronic hypoventilation.
Pickwickian syndrome, or obesity-hypoventilation syndrome, is a constellation of abnormalities, including an increase in body weight of
more than 50%, depressed
ventilatory response to in
creased Peo2, obstructive sleep apnea, and weaker than
normal respiratory muscles.
Acute respiratory acidosis is the result of a de

crease in alveolar ventilation to the degree that
ventilation
is insufficient
to excrete the CO2
load presented to the lungs. The CO2 load presented to
the lungs may be increased by increased metabolism
(catabolic states), metabolic acidosis with bicarbonate
buffering, and nutrition high in carbohydrate.
The de
crease in ventilation occurs when the work of breathing
is increased or the ventilatory drive is decreased. The
work of breathing includes both resistive work, which is
increased
in obstructive
processes,
and elastic work,
which is increased in restrictive processes. Ventilatory
drive is controlled by the respiratory center and may
be decreased by a variety of mechanisms
(see Nos. 5
and 15).
1m
Generalized
pulmonary edema with severe hypoxia and CO2 retention <..'Onstitutes adult respiratory distress syndrome (AHDS). Many conditions are associated
with this disorder,
indudin~
infections, trauma, aspiration,
drug overdose, inhaled
toxins, intravascular
coagulation,
uremia, pancreatitis.
and increased intracranial pressure.
Respiratory acidosis occurs late in the COHfS() of

pulmonary edema. Although the exact mechanism is unclear, one theory states that an increase in Peo2 is more a function of the increased work
of breathing
than CO2 retention and usually si~llifies
the need for ventilatory support.
Hypoventilation
is a late manifestation
of pulmonary embolism and signifies respiratory muscle fatigue, Because the Pc02 is usually de
creased in the period immediately following pulmonary
embolism, an increase in the Pc02 usually means that
ventilatory support in needed.
II
Respiratory
muscle strength is best measured
by maximum inspiratory pressure (Plmax) and
maximum expiratory
pressure
(PEmax). The
normal values are age- and sex-dependent.
Plmax ranges
from -75 to - 12.5 cm H20 in males and - 66 to - 90
cm H20 in females. PEmax mngcs from 130 to 2],5 em
H20 in males and from 105 to 135 cm H20 in females.
Both neurologic and primary muscular ahnonnalities affect these measurements,
as does nutritional status.
III
Guillain-Barre
syndrome is the prototype of the
peripheral neuropathies
that may prodlll ..;c sufficient respiratory muscle weakness to cause hypoventilation.
Iso]ated phrenic neuropathy,
as well a'i
alcoholic neuropathy, usually associated Vvilh hypophosphatemia, may also cause respiratory failure,
~
II
The forced expiratory volume over I second

(FEVI) and the peak expiratory Row rate are
useful tests in the diagnosis of airflow obstru(;tion. Respiratory acidosis in the setting of obstructive
disease is an ominous sign and usually signifies profound
respiratory muscle fatigue. An FEVl of less than 1 U
see and a peak flow of less than 100 Umin are associated with severe aiIWay obstruction
and increased risk
of hypercarbia.
II
Drug-induced
hypoventilation
may be caused
by depression of the respiratory center by opiates, anesthetics,
tricyclic antidepressants
(in
large doses), tranquilizers,
and barbiturates.
Paralysis of
the respiratory muscles may be induced by depolarizing
agents such as succinylcholine,
Compensatory respiratory acidosis

~COPD
Parenchymal lung disease ~
End-stage Interstitial lung disease
ChronIC
respiratory
acidoSIS
1
Hyper~rbl.
(hypoventilation)
P~>45mmHg
Anatomical
-----;c
7
KyphoscoliosIS
PlckwlCklan syndrome
Pol,o
Amyotrophic lateral sclerOSIS
Neuromuscular
Spinal cord Injury

Muscular dystrophy
p"eumO"ia
Parenchymal lung disease
____
r
L
10
AROS
11
Pulmonary edema
~
12
Pulmonary embolus
Pneumothorax
Anatomical
Flail chest
Airway obstruction
Acute
respiratory
acidosis
Bo"h'm
Neuromuscular weakness
Hypokalemia
Hypophosphatemia
{
14
GUillatn-Barre syndrome
Myasthenia gravIs
Asthma
Obstructive disease --{
6
CNS
Cecil Chapter
Harrison Chapter
90
Emphysema with acute

bronChospasm
Drugs
CNS lesion
O2 administered
in chrooic hypoxia
263
CO2 inhalationlrebreathing
Bibliography
Braman SS (00): Pulmonary signs and symptoms. Clin
Chest Med 8(2),21-26,
1987.
O'Neil KM, Lazarus AA: Hemoptysis
indications
for
bronchoscopy. Arch Intern Moo 151:171-174,1991.
Poe RH, Israel RH: Problems in Pulmonary Medicine

for the Primary Physician. Philadelphia,
Lea & Febiger, 1982.
Taylor RB: Difficult Diagnosis
2. Philadelphia,
WB
Saunders, 1992.
Vladutio
1986.
AO:
Pleural
Effusion.
New
York,
Futura,
Hypercarbia 23
Cardiovascular Disorders
Signs and symptoms:
Chest pain
Hypotension
Syncope
Edema
Cardiac troponin I (cTn I) is an extremely sensitive

indicator of myocardial damage. It is found in the blood
within minutes after the infarction and is the earliest
marker now available. Cardiac troponin I may replace
CK-M B as the enzymatic indicator of choice. Serum
arpartate aminotransferase
(AST, formerly SCOT) and
lactic dehydrogenase (LDH) are also elevated between 1
and 3 days after myocardial infarction and may be measured if the first enzyme measurements
are performed
after the CK-MB may have peaked or returned to normal.
Hypertension
Murmurs
Labs:
Cardiomegaly
SIGNS AND SYMPTOMS

CHEST
PAIN
Chest pain is one of the most common
medical
complaints. The cause of the pain may be obvi-
ous, but the pain may present in an atypical

manner in a significant number of patients. Because the
etiology of chest pain can range from trivial to lifethreatening,
a thorough and extensive evaluation may
be necessary. Any of the structures
within the chest
except the lung parenchyma and the visceral pleura may
be responsive to painful stimuli. The mechanism of pain
from the ischemic myocardium is poorly understood but
is the result of an oxygen supply-demand
imbalance.
II
The diagnosis of myocardial ischemia is of great

importance in patients with chest pain. A history
of "typical" ischemic pain such as substernal
pain, a pressure or squeezing sensation with radiation to
the jaw, shoulders, or the ulnar aspect of one or both
arms, requires further evaluation. In addition, pain associated with exertion, heavy meals, or emotional stress is
suspicious. Rest pain, especially at night, may also represent ischemia related to coronary artery spasm. Patients
with risk factors for coronary artery disease should be
evaluated even if the pain is not typical for angina. These
risk factors include age, family history, hyperlipidemia,
hypertension, smoking, and diabetes.
The most reliable enzymatic indicator of myocardial infarction has been creatine kinase (CK).
An elevation of the myocardial specific fraction,
or MB isoenzyme, is diagnostic of myocardial damage.
The CK-MB increases in the serum 1 to 3 hours after
the infarction and peaks between 12 and 24 hours. The
level of CK-MB may return to normal within 36 hours.
Therefore, serial measurements
of this enzyme should
be started as soon as possible after the episode of pain.
24 Cardiovascular Disorders
Chest Pain
When myocardial ischemia is suspected to be a

cause of the chest pain, but no supportive evidence can be obtained from the electrocardiogram (EKe) or the cardiac enzymes, exercise testing
may be necessary. The standard treadmill examination
is a graded exercise test in which an attempt is made to
achieve 80% to 85% of maximal predicted heart rate.
ST segment depression of 1 to 2 mm on EKe during
the treadmill examination will predict myocardial ischemia in up to 75% of cases. An ST depression greater
than 2 mm will predict up to 95% of patients with
myocardial ischemia. The sensitivity of the standard
treadmill
may be greatly reduced by baseline EKe
abnormalities,
including digitalis effect, left ventricular
hypertrophy
(LVH), hyperventilation,
left bundle
branch block, mitral valve prolapse, or other conduction
abnormalities.
I n these cases, more specific imaging
using nuclear or echocardiographic
techniques
may be
necessary. The thallium treadmill is the standard treadmill examination with the addition of injected radioactive thallium. The thallium is not taken up in poorly
perfused areas of myocardium
and may therefore increase the sensitivity of the standard treadmill and aid
in treadmill interpretation
when the baseline EKe is
abnormal. Recently, the stress echocardiogram
has become a useful tool in the diagnosis of ischemic cardiac
disease. The test combines the standard treadmill exam
ination with an echocardiographic
image of cardiac
function. This technique
gives a sensitive indicator of
the presence and location of the ischemia. In skilled
hands, the stress echocardiogram
may substitute for the
thallium test, thereby eliminating the need for raruonuelide administration.
The Holter monitor may be useful
in determining
whether
those patients experiencing
chest pain at rest manifest any ischemic changes on
EKG. Future advances in magnetic resonance imaging
(MRI), as well as positron emission tomography (PET),

may further refine the diagnosis of myocardial ischemia.
II
If, by history and absence of risk factors, a

cardiac souree of chest pain is unlikely, the
physical examination may help differentiate between noncardiae causes of chest pain. Positive findings
on physical examination
related to chest pain include
dyspnea, tachypnea,
wheezing, intercostal
muscle retraction, use of accessory muscles of breathing.
decreased or absent breath sounds, rhonchi, rales, fever,
cough, hemoptysis, and cyanosis. It should be noted,
however, that many of these same physical signs may be
present with cardiac chest pain as well.
Lung imaging is usually begun with a nuclear
ventilation-perfusion
scan when pulmonary embolism is suspected. Mismatched defects in the
perfusion scan are suggestive of pulmonary embolization. Many abnonnalities
of the lung and pleura may
cause an abnormal lung scan; therefore, a positive scan
indicates only a high probability of pulmonary emboli.
The definitive
diagnosis of pulmonary
embolization
must be made with a pulmonary
angiogram. Where
available, spiral computed tomography (CT) of the lungs
may provide a one-step definitive diagnosis.
Many patients with mitral valve prolapse complain of occasional chest pain. At times the pain
associated with mitral valve prolapse may be
indistinguishable
from typical angina but is more often
sharp and well localized. The pain is usually unrelated
to exertion and may last from minutes to days. The
mechanism
for the pain is poorly understood,
but
stretching of the valve leaflets, coronary artery spasm,
and increased ventricular
wall tension have all been
proposed as possible etiologies.
Herpes zoster may present as chest pain prior

to the onset of typical skin lesions. The burning
quality of the pain,' its location, and the age
of the patient are important
clues to the diagnosis.
Postherpetic
neuralgia is common and may last well
after the skin lesions have cleared.
II
Costochondritis,
or TIetze's syndrome, is one of
the most common causes of chest pain. The
pain is due to an inflammation of the costochondral cartilage. Costochondritis
may be associated with
trauma or exercise and commonly occurs following viral
Hypertrophic
a1rdiomyop1th)'
Perk:arditi.
AortieJlel'lOllJs
Myocarditil
7
MilrlilJvaNe
prolapse
Aortic aneurysm
PM""""",,
Pleoraleltullon
P~"""
illnesses. The most common sites for pain are over the
second, third, and fourth costochondral
cartilages. An
important clue to the diagnosis is point tenderness elicited by palpation directly over the cartilage. A palpable
enlargement
of the cartilage is also common.
1m
Many diseases of the gastrointestinal

(GI) system may cause chest pain. Chest pain most
often results from abnonnalities in the esophagus, stomach, or gallbladder. Evaluation of the GI tract
may include upper GI series, esophageal motility studies, the Bernstein lest, gallbladder and pancreatic ultrasound, and cr scanning, as well as liver and biliary tract
nuclear scanning.
II
Variant angina, also known as Prinzmetal's angina,

is chest pain wiO} a propensity to occur at rest.
The EKe may have associated ST segment ele
vation. The pain is due to myocardial ischemia, thought

to be caused by coronary artery spasm. The spasm
usually occurs in conjunction with some fixed coronary
artery lesion. The pain is relieved by nitrates. Variant
angina is usually diagnosed by finding ischemic EKG
changes during rest pain. The spasm may be evident on
coronary angiography only when provocative tests such
as the administration
of ergonovine are performed.
Cecil Chapter
38
Harrison
13
Chapter
Cardiovascular Dlsorden
Chest Pain 25
HYPOTENSION
II
Hypotension
is defined as an abnormally low
blood pressure accompanied
by systemic symp-
toms. These symptoms include lightheadednes5,

visual changes. decreased mentation, syncope, and
shock. Because blood pressure may vary so widely
among various individuals, a "low blood pressure" in the
absence of the above symptoms may be normal and
should not be considered true hypotension.
Orthostatic hypotension is commonly defined as
a drop in systolic hlocxl pressure of 10 mOl Hg
or greater, accompanied by an increase in heart
rate of 10 hpm or greater when the patient assumes a
sitting or standing position. These changes must persist
for more than 2 minutes. Certain drugs or cardiac conduction abnormalities
may prevent the expected
increase in heart mle and may make the hypotension
Orthostatic
hypotension
vere forms of peripheral
eases most commonly
neuropathies
include diabetes
amyloidosis, Wernicke's disease,
may be caused by seneuropathy. The disassociated

with these
mellitus, renal failure,
syphilis, and porphyria.
Hypotension
accompanied
by decreased tissue
perfusion is the definition of shock. Inadequate
tissue perfusion is manifested by organ dysfunction and a change from aerobic to anaerobic metabolism
at the cellular level. The metabolic end product of
anaerobic
metabolism
is lactic acid with a resultant
increased anion gap metabolic acidosis. The most reliable indicators of organ dysfunction due to inadequate
tissue perfusion include decreased mental status, absence
of peristaltic activity in the intestines, decreased pulmonary gas exchange. and cool pale skin. Any of these signs,
with the exception of the lactic acidosis, may. however,
be associated with other disease processes.
more severe.
Intravascular
blood volume may be evaluated
by physical examination.
The most reliable
physical findings include skin turgor, moistness
of the mucous membranes, amount of axillary perspiration, and the height of Ule jUboular venous blood column.
When these signs are not readily apparent, or when a
more accurate assessment of intravascular blood volume
is necessary, central venous or pulmonary artery wedge
pressure may be measured.
26 CardiovaKular Disorders
Hypotension
Symptomatic nonorthostatic
absence of decreased tissue
due to transient vasomotor
sode of hypotension
is short-lived
to either stimulation of the vagal
vagal tone.
hypotension in the
perfusion is usually
instability. The epiand usually related
nerve or increased
Decreased intravascular blood volume may be

actual or relative. Actual hypovolemia is caused
by the loss of red blood cells or plasma water
from the vascular space. Relative hypovolemia is due to

vasodilatation with subsequent
inability of the circulating blood volume to maintain the blood pressure. Vasodilatation is the cause of the hypotension
that occurs
with sepsis, neuropathic hypotension, anaphylactic reactions, and some drugs. The clinical signs associated
with actual and relative hypovolemia are similar. The
determination
of whether actual blood volume has been
lost may require measurement
of systemic vascular resistance and cardiac filling pressures by a balloon Rotation catheter.
Neuropathic
forms of hypotension
are caused
by interruption
of the descending pathways in
the spinal cord associated
with spinal cord
trauma, including trcUlsection and edema, syringomyelia,
and spinal tumors. Epidural and spinal anesthesia may
also cause profound neuropathic
hypotension.
Certain
drugs. most notably the barbiturates,
may also cause a
neuropathic form of hypotension. Cerebral hemorrhage,
especially in the pontine area, may interrupt the descending sympathic pathways, causing profound hypotension.
Valvular abnormalities
that may lead to hytX)tension and shock include critical aortic stenosis, acute aortic insufficiency, and acute mitral
insufficiency. The latter is usually caused by a ruptured
papillary muscle or chordae lendineae.
Blood loss
Dehydration
3rt! spacing 01 fluid ~
Asci18S
Pleural effusions
Edema
Antihypertensives
Nilrales
Phenothiazines
Minor tranquilizers
Tricyclic antidepressants
1
Hypotension
TOllie shock syndrome

Hypovolemia
Sepsis
NeuropathIC
Anaphylactic
Drug-induced
Addisonian crtsis
Metabolic acidosis
-1
9
Cardiovascular hypotension
Cecil Chapter
Harrison Chapter
Heart lallure
Valvular dysfunction
Pericardia] tamponade
Arrhythmia
Pulmonary embolus
94
371
Cardiovascular Disorders
Hypotension
27
SYNCOPE
Syncope is defined as a sudden loss of consciousness and vascular tone. Similar altered
states of consciousness such as seizure. vertigo,
coma, or narcolepsy must be excluded from this definition, as the mechanism and etiology of these disorders
may be markedly different from those of true synrope.
Syncope is a common disorder, with up to 30% of the
population reporting at least one episode in their life.
Syncope must be evaluated especially in the elderly
patient, because the syncopal episode may predict future life-threatening events. In patients suffering a first
episode of syncope. approximately 55% of episodes will
have a vasovagal or psychobiologic etiology. 10% of
episodes will have a cardiovascular cause, 10% will be a
first seizure. 5% of patients will have other neurologic
wsorder.;, 5% of episodes will be drug-induced, and
15% will remain undiagnosed.
II
Syncope is associated with numerous drugs.

The mechanism may be the postural hypotension occurring INith many of the antihypertensive agents, diuretics, and nitrates, and various antiarrhythmics associated with torsades de pointes.
Orthostatic hypotension with occasional syncope is also
associated with the phenothiazines as well as some of
the minor tranquilizers and the tricyclic antidepressants.
Drugs of abuse have become increasingly associated
INith syncope. These include marijuana, cocaine, and
alcohol. Anaphylactic reactions, drug overdoses, and
drug-induced arrhythmias are also causes of syncope.
ShyOrager syndrome (idiopathic orthostatic
hypotension) is a rare disorder occurring usually
in middle age. The syndrome causes progressive
autonomic dysfunction. In addition to the orthostatic
hypotension, which may result in syncope, extrapyrami.
symptoms, se.U1alimpotency, urinary hesitancy, and
28 Cardiovascular Dlsorden Syncope
anhidrosis may be prominent features. The illness leads

to severe disability and death, usually INithin 5 to 15
year.;.
Subclavian steal syndrome is an unusual disor
der causing syncope as well as other symptoms
of vertebrobasilar
insufficiency. Blood is
shunted from the vertebrobasilar artery via the subclavian artery to one of the arms. The hallmark of the
disorder is the finding of differences in the blood pressure and pulse between the patient's arms. Syncope may
follow upper arm exercise.
Syncope is an uncommon presentation of a

transient ischemic attack (TlA). A TIA should
be suspected when syncope is associated with
other neurologic symptoms, especially in the vertebrabasilar artery distribution. A TIA should also be suspected when no cause of syncope can be found in a
patient at risk for cerebrovascular disease.
Many forms of cardiac monitoring are available

for the evaluation of the patient with syncope.
The standard 12-lead EKG should be perfonned to rule out obvious rhythm disturbances such as
heart block, other fonDS of bradycardia, and frequent
ventricular ectopy. The brief 12-lead EKG, however, is
often unrevealing, and a 24- or 48hour continuous
EKG reoording may be necessary. A diagnostic srudy
currently in use is the signal-averaged EKG. With this
method, the surface EKG is computer-enhanced to detect low-amplitude, high-frequency components that
may predict the possibility of inducible ventricular
tachycardia, especially in patients with underlying car
diac disease. T f an episode of syncope occurs during
continuous EKG monitoring without associated rhythm
disturbances, a cardiac etiology for the syncope can be
ruled out.
II
Carotid sinus massage may be useful in demonstrating carotid sinus h

ractivity as a source
of syncope when other >'tgnOStiC studies have
not been helpful. A positive result is obtained if an
asystolic pause of greater than 3 seconds occurs or a
decrease in systolic blood pressure of more than 50 mm
Hg without a change in pulse is noted. A history of
syncope associated with ruming of the head or tight
collars may give further clues to the diagnosis. Carotid
sinus massage should be performed with great caution
in elderly patients, as pennanent neurologic deficits
have followed this maneuver.
Vasovagal syncope is by far the most common

cause of loss of consciousness. It may occur at
any age but is more common in young patients.
The syncope usually occurs in response to emotional
stress or injury. The syncope is usually preceded by
symptoms of weakness, lightheadedness, sweating, nausea, and dimming of vision. The mechanism for the
syncope is probably dilatation of large vascuI", beds,
such as the mesentery, renal, and cerebral vessels, with~
out a compensatory increase in heart rate and cardiac
output. rut table testing has become an important diagnostic tool.
Situational syncope refers to syncope occurring

during nonnal bodily functions such as micturition, defecation, coudl, and swallowing. Micturition syncope occurs in middle-aged men, usually at
night and many times following consumption of large
amounts of alcohol. Rarely, micturition syncope has
been associated with a pheochromocytoma of the bladder
wall. Cough syncope follows a paroxysm of coughing.
Cough syncope most commonly occurs in obese middleaged men, many of whom also have a history of heavy
alcohol use. Acute pulmonary processes like asthma.
chronic obstructive pulmonary disease, and bronchiectasis have also been associated with rough syncope.
Blood loss
Hypoglycemia
Dehydration
Idiopathic postural hypotension
Stroke
Associated
neurologic
symptoms
-j
4
Shy-Drager syndrome
Subclavian steal syndrome
Peripheral neuropathy
Neurogenic syncope
Cerebral vasculitis
Post sympathectomy
Prolonged recumbency
Transient IschemIc attack (TIA)
Druginduced syncope
Spinal cord disease
Pulmonary embolus
1
Syncope
Pertorm
history
and
physical
Pulmonic stenosis
Dyspnea
Aortic stenosis
Perform
V/Q
scan
Septal hypertrophy (IHSS)

Mitral stenosis
Myocardial infarcation
Pericardial tamponade
Hyperventilation
Mass lesion
Hematoma
AV malformation
Pertorm
cardiac
monitoring
Epilepsy
Carotid sinus syncope
Perform
1 carotid
sinus
massage
Vasovagal syncope
Cecil Chapter
447
Situational syncope
Idiopathic syncope
Harrison Chapter
20
Cardiovascular Disorders.
Syncope 29
EDEMA
Edema is the excess accumulation of Auid in
the tissues. The etiology of the fluid accumulation may be the result of increased filtration of
fluid out of the vascular space or decreased removal or
interstitial fluid by the lymphatic system. The movement
of fluid out of the intravascular space is governed by
the relationship of hydrostatic pressure, oo<.'Otic pressure, and capillary permeability. An increase in hydro.
static pressure or capillary permeability or a decrease in
oncotic pressure will increase the movement of fluid
out of the intravascular space.
Intracardiac filling pressure can be estimated or

measured by a variety of methods. Right-sided
pressures can be estimated
by evaluating the
height of the jugular venous blood column. True right
atrial pressure,
or central venous pressure,
may be
measured directly by placing a catheter into the right
atrium through a peripheral, subclavian, or jugular vein.
Left-sided intracardiac pressures can be estimated using
a balloon-tip flotation catheter to measure the pulmonary capillary wedge pressure.
II
A two-dimensional
echocardiogram
can help
differentiate
between ventricular failure due to
poor myocardial contractility and restriction of
diastolic filling by pericardial disease. The two':'dimensional echocardiogram
will clearly demonstrate
ventricu
lar function and the presence of pericardia] thickening
or fluid. When pericardial restriction of ventricular filling becomes severe, cardiac tamponade
occurs. The
presence of a pulsus paradoxus of greater than 10 mm
Hg on physical examination or the equalization
of the
right atrial, pulmonary artery diastolic, and pulmonary
artery wedge pressures is diagnostic of pericardial tamponade.
30 Cardiovascular Dlsorden Edema
Many drugs have been associated with the formation of edema. Various mechanisms may be
involved, but the edema most often results from
the retention of salt and water or changes in capillary
permeability. The drugs most commonly associated with
edema include hormones
such as the corticosteroids,
estrogen,
progesterone,
and testosterone;
anti-inflammatory agents such as phenylbutazone,
naproxen, indomenthacin, and ibuprofen; antihypertensive
agents such
as minoxidil, c1onidine, hydralazine, the rauwolfias, and
some ~- and calcium channel blockers. Other drugs,
including the monoamine oxidase (MAD) inhibitors and
amantadine,
have also been associated with edema for
mation.
II
Idiopathic
edema occurs most commonly
in
women. Edema develops during the day and
resolves at night from the diuresis associated
with recumbency. Water excretion tests are occasionally
abnormal and can aid in the diagnosis. Compulsive salt
eaters may also present with idiopathic edema.
Edema associated with nutritional

deficiency
alone is uncommon in Westem cultures. When
food availability is nonnal, anorexia nervosa is
the most common
cause of malnutrition
and nutri
tionally associated edema. \hen edema is secondary to
decreased
protein synthesis from malnutrition,
other
signs, including cheilosis, red tongue, and severe weight
loss, are usually present.
The venogram is the definitive test to determine the resence of venous obstruction.
The
test itself,1owever,
has considerable
morbidity.
Adverse reactions to the venogram include infection,
allergic reactions
to the iodinated
contrast,
dye-induced renal failure, and as high as a 10% incidence of
new venous thrombosis
associated with the procedure
itself.
Lymphedema
is usually firm and nonpitting on
examination.
It is usually progressive and painless, with no evidence of venous stasis. The
edema may be due to inflammation
from infection,
surgery, trauma, or rAdiation. Lymphedema
from malignant involvement
of lymph nodes occurs most commonly with gastrointestinal
or genitourinary
tumors as
well as lymphomas. Magnetic resonance imaging alone
or combined with technetium
Tc 99m colloidal sulfur
Iymphoscintigraphy
is useful in detecting the site of the
lymphatic obstruction.
Noninvasive vascular testing provides a specific,

if somewhat less sensitive, method of detecting
venous obstruction.
Noninvasive testing such as
impedance plethysmography
and Doppler ultrasonography may be used in place of venography to avoid the
associated morbidity (see No.7). Impedance plethysmography measures blood volume changes in the calf produced by venous occlusion. These changes are detected
by changes in electrical resistance
measured by skin
electrodes.
Impedance
plethysmography
is a sensitive
predictor of proximal vein thrombosis with an accuracy
approaching
98%. The test is much less sensitive for
detecting calf vein thrombosis,
as many of the distal
vein thrombi arc nonocclusive.
Doppler ultrasonography, which measures changes in the velocity of blood
flow through the veins, is also a sensitive test for the
detection of proximal vein thrombosis but is more diffi
cult to interpret than impedance plethysmography.
l'2:lI
fibrinogen scanning detects thrombi that are making
fibrin. This test may be useful in the detection of calf
vein thrombi during their early development.
II
Edema associated with musculoskeletal

disorders is frequently fainful and acute in onset.
Common causes 0 musculoskeletal
edema include acute arthritis, tenosynovitis,
Baker's cyst, calf
muscle tears, and reflex sympathetic dystrophy (exaggerated edema fonnation following trauma).
Drug-induced
Idiopathic edema
1
Edema
Malnulrition
Uppe<
extremity
ma
Check
Jugular
venous
pressure (JVP)
Venous obstrudion
Capillary leak
Abnormal
proteln
lymphatic
obstruction
synthesis
Lower extremity edema
Extrinsic compression
Cecil Chapter
47
Harrison Chapter
37
Musculoskeletal
edema
Cardiovascular Disorders Edema 31
HYPERTENSION
Although some controversy exists, it is generally
agreed that a diastolic blood pressure of greater
than 90 mm Hg on two or more measurements
constitutes a diagnosis of hypertension.
A systolic pres~
sure of 140 mm Hg or more constitutes systolic hypertension. Systolic hypertension can be an isolated phenomenon or can occur in association
with diastolic
hypertension. The systolic blood pressure is much more
sensitive to transient elevation related to stress or other
external stimuli than is the diastolic blood pressure. Isolated systolic hypertension is most commonly associated
with advanced age, but other factors such as the decrease
in peripheral resistance seen with Paget's disease. arteriovenous shunts, and nutritional deficiencies like beriberi
can result in systolic hypertension.
Conditions that increase cardiac output such as anemia and thyrotoxicosis
are also associated with elevated systolic blood pressure.
II
Aldosterone excretion is best determined by the

measurement of 24hour urinary aldosterone ex
cretion after correction of hypokaJemia and fol-
lowing 3 days of salt loarung (200 mEqlday). Using this
technique, an aldosterone excretion of greater than 14 .

g
in 24 hours has a greater than 90% sensitivity and speciRcity for primary aldosteronism.
cr and MRI of the
adrenals should be penormed when the workur for primary aldosteronism is positive. If these tests fai to localize the tumor, adrenal vein sampling may be helpful.
Primary aldosteronism
accounts for only 1% of
the causes of hypertension.
Other syndromes
of mineralocorticoid
eX<..'Css,such as congenital
adrenal hyperlasia and defects in steroid synthesis, are
even more rare. Once the diagnosis of primary aldosteronism is made or suspected, cr or MRI of the adrenals
is the most useful diagnostic study to isolate the lesion.
Adrenal adenomas (60% to 85%), bilateral adrenal hy.
perplasia (15% to 40%), or, rarely. adrenal carcinoma
may be responsible for the increased aldosterone
synthesis. The importance of making this diagnosis lies in
the fact that the hypertension
is surgically curable.
Although secondary causes of hypertension

ac
count for only 5% of the estimated 60 million
people with hypertension
in the United States,
the incidence is much higher when the onset of hypertension occurs before the age of 30. In these young
patients, evaluation for secondary causes of hypertension is justified because not only is the incidence of
secondary hypertension
higher but the morbidity and
cost of lifelong medical treatment
may be avoided if a
curable form of hypertension
is found.
32 CardlOaSCular Disorders
Hypertension
II
In the past, the measurement

of 24-hour uri
nary excretion of 3-methoxy-4hydroxymandelic
acid, metanephrine,
and normetanephrine
were
the most commonly used tests for determining
excess
catecholamine
secretion. Currently, however, serum catecholamine determination
has been found to be a more
sensitive indicator. Sampling for serum catecholamine
levels must be performed
at least 30 minutes after
venipuncture
with the patient at rest in order to avoid
measuring the transient elevation in serum catecholamines resulting from pain and stress. Serum catechola
mine levels are extremely high in patients with pheochromocytoma,
with the mean approximately 8000 ngfL.
Pheochromocytomas
are rare tumors of neural
crest tissue. Approximately
85% are benign.
These tumors account for 0.5% to 1.0% of all
cases of hypertension.
Ninety percent of the tumors are
located in the adrenal medulla; the other 10% may
occur anywhere along the distribution
of the neural
crest (autonomic tissue). Approximately
10% of pheochromocytomas
are bilateral. Once a pheochromocytoma is suspected, cr scanning is the most useful diagnostic study. Tumors less than I cm in size may be
detected using 1311 metiodobenzylguanide
(1311
MIBG)
nuclear imaging. There is a strong association between
pheochromocytomas
and certain genetic diseases, including multiple endocrine adenomatoses
and neurocu
taneous disorders such as von Recklinghausen's
disease.
The administration
of central
adrenergic
blocking agents like c10nidine may be useful
when the serum catecholamine
level is mini
maUy elevated in a hypertensive patient. If the elevation
in catecholamines
is secondary to a pheochromocytoma,
the level will not be suppressed
by the drug. The test
is performed by administering 0.2 to 0.3 mg of clonidine
orally. If the serum catecholamine
is not within the
nonnal range after 2 to 3 hours, a pheochromocytoma
should be suspected.
The administration
of an angiotensin-converting
enzyme (ACE) inhibitor
like captopril
will
cause an exaggerated rise in plasma renin activ
ity (PRA) in patients with renal artery stenosis. The test
is performed
with the patient off all antihypertensive
medications and on a normal sodium intake. After the
patient is seated for 30 minutes, a baseline PRA is
obtained.
Fifty milligrams of captopril is given orally
uncler careful blood pressure monitoring. A PRA sample
is obtained at 1 hour. A positive test is determined
by a
stimulated PRA of 12 nwmllhr and an absolute increase
of 10 nwmllhr, or a 150% increase in PRA (the PRA
increase must be greater than 400% if the baseline PRA

is less than 3 nWmJlhr). This test has been shown to
have a sensitivity of 70% to 90% in screening for renal
artery stenosis and carries less morbidity than the rapidsequence intravenous
pyelography (IVP). ACE inhibi
tion combined with a WmTcdiethylenetriamine
pentatate
131
acid (DTPA) or a 1 orthohippurate
(Hippuran)
renal
scan witi) or without concomitant
furosemide administration has also been found to have a 95% to 98%
specificity and sensitivity in detecting renal artery stenosis. With these tests, a delay in the uptake of isotope by
the affected kidney not only predicts the presence of
renal artery stenosis but may help to predict the pa
tient's response to therapy.
II
Renal artery stenosis occurs in the young patient as a result of fibromuscular disease or in
the elderly patient as a result of artherosclerotic
disease. Among those patients with fibromuscular
dis
ease, there is a strong female predominance.
Atheroscle
rotic disease accounts for the remaining two thirds of
the cases of renal artery stenosis. Patients with rapid
onset of resistant hypertension,
especially in their early
twenties or late fifties, are highly suspect for renal ar
tery stenosis.
1m
Because the sensitivity of the captopril challenge may be as low as 70%, a renal angiogram
may be necessary to completely exclude renal
artery stenosis when plasma renin levels are markedly
elevated. The angiogram should be performed if there
is a strong clinical suspicion of renal artery stenosis or
if physical findings such as a renal artery bruit are
present. MRI of the renal arteries approaches the accuracy of the traditional arteriogram.
MRI tomography is
now available at many large medical centers and will
soon be more widely available. It should be noted that
elevated renin levels are seen in many hypertensive
patients witli normal renal arteries.
Resistant hypertension is defined as the inability

to control blood pressure with three agents.
When these patients are studied, 50% of them
will be resistant due to inadequate
dosing or issues
of compliance.
Many antihypertensives
cause a saltretaining state and a diuretic should be used before the
patient is con!idered
resistant. Other causes of resis
tance include drug interactions, possibly with overthe
counter (OTC) medications;
dietary changes; alcohol
ingestion; and stress reactions. All of these possibilities
should be thoroughly investigated before an extensive
workup for secondary causes is undertaken.
Birth control pills
Sympathomimelics
Cocaine
Drug-induced
hypertension
Corticosteroids
Primary hyperaldosteronism
Mineralocorticoids
Positive
1
Hypertension
Vasopressin
2
Check
urinary
akiosterone
excretion
Essentialhyperten~
Other secondary hypertensioo (see below)
Pheochromocytoma
Perform
c\onidine
suppression
test
Essential
hypertension
Renal artery
stenosis
Check
plasma
renin
Cecil Chapter
55
Harrison Chapter
35
CardiOaS<.ularDisorders
Hypertension 33
MURMURS
Cardiac munnurs are caused by the abnormal
flow, velocity, direction, or turbulence of blood
across an intracardiac
opening. Murmurs can
be characterized
by their location, radiation, intensity,
and quality. These features are extremely useful in the

diagnosis of the underlying abnormality. Murmurs may
be described as high- or low-pitched. Their con6gura.
tion may be crescendo,
crescendo-decrescendo,
even,
or variable. The murmur may be heard in systole or
diastole or continuously.
The portion of the cardiac
cycle, Le., early, mid-late, or throughout
(holo-), in
which the murmur is present has importance
in the
differential
diagnosis of the cardiac abnormality.
The
intensity of the murmur is typically described on a scale
of 1 to 6. A grade 1 murmur is barely audible with a
stethoscope. A grade 2 murmur is fainl but easily heard.
A grade 3 murmur is prominent but not loud. Grades 4
through 6 murmurs are accompanied
by a thrill.
The phonocardiogram
is a useful adjunct to
auscultation of the heart when the location of
the murmur is unclear or when more than one
murmur is present. The phonocardiogram
provides a
graphic display of the murmur, including its relationship
to the normal heart sounds. Simultaneous
recording of
the phonocardiogram
and carotid or jugular pulse waves
may also provide useful information. Some laboratories
may have the capacity to do simultaneous
phono- and
echocardio-graphic
recordings, thereby saving an extra
step in diagnosis. Pulsed-wave Doppler and color-flow
Doppler ultrasonogl1lphy add a further dimension to

standard echocardiography.
Both of these techniques
can sample Doppler shifts in moving objects. This is
especially useful in measuring peak velocity through
stenotic lesions.
34 Cardiovascular
Oisorders
Murmurs
II
Acute mitral regurgitation

may present as an
early systolic murmur instead of the more charac
teristic holosystolic murmur. This phenomenon
occurs because the regurgitant blood flow is into a normalsized and less distensible left atrium. As the pressure
in the abium rises rapidly, the blood flow is stopped during the early phase of ~tole. Over time, as the left abium
distends, the regurgitant blood flow may last throughout

systole. Papillary muscle rupture or dysfunction
most common cause of acute mitral regurgitation.
is the
II
When ventricular
septal defects (VSDs) are
large, the left-to-right shunting will cause pressure overload in the right ventricle and the pulmonary vasculature. As pressure in the right heart and
pulmonary resistance increase, there is a decrease in the
duration of the left-ta-right blood Row through the VSD,
decreasing the length or time the munnur is audible.
~
II
Many murmurs heard typically during midsystole are not associated witll any anatomic abnormality. These murmurs may be related to increased blood Row across one or more valves, as occurs
with anemia, fever, exercise, thyrotoxicosis,
and occasionally in normal persons. Benign murmurs may also
be due to other fonns of turbulence of the blood now
through the great vessels such as the pulmonary trunk
and aorta. Stilrs murmur is a benign murmur thought
to originate from periodic vibrations of the aortic or
pulmonary valve leaflets.
No.4).
In murmurs without valvular abnonnality, cardiac catheterization
may be necessary to diagnose the
etiology of the murmur.
Middiastolic
murmurs
may be the result of
increased blood flow or velocity across normal
atrioventricular
(A-V) valves. The murmurs may
be the result of blood low across the mitral valve in the
presence of V5Ds or a patent ductus arteriosus. Abnormal Row across the tricuspid valve is seen with ostium
secundum atrial septal defects.
The mid-diastolic
murmur heard in the presence of a mmplele
heart block is due to aotegrade Row across an AN valve that is in the
process of closing. The blood How occurs when atrial
contraction
mincides with the phase of rapid diastolic
filling in the recipient ventricle.
AV fistulas may occur in several arcas of the

heart. The most common connections
are between coronary artery and vein, as a left coronary artery arising from the pulmonary trunk. and as
communication
between a sinus of Valsalva aneurysm
and the right heart. The conllguration.
intensity, and
location of the murmurs will vary depending on the site
of the fistula.
1m
Noncardiac continuous murmurs usually result

from disturbances
to blood low in constricted
systemic or pulmonary arteries. These murmurs
most commooJy occur in patients with severe peripheral
vascular disease. Occasionally, continuous murmurs can
be heard with normal vasculature. An example is the
mammary souffie heard over the lactating breasts in late
pregnancy or the early postpartum period.
In the absence of valvular abnormalities,

holosystolic munnurs are the result of intracardiac
shunts between high- and low-pressure
cham.
bers or vessels. As the hemodynamic
consequences
of
the shunt cause pressure gradients to change over time,
the murmurs may change in intensity or duration (see
Large ventriculat septal delect
Aortic stltllOSislsderos
PulmorllCste~
1
Mitral regurgitation
Co"''''
murmur
Tricuspicl
regurgitatIOn
Small ventricular seplal defect

Aortic regurgflalion
Pulmonic regurgitation (high pressure)
Tricuspid regurgitation
Mitral stenosis
Tricuspid sHM'llls
PuVnonic regurgitation (low pressure)
Diastole murmuf
Ventricular septal del9Ct

Ostium secundum atrial septal defect
Patent ductus aneriosus
Complete hean block
Patent dJduI ar1eriosus

Aorticopulmonaty winc:low
Continuous
Cecil Chapter
Harrison
Chapter
murmur
38
Arteriovenous fistula
Exttacardiac
source
127
CardIOUCular Disorders
Murmun: 35
LABS
High-output
states cause cardiomegaly
by increasing cardiac work and increasing intracardiac blood volume. Clinical conditions associat~ with high cardiac outputs include severe anemia,
polycythemia vera, renal insufficiency, arteriovenous
fistulas and anastomoses,
erythrodenna,
Paget's disease,
hyperthyroidism,
and chronic hypoxemia. Both left- and
right-sided heart enlargement
may occur, and heart failure is common.
CARDIOMEGALY
Carwomegaly
is defined as any abnormal increase in the size of the heart. The increase in
size may be due to local or global increases in
chamber size, hypertrophy or infiltrative disease of the
myocardial muscle, pericardial effusion, or an aneurysm
of the myocardium.
Cardiomegaly
may be suspected
on physical examination or, more commonly, on chest
radiograph. These techniques may. however, underestimate or overestimate actual heart size, because hypertrophy of less than 1 em or single-chamber
enlargement
is difficult to detect by these methods alone. Techniques
such as echocardiography
(see No.2) have been developed to accurately measure cardiac size. Cardiomegaly
is usually the result of a chronic process; therefore, a
complete evaluation is necessary to determine
the disease process causing the cardiomegaly,
as well as the
physiologic consequences
that may result from the cardiomegaly itself.
Echocardiography
can provide invaluable information regarding both the anatomy and function of the heart. Chamber
size, myocardial
thickness, valvular motion and calcification, valve leaflet
thickness, and pericardial disease can all be detennined
accurately. Two.-dimensional and Doppler echocardiography can also give accurate assessments of overall cardiac function and regional abnormalities.
II
Infiltrative diseases of the myocardium include

amyloidosis, sarcoidosis, hemochromatosis,
and
Ulmer's myocarditis. The hypertrophy
of the
myocardium is secondary to the deposition of material
within the myocardial fibers themselves.
Infiltration of
the myocardium with melanoma, lymphoma, leukemia,
and metastatic carcinoma of the lung or breast has also
been described.
Congestive cardiomyopathy
with cardiomegaly
due to primary myocardial disease a<"'CQuntsfor
approximately
1% of the cardiac disease in the
United States but may represent up to 15% of cardiac
disease worldwide. Although the symptoms of a primary
myocardial disorder are similar to those of other fonns
of heart disease, the diagnosis should be suspected
when cardiomegaly
is discovered
in a patient who is
yo.ung. and nonnotensive
and has no evidence of ischemic disease.
The mechanism of cardiac dilatation secondary

to chronic ethanol ingestion is unknown but
appears to be metabolic in origin. The severity
of the disease is related to both the quantity and the
duration of the ethanol consumption.
Arrhythmias, congestive heart failure, and thromboembolic
events are
the hallmarks of this disorder. The 3-year mortality
exceeds 40%.
Asymmetric hypertrophic cardiomyopathy

(idiopathic hypertrophic
subaortic stenosis rIHSS])
occurs in both familial and sporadic
forms.
IHSS is defined as a septal.to-posterior
wall thickness
ratio of greater than 1.3 on echocardiogram.
Although
many patient's are asymptomatic, the most common clinical manifestations
include angina, dyspnea, syncope,
and palpitations. Most patients demonstrate
significant
obstruction to aortic outflow, which further intensifies
the left ventricular hypertrophy. A few patients will have
no evidence of outRow obstruction.
Drugs that increase
the force of left ventricular
contraction
or decrease
systemic resistance worsen the hemodynamic
effects
of the outRow obstruction and increase or precipitate
symptoms.
36 Cardiovascular Disorden
Cardiomegaly
Cardiomegaly secondary to a congestive cardiomyopathy may occur following a viral myocarditis. Croup B coxsackieviruses and the poliomyelitis virus are the most frequently associated agents.
Other viral illnesses that have also been implicated in
cardiomyopathies
include measles, mumps, influenza,
varicella, and infectious mononucleosis.
Myocardial in
jury probably results from direct cellular invasion by the
virus or from immunologic

well defioed.
processes
that are not yet
II
Doxorubicin
(Adriamycin)
myocarditis
is the
prototype of a drug-induced
myocarditis leading
to cardiomegaly.
The cardiomyopathic
effect
may occur at any dose but occurs most commonly if the
2
cumulative
dose exceeds 400 mg/m of body surface
area. Other drugs that have been associated with cardiomyopathies include emetine, tricyclic antidepressants,
the sulfonamides, and the phenothiazines.
II
The familial cardiomyopathies

are rare causes
of cardiomegaly. Cardiac enlargement
is due to
congestive
cardiomyopathy.
Included
among
this group of diseases are endocardial fibroelastosis, Fabry's disease, Pompe's disease, and Hurler's syndrome.
II
Laboratory examination in the evaluation of cardiomegaly

should include a complete
blood
count (CBC), sedimentation
rate, electrolytes,
glucose, Ca, Mg, P04, antinuclear
antibodies (ANA),
blood cultures for bacteria and fungi, and thyroid func
tion studies.
II
Several of the collagen-vascular

diseases are associated with congestive cardiomyopathy
and
resultant
cardiomegaly.
Progressive
systemic
sclerosis (scleroderma)
may cause myocardial fibrosis.
Systemic lupus eryt.hematosus
(SLE) may affect any
area of the heart, including the myocardium. Rheumatoid arthritis usually involves the pericardium
but may
occasionally involve the myocardium itself.
Bibliography
Alpert JS. Rippe JM (ecls), Manual of Cardiovascula,
Diagnosis and Therapy. Boston, Little, Brown, 1985.
Goldman L. Bennett JC (eds), Cecil Telrlbook of Medicine. 21st ed. Philadelphia, WB Saunders, 2000.
Horwitz LD, Croves BM (cds): Signs in Cardiology.
Philadelphia, JB Uppincott,
1985.
Kapoor WN: Diagnostic evaluation of syncope. Am J
Med 90,91-103, 1991.
Taylor RB: Difficult Diagnosis 2. Philadelphia,
WB
Saunders, 1992.
Asvmmetnca,
-HypertrophIC
1
Cardiomegaly
Muscular hypertrophy
cardiomyopathy
(IHSS)
Hypertension
Coarctation 01 aorta
Pulmonary stenosIs
ASO
Congenital
{disease
Symmetrical
Anatomic abnormality
VSD
PDA
Ebsteln's
anomaly
Fallot's tetralogy
Effusion
Infiltrative disease
PericardJa!disease {
Valvular Aortic
disease- stenosis
~[Hjgh-output
Normal
anatomy
:rCor
stales
pulmonale
Infinrative disease
Subacute
bacterial endocarditis
Mitral insufficiency
Valvular abnormality
Mitral valve prolapse
{
Aortic insufficiency
Marfan's syndrome
ETOH
Posl viral
DNg.
Post radiation
Ischemic cardiomyopathy
Familial disorders
Renal failure
Dilated chambers
(congestive
cardiomyopathy)
VaNes normal
Cecil Chapter
Harrison Chapter
44
227
Silent ischemia
Idiopathic cardiomegaly
Cardlcwascular Disorders
Cardiomegaly 37
II Gastrointestinal
Signs and symptoms:
Constipation
Diarrhea
Gastrointestinal bleeding
Dysphagia
Abdominal pain
Jaundice and
hyperbilirubinemia
Hepatomegaly
Ascites
Labs:
Transaminitis
Elevated alkaline
phosphatase
SIGNS AND SYMPTOMS
Disorders
tered. bowel habits with constipation. The cause is not
known, but the disorder is seen more commonly in
association with long.standing diabetes. Autonomic de
nervation of the proximal gut is the likely etiology.
4~
Although a very rare cause of constipation, diuretics can result in constipation by causing
dehydration or hypokalemia.
Calcium- and aluminum-{X)ntainingantacids are

a frequent cause of constipation. Magnesium.
containing antacids are associated with diarrhea.
Approximately 25% of large bowel cancer occurs in the rectum so that digital rectal exami
nation is essential to the investigation of consti
CONSTIPATION
There is no universal definition of constipation
because bowel habits vary widely among individuals. Constipation must be discussed in the
setting of change from the baseline habits of an individual Bowel-conscious patients may report constipation
because they are fixated on the amount and regularity
of bowel movements they perceive as "normal," when
in fact no abnormality exists. In addition, subjective
reports of stool frequene-y are often inaccurate. In gen-
eral. fewer than three bowel movements a week is very

unusual. The term constipation is often used by patients
to refer to a variety of abnormalities. The use of the
word "constipation" should be investigated individually
with each patient to identify the meaning they have
ascribed to the word. Constipation can be defined as
infrequent bowel movements, but most patients with
chronic constipation complain of the need to strain to
defecate. Straining to defecate is one of the best indica
tors of constipation. Other patient complaints with con
stipation include incomplete evacuation, painful defeca
tion, or hard stools. If constipation is chronic by history,
a trial of bulk agents is usually indicated. prior to the
initiation of medical evaluation.
II
3
Although the gastrointestinal (CI) manifesta

tions are most commonly vomiting and war
rhea, autonomic neuropathy can result in al
38 Gastrointestinal Dlsorden Constipation
II
Megacolon can be congenital or acquired and is

a frequent cause of constipation. Hirschsprung's
disease is due to a congenital absence of intra
mural neural plexuses. The diagnosis of Hirschspnmg's
disease is made on fullthickness biopsy of the rectum
in which ganglion cells of Meissner's and Auerbach's
plexuses are absent. Acquired megacolon is much more
common than congenital megacolon. The acquired fonn
is secondary to obstruction of any etiology but usually
is due to laxative abuse.
pation.
Sigmoidoscopy is the most sensitive and specific
test for detecting rectal and sigmoid lesions.
Direct visualization of rectal and sigmoid mu
rosa allows for simultaneous biopsy of any abnonnality.
Barium enema is unreliable as a primary diagnostic test
because of poor resolution of the rectum. Barium en
ema should follow examination with the sigmoidoscope
in order to detect lesions higher in the bowel that may
not be seen with the sigmoidoscope.
Sigmoidoscopic examination may reveal a su

pemcial brown pigmentation of the rectal mu
rosa that occurs in patients who abuse laxatives.
Called melanosis coli, the pigmentation is most com
monly due to the use of anthraquinone laxatives such as
cascara and senna. The condition is not pathologically
significant except to prevent extensive, unnecessary
workup by identifying the patient who denies laxative
II
II
Metabolic abnormalities are rarely causes of

constipation but must be excluded before con
stipation can be considered to be idiopathic.
The milka1kali syndrome is due to ingestion of

large amounts of antacids that contain calcium
(>5 glday). Hypercalcemia results and, if long.
standing, can lead to renal failure. The syndrome was
more common in the past when milk and calciumcontaining antacids were used in the treatment of peptic
ulcer disease.
use.
Physical exam should include anal inspection,

digital exam, and proctoscopy.
that act by increasing coioniciropulsive motor activity

and stimulating intestinal Hui secretion. Examples of
stimulant laxatives include senna, castor oil, and the
biguanides.
Cathartic colon is the consequence of pro

longed use of laxatives and is a common cause
of constipation. Long.tenn laxative abuse can
destroy intramural nerve plexuses in the large bowel,
resulting in constipation. This disorder is most fre
quently associated with the use of stimulant laxatives
III
Irritable bowel syndrome is a functional cause

of constipation that has no demonstrable or
ganic etiology. The syndrome is common and
presents as episodes of abdominal discomfort and alter
nating diarrhea and constipation. Other organic causes
of constipation, diarrhea, and abdominal pain should
always be sought prior to making a diagnosis of irritable
bowel syndrome.
II
Poor bowel habits refers to suppression of defecation by patients who are "too busy" to defe
cate or who do not defecate when the urge
presents at an inconvenient time.
~
Hemorrhokial
disease
Poor dietlfluld
Intake
t d
-{
P syc h la nc l$Orders
Depression
Victim
Debilltationlinactivity
Intercurrent
disease
Fecal impaction
Spinal
sulfate
carcinoma
Antacids---{
Parkinson's
Diabetes
Dementia
Aluminum-containing
Cerebral
1
ConstIpation
Extrinsic
c:ompression-{
Rectal
abuse
_____
r Scleroderma
carcinoma
Collagen-vascular
dj~
DermatomY$Ositis
Fissures
sulfate
Phenothiazines
Stricture
Antihypertensives
Abscess
Lead poisoning
Hemorrhoids
Pregnancy
AbdominaVpeMc
palsy
CVA
Anticonvulsants
Laxative/enema
disease
mellitus
Calcium-containing
Antidepressants
Barium
cord injuryltumor
CNStumors
Anticholinergics
RectaJ/colon
dystrophy
disorders
Narcotics
Drugs
S
Neurologic
abuse
sclerosis
Muscular
Diuretics
Ferrous
Previous abdominaV
perineal surgery
of sexual
Multiple
Hypothyroidism
Perineal
abscess
Diverticulitis
tumor
8
Melanosis
coli
Anal stenosis
Fecal impaction
Cathartic
Megacolon
Neoplasm
cokw1
Acquired
Idiopathic
Hirschsprung's
Stricture
Chagas'
Volvulus
~etabolic
disorder
-f
Irritable
Harrison Chapter
132
Hypercalcemia
Hyperparathyroidism
~
Milk-alkali
syndrome
Hypokalemia
constipation
Poor bowel
Cecil Chapter
Hypothyroidism
bowel syndrome
Idiopathic
Chronic
disease
disease
habits
laxative
use
Porphyria
42
Gastrointestinal
Disorders Constipation 39
DIARRHEA
Acute Diarrhea
In general, one objective definition of diarrhea
is based on volume. The patient is considered
to have diarrhea if the stool bulk exceeds
150 mVday. As far as taking a medical history is concerned, a more practical definition of diarrhea should be
based upon the change in the stool patterns, including
frequency and consistency of the stool. History should
include the duration of the diarrhea, as well as any
history of medications, food and water exposures, travel
history, human immunodeficiency virus (HIV) history.
and pertinent medical problems such as immunosuppression. The acuteness of onset of the diarrhea and
the "toxicity" of the patient (fever, chills, leukocytosis)
determine whether the diarrhea should be treated
symptomatically or a diagnostic evaluation initiated. Patients with diarrhea who are "nontoxic" can be treated
symptomatically. Diagnostic evaluation of the nontoxic
patient should begin if the diarrhea persists after 3 to 4
weeks of symptomatic treatment. A mild, self-limited
acute diarrhea would suggest a viral etiology, and no
evaluation should be undertaken. Acute bloody diarrhea
with associated fever demands immediate evaluation.
Acute diarrhea is defined as diarrhea of less

than 2 weeks' duration. The most common
cause of acute diarrhea, viral gastroenteritis, is
self-limited, and likely win not lead to an extensive
evaluation. Diarrhea that is chronic and persistent is
less likely to be of infectious etiology, but should not be
overlooked, especially with HIV and immunosuppressed patients.
Drugs are a common cause of diarrhea. Laxatives are the most common cause of drug-induced diarrhea, and antibiotics are the second
most common cause. Antibiotics most commonly cause
a mild diarrhea that stops once the antibiotic is discon
tinued. A more serious fonn of antibiotic-associated
40 Gastrointestinal Disorders Diarrhea
diarrhea is pseudomembranous colitis. This disorder is

due to the proliferation of Clostridium difJicile. The
bacteria produce a pathogenic toxin that damages the
colonic mucosa and forms a pseudomembrane. The
pseudomembrane is composed of fibrin, leukocytes, and
epithelial debris. Diarrhea usually begins between the
5th and 10th day of antibiotic treatment but may occur
when the antibiotics are instituted or as long as 3 weeks
after the antibiotics have been discontinued. Broad~
spectrum antibiotics have been most commonly associated with pseudomembranous colitis, especially lincomycin, clindamycin, and ampicillin. Pseudomembranous
colitis can occur even when the antibiotics have been
used parenterally. If pseudomembranous colitis is suspected, a fresh stool ~imen
should be evaluated for
the presence of C. diJjzcile toxin.
4
:.t
Antacids containing magnesium, carbenoxolone,

and other licorice derivatives can cause diarrhea.
Stool culture and examination for ova and parasites are important, especially with a history of
recent travel to an endemic area. Examination
for ova and parasites should be repeated on three separate occasions before being considered negative, although sensitivity of the stool examination is poor despite multiple examinations.
lamblia is the most common parasitic

cause of traveler's diarrhea. Infection with Giardia is most commonly due to ingestion of contaminated water. If Giardia infection is suspected, trophozoites or cysts may be identified on stool exam,
enzyme-linked immunosorbent assay (ELISA) can identify fecal Giardia antigen, and detection of anti-Giardia
IgM can be measured in acute infection. A string test
or duodenal aspirates may be necessary in patients suspected to have Giardia but with persistently negative
stool samples. Ultimately, a therapeutic trial of metronidazole may be diagnostic if symptoms resolve.
Traveler's diarrhea is defined as diarrhea that

occurs within 2 weeks of traveling to countries
whose water supply is likely to be contaminated.
The diarrhea is self-limited (lasting less than 10 days)
and is most commonly due to an enterotoxin-producing
Escherichia coli. Other common bacterial causes of traveler's diarrhea are SalmoneUa sp., ShigeUa sp., Yersinia
enterocolitica,
and Campylobacter
sp. Most cases of
bacterial diarrhea are caused by ingestion of contaminated food or water. A stool culture will screen for the
common enteric pathogens and can be useful to diagnose the presence of Salmonella, Shigella, Yersinia, and
Campylobacter.
Sigmoidoscopy is not routine for uncomplicated

cases of acute diarrhea. Most cases of acute
diarrhea last less than a week to 10 days and are
self-limited. The need for a more extensive evaluation,
including sigmoidoscopy, rather than supportive care
(8uids, adsorbents, antisecretory, and antiperistaltic
agents), is determined by the "toxicity" of the patient,
as well as the history (HIV, immunosuppression) and
physical exam findings. Rectal or colonic masses, such
as carcinoma or impacted stool, may cause diarrhea
when liquid stool passes around the obstruction. Often
the liquid stool appears as fecal incontinence. Fecal
impaction should be considered in elderly or debilitated
patients who have diarrhea.
Giardia
II
The diagnosis of food poisoning is based on the

historical aspects of the onset of the diarrhea.
Staphylococcus
aureus and Clostridium
perfringens cause diarrhea owing to ingestion of preformed
toxins in contaminated food. The symptoms of vomiting
followed by diarrhea, occurring within 2 to 6 hours of
eating the contaminated food, are suggestive of a toxininduced diarrhea. If other persons eating the same food
are also afflicted, the diagnosis of food poisoning is
highly likely.
Indomethacin
Pseudomembranous colitis
Quinidine
Laxatives
Antibiotics
Colchicine
Evaluate stool
for Clostridium
ditficife toxin
Lactulose
Lactose intolerance (chronic)
Antacids
Antibiotic-associated diarrtlea
Methy1dopa
Cryptosporidium
Guanethidine
Giardia lambfia
Parasitic
Hydralazine
2
Entamoeba histofytica
Caffeine
Diuretics
Strongfyoides stercorafis
Theophylline
Tapeworms
Ascaris lumbricoides
Hookworm
1
Diarrhea
Escherichia coli
7
Bacterial
--1
Salmonella typhimurium
Shigella sp.
Campylobacter
Yersinia enterocofitica.
Vibriosp.
Chronic
diarrhea
Rotawus
(continued on page 43)
Fecal Impaction
Viral gastroenteritis
9
Cecil Chapter
Harrison Chapter
Food poisonin~
Norwalk-hke agents
CahclVlruses
Adenovlruses
r Clostridium pertringens
Staphylococcus aureus
133
42
Gastrointestinal Disorders
Diarrhea 41
DIARRHEA
(CAntinued)
inflammation) is present. Colitis can be due to infection

with mucosal invasion and inAammation or to chronic
inflammatory conditions.
Chronic Diarrhea
1m
Chronic diarrhea can be defined as diarrhea
lasting for more than a month. Other than H tv

related diarrhea,
more than 90% of chronic
diarrhea is due to three disorders: chronic inAammatory
bowel disease, colon carcinoma, and irritable bowel syndrome. Except in patients with HIV, or immunosuppression, diarrhea is Jess likely to be infectious when it
is chronic.
Nursing home patients often sufTer fecal impaction and subsequent

diarrhea (see No. B,
Acute Diarrhea) due to their debilitated,
inactive state. But drugs such as tricyclic antidepressants
and anticholinergic
medications are often used in nursing home patients and may be a cause of fecal impaction
with subsequent diarrhea.
Surreptitious
ingestion
of laxatives
(only the
phenolphthalein type) can be detected by add-
ing sodium hydroxide to a fresh stool sample.

Presence of phenolphthalein
will turn the stool pink and
implicates use of phenolphthalein-containing
stimulant
laxatives. Laxative abuse is a mre cause of chronic mar
rhea, but the test can be done quickly and easily when
phenolphthalein-containing
laxative abuse is suspected.
A positive test prevents unnecessary
extensive evalua
tion.
Methylene blue or Wright's stains can be used

to detect the presence of white blood cells in
the stool. Blood can be detected by gross examination of the stool or by testing for occult blood. The
presence of blood or pus indicates that colitis (intestinal
42 Gastrointestinal Disorden
Diarrhea
III
Although infection is usually not a source of

chronic diarrhea,
some pathogens
can cause
chronic diarrhea.
Therefore,
stool should be
cultured and examined for the presence of parasites
when blood or pus is present.
4
II
If the stool culture and repeated (at least three)

evaluations for parasitic infections are negative,
proctosigmoidoscopy
should be undertaken
without prior 00we1 preparation.
Direct visualization
of the mucosa will identify inAammatory
conditions.
Mucosal biopsy can be perfonned
simultaneously
with
endoscopic examination to confirm inAammatory disorders and will detect diseases that might not be grossly
evident. Biopsy may detect evidence of inAammation
that was not detected
by endoscopic
visualization.
In
addition, biopsy will aid the diagnosis in a nonnalappearing mucosa, such as amyloidosis or Whipple's disease .
II
Diarrhea of unknown origin is the term used to

refer to diarrhea for which full evaluation fails
to reveal a diagnosis. Patients .
ith this condition require dose follow-up and careful reevaluation,
which should include documentation
of stool volumes
and quantitative
ft.'Cal fat determinations.
lEI
The malabsorption
syndrome refers to a group
of signs and symptoms that result when intestinal absorption of various dietary components is
altered. The absorption abnonnality can involve protein,
fat, vitamins or minerals, or carbohydrates.
Symptoms
include the presence of stools that are light yellow or
gray, soft, and greasy. In addition, there may be evidence of weight loss and anorexia. Celiac disease is the
most common cause of malabsorption,
but there are
many disorders that result in malabsorption.
including
pancreatic
insuf6ciency,
gastrectomy.
infection,
and
drugs. The clinical manifestations depend upon the specific absorptive defect.
:
Diarrhea of unknown origin (see

o. 17) is
most commonly
due to irritable bowel syndrome, bile salt malabsorption,
and surreptitious laxative abuse when no colonic inAammation (no
blood or pus) can be documented.
II
If the diagnosis of chronic diarrhea is not evident after proctosigmoidoscopy

and biopsy. bar
ium radiographic
examination
should be perfonned. Barium studies may identify the diagnosis of
diarrhea-causing
disease that does not involve the murosa accessible to the sigmoidoscope.
At times, a barium
study is perfonned,
even when endoscopic examination
has revealed evidence of mucosal disease, to detennine
the extent of involvement.
Colonoscopy
is necessary
when the diagnosis of inflammation
or carcinoma
is
likely but has not been con6nned
with sigmoidoscopic
or radiographic examination.
II
Irritable bowel syndrome can usually be sus

pected on the basis of history and negative
barium studies. Colonoscopy is usually not necessary. The patient has a history of intennittent
diarrhea
alternating with constipation,
abdominal pain, and no
systemic symptoms. There is no evidence of intestinal
abnonnality with stool examinations or proctosigmoidoscopy.
Orug-lnclucecl (see previous "Acute- diarrhea algorithm)

Fecal impaction
_ism
Ca~
Diabetes mellitus
'--
Entamoebahis~
Mycobacterium avlum-lntraaJlhAare
Giardia lamblia
Cryptosporidium
HIV-related
No pathogen identified
Paraslles (see Acute diarrhea algorithm)

Bacteria (see Acute diarrhea algorithm)
=1
Ulcerative coIilisiproctitls
""noma
iUs
Crohn's disease
Racliatloncolilis
AIDS-related (see above)

Carclooma
Ulceratlveootitis
Vilous adenoma
Ca"""""'"
Colitis (see above)
Ulcerative proctitis
Inftammatory bowel disease
Ulcerattve colitis
Carcinoma
Crohn's disease
Celiac disease
Scleroderma
Radiation colitis
Pancreatic insufficiency
Carcinoid
Bacterial oYergrowth (blind loops)
Villous adenoma
Crohn's disease
Lymphatic obstructk>n
Metabolic
Postsurgical
Drug-lnduced
Small bowel disease
Ileal
Cecil Chapter
Harrison Chapter
r888Ctlorl
I])
42
Gastrointestinal Disorders.
Diarrhea. 43
GASTROINTESTINAL
BLEEDING
Prior to attempts to localize and diagnose the

source of GI bleedin ,the patient must first be
stabilized so that a1equate blood pressure
is
maintained. At times blood loss is so massive and rapid
that it becomes necessary to attempt to localize the
bleeding source operatively without the benefit of preoperative evaluation.
The evaluation
presented
here
presumes that the patient has been stabilized.
The most important

factor in localizing
the
source of GI bleeding lies in the nature of the
blood loss. Hematemesis
is due to upper GI
bleeding. Stool quality further provides clues to the
location of blood loss. The quality of the stool (black,
maroon, or bright red) depends upon the volume. rapid~
ity and location of the bleeding, as well as the length of
time (transit time) the blood remains in the GI tract.
Blood with a long transit time through the GI tract will
become black (melena) because of the breakdown of the
blood by acid. Blood also acts as a cathartic. however. so
that the presence of large amounts of blood will result
in a decreased transit time through the GI tract, and
the stool may be maroon (hematochezia)
rather than
black. Hematemesis
and melena usually result from
upper GI bleeding. Hematochezia
can be due to either
upper or lower GI bleeding.
Bright-red
rectal blood
(BRBPR) is usually due to lower GJ bleeding. Anatomically, the ligament of TreHz is considered
to be the
dividing point for upper and lower GI bleeding. Black
stool must be tested to document the presence of blood,
because a variety of other substances
may cause the
stool to turn black. Ingested bismuth, charcoal, spinach.
and. most commonly, iron wiD result in black stools in
the absence of blood. Other history, such as the use
of aspirin,
nonsteroidal
anti-inflammatory
agents
(NSAIDs), and alcohol, gives clues to peptic ulcer disease. Skin exam showing stigmata of liver disease (spider
angiomas, palmar erythema) and ascites points to variceal bleeding.
Upper GI endoscopy is the most sensitive and

speeific test for diagnosing the source of upper
GI bleeding. Endoscopy detects a definitive or
44 Gastrointestinal
Disorders
Gastrointestinal Bleeding
a potential bleeding site only 80% of the time. Detection is increased when the bleeding is more severe. In
the presence of rapid bleeding such that visualization
by endoscopy is impossible, angiography
may help to
localize the bleeding source.
The most common sources of upper GI bleeding are peptic ulcer. esophageal
varices, and
acute mucosal lesions such as acute esophagitis,
gastritis, or Mallory-Weiss tears. Gastroesophageal
(GE)
reflux is not an endoscopic diagnosis, but the diagnosis
can be suspected by the mucosal changes seen in the
lower esophagus upon endoscopy.
Peptic ulcer disease may lead to GI bleeding,

usually hematemesis
or melena. The major
cause of gastritis and peptic ulcer disease is
Helicobacter pylori infection. H. pylori is associated
with 70% to 90% of gastric ulcers and 90% to 95% of
duodenal ulcers. NSAIDs are another major cause of
peptic ulcer disease and upper GJ bleeding.
Melena usually arises from upper GI bleeding.

An upper endoscopy is the first test that should
be performed
in evaluating the source of melena. Hematochezia
can rt:sult from either upper or
lower GI bleeding. In order for hematochezia
to occur,
the upper GI bleeding must be of a volume of at least
1000 m!. Bleeding lesions lower in the GI tract may
present as hematochezia
at lower volumes of blood loss.
Colonoscopic
examination
may be difficult in
the presence of active bleeding. If the patient
is not actively bleeding and is stable for 48
hours, barium enema can be perfonned
alternatively,
but colonoscopy is a more sensitive and specific test.
Barium enema examination is not useful in the face of
active bleeding, because the barium wiD interfere with
angiography
and will also preclude subsequent
endoscopic visualization of the colon.
8:
Angiodysplasia. or vascular malformations,

have
been found to be a more common cause of
lower GJ bleeding
than was previously
sus-
peeted. In the past, bleeding from the right side of the

colon was attributed
to diverticula, if diverticula were
demonstrated
on barium enema. With the advancement
of endoscopic techniques. it is now known that vascular
malfonnations
are more commonly the site of active
bleeding. This observation underscores the need to confirm that a lesion is actually the site of hemorrhage by
obsemng active bleeding with endoscopy or arteriography.

Primary amyloidosis results in amyloid deposition in the connective tissue and in the walls of
blood vessels. GI bleeding is common and can
be severe.
1m
Small bowel enteroclysis

is a study in which
barium and air are placed in the small bowel
and viewed radiographically.
The procedure is
similar to the aiN.'ontrast barium enema. This technique
enables graphic visualization of mucosal lesions in the
small bowel. This technique does not enable visualization of angioma or angiodysplasia,
which can be detected only by endoscopic examinatiOIl.
II
If bleeding continues
but the lesion has not
been directly visualized or localized by endoscopic exam, an angiogram may become necessary. An angiogram will not identify the type of lesion
but will help to locali7 the site of the bleeding lesion.
If available, a radioisotope-tagged
erythrocyte study can
be used prior to the more invasive angiogrdm.
II
Gastric mucosa, present in Meckel's diverticulum 15% to 30% of the time, can be detected
with a technetium
isotopic scan. However, only
half of all bleeding Meckel's diverticulum are found to
contain gastric mucosa. Acid-secreting
gastric mucosalined Meckel's diverticulum
may also cause adjacent
ileal mucosal ulceration and bleeding. In a young patient with GI bleeding. a Meckel's scan should probably
be performed
prior to angiography, because 50% of
cases of lower GI bleeding are due to Meckel's diverticulum in children, and many cases have been reported
in young adults. Meckel's diverticulum
is present in
approximately 2% of the population.
Mallory-Weiss tear
5
Peptic ulcer
GastriC
Duodenal
Esophagitis
Gastritis
Anastomotic ulcer
Esophageal varices
Gastric varices
Gastric carcinoma
lesion not visualized
Angiodysplasia
Infectious colitis
GE reflux
Crahn's colitis
Polyps
Arterial-intestinal
Ulcerative colitis
Colon carcinoma/neoplasm
fistulas
Angiodysplasia
Diverticulosis
Gastrointestinal
Ischemic bowel
bleeding
Hemorrhoids
Perform
history
and physical exam,

stool exam
Amyloidosis
Polyps
Colonic
(continued
on page
ulcer
47)
Tumor
Vascular lesions
Arterialintestinal
fistulas
Meckel's diverticulum
Bleeding stopped
Cecil Chapter
I Harrison
Chapter
123
44
Gastrointestinal Bleeding 45
GASTROINTESTINAL
BLEEDING (Continued)
Rectal blood is usually due to lower CI bleeding, most commonly from internal hemorrhoids.
A proctosigmoidoscopy is most sensitive and
specific in detecting the bleeding lesion. If the lesion
cannot be identified by sigmoidoscopy, a more proximal
source must be investigated via coJonosoopy.
III
~
Routine physical examination includes fecal oc

cult blood tests to screen for occult GI blood
loss. Because the cost of investigating false-
46 Gastrointestinal Disorders Castrointestinal Bleeding
positive results is considerable, the sensitivity of the

screening test should be known. (Specificity should also
be known to prevent patient morbidity caused by falsenegative results.) A combination of screening tests, i.e.,
both a guaiac test and an immunologic assay. can be
used to detect occult CI bleeding with greater sensitiv
ity and specificity prior to full GJ evaluation. Additionally, some of the common sources of false-positive test
results should be considered. Oral iron supplementation, which can turn stool black, is a cause of falsepositive occult blood tests. Vitamin C in large doses may
result in falsenegative occult blood results, because it
interferes with the chemical reaction in the test. In the
presence of a positive stool test for occult blood, a
hematocrit should also be measured. Occult blood can

be measured from any source, including swallowed
blood subsequent to a nosebleed. Evaluation of both
the upper and lower GI tract is necessary when occult
blood is discovered.
II
If diagnostic evaluation is un revealing. stool

must again be examined for the presence of
occult blood within 6 months and a full endoscopic examination repeated if occult blood is present.
If reevaluation remains negative after three subsequent
examinations (every 6 months over an IS-month period), it is unlikely that the lesion is signi6cant.
Infectious
colitis
Angiodysplasia
Diverticulosis
Colonic
Hemorrhoids
Crahn's colitis
ulcer
Polyps
Ulcerative coUtis
Fissures
Colon carcinoma
Crohn's
Inflammatory
disease
bowel disease -{
Ischemic colitis
Angiodysplasia
Ulcerative colitis/proctitis
Rectosigmoid carcinoma
Diverticulosis
Ischemic
bowel
Hemorrhoids
Amyloidosis
Polyps
Bleeding
Crahn's
2 Perlorm history
and physical exam,
stool exam
has stopped/reevaluate
colitis
Ulcerative colitis
C<on carcinoma
Angiodysplasia
Diverticulosis
Ischemic
bowel
see hematemesis
(page 45)
Angiodysplasia
Tumor
Polyps
Angioma
15 Follow/repeat
hemoccult
and reevaluate
at 6 mo.
Cecil Chapter
Harrison
Chapter
123
44
GastrolntestinaJ
Dlsorden
Gastrointestinal Blt:et);ng 47
disease. Often. symptoms of solid dysphag;a can be
DYSPHAGIA
Dysphag;a is defined as difficulty with swal-
lowing and refers specifically to the difficulty of

passing solids or liquids from the mouth to the
stomach. History and physical examination are the initial
steps in the diagnosis of dysphagia. Swallowing difficulty
that progresses from solids to liquids over time indicates
the presence of a progressive lesion such as carcinoma.
If swallowing difficulty remains fixed with a certainsized quantity of food, a stationary obstruction
such as
stricture is suspected.
If dysphagia occurs with both
solids and liquids, a motility disorder is the likely source
of the dysphagia. The patient may be able to localize
the site of obstructive lesions by indicating where he or
she experiences the sensation of the food being stuck.
Dysphagia associated with hiccups suggests distal esoph.
ageallesions.
Pain associated with swallowing is referred to
as odynophagia and mayor may not accompany
dysphagia. Painful oral lesions can account for
odynophagia
and can be seen with a variety of oral
infections
and malignancy.
With odynophagia
alone,
swallowing may be difficult secondary to pain, but the
material ean be passed easily from the oropharynx to
the stomach onc'e swallowing has been initiated. The
most common causes of odynophagia are herpes simplex
and Candida stomatitis or esophagitis.
Abscesses and
oral carcinomas are very rare causes of odynophagia.
Endoscopic evaluation with biopsy is the most

specific test in establishing the presence of anatomic lesions and documenting
complications
due to motility disorders. Endoscopy is the best test for
the evaluation of dysphagia, but barium swallow is still
orten used as the initial test. The barium swallow is a
radiographic evaluation of the pharynx and esophagus
as the patient swallows a bolus of contrast medium.
Cineradiography
is usually performed
simultaneously.
Because dysphagia can be present with solids and absent with liquids, a normal study with liquid barium
cannot be taken as conclusive evidence of absence of
48 Gastrointestinal Disorders
Dysphagia
reproduced
mallow.
with the use of a barium capsule
or marsh-
II
The Plummer.vinson
syndrome
(also known
as Paterson- Kelly syndrome and siderophagic
dysphagia)
is an extremely
rare condition
in
which dysphagia is associated with hypochromic
anemia. The condition
is seen in women. Dysphagia is
due to an esophageal
web and is thought to be a
premalignant
condition ultimately resulting in pharyngeal carcinoma.
Scleroderma
peristalsis,
source of
derma. Dysphagia
of the formation of
esophageal reflux.
causes a decreased
esophageal
but this dysmotility
is rarely the
dysphagia
associated
with scleroin scleroderma
is usually the result
inflammatory strictures from gastro-
II
External compression of the esophagus is a possible but extremely rare cause of dysphagia. Of
interest is the anomalous right subclavian artery.
The right subclavian
artery usually arises from the
brachiocephalic
artery and passes anterior to the trachea. In approximately
I % of the population, the right
subclavian artery arises as the last branch of the aortic
arch and passes from left to right behind the esophagus
and trachea. The compression
of the esophagus be
tween the anomalous artery and the semirigid trachea
can result in dysphagia. Plain chest films may aid in
identifying some external masses impinging upon the
esophagus.
Esophageal stricture is likely with a history of

reflux esophagitis.
Rare skin disorders such as
cicatricial pemphigoid
and epidermolysis
bullosa involve the esophagus
as well, resulting in stricture.
Zenker's diverticulum
is an outpouching
of the
esophagus above the upper esophageal sphincter. Patients may complain of regurgitation
of
food into the mouth, halitosis, and a mass in the neck.
Although extremely rare, the pouch may enlarge to such
a degree that compression on the adjacent esophagus is
the primary cause of dysphagia.
Motor abnormalities
\vill be suspected by the
appearance
of the esophagus upon endoscopic
examination,
or by cineradiography
or fluoroscopy. Manometric
measurements
are more useful in
characterizing
the exact nature of the motility disorder.
Manometry measures intraesophageal
pressures at sev
eral points simultaneously.
A long catheter with pressuresensitive
transducers
at various intervals is introduced into the esophageal lumen and used to measure
and record the intraluminal
pressure. Dysmotility can
be detected by measuring muscular activity in terms of
amplitude,
velocity, and duration of waves. Although
disorders such as scleroderma and gastroesophageal
reAux will be detected by esophagoscopy,
manometry is
often performed
subsequently
in order to characterize
and confirm the nature of esophageal dyslllotility.
1m
Diffuse esophageal
spasm is the synchronous
contraction
of tht.' esophagus rather than orderly peristalsis. Manometry is confirmatory.
Achalasia
is a disorder
in which the lower
esophageal sphincter fails to relax, which results
in the dilatation of the upper esophagus. Manometry will confirm suspected achalasia by demonstrating failure of the lower esophageal sphincter to relax
and reduced or absent peristalsis in the distal half of
the esophagus.
II
Globus hystericus is the sensation of a lump in

the throat. The patient feels something in the
back of the throat "all the time." The disorder
conveys a sense of dysphagia, but swallowing is nonnal.
The sensation is due to the tightening of the upper
esophageal sphincter. The "'ump" disappears transiently
when the patient swallows. The condition is benign.
Anomalous right subclavian artery
Reflux esophagitis
4
Aphthous stomatitis
Pharyngitis
Herpes stomatitis/esophagitis
Candida! stomatitis/esophagitis
Mumps
Vincent's angina
Abscess'----
Peritonsillar abscess
[
Oral carcinoma
Retropharyngeal abscess
Oral erosive lichen planus
Plummer-Vinson syndrome
Mediastinal tuberculosis
Gastric carcinoma
Thyroid enlargement
Lower esophageal ring
CelVical vertebral hyperostosis
External compression'----+
Bronchial carcinoma
Pharyngo-esopllageal
web
Pulmonaryabscess
Esophageal stricture
Empyema
Postcricoid carcinoma
Pericardia! effusion
Zenker's diverticulum
Aortic aneurysm
=1
Esophageal carcinoma
Anatomic abnormalitie
Lymphoma
Esophageal candidiasis
Paraesophageal hernia
Peripheral neuropathY
Scleroderma
Diabetes mellitus
Lead poisoning
Radiation xerostomia
Dermatomyositis/polymyositis
A}coholism
SjOgren's syndrome
Amyloidosis
Hypercalcemia
Cortical dysphagia
Laryngeal nerve damage
Oral pemphigus vulgaris

Cicatricial pemphigoid
Beh(fElt's syndrome
Stroke (eVA)
Dysphagia
Parkinson's disease
Muscular dystrophy
Multiple sclerosis
Amyotrophic lateral sclerosis (ALS)
Myotonic dystrophy
Hypertonic cricopharyngeal musculature
3
Perform
esophagoscopy
and/or
barium
Motor/motility disorders-
Myasthenia gravis
Polio
swallow
Syringomyelia
Glossopharyngeal neuritis
Brain stem tumors/strokes
10 [ Diffuse esophageal spasm
--------11
[AChalasia
Diabetic neuropathy
Cecil Chapter
Harrison
Chapter
122
40
Dysphagia. 49
ABDOMINAL
PAIN
Abdominal pain may result from intra-abdominal inflammation or abdominal wall disorders or
may be pain referred from areas outside of the
abdomen. Common sources of pain referred to the
abdomen include retroperitoneal processes, such as renal colic. and intra-thoracic processes, such as myocardial infarction and pneumonia. Conversely, abdominal
processes can refer pain to extra-abdominal sHes. The
pain of acute cholecystitis can be referred to the tip of
the scapula. Pain associated with acute pancreatitis can
be referred to the mid-back.
Thorough history and physical examination are

the most important "tests" in diagnosing abdominal pain. The sources and severity of abdominal pain are so diverse that no one diagnostic test
is available that will allow speci6c and rapid identification of the cause. Perhaps the most useful historical fact
in the diagnosis of abdominal pain lies in the location
of the pain. Despite localization of pain to one area of
the abdomen, a large amount of overlap exists, so that
the diagnosis usually consists of several entities of high
likelihood. In addition, the nature, quality, and radiation
of the pain are important aspects of the history that will
aid in the differential diagnosis. Pain associated with
peritoneal inRammation is aching, steady, and made
worse with movement, so that the patient tends to lie
Abdominal Pain
very still. Pain is usually localized directly over the

inHammed area. The presence of rebound tenderness
confirms peritoneal inAammation. Intermittent, colicky
pain causes the patient to be restJess. Colic is associated
with obstruction of hollow viscera. Although colic is
typically intermittent, it can be constant and of lowgrade intensity. Colicky pain is crampy and poorly localized. Pelvic and rectal examination should be included
in every patient with abdominal pain, because pelvic
disorders can cause abdominal pain, and rectal examination win add additional information to determine the
diagnosis.
Upper abdominal pain is usually associated with
intrathoracic processes or visceral pain from organs derived from the embryonic foregut. Lesions most commonly associated with upper abdominal
pain include biliary colic, hepatitis, peptic ulcer disease,
pancreatitis, and splenomegaly. Extra-abdominal, specifically thoracic, sources of pain should always be considered and sought in the presence of any upper abdominal pain. Chest radiograph and electrocardiogram
(EKG) may rule out common sources of referred thoracic pain by detecting myocardial infarction, pericarditis, pleural effusion. pulmonary infarction. and pneumonia. It is important to keep in mind that any localized
pain may be neurogenic in origin, e.g., herpes zoster,
when there is a paucity of other physical findings such
as fever and leukocytosis to indicate an intra-abdominal process.

Generalized abdominal pain is most difficult to
dia ose because of the lack of specificity for
un~rlying structures. Often, abdominal pain is
diffuse initially and localizes to a specific area as the
disease progresses. This phenomenon is particularly
common with acute appendicitis in which the patient
presents with diffuse abdominal pain, tenderness, fever,
nausea, and vomiting. With time, appendiceal pain localizes to the right lower quadrant. This progression of
pain localization underscores the importance of frequent, repeated examinations during the course of investigation in patients presenting with generalized abdominal pain.
Periumbilical pain is usually from the small intestine but can also result from lesions in the
cecum, right colon, and appendix. Pain from
abdominal aortic aneurysm is typically in the central
abdomen.
Lower abdominal pain may arise from processes

involving the abdominal structures or pelvic
structures, including the female reproductive
organs and the urinary bladder. Even prostatic inRammation can present with lower abdominal pain.
see page 52
3
see page 54
see page 56
1
Abdomlnlll
pain
Per10rmhistory
and physical exam,
nalurelk>cation
see page 58
Cecil Chapter
Hamson Chapter
136
14
Gastrointestinal Dlsordtlrs Abdominal Pain 51
ABDOMINAL
PAIN (Continued)
Right Upper Quadrant and Left Upper

Quadrant Abdaminal Pain
II
Pain due to intrathoracic lesions is commonly
referred to the upper abdomen. Initial examination should include routine chest film and EKG
to exclude thoracic sources of abdominal pain.
Plain abdominal radiography is a simple, inexpensive screening test that may provide much
infonnation about the source of upper abdominal pain. Although only 20% of gallstones are radiopaque. their detection on plain film is a clue to diagnosis. Renal stones may also be detected on abdominal
film. Hepatomegaly
may be missed on physical examina-
tion because of guarding but may be seen on abdominal

film. Free air due to a perforated viscus or dilated bowel
loops can also be seen on abdominal film. A plain
abdominal film may reveal an enlarged spleen that could
not be palpated on physical examination.
A common cause of acute splenic enlargement
and left upper quadrant (LUQ) pain is infectious mononucleosis. Other causes of splenic
enlargement associated with pain include vascular congestion, acute infections, and infiltrative diseases.
II
If available, endoscopic ultrasound can be utilized in the diagnosis of right upper quadrant
(RUQ) pain if transabdominal ultrasound is
negative.
~
Elevation of serum amylase is not specific for

pancreatic disease, because amylase is present
in other tissues as well. An elevated serum amy-
52 Gastrointestinal Disorders AbdominalPain
lase can be present with acute pancreatitis, acute chole

cystitis, perforated peptic ulcer, and small bowel obstruction, especially with bowel infarction. Operable causes of
abdominal pain cannot be ruled out on the basis of an
elevated amylase level. Serum lipase is also elevated in
acute pancreatitis and may remain elevated for as long
as 2 weeks after the serum amylase returns to normal.
Lipase is also elevated with perforated peptic ulcer and
pancreatic duct obstruction. Elevated serum transami
nases (aminotransferases) are a clue to hepatic disease.
History and physical examination are not diagnostic for pancreatitis, but the diagnosis is less
likely in the presence of RUQ pain. Pancreatitis
more commonly presents with epigastric pain with a
left-sided component. In approximately 30% of patients
with acute pancreatitis, the serum amylase may be
within normal limits early in the disease. Therefore,
even with a normal amylase, pancreatitis should be
considered in the appropriate clinical setting.
II
The importance of pelvic ex.amination in all

patients with abdominal pain is emphasized by
gonococcal perihepatitis (Fitz-Hugh-Curtis
syndrome) as a source of RUQ pain. The diagnosis is
suspected when adnexal tenderness is palpated on pelvic
examination and is confirmed by a cervical smear reveal
ing gonococci.
II
Hepatic inflammation and cholecystitis are the

:
most common causes of RUQ pain. If acute
cholecystitiS is not detected on ultrasound
exam, an oral cholecystogram can be performed. A radionuclide technetium Tc Wm lidofenin (HIDA) scan
can ultimately be performed if acute cholecystitis is not
detected and not suspected in light of a normal amylase
level. The radionuclide scan is very sensitive in detecting acute cholecystitis.
Upper GI disorders, although most commonly

presenting as epigastric pain, can be referred to
the right or left upper quadrant. An upper GI
endoscopy should ultimately be performed in the evaluation of right and left upper quadrant pain if all previous
tests are not diagnostic. An additional endoscopic procedure, endoscopic retrograde cholangiopancreatography
(ERCP), can be performed when indicated. ERCP is
not a first-line test because of cost and potential complications, but it is invaluable in further evaluation of the
biliary tree and the pancreas after preliminary diagnostic
testing has been performed. ERCP is especially useful
when ultrasound is normal but liver function tests are
abnormal or amylase levels are elevated.
1m
Splenic infarction may be the source of LUQ

pain in patients with sickle cell disease. RUQ
pain in these patients is typically due to gallstones as a result of chronic hemolysis.
II
Neurogenic causes should always be considered

in the differential diagnosis of well-localized
abdominal pain. Herpes zoster commonly presents with severe localized pain in the absence of skin
lesions. Only as the disease progresses and typical skin
lesions appear is the diagnosis suspected.
II
Although most commonly presenting as right

lower quadrant (RLQ) pain, acute appendicitis
should also be considered as a source of RUQ
pain. RUQ pain with appendicitis is due to a retrocecal
location of the appendix. In the analysis of over 10,000
cadavers, the appendix was found in a retrocecal location in 64% of the cases. The frequency of a retrocecal
location of the appendix underscores the importance of
rectal exam in all patients with abdominal pain.
MYOCardial
infarction
Pericarditis
Pleuritis
Intrathoracic pain
Basilar
pneumonia
Free air present--
Pleural effusion
Perforated viscus
[ Gallstones
Opacities present
3
Renal stones
Splenomegaly
Hepatomegaly
[ Obstruction
Dilated bowel
InfarctIOn
Acute cholecystitis/cholangitis
Gallstones
Hepatic abscess
Subphrenic abscess
Subhepatic abscess
Abdominal
pain
Splenomegaly
Perform history
and physical exam
naturellocation
Pancreatic pseudocysVmass
Acute pancreatitis
Parenchymal liver disease
l Periumbilical I
5
Cholecystitis/cholangitis
Perforated
peptic
ulcer
Viral hepatitis
Biliary
Gonococcal perihepatitis
Hepatic abscess
Parenchymal
liver disease
Gastric
disease
Peptic ulcer
disease
ulcer
Anastomotic
ulcer
Gastritis
Duodenal
ulcer
Gastric
tumor
Gastroesophageal
reflux disease
Diffuse esophageal
spasm
10
Cecil Chapter
Harrison Chapter
136
Splenic infarct
11
Herpes zoster
12
Appendicitis
Idiopathic
Irritable bowel syndrome
14
Gastrointestinal
Disorders
AlxIominal Pain 53
ABDOMINAL
PAIN (ulntinued)
Epigastric Abdominal
Pain
Pain from intrathoracic processes can be referred to the upper abdomen, most commonly
the midepigastrium. The evaluation of upper
abdominal pain should always include a chest radiograph and an ECG. AddJtional tests that should be
performed early on in the evaluation of epigastric pain
include serum amylase, lipase, bilirubin levels, and
transaminases (aminotransferases). These tests will help
further direct the diagnostic evaluation. Abnormal serum amylase and lipase, for example, indicate a pancreatic process, whereas abnormal bilirubin and transamioases would point to a hepatic process.
Allhough an UppeT GI series, including a barium swallow with cineradiography, is a good

screening test in the evaluation of epigastric
pain, upper CI endoscopy is more specific. Upper en-
54 Gastrointestinal
Disorden
Abdominal Pain
doscopy can identify mucosal evidence of gastroesophageal reflux esophagitis as well as gastritis, which will
not be identified by barium studies. Conversely. diffuse
esophageal spasm will not be identified with upper endoscopy, whereas cineradiography may capture and
identity diffuse spasm (see No.5).
Acute cholecystit;s typ;cally beg;ns w;th RUQ
pain but may present initially as LUQ or epigastric pain. As the disease progresses, the pain
usually shifts to localize in the RUQ. Ultrasound is the
simplest and most reliable method to identify gallstones
as a cause of cholecystitis, because abdominal radiographs will reveal opacities in only about 20% of patients with gallstones. Radionuclide scanning is the most
reliable method to confirm acute cholecystitis if the
diagnosis is suspected.
4
:.t
Acute pancreatitis is a common cause of midepigastric pain. An LUQ component to the pain
is a useful clue to the diagnosis of pancreatitis.
Measurement of amylase may not always be useful in

the diagnosis, because elevated amylase levels are nonspecific and may be found in association with other
inHammatory conditions associated with epigastric pain.
Elevated serum amylase levels may occur in association
with peptic ulcer disease, acute cholecystitis, and intestinal obstruction. Conversely, amylase levels may be normal, especially in the early stages of pancreatic inflammation. In addition to abdominal processes, ruptured
ectopic pregnancy and ruptured ovarian cysts can result
in elevated amylase, but the pain with these conditions
is more likely to be located in the lower abdomen.
Diffuse esophageal spasm will not be identified
with upper CI endoscopy but may be suspected
on barium swallow with fluoroscopy or cineradiography (see No.2). Esophageal manometry is the best
test to confirm the diagnosis of diffuse esophageal spasm
(see Dysphag;a algorithm).
Myocardial
inlarction
Pericarditis
Pleuritis
Intrathoracic
pain -
referred
Pneumoma
Pleural
Perform
UGI endoscopy
barium swallow
effusion
Gastric
f
Gastroesophageal
reHux disease
Perform history
and physical exam,
nature/location
Acute
Chapter
Lymphoma
Kaposi's
sarcoma
pancreatitis
Abdominal
Diffuse
Harrison
ulcer
ulcer
3 Acute cholecystitis
-1 Periumbilical
Cecil Chapter
Duodenal
carcinoma
f
Abdominal
pain
ulcer
Anastomotic
wall hernia
esophageal
spasm
136
14
AbdominalPain. 55
ABDOMINAL
PAIN (Continued)
Generalized Abdominal Pain

Generalized abdominal pain is the most difficult
II
to diagnose because it is so nonspecific.

Determining the nature of the pain is helpful in
the diagnosis by identifying the presence or absence of

peritoneal inflammation (peritonitis). In general, peritoneal inflammation will localize to an area directly over
the inflamed lesion, but with generalized
abdominal
pain, the differential diagnosis is broad.
Dilated loops of bowel can be seen on plain

abdominal films and are a clue to the diagnosis
of bowel obstruction.
56 GastrointestinaJ Disorders
Abdominal Pain
Only 20% of gallstones arc radiopaque and visible on abdominal
films. Renal
stones
can be
visible on abdominal films but rarely arc a cause
of generalized
abdominal
pain.
Bowel ischemia and infarction can result from

venous or arterial occlusion (thrombosis or embolism) and can cause generalized
abdominal
pain. Because vascular disease is more common in the
elderly, bowel infarcts are more common in elderly
patients. Despite the severity of the condition, symptoms may be mild initially, especially in elderly patients.
Severe, poorly localized abdominal pain is generally the
hallmark of intestinal ischemia, with pain often out of
proportion to the objective findings. Initially, there may
be no abdominal abnormalities
upon examination. Abdominal tenderness and peritonitis may be late findings.
Porphyria (especially acute intermittent por-
phyria) and lead colic frequently cause abdominal pain due to severe hyperperistalsis.
The pain
may be localized to the midline or may be generalized.
Lead poisoning may be associated with signs of peripheral neuropathy and a blue "lead line" on the gums.
Metabolic disturbances such as diabetic ketoacidosis (DKA) and uremia may result in diffuse,
generalized abdominal pain. It is important to
remember that DKA is often the result of infection, so
acute appendicitis must not be overlooked in a patient
with DKA and generalized abdominal pain. If the metabolic disturbance
is corrected
in DKA but the pain
persists, further investigation should be undertaken
to
determine the source of the abdominal pain.
Trauma
Foreign body puncture
Gangrenous cholecystitis
Peptic ulcer disease---{
Appendicitis
Gastnc ulcer
Duodenal ulcer
Diverticulitis
Strangulated bowel
Inflammatory bowel disease (toxic megacolon)
Meckel's diverticulum
Ischemic bowel
Carcinoma
Instrumentatioo
2
3
Abdominal
poln
Bowel obstruction
Stones
Peritonitis
-f
Endoscopy
Therapeutic abortion
ParacentesIs
Gallstones
[
Renal stones
Ascites (see ascites algori4hml

Pancreatitis
Kid~y
Ovanan cyst
Ruptured abscess or cyst

Dissecting aortic aneurysm
Fallopian tube
H$Ubhe"patic
abscess
b
epa IC a seess
Spleen
~
Metabolic disturbance
-:t
6
Cecil Chapter
Hamson
Chapter
Porphyria (AlP)
~~:~i':lC
DIabetic ketoacidosis (OKA)
136
14
Gastrointestinal
Dlsorden
Abdominal Pain 57
ABDOMINAL
Periumbilical
PAIN (Continued)
Abdominal
Po;n
Plain radiographs
and ultrasound
examination
of the abdomen are the simplest and most ef~
fective screening tests in investigating
the
source of periumbilical abdominal pain.
Evidence of dilated bowel loops and the presence of "fingerprinting"

of the bowel mucosa
on radiographs are indicative of obstruction and
edema of the boweL Obstruction can be secondary to a
variety of lesions, including volvulus, adhesions, intrinsic
or extrinsic tumor, or intussusception. Pain referred to
the periumbilical
area can arise from the jejunum, ileum, cecum, or right colon.
Abdominal Pain
Vascular occlusion of the superior mesenteric

artery is a catastrophic
event caused by the
extensive contribution of this artery to the blood
supply of both the large and small bowel. Subsequent
infarction of bowel may occur in the transverse colon,
jejunum,
cecum, and ileum, all of which will cause
periumbilical
pain.
Acute appendicitis
characteristically
begins as
generalized
or periumbilical
abdominal
pain
and later localizes to the right lower quadrant.
The pain associated

with metabolic
diseases
such as acute intermittent
porphyria (AlP) and
lead colic is due to the induction of hyperperistalsis. The associated pain can be diffuse or localized to
the periumbilical area.
Meckel's diverticulum is a congenital abnormality of the gut that occurs in approximately 2%

of the population. The diverticulum is located
30 to 90 em proximal to the iliocecal sphincter and
therefore is not visualized with an enema contrast study.
Gastric mucosa, which is present in the lumen of approximately 15% to 30% of Meckel'~ diverticulum patients, can be detected by a technetium
isotope scan.
Most symptomatic
Meckel's diverticulum contains gastric mucosa, and a Meckel's scan can be useful when
enema contrast studies are negative.
Abdomln.'
pa'n
Aortic widening - aortic aneurysm
Dilated loops of bowel
-i
3
Regional enteritis
Perlorated peptic ulcer
Intestinal obstruction
~~:~ulation
Abscess
AdheSIons
Bowel infarction --{
Superior mesentenc artery embolus

Superior mesentenc artery thrombosis
AppendICItIS
DivertICulitis
..
-(
HyperpenstalSls
Meckel's divertICulitis
Cecil Chapter
Harrison Chapter
Porphyns. (AlP)
lead colIC
136
14
Gastrointestinal Disorders Abdominal Pain
59
ABDOMINAL
II
The most common cause of RLQ quadrant

is acute appendicitis.
PAIN (Continued)
Right lower Quadrant and left lower

Quadrant Abdominal Poin
Pelvic and rectal examinations
are mandatory
in
the evaluation of lower quadrant pain. Inflam-
mation of the ovaries or Callopian tubes can

be suspected 011 pelvic examination.
Ruptured ectopic
pregnancy should be considered
in women with right
lower quadrant (RLQ) or left lower quadrant
(LLQ)
p<'\in regardless of menstrual history. A pregnancy test
should be performed in all women of childbearing
age.
Additional tests that should be perfonned
early in the
evaluation include white blood cell count (WBC) and
urinalysis. Only if the pregnancy test is negative and
pregnant)' is otherwise unlikely should any radiographic
studies be undertaken in women of childbearing potential.
60 Gastrointestinal Disorders Abdominal Pain
pain
Diverticulitis
is the most common
cause of
LLQ pain. Often a mass can be palpated in the
LLQ in the presence of diverticulitis. Complications include abscess formation, perforation, and fistula
fonnation.
Diagnosis can be confirmed on sigmoidoscopy with minimal
preparation.
If diverticulitis
is
strongly suspected, barium enema is not used for fear
of increasing intraluminal pressure and causing perforation.
Regional enteritis, also known as Crohn's dis

ease, commonly involves the distal ileum. Although pain may be referred to the periumbilical region, the RLQ is most often tender and painful,
and, at times, a mass can even be palpated in the RLQ.
The diagnosis of Crohn's ileitis can be suspected by the

clinical pattern of recurrent abdominal pain and RLQ
tenderness in which dilated loops of small bowel can be
demonstrated
on plain Rims of the abdomen, suggesting
partial obstruction. The diagnosis can be confinned with
upper and lower GI barium studies.
Inguinal hernia with entrapment

and strangulation is a rare cause of LLQ pain. Complete
physical examination
is adequate to make the
diagnosis.
Herpes zoster can cause severe localized abdominal pain in the absence of skin lesions.
The diagnosis becomes apparent as typical skin
lesions develop within days of the first occurrence
of
the pain.
Perform history
and physical exam,
natureAocation
Abdominal
pain
Ectopic pregnancy
Salpingitis
Ovarian cyst
Perform pelvic and

rectal exam, WBC.
and pregnancy test
Pelvic inflammatory disease (PID)

2
3
Appendicitis
Diverticulitis
Ulcerative colitis
Inflammatory bowel disease -{

Bowel ischemia
R '
I ""
eglona en en
IS
Abscess
Tumor
Adhesions
Ureteral tumor
Ureteral stone
Volvulus
5
Hernia
Herpes zoster
Irritable bowel syndrome
Cecil Chapter
Harrison
Chapter
136
14
Abdominal Pain
61
ABDOMINAL
PAIN (Continued)
Pelvic Pain
The hypogastrium, or suprapubic region, is the
area in which pain localizes from lesions in the
pelvis or hindgut structures. Thorough physical
examination,
including pelvic examination
in females
and rectal examination in both sexes, will provide the
most information
regarding
the source of the pain.
However, clinical examination by itself results in significant error in the evaluation of pelvic pain. If pelvic
abnormality remains highly likely despite a normal pelvic examination, careful consideration must be given
to further diagnostic intervention
such as laparoscopy.
Laparoscopy can also be used to establish a definite
diagnosis when the pelvic exam is abnormal but the
diagnosis is not readily apparent. Distention of the uri-
nary bladder is the most common cause of suprapubic

pain and can be suspected upon percussion of the lower
abdomen. As with RLQ and LLQ pain, a pregnancy test
should be performed in all women of childbearing
age.
62 Gastrointestinal Oisorden Abdominal Pain
Prostatitis,
proctitis, acute cervicitis, and rectal
carcinoma can produce both pelvic and poste

rior midsacml
II
pain.
Although innervation of the ovaries and fallopian tubes is unilateral, pain from these structures can be referred to the hypogastrium.
Bilateral inAammation of the ovaries or fallopian tubes is
usually experienced
as midline pain. Examples include
pelvic inRammalory disease and acute salpingitis. Pelvic
ultrasound may be a useful adjunctive test.
4~
If distention of the urinary bladder is suspected

on abdominal percussion, catheterization
of the
bladder will be both diagnostic and curative.
Fiberoptic sigmoidoscopy is the most sensitive

and specific test available to diagnose the various sigmoid colon lesions that give rise to pelvic
pain. Diverticulitis is a focal inflammation of a <.:clonic
diverticulum
that commonly occurs in the sigmoid colon. The pain of diverticulitis is more commonly 10<:.'\1-
ized to the LLQ. but can occur in the hypogastrium.

Other useful tests in the diagnosis of diverticulitis include barium enema (with water-soluble contrast material), computed tomography (Cr), and plain abdominal
films. Pregnancy
must be ruled out prior to radiographic studies.
Abdominal
poln
Perlorm history
and phYsfcal exam,
natureAocatoo
PeMc inflammatory disease (PID)

Prostatitis
Pelvic/rectal
exam abnormal,
pregnancy test
positive
Rectal carcinoma
Proctitis
Pelvic abnormality
Perlorm petvic and

rectaJ exam and
pregnancy test
Ectopic pregnancy
Endometriosis
Ruptured uterus
Acute cervicitis
Endometritis
Distended bladder
Sigmoid carcinoma
Crahn's disease
Uk:erative proctitis
Divertk:ulitis
Divertk:ular abscess
Cecil Chapter
Harrison
Chapter
136
14
GutrointestinaJ Disorders. AbdominalPain. 63
JAUNDICE AND
HYPERBILIRUBINEMIA
Jaundice refers to the yellow coloration of the

skin and sclerae due to deposition of bile pig.
ments. Beta carotene and quinacrine
are hvo
substances that can color the skin yellow and may be

mistaken for jaundice.
not color the sclerae.
These substances.
however, do
Because uTlconjugated bilirubin
stains fat heavily, jaundice due primarily to unconjugated bilimbin results in yellow staining in areas where
fat accumulates.
Conjugated
bilirubin
concentrates
more easily in elastic tissues. Jaundice due primarily to
conjugated bilirubin is more evident in the skin, mucous
membranes,
and sclerae. In general, when the total
bilirubin level is greater than 2 rng/dl. jaundice will be

clinically evident. However, unless the patient is obseNed in bright daylight, jaundice may not be detected
unless the total bilirubin level is greater than 4 mg/dl.
The unconjugated
or indirect bilirubin
level
rises when there is excess bilirubin production
or a defect in bilirubin l.'Onjugation. Hemolytic
anemia is the most common source of increased bilirubin production. In gener-.i1, the liver is able to accommodate the excess bilirubin by increasing the rate of conjugation to six times its nonnal rate. Therefore, hemolysis
alone causes only a minimal increase in the total bilirubin level, to 2 to 3 mg/dl. If the bilirubin level rises to
4 to 5 mg/dl, hemolysis is most likely accompanied
by
hepatocefiular dysfunction. It is important to remember
that the entire clinical picture must be taken into ac~
count when evaluating hyperbilirubinemia.
If obstructive jaundice occurs in the presence of hemolytic dis
ease, marked
elevations
of both conjugated
and
unc..'Onjugated bilirubin would occur. For example, gallstones can complicate chronic hemolytiC diseases such
as sickle cell anemia and result in a mixed hyperbilirubinemia. Direct bilirubin is watersoluble,
so any excess
in the serum will be excreted in the urine. Absent
bilirubinuria
in a jaundiced
patient indicates unconjugated bilirubinemia.
Gilbert's disease is an autosomal dominant disorder in which the transport of free bilirubin from
the blood. to the site of conjugation is impaired.
TIle intennittent episodes of jaundice (unconjugated hyperbilirubinemia)
that occur in Gilbert's disease may be
mistaken for viral hepatitis. The total serum bilirubin
usually remains below 3 mgtdl. Increases in bilirubin may
occur with concurrent
illness. Gilberts disease is not
associated with any other liver abnormality.
Drugs such as propranolol,

rifampin, and probenecid can interfere \vith the microsomal conjugation of bilirubin and result in an unconjugated hyperbilirubinemia.
II
Measurement
of the alkaline phosphatase
level
(alk phos) is most useful in distinguishing
whether the source of jaundice is an obstructive
process (cholestatic jaundice) or acute hepatocellular
damage.
Marked elevation
of alkaline phosphatase
(greater than three times nonna!) suggests extrahepatic
obstrudion.
Lesser elevation of alkaline phosphatase
may accompany hepatocellular
disease \vithout biliary
obstruction.
Although the source of alkaline phosphatase is mainly the cells that line the biliary tree, alkaline
phosphatase
may also be released from bone osteoblasts, the small intestine,
and the placenta.
In the
presence of jaundi<..-e and suspected
liver disease, the
source of alkaline phosphatase is fairly clear.
Cholestasis can be due to ~intrahcpatic~ obstruction in which there is an interference with the
flow or transport of bile in the C'J.nalicular ~ystem
or to ~extrahepatic" obstruction when cholestasis is caused
by obstruction of the larger bile ducts and channels. Clues
to ertrahepatic
obstruction
include hepatomegaly
with
RUQ Icndemcss,
as weU as fever (UlJ Icukocytosis if
secondary infection occurs. Intrahepatic
cholcstasis
is
rarely accompanied by hepatomegaly or tendemess.
II
Noninvasive tests such as ultrasonogmphy

or
can be used to detennine
the presence of
dilatation of the intra- or extrahepatic
biliary
system. Increased biliary pressure due to obstmction
is
implied if dilatation is present. In addition to demonstrating biliary dilatation, these tests may demonstrate
the presence of a stone or a mass. If biliary dilatation is
demonstrated,
direct ductal visuali7..ation is indicated to
localize the site of obstnlction.
Investigation
may include the use of special tests such as percutaneous
transhepatic cholangiography
or ERCP. If ultrasonography is negative, however, further invasive testing may
still be indicated if extrallepatic
obstnlction
is highly
suspected, because ultrasonography
is only 85% sensitive. False-negative
ultrasound examination
may occur
in the presence of gallstones, which may cause only
partial or intermittent
biliary obstruction
so that bile
aucts are not significantly dilated. Sclerosing cholangitis
usually causes stricture and beading of the intrahepatic
ducts as well as narrO\ving of the extrahepatic
biliary
ductal system. This disorder is another common source
of false~negative ultrasound examinations.
64 Gastrointestinal Disorders Jaundice and Hyperbilirubinemia
cr
Drugs are a common

cause of intrahepatic
cholestatic jaundice, presumably on the basis of
interference with conjugated bilinlbin trdIlsport.
Mull'ifocal der~)sits of metastatic tumor or granulomas can result in intrahepatic

cholestasis.
scan or magnetic resonance imaging (MRI)
is useful in diagnosing tumor and granuloma and in
addition may reveal the presence of infiltrative diseases
sllch as amyloid or lymphoma that also cause intrahe
patic cholestasis.
Liver biopsy is the definitive test to
diagnose these disorders. Percutaneous
needle biopsy
can alternatively be performed under ultrasound or cr
guidance for diagnosis of tumors or metastases.
cr
1m
Hepatocellular
carcinoma is the most common
primary tumor of the liver. It can present as a
solitary mass or multifocal masses. It is related to
hemochromatosis,
cirrhosis. late chronic infectious hepatitis, or anabolic steroid use. Alpha~fetoprotein is elevated
in 70% of patients with hepatocellular carcinoma.
If a sudden fall in blood pressure is superimposed on chronic passive liver congestion, hepatic necrosis and jaundice can occur in the
postshock perioo.
II
Primary hiliary cirrhosis is a disease of unknown

etiology in which there is a progressivc destruction of the small intrahepatic biliaT)' ducts. The
disorder is seen primarily in middle-aged women. Bile
duct injuT)' is thought to be due to an immunologically
mediated mechanism.
The presence of antimitochondrial antibody can be found in 85% to 95% of patients
with this disorder.
lEI
Although the alkaline phosphatasc

level is the
most useful test to determine the cause of the
jaundice, in reality liver transaminases are measured Simultaneously. The overall pattern of these tests
helps determine
the diagnosis.
Extremely
high (>
500 UfL) transaminase
levels are associated with acute
cellular necrosis of the liver.
III
Viral serologies are the most specific tests that

aid in the diagnosis of acute hepatitis. Hepatitis
A, B, C, D, and E are the most common causes
of jaundiee~causing
hepatitis.
Epstein-Barr
virus alld
cytomegalovirus
are other, less common causes of acute
hepatitis manifesting with jaundice. Specific serologic
tests to determine the exact viral etiology of hepatitis or
jaundice usually do not influence the management ofthe
disease, but can help to detemline
the prognosis and
transmissibility
of the virus. The onset of hepatitis is
~
,.Gilbert's
C"glef-Naij8f
AIDSchcMngIOPlIthy
syndrome
Stones
syndrome
Drugs
llpid'flOOfhypefalimentation
Lymph'-'
AmpulladVater
T''''''--------
Commonblleducl:
Extemal
lymph
OOlTlpl'ession
Para8lltic
===:---{
lumorlpanc:reatitia
nodes
Lymphoma
StriC!uretlatresia
-"'-""'"""'
Oralc:ontraceptivesiestrog6nS
ErythrornyclneSlOlate
"oni.'"
"""""'"
IntJahepll1ic choIestasis
11
of pregnancy
-""
Postshock
Befllgnrecurrentcholestasis
12
Pm\ary biliary 0rrtl0sis
Vnlhepalitis
Graftversus-hostdl5ease
Cecil Chapter
Harrison Chapter
144
45
accompanied
by an elevation of the alanine transaminase (ALT) to a greater degree than the aspartate transaminase (AST), ranging from levels of 300 U/L to
greater than 1000 UIL, while the level of alkaline phosphatase is only moderately increased. The bilimbin lev4
cIs bceome elevated after the prodromal phase in which
the transaminases
rise. Antibodies can be measured as
anti-HAY, anti-HeV,. anti-HDV, anliHE\', and a variety
of antibodies
to hepalitis
B proteins to help de6ne
HBV infection, including hepatitis B surface antigen
II
Intrahepatic
cholestasis and jaundice may ac
company severe hepatocellular
disease due to
the acute damage to the hepatocyte and impair.
ment of the mechanical or metabolic transport of conjugated bilirubin to the biliary canaliculi. Hepatocellular
damage occurs most frequently with viral hepatitis but
can accompany a variety of infections or ethanol intoxi
cation. Toxins such as carbon tetrachloride
and phos.
phorus can also result in hepatocellular
disease.
II
Dubin-Johnson
syndrome and Rotor's syndrome
are both benign. autosomal recessively inherited diseases that can manifest \vith jaundice
clinically. A conjugated
hyperbilirubinemia
exists, but
other liver function tests, including serum transaminases
and alkaline phosphatase,
are normal. The two syndromes are rare and can be distinguished
from each
other when basis of liver biopsy.
(HBsAG) and anti-HBs.

Gastrointestinal
Disorders
Jaundice and H}l>erbilirubinemia
65
HEPATOMEGALY
II
The liver edge may be palpable without the

presence of true hepatic enlargement.
Therefore, the Liver span must be estimated on physical examination by percussion. The nonnalliver
span is
6 to 12 em in the midclavicular line and 4 to 8 em in
the midstemal line. Apparent hepatomegaly
on examination can be oollfinned by plain abdominal radiography, ultrasonography. liver-spleen scan, or cr scan. Al!.hough ultrasound
is probab~y th~ simplest and most
cost-effective test to determme liver Size. a cr scan
will also provide detailed infonnation
with. re~.
to
parenchymal
consistency and focal defects m addition
to size.
II
Acute viral hepatitis is suspected on the basis

of the pattern of liver function .abno~a1ities
in
addition to clinical symptoms, mcluding tender
hepatomegaly.
In acute viral hepatitis,
transaminases
(aminotransferases)
rise rapidly to levels greater than
300 UIL and may even exceed levels as high as 1000 VI
L. The rise in transaminase
levels is followed by a
moderate rise in the alkaline phosphatase
and bilirubin
levels. Viral serologies are the most specific tests in
determining
the diagnosis of hepatitis A, B, C, D, and
E. as well as hepatitis due to cytomegalovirus
(CMV)
and Epstein-Barr
virus (EBV).
66 Gastrointestinal Disorden Hepatomegaly
II
Chronic hepatitis is a syndrome characterized

by liver inflammation and cellular necrosis that
lasts longer than 6 to 12 months. The symptoms
are variable and may be accomranied
by hepatomegaly.
There are a variety of causes 0 chronic hepatitis which
include viral, toxins, drugs, and inborn errors of metabolism. Only liver biopsy establishes the diagnosis, but the
disease cannot be classified on the basis of histopathol.
ogy alone. Therefore, the terms chronic acti~e hepati~
and chronic persistent hepatitis have come mto use In
order to communicate
the severity of the disease process. Chronic active hepatitis (CAH) is more histologically severe. CAH has the greatest potential for progression to cirrhosis and liver failure. Hepatitis B, C, and 0
are the most common viral causes of CAH, with hepatitis B (with or without hepatitis D) accounting for approximately 20% of all CA}-1. Other causes of CAH
include drugs and toxins, Wilson's disease, and alphalantitrypsin deficiency.
Chronic persistent
hepatitis (CPH) is an inHammatory process of the liver which is usually
not progressive, and significant fibrosis and dr
rhosis are not present. Hepatitis C is the major cause
ofCPH.
4~
II
Central venous pressure can be estimated via

observation
of the jugular venous pressure
(JVP) on physical examination. Vascular congestion can cause mild transaminitis and hepatomegaly.
Both acute and chronic congestive heart failure

may result in elevated serum transaminases and
an enlarged, tender liver. If an episode of hypotension is superimposed
on chronic hepatic venous congestion, severe centrilobular
necrosis may result wit~
acute tenderness,
marked elevation of serum transamlnases, and hyperbilirubinemia.
At times, it may be dif
ficult to clinically distinguish centrilobular necrosis from
acute viral hepatitis except by the subsequent. course.
The serum transaminase
levels should fall rapidly following a hypotensive episode, whereas with viral hepati.
tis, transaminase
levels decrease much more slowly.
Tricuspid insufficiency is most commonly due

to right ventricular
hypertrophy.
In addition,
trauma, bacterial endocarditis,
and congenital
heart disease may all cause isolated tricuspid regurgitation. In the setting of an acute myocardial infarction,
right-sided heart failurc and tricuspid insufficiency may
result in acute hepatic enlargement
and tenderness.
Liver dlsplacemen
Palpable adJacen1mass
Thin body habl1us
---t
Gallbladder
Feces
ColonIc neoplasm
Cytomegalovirus (CMV)
Normal vanant
EpsteinBarr virus (EBV)
Riedel's lobe
Hepatitis A
--.rLAs1hma
Dfaphragm displaced downwaru---
Hepatitis B
Emphysema
Subdl8.phragmatic abscess
Hepatitis C
Hepatitis D
Hepa1itis E
Hepatomegaly
Chronic hepatitis
1 Perfonn history
and physical exam
-4
4
Chronic active hepati1is

Chronic persistent hepa1itis
Primary
Tumor -{
Abscess
Metastatic
Polycyslic disease
Echinococcal cysts
Congenital hepatic fibrosis
Congestive heart failure (CHF)
Vascular congesti
Constrictive pericarditis
~
Tricuspid regurgitation
Cecil Chapter
144
Harrison Chapter
291
Gastrointetdnal
Disorders
Hepatomegaly 67
HEPATOMEGALY (Continued)
II
Fat infiltration of the liver is due to the collection

:
of triglycerides in the hepatocytes. Liver function
can be well preserved in the presence of fatty
innhmtion so that liver function tests are nonnal. Common causes of fatty liver infiltration are uncontrolled
cliabeles meUitus. obesity. protein-calorie malnutrition,
corticosteriods, alcohol. jcjunoileal bypass operations, hypcralimentation, and ratty liver of pregnancy.
Toxic hepatitis may be due to a variety of drugs
and chemicals. The amount of hepatic injury
can be drug- and dose-dependent or can be
idiosyncratic. One drug may induce different types of
hepatic injury in different individuals. Examples of
drugs that commonly cause hepatitis include acetaminophen, erythromycin estolate. riCampin, oral contraceptives, aspirin. chlorpromazine. halothane, isoniazid, and
methyldopa. If drug-induced hepatitis is SliSpected, the
drug should be withdrawn, with further evaluation if
hepatomegaly and liver function abnonnalities persist
despite drug withdrawal. Drugs can be a common cause
of chronic hepatitis; however, diagnosis may be difficult,
even with the added benefit of liver biopsy. because
drug-induce<1 liver injury is usually not associated \vith
a sp<..'cifichistopathology. Nevertheless, liver biopsy may
provide illformation that may rule out a drug as a cause
of liver injury.
68 Gastrointestinal
Oisordel'"S Hepatomegaly
1m
Cirrhosis refers to progressive hepatic fibrosis,

which may be due to a variety of pathologic
processes. Although the liver may be initially
enlarged, in its end stage a cirrhotic liver becomes
shrunken. Cirrhosis is a final common pathway, so that
causes of cirrhosis include all the previously mentioned
etiologies. i.e., hepatic injury due to drugs and toxins,
viral hepatitis, biliary obstruction, metabolic and storage
diseases, cardiac failure. and venous thrombosis.
A large number of infections other than viral

hepatitis can result in hepatomegaly and liver
inflammation. EBV. CMY, and yellow fever, as
well as other infectious agents and parasites such as
leptospirosis. salmonellosis, malaria. secondary syphilis.
toxoplasmosis, Q fever, ascariasis, schistosomiasis. echinococcosis, and entamebiasis, can result in chronic hepatitis with hepatomegaly.
II
II
CAH is associated \vith chronic hepatitis Bin

fection approximately 20% of the time. Other
causes of CAH include hepatitis C. hepatitis D.
Wilson's disease, alpha,-antitrypsin deficiency. and
drugs. Drugs associated \vith CAH include acetominophen. aspirin, isoniazid. methyldopa, sulfonamides, clan
trolene, and nitrofurantoin. Ethanol consumption accel
erates the progression of chronic hepatitis C. The cause
of CAH is unknown, or cryptogenic, in many cases,
although a variety of antibodies are found in approxi-
matcly 75% of these cases of CAH. which suggests an

autoimmune basis for the disease.
Thrombosis or occlusion or the hepatic veins

may result from hypercoagulable states, including polycythemia rubra vera. from the use of
birth control pills. and from hemoglobinopathies. Also
known as the Budd-Chiari syndrome, this oondition manifests itself clinicallywith mild elevations of transaminases
and bmrubin, as well as an enlarged. tender liver. onthrombotic occlusion of the hepatic veins may also cause
a Budd-Cluari-like syndrome. TIlis so-called veno-occlu
sive disease can occur in patients with alcoholic hepatitis
and cirrhosis, in patients who have been treated with
certain chemotherapeutic agents, in patients who have
eaten plants containing pyrrolidizine alkaloids, and in
patients follov.ing bone marrow transplantation.
III
Obstruction of the inferior vena cava (IYC)

presents in a clinically similar fashion to hepatic
vein obstmction, with ascites and hepatomegaly.
Tumor is a common cause of ryc obstruction. Definitive diagnosis of hepatic vein or IVC obstruction depends on direct demonstration or the site of venous
occlusion by venography.
~
Although most infiltrative and inAammatory liver

diseases are associated with elevated transaminases, isolated measurements may be nonnal.
Uver biopsy may be necessary to confinn the diagnosis.
II
Delta hepatitis
Wilson's disease
Extramedullary hematopoiesis
Lymphoma
Fatty infiltration
Gaucher s disease
Amyloid
Granuloma
9
Toxic hepatitis
Glycogen infiltration
Alpha1antitrypsin deficiency
(continued from page 67)
Iron infiltration
10
Cirmosis
Biliary obstruction
11
12
Infection
Hepatic vein thrombosis
Vascular congestion
Hepatic vein webs
Chronic active hepatitis
Inferior vena cava (IVe) obstruction
Liver nonnal (reevaluate 6 mo.)

Wilson's disease
Extramedullary hematopoiesis
Tumo
r--{Primary
Metastatic
Abscess
Cyst
Hemangioma
Lymphoma
Polycystic disease
' EchinococcaJ cysts

Congenital hepatic fibrosis
Fatty Infiltration
Gaucher's disease
Amylold
Granuloma
(continued from page 67) ~
Toxic hepatitis
CT scan
Glycogen infiltration
Alpha1-antitrypsin deficiency
Iron infiltration
Clrmosis
Biliary obstruction
Infection
Cecil Chapter
144
Harrison Chapter
291
Vascular congestion
liver nonnal (reevaluate 6 mo.)
Chronic active hepatitis
Hepatomegaly
69
ASCITES
Abdominal distention, although commonly a result of ascites. can be due to a variety of other
disorders. Obesity. large ovarian cysts, abdominal abscesses, hematomas, abdominal malignancies, and
intestinal obstruction may mimic ascites. Patients with
ascites may complain of an increase in clothing size, a
feeling of abdominal tightness or pulling, low back pain,
or the new appearance of umbilical or inguinal hernias.
Examination of the abdomen in the presence of ascites
may reveal bulging flanks and an everted umbilicus. It
is difficult to detect less than 1.5 L of abdominal fluid
upon physical examination. Tests to confirm the presence of abdominal fluid include the demonstration of a
fluid wave and of dullness to percussion that shifts with
change in position of the patient. With the patient
positioned on the hands and knees, dullness with percussion of the central abdomen is sensitive enough to
detect as little as 400 ml of abdominal fluid. This test is
particularly useful in the presence of obesity because
other physical tests become less sensitive. Cirrhosis is
the most common cause of ascites, accounting for almost 80% of the causes of ascites. Other common
causes of ascites include congestive heart failure (CHF),
malignancy, and tuberculosis. Over 90% of the ultimate
diagnosis of ascites can be accounted for by these four
diagnoses.
Once ascites is suspected, a diagnostic paracentesis should be perfonned. At least 55 ml of

fluid should be withdrawn and evaluated for
(''ell count, Gmm stain, bacterial culture, and ascites
albumin measurement. Serum albumin should be drawn
at the same time as the paracentesis so that the serumascites albumin gradient (SAAC) can be calculated. If
the SAAC is low 1.1 glelI), other tests that may be
required include cytology, acid-fast stain, mycobacterial
culture, and amylase measurement. Withdrawal of turbid fluid may indicate inflammatory cells associated with
infection, or with chylous ascites in which the triglyceride level is markedly elevated. Fluid should always be
cultured (10 ml into each of two blood culture bottles
at the time of paracentesis), but also triglycerides should
be measured if the fluid is turbid (see No.9).
70 Gastrointestinal Disorders Ascites
The SAAG is detennined hy subtracting the

albumin concentration of the ascites from the
albumin concentration of the serum. If the
SAAC level is greater than 1.1 glell, portal hypertension
is the most likely cause of the ascites. With high ascitic
albumin and correspondingly low SAAG 1.1 gidJ),
most likely causes of ascites include neoplasms, pancreatitis, and tuberculosis.
Meigs' syndrome is a low protein ascites and

hydrothorax associated with ovarian tumors.
Most commonly associated with ovarian cystadenomas, Meigs' syndrome was originally described in
association with ovarian fibromas.
Tuberculous peritonitis can cause ascites. The

mycobacteria can be detected on acid-fast stain
and culture of ascitic fluid. Elevated white
blood cell count (>250/ml) in the ascitic fluid is a useful
clue to tuberculous infection but is also associated with
other infections and malignancy.
Spontaneous bacterial peritonitis (SBP) occurs

in approximately 10% of cirrhotic patients with
ascites. In two thirds of the cases, the infective
organism is the gram-negative rod, Escherichia rolL
Other common causative organisms include pneumococci, Listeria monocytogenes, Neisseria meningitidis,
Haemophilus influe'IUle, and anaerobic organisms. The
mechanism of infection is not known but is thought to
be an "autoinfection" such as leakage of bacteria from
the intestines or hematogenous bacterial seeding of ascitic fluid.
Several clues to the presence of intra-abdominal malignancy can be gleaned from analysis of
ascitic fluid. Bloody ascitic fluid is a common
indication of tumor but may also be present with tuberculous ascites, pancreatitis, abdominal trauma, endometriosis, and perforated viscus. A high lactate dehydrogenase (LDH) level is indicative of intra-abdominal
malignancy. The ratio of ascitic LDH to serum LDH is
more useful than an isolated LDH measurement and is
suggestive of malignancy at a ratio greater than 0.6.
However, 15% of cirrhotic ascites may be found to have

a high LDH ratio in the absence of malignancy. Other
tumor markers have been measured in ascitic fluid,
including the carcinoembryonic antigen (CEA). The
CEA level is increased in only about half the cases of
malignant ascites, but is very specific for malignam.ywhen
present. Pelvic and rectal exams remain important in
patients with ascites and may lead to the diagnosis of
malignancy. Other tests that are helpful in diagnosing
malignant ascites include ultrasound, cr, and laparoscopy.
Chronic pancreatic disease can result in massive
ascites. The ascitic fluid contains high levels of
amylase that may exceed 20,000 Somogyi units.
Pancreatic ascites accounts for approximately 3% of all
causes of ascites and is usually associated with pancreatic disease due to alcohol or abdominal trauma.
Recovery of a turbid fluid on paracentesis

should prompt the measurement of triglyceride
levels. An elevated level of triglyceridcs is diagnostic for chylous ascites. Chylous ascites is due to
malignancy in about 30% of cases. Another 30% of cases
are due to various inflammatory conditions, including
infection. The remaining cases are due to congenital
disorders. trauma, or lymphangiectasia, or they are idiopathic.
1m
Ascites with a high protein level may acc..'Ompany myxedema. The ascitic fluid may evcn be
gelatinous. Myxedema may, conversely, cause
low protein ascites with a low SAAC as well, due primarily to CHF caused by the myxedema. Either way,
the ascites usually clears quickly once thyroid replacement has begun.
II
There are a multitude of causes of ascites in

patients with AIDS. Although the ascites may
be due to the HIV itself, ascites in these patients is most likely due to underlying liver disease,
including cirrhosis, chronic hepatitis B, hepatitis C, alcoholism, and other infectious causes, including tuberculosis, coccidioidomycosis, microsporidia, histoplasmosis,
bacillary angiomatosis, and pneumocystosis.
Cirrhosis
Fulminant hepatic failure
Fatty liver of pregnancy
Ive obstruction
Hepatoma
Portal hypertensio
Uver metastase~
:-{
Hepatic vein obstruction
Hepatic congestion
BuddChiari syndrome
Vasculitis
Constrictive pericarditis
CHF
Portal vein occlusion

Ovarian fibroma
[ Struma ovarii
Meigs' syndrome
Hypoalbuminenia
1
2
Ascites
Perform
paracentesisand
serum albumin level
-{
Ovarian cystadenoma
--f
Nephrotic syndrome
Protein.loslng gastroenteropathy
Malnutrition
Candidiasis
Tuberculous peritonitis
Histoplasmosis
Fungal peritonitis
Coccidioidomycosis
S6P (spontaneous bacterial

peritonitis)
Cryplococcosis
Parasitic peritonitis
Toxoplasmosis
Chlamydiafgonococcal
8 Pancreatic
ascites.
9
0
1
Chylous ascites
Myxedema
Bile ascites
Granulomatous
peritonitis
[ lymphoma
Mahgnancy-------,
Carcinoma
Trauma
Intestinal lymphan9iectaji8
Pancreatitis
Tuberculosis
Ruptured chylous cyst
Adhesions
Peritoneal inflammation
Portal vein thrombosis
-1
Foreign body (starch)

Tuberculosis
Sarcoidosis
Cecil Chapter
Harrison Chapter
142
Chronic nonspecific
peritonitis (AIDS)
46
Ascites 71
LABS
TRANSAMINITIS (ELEVATED
AMINOTRANSFERASES)
The most commonly measured
transaminases
(aminotransferases)
are aspartate transaminase
(AST) and alanine transferase (ALT), formerly
known as SCOT and SePT, respectively.
Both these
enzymes measure below 40 UIL nonnally. Elevated levels of these enzymes are sensitive indicators of hepatocellular disease but are not specific. Transaminases
are
present in other tissues, including skeletal muscle. kidney. myocardium, pancreas, and small intestine. Other
abnormal liver function tests help to define the liver
disease indicated by elevated transaminases.
Isolated
elevations of transaminases
should instigate evaluation
to determine the source of the elevated transaminases.
Serum creatine phosphokinase

(CK or CPK) is
elevated with acute atrophy or necrosis of striated muscle. CK levels remain normal in liver
72 Gastrointestinal Disorders Transaminitis
disease and biliary obstruction.

If an isolated transaminitis is measured, CK can be a useful way to determine
the source of the elevated transaminases.
CK can be
fractionated to determine the source of its release. The
CK-MB isoenzyme elevation is specific for myocardial
injury. The CK-MM isoenzyme is elevated when striated
muscle is crushed or injured. The AST level is elevated
in myocardial infarction, although the elevation is not
specific for myocardial injury. If the myocardium is not
damaged, as with angina pectoris, coronary insufficiency,
and pericarditis, serum AST and CK will remain within
normal limits.
Approximately
50% of patients with extensive
cerebral infarctions (cerebrovascular
accidents
[GYAs]) have elevated levels of CK and AST.
The CK-M B isoenzyme

or infarction.
4~
is not elevated
with brain injury
Measurement
of the alkaline phosphatase
level
(alk phos) is most useful in distinguishing
whether the source of jaundice is an obstructive
(Elevated Aminotransferases)
process (cholestatic jaundice) or acute hepatocellular

damage.
Marked elevation
of alkaline phosphatase
(greater than three times normal) suggests extrahepatic
obstruction.
Lesser elevations of alkaline phosphatase
may acc..'Ompany hepatocellular
disease without biliary
obstruction.
Although the source of alkaline phosphatase is mainly the ceUs that line the biliary tree, alkaline
phosphatase
may also be released from bone osteoblasts, the small intestine. and the placenta. An elevated.
alkaline phosphatase
is often found on routine blood
chemistry panels in growing adolescents. Since placenta
and bone growth can both cause an isolated elevation
of alkaline phosphatase,
the clinical setting should be
acknowledged
prior to initiating an extensive evaluation
in an otherwise
healthy patient. In the presence of
transaminitis and suspected liver disease, the source of
alkaline phosphatase is fairly clear.
Acute myocardial infarction
Cerebral infarction
Intramuscularinjection
Acute muscle inju
Muscle trauma -----< [
Severe/prolonged
exercise
Status epilepticus
Polymyositis
Parturition
2
1
Tranumlnltl.
(nl AST <40 lUll)
(nl Al T <40 lUll)
Measure
CK level
(nI40-180
Cholestatic jaundice (see Jaundice algorithm)

UIL
Measure serum
alk phos
(n1<105 UIL)
Measure
serum bilirubin
(nl total bili < 1.2 mgldl)
(nl conj. < 0.4 mg/dl)
Viral hepatitis
Acute hepatocellular
disea
Drugslloxins/ak:ohol
Chronic liver disease
Idiopathic transaminitis
Cecil Chapter
149
Harrison Chapter
292
Gastrointestinal
Disorders
Transaminifu (Elevated Aminotransferases) 73
ELEVATED ALKALINE
PHOSPHATASE
Serum alkaline phosphatase
is derived mainly
from the cells of the biliary tract, the mucosal
cells of the small intestine. the placenta, and
bone osteoblasts. The most valuable use of the alkaline
phosphatase
measurement
lies in distinguishing
an obstructive biliary process (cholestasis) from hepatocellular
damage (see Jaundice algorithm, page 65). The alkaline
phosyhatase
level is measured
on routine chemistry
pane and may be found as an isolated abnormality. The
clinical setting should be taken into account prior to
initiating an extensive evaluation if an isolated abnormality is found. For example, an isolated elevation in
in an otherwise healthy, growing
adolescent boy (bone osteoblast production)
or in an
otherwise healthy pregnant female (placenta) should be
ignored. Alkaline phosphatase
from the intestine can
account for as much as 60% of the total serum value in
some individuals but is an unlikely source of elevated
serum levels in the absence of overt intestinal disease.
The highest levels of serum alkaline phosphatase occur
with biliary obstruction and Paget's disease. The alkaline
phosphatase
may be elevated to three or more times
the nomlal level.
The main sources of alkaline phosphatase in the

nonpregnant
adult are bone and liver. Serum
can be elevated normally
with pregnancy and growth, or with space-occupying
and infiltrative diseases of the liver in the absence of
significant bilirubin elevation. The measurement
of the
serum level of the enzyme 5' -nucleotidase
will distinguish between a bone and liver source of the alkaline
phosphatase. 5' -Nucleotidase
is found mainly in the bile
canaliculi of the liver and is not present in bone. Another enzyme used to detennine
the presence of liver
disease is serum -y-glutamyl transpeptidase.
This enzyme is absent in bone and placenta and is sensitive for
liver disease but is not very specific. Although the 5' nucleotidase
is not as sensitive, it is very specific for
hepatobiliary
disease. Alternatively,
heat inactivation
74 Gastrointestinal
Disorders
(fractionation) of alkaline phosphatase can be used to
Coffman DA, Chalslrey ), Smith-Laing G: Gastrointesti-
determine its source. The differentiation

between a hepatic and bone source is based on the fact that alkaline
phosphatase derived from bone is heat-labile (hence the
phrase "bone bums") and that liver alkaline phosphatase
is heat-stable.
nal Disorders.
New York, Churchill
Livingstone,
1986.
Cohen S; Clinical Gastroenterology:
A Problem-Oriented Approach. New York, John Wiley & Sons, 19&3.
Dill JE: Diagnosis and treatment of right upper quadrant abdominal pain. Va Moo Q 123;27-29, 1996.
Feldman M, Scharschmidt
SF, Sleisenger MH (eds);
Sieisenger and Fordtron's Gastrointestinal
and Liver
Disease. 6th ed. Philadelphia, WB Saunders, 1998.
Frank BS: Clinical
evaluation
of jaundice.
JAMA
262(21),3031--3034,
1989.
Koch A, Voderholzer WA, Klauser AG, et aI: Symptoms
in chronic constipation. Dis Colon Rectum 40(8);902906,1997.
Lancaster-Smith
MJ, Chapman C (cds); Gastroenterology. Littleton, MA, PSG, 1985.
Lancaster-Smith
Williams K: Problems in Castroenterology. Philade phia. FA Davis, 1982.
McGuire HH: Gains and losses in the modem diagnosis
of abdominal pain. Va Med Q 124(1),14-17, 1997.
McHutchison
JC: Differential
diagnosis
of ascites.
Semin Liver Dis 17(3):191-201,
1997.
Schmidt E, Schmidt FW: Progress in the enzyme diagnosis of liver disease; reality or illusion? Clin Biochem
23:375-382, 1990.
Siewert S, Raptopoulos V, Mueller MF, et al: Impact of
cr on diagnosis and management of acute abdomen
in patients
initially treated without surgery. AJR
168,171-177,
1997.
Stelling HP, Maimon HN, Smith RA, et al; A comparative study of fecal occult blood tests for early detection of gastrointestinal
pathology. Arch Intem Med
1SO,I00I-I00s,
1990.
Wanke CA; Practical approach to diarrheal illness. Mecliguide Infect Dis 17(1):1-8, 1997.
Wilcox CM, Forsmark
CE, Darragh T, et a1: Highprotein ascites in patients with the acquired immunodeficiency syndrome. Castroenterology
100;745-748,
1991.
The placenta is an active source of alkaline

phosphatase, and serum levels become elevated
in late pregnancy. The serum alkaline phosphatase level returns to normal by 3 weeks post partum.
The Regan isozyme is an isozyme of alkaline phosphatase that is identical to the placental isozyme but is
found in the presence of certain malignancies, especially
lung carcinoma (see No.6).
II
Any bone lesions that produce increased osteoblastic activity will result in elevated serum alkaline phosphatase
levels. At times, bone lesions such as osteogenic
sarcoma
and metastatic
carcinoma may be suspected on the basis of an elevated
alkaline yhosphatase level obtained on a routine chemis;,
try pane.
An
elevated
alkaline phosphatase,
resulting
from normal bone growth, is often found on
routine blood chemistry panels in children and
adolescents.
II
Malignancy not involving the bone or the liver

can produce an isozyme of alkaline phosphatase
and result in an elevated level of serum alkaline
phosphatase. One such isozyme, the Regan isozyme, has
been found to be identical to the placental isozyme and
is associated most commonly with lung carcinoma. The
Regan isozyme is found rarely in normal persons.
Bibliography
BarlcMln TJ, Bergus CR, Weissman AM; Diagnostic imaging to identify the cause of jaundice.
Am Fam
Physician 54(2),55&-562, 1996.
MI'
-----1[
Cholestasis
Intrahepatic (see Jaundice algorithm, page 65)
Extrahepatic
LeUkemi8
Infiltrative
disease
liver disease
Granulomas'-------,
[ Tuberculosis
Sarcoidosis
Amyloid
CYsts
Mass lesions
Parenchymal
1
EJeveted
Alkaline Phoaph.t
>105 UIL
Abscesses
Metastatic
carcinoma
[ Pnmary
hepatoma
Neoplasms'-------~
disease
Measure
5' nucleotidase
level (01 <15 UIL)
or fractionate elk phos
Healing fractures
Pagers disease
Osteogenesis Imperfecta
Rickels
Vitamin D admlnlstratiOrl
Bonedisease-----LOSteitis
fibrosacystica
Polyostotic fibrous dysplasia
Familial osteoectasia
Pregnancy
g::=:~~~
lumors-----~[
Metastatic
carcinoma
Osteogenic sarcoma
Growth
Malignancy
Intestinal
ischemia
Hyperthyroidism
Cecil Chapter
147
Harrison Chapter
292
75
Renal Disorders
Signs and symptoms:
Oliguri"
Labs:
Hematuria
Proteinuria
SIGNS AND SYMPTOMS

OLIGURIA
II
Oliguria is defined as a urine output of less than

400 mV24hr. Urine output below this quantity
is llsually evident'C of it decrease in glomerular
filtmlin!l mte (erR). Normal metabolism produces between 400 and 500 mOsm of solute per (L'lY. The kidneys cannot concentrate
the ul'"ine to greater
than
1200 mOsmlkg.
so that a urine output of less than
400 mll24hr \ViII not allow for excretion of the entire
daily solute load. The simultall( ..--ous accumulation
of
nitrogenous wastes and all increase in the blood urea
nitrogen (BUN) arc commonly seen in the setting of oli~uria.
Unne sodium (U,.) is a sensitive iudic-dlOT of

renal perfusion. As long as tubular function is
intact, the kidneys will I1Hl'(imally reabsorb s0dium when renal perfusion is decreased. The source of
the decreased perfusion is not important; the decrease
may result from true intravascular
volume depletion
or d<'Creased renal blood flow as seen with cardiac
insuffidcncy or vascular obstrudion.
TIle fmctional excretion of sexlium (FE ......) relates the excretion of sodium
to the GrH and is thought to be an even more sensitive
indicator of renal perfusion than UN. alone. The FEN.
is defined by the formula
of drugs, especially the prostaglandin

synthesis inhibi
tors and the converting enzyme inhibitors, have been
associated with oliguric renal failure. Inhibitors of pros
taglandin synthesis such as propionic acid derivatives
(ibuprofen,
fenoprofen,
nuproxen) and indolacetic acid
derivatives (indomethacin,
tolmetin sodiuln) decrease
renal blood flow and CFR, especially in patients with
decreased
effecth'e arterial volumes or renal vascular
disease.
A nephritic urine sediment contains the products of glomerular inflammation. These include
red blood cells. while blood cells. red blood
cell casts, hyalin casts, and cellular debris. Individual

elements of nephritic urine. \vith the exception of red
blood cell casts, may be seen in other renal disorders,
but this combination
usually signifies glolllenilonephritis.
Oliguria is most commonly associated with the
mpidly progressive fonns of glomenalonephritis
(RPCN). RPCN may be seen in imlllune disorders such as anti-glomerular
basement membrane anti
body disellse (anti-CBM)
or idiopathic crescentic glomerulonephritis.
RPGN can also occur following
infection with some forms of streptococci and hepatitis
B virus and during the course of bacterial endocarditis.
Certain systemic disorders may also cause RPCN. The
most commonly associated disorders are systemic lupus
erythematosus,
poIY.:lrteritis, cryoglobulinemi , allergic
angiitis, llenochSchonlein
purpura, and systemic nec
rotizing vasculitis.
The renal ultrasound is a sensitive noninvasive

way to image the intrarenal collectin
system.
Dilatation of the calyces and the ren:Y pelvis is
indicative of extrarenal
obstruction.
The renal ultrasound may be negative in the first 24 to 36 hours after
obstruction
has occurred and should be rcpeated if a
strong suspicion of obstruction exists.
where P'l. is plasma sodium,

Pl' is plasma creatinine.
U~. is urine creatinine,
and
Prerenal oliguria is decreased urine output resulting from underperfusion

of the kidney and
is the most common form of oliguria. Cardiac
insufficiency and overuse of diuretics arc the most commonly associated causes. The kidneys are perfectly normal, and correction
of the underlying
condition will
restore renal fundion to nonnal. Several newer classes
76 . Renal Disorders Oliguria
Vasculitis resulting in oliguric renal failure may

occur without associated
glomerular
injury.
Among the vasculitides that do not usually affect the glomeruli
are idiopathic
systemic vasculitis,
scleroderma
vasculitis,
malignant
hypertension,
and
drug. related vasculitis.
TIle gallium scan is usually positive in inflam-
matory processes of the kidney such as interstitial nephritis. The scan should be interpreted
with caution, however, because it may also be positive
in other nonintcrslitial
disorders such as infections. The
finding of eosinophils in the urine at this point in the
evaluation would make the diagnosis of allergic-type
interstitial nephritis extremely likely. and may obviate
the need for the gallium scan.
II
Allergic forms of interstitial nephritis are usually drug.related.

The prototype of this form of
interstitial nephritis is seen wilh the semisynthetic penicillins such as nafcillin. Other antibiotics,
including the cephalosporins,
sulfa drugs, tetracycline,
rifampin,
and ethambutol,
have been implicated
as
causes of interstitial
nephritis.
Nonsteroidal
antiinHammatory agents, thia7jde diuretics, allopuriuol. aspirin, cimelidine,
methyldop<1., phenytoin, and clofibrate,
among others, have also been associated with allergic
fonns of interstitial nephritis.
1m
onallergic
usually due
phritis may
tions, toxoplasmosis,
syphilis, mycoplasma
and Rocky Mountain
forms of interstitial nephritis are

to infectious agents. Interstitial ne
be caused by streptococcal
infecinfectious mononucleosis,
measles,
infections,
legionnaires'
disease.
spotted fever.
The ischemic form of acute tubular necrosis

(ATN) is due to the lInderpcrfusion
of the renal
tubules. The most common cause of tubular
ischemia is hypotension due to volume loss, poor cardiac
output. the vasodilatation seen with sepsis, rhabdomyolysis, postpartum hemorrhage, and pancreatitis. Prerenal
forms of oliguria may progress to ischemic AT if not
adequately treated.
II
Many substances are toxic to the renal tubules.

Common toxins include the aminoglycoside antibiotics; amphotericin
B; pentamidine;
vancomycin; foscamet; heavy metals such as lead and mercury, as well as heavy metal-based
antineoplastics
like
cisplatin; endotoxin; myoglohin; Bence Jones protein;
iodinated contrast media; fluorinated
anesthetics;
organic solvents; ethylene
glycol: acetaminophen;
and
paraquat.
Embolism
Bilateral renal vascular obstruction --{
"ThIrd spacing" of Huids
Hypovolemia {
Thrombosis
G~Io~S
Diuretic use
Blood loss=--{ Bacteremia/sepsis

Peripheral vasodilatation
ArItihypertensives
[ ACE inhibitor with renal artery stenosls
Aheration in renal autoregulation --------[
Prostaglandin synthesis inhibitors
~::rdial
Impaired cardiac function
tamrx>nade
Cydosporine
Pulmonary embolus
-{
Myocardial infarctiofl
{ Toxemia of pregnancy
Increased blood viscosity
Hepatorenal syndrome
Anesthesia
Increased renal vascular resistance
5
Acute glomerulonephritis
Surgery
Malignant hypertension
Disseminated intravascular coagulation
1
Ollgurla
400 ml per 24 hr)
Renal
='
Acute tubular necro6lS (ATN)
lntrauret8ral
Bilateral ureteral obstruction

Bladder neck obstruction
Postral'\8l
{Autonomic
neuropathy
Urethral obstructIOn ---{
Cecil Chapter
Harrison
Extraureteral
~s':~~ypertrophyL
-.!.!r
-:;:;L
12
IschemIC
To>~
Stones
PyogenIC debris
Edema
Papillary debns
Tumor
Retroperitoneal fibrosis
UreteralllgatlOl'l
391
Chapter
Renal Olsorders Oliguria 77
LABS
HEMATURIA
Hematuria is the presence of abnormal num
bers of '00 blood cells (RBCs) in lbe urine.
Nonnally, up to 1 X 10' RBCs pe' day may appear in the urine. The presence of more than two or
three RBCs per high power field 00 routine urinalysis.
however, warrants further investigation. The midstream
urine collection is the most accurate for detection of
hematuria. Cigarette smoking. strenuous exercise. and
fever have been reported to cause hematuria without
any underlying pathologic change. A positive test for
blood on a urine dipstick in the absence of RBCs may
indicate the presence of myoglobin resulting from muscle necrosis, free hemoglobin resulting from intravascular hemolysis, or lysis of RBes in the bladder due to
hypotonic urine. Hemoglobinuria has been associated
with the ingestion or inhalation of certain toxins such as
carbon monoxide, poisonous mushrooms, naphthalene.
sulfonamides, and tin-containing compounds. The appearance of RBe casts is indicative of intrarenal abnormality. Glomerulonephritis and renal vasculitis are most
commonly associated with RBe casts.
Although spontaneous bleeding in the urinary

tract can occur with the use of anticoagulant
drugs and with coagulopathies, several studies
have reported that more than 50% of patients with this
disorder have underlying urinary tract disorders. Further
evaluation of the urinary tract with cystoscopy or intravenous pyelogrnphy (lVP) is advisable fo, lbese patients.
II
Hematuria is more common in patients with

sickle cell trait (Hb AS) than in patients with
the homozygous form of the disease (Hb 55).
II
78 RenaJ Disorders.
Hematuria
The hematuria is painless and 80% of the time comes

from the left kidney only. As with other ooagulopathies,
there is a high incidence of associated urinary tract
disease (see No.2).
Urinary protein excretion of more than 1 'd
day usually indicates glomerular damage. Some
glomerular lesions or dysproteinemias such as
multiple myeloma may be associated with a protein
excretion of less than 1 'dday, but these diseases are not
usually associated with hematuria.
Computed tomography (CT) enhanced excretory urograms are several times more accurate
than the traditional IV]>even with tomogrnphic
cuts. Total radiation is lower and dye loads may be less.
Future refinements in urinary tract imaging include
spiral cr, which may eliminate the need for (..'Ontrast
material in up to 90% of studies.
Renal cell carcinoma accounts for 85% of all

renal tumors, with the highest incidence in the
sixth decade of life. Hereditary. viral, hormonal,
and environmental factors have all been implicated in
the etiology of this tumor. There is a two to eightfold
increase in renal cell carcinoma in tobacco users. Certain foods containing nitrosamines, as well as coffee and
high fat diets, have also been suspected as etiologic factors.
Isolated renal cysts rarely cause hematuria. Ten

percent to 15% of patients with polycystic kidney disease. however, will present with gross or
microscopic hematuria. Bleeding into a renal cyst in
polycystic kidney disease may at times cause massive
hematuria.
Four percent of all urinary tumors are urotheIial. The most common, transitional cell carcinoma, accounts for more than 90% of the ureteral tumors. The remaining 8% to 10% of tumors are
squamous cell carcinomas. Adenocarcinomas are also
occasionally found. These tumors occur most frequently
in the sixth decade of life, with a 4: I male predominance.
Tumors of the bladder have a strong male predominance. There is a greatly increased incidence of bladder carcinoma in tobacco users.
The highest incidence of bladder carcinoma oc'Curs in
cigarette smokers, but pipe and cigar smoking as well
as the use of chewing tobacco are all associated with an
increased incidence of carcinoma of the bladder.
1m
Both acute and chronic forms of glomcrulonephritis are associated with hematuria. Smoky
urine and red blood cell casts arc indicative of
hematuria of renal parenchymal origin. Hematuria is
not specific for any form of glomenllonephritis, but
membranoproliferative glomerulonephritis, focal glomerular sclerosis, and IgA nephritis (Berger's disease)
are the most common glomerular diseases associated
with hematuria.
Bactenal cystitIS
TB
Infection
Pyelonephntls
ProstatitiS
Urethritis
Papilla.y necrosis
Renal
i
6
Tumor
Cysts
Stones
Medullary sponge kidney
8t
Ureteral
Tumors
Stones
Diverticula
Tumor
Stone
Diverticula
Vasculitis
Interstitial cystitis
A-V malformatk>n
Renal infarction
Tumors
Cysts
Cortical necrosis
Renal vein thrombosis
Glomerulonephritis
Intestinal nephritis
Vasculitis
Benign familial hematuria

Aunner'slmarch hematuria
Cecil Chapter
Harrison Chapter
100
Idiopathic hematuria
47
Renal
Dlsorden Hematuria 79
PROTEINURIA
Most healthy persons excrete between 45 and
ISO mg of urinary protein daily. Values as high
as 300 mg/day have been found after exercise.
About 30% of the protein in the urine of nomlal persons
is albumin, with the remainder a variety of filtered and
secreted globulins. Dye-impregnated
strips are the most
common method of detecting proteinuria. The intensity
of the color change is proportional to the concentration
of protein in the urine, ,'lith trace = to mg/cll, 1 +
~ 30 mgl(U, 2 + = 100 mgldl, 3 + ~ 300 mgldl, and
4 + = > 1000 mgtdl. The dipsticks may underestimate
the proteinuria
if large aillounts of globulins or light
chains are present, because the sticks are much more
sensitive to albumin than to other proteins.
The 24-hour urine collection is the simplest

method of quantifyin
urinary protein excretion. Simultaneolls 24-~our creatinine excretion
should also be measured to assess the completeness
of
the collection. Proteinuria
can be divided into three
etiologic types. Overflow proteinuria
results from an
increase in the concentration
of a plasma protein, usually because of overproduction.
Tubular proteinuria
is
the result of the impairment of tubular reabsorption of
the smaller-molecular-weight
proteins normally filtered
at the glomerulus. Glomerular proteinuria
is the result
of increased permeability
of the glomerular
capillary
wall to protein. Tubular and overflow proteinuria rarely
exceed 2 i24 h
II
Monoclonal light chains, either K or A, are commonly seen in the urine in multiple myeloma.
TIle proteinuria
may be a result of overflow
from the increased production
of both myeloma paraprotein and light chains, or due to direct glomerular or
tubular damage from the paraprotein
itself. Amyloidosis
occurs in approximately
10% of patients with multiple
myeloma and may also cause proteinuria,
usually in
excess of 3 gI24 hr. TIle urine dipstick may be falsely
negative in this disorder because the light chains or
paraproteins
do not react with the chemical impregnated on the stick.
II
Beta2-microglobulin,
with a molecular weight of
4
12,000, is the standard marker in the urine for
tubular proteinuria. The normal urinary excretion of 100 IJ.gI24 hr may be increased 10- to lOO-fold
in tubular disea. e.
80 Renal Dlsorden
Proteinuria
Hereditary
forms of tubular disease causing
proteinuria
include polycystic kidney disease,
Wilson s disease, cystinosis, oxalosis, and medullary <-')'stic disease.
Congenital
forms of tubular disease causing
proteinuria include some fonns of renal tubular
acidosis and all forms of Fanconi's syndrome.
II
Acquired tubular diseases causing proteinuria

include heavy metal toxicity, pyelonephritis,
interstitial nephritis, obstructive
uropathy, radiation nephritis, and vitamin D intoxication.
8:
Immunologic
forms of tubular proteinuria may
include renal transplant
rejection, sarcoidosis,
drug hypersensitivity,
and Sjfigren's syndrome.
Several infectious diseases are associated with

nephrotic-range
proteinuria.
Poststreptococcal
glomerulonephritis,
hacterial
endocarditis,
"shunt" nephritis, and syphilis are associated with nephrotic-range
proteinuria.
Several other viral disorders,
including HlV and hepatitis Band C, have also been
associated with proteinuria.
1m
enytoin
Drugs that have been associated with proteinuria of greater than 3 glday include nonsteroidal
anti-inflammatory
agents, penicillamine,
meph(Mesantoin), and probenecid.
II
Familial disorders associated with nephroticrange proteinuria

include Alport's syndrome,
sickle cell disease, Fabry's disease, and nailpatella syndrome.
Neoplastic diseases may cause proteinuria

by
direct toxicity to the kidney, as seen in some
lymphomas
and leukemias as well as Wilms'
tumor, pheochromocytoma,
and multiple
myeloma.
Neoplasia can also cause proteinuria
by secondary glomerular damage, as in the case of the membranous
nephropathy
associated with carcinomas of the lung,
breast, and colon.
At least two abnormalities

have been identified
that account for the increased glomerular capil~
lal)' wall permeability to protein seen in glomerulonephritis. First, there is a loss of the normal negative
charge on the capillary wall. The loss of a negative
charge eliminates the repelling forces between the neg-
ative charge on the protein molecule and the capillary

wall. Second, there is alteration in the size barrier to
passage of large molecules. The alteration may be the
result of gaps in the glomerular basement membrane,
detachment
of epithelial cells, and the deposition of
materials along the basement
membrane
that further
disrupt the integrity of the capillary wall .
II
The glomerular injury seen in the multisystem

disorders may be the result of direct trauma
to the renal vascular system, the deposition of
antibodies directly in the glomerulus, or the deposition
of circulating
antigen.antibody
complexes within the
glomerulus.
The mechanism of the proteinuria
is the
same as that described above (see No. 13).
4
Bibliography
Brenner BM: Brenner and Rector's The Kidney. 6th ed.
Philadelphia, WB Saunders, 2000.
Glassock RJ: Current Therapy in Nephrology and Hypertension
1984-1985. St Louis, Mosby-Year Book,
1984.
Kurtzman
NA, Batlle DC: Acid-base disorders. Med
C!;n North Am 67A, 1983.
Narins RG. Jones ER. Stein T, et al.: Diagnostic strate
gies in disorders of fluid, electrolyte, and acid-base
homeostasis. Am J Med 72:496-520, 1982.
Schrier RW: Renal and Electrolyte Disorders. Boston,
Little, Brown, 1986.
Stein JH: Nephrology:
The Science and Practice of
Clinical Medicine. Vol 7. New York, Grone & Stratton, 1980.
Taylor RB: Difficult Diagnosis
2. Philadelphia,
WB
Saunders. 1992.
Multiple
Ughtchains {
myeloma
Ught chain nephropathy

Minimal
change
disease
Albumin only {
Transient
(related
to
(see below)
exercise or fever)
Check
urine
Orthostatic
protein
electrophoresis
Hered.tal)'
~I mlcroglobulln
- Tubular
protelnuna
-H
6
Congenital
AcqUired
ImmunologIC
Mixed (see below)
Infections
Drugs
Allergic
reaction
Familial
disorders
Neoplastic
disease
Minimal
change
disease
Focal sclerosis
13
Glomerulonephritis (GN)
Membranous GN
Proliferative GN
Unclassified GN
Diabetes mellitus
Systemic
lupus erythematosus
Polyarteritis
Hypertension
Essential
{
Malignant
Amyloidosis
Multisystem disease
Myxedema
Takayasu's
syndrome
Goodpasture's
syndrome
Dennatitis herpetiformis
Henoch-$chOnlein
Cecil Chapter
Harrison
Chapter
100
purpura
Sarcoidosis
42
R.enal Disorders
Proteinuria
81
III Acid-Base
and Electrolyte Disorders
LABS:
Hyponatremia
Hypematremia
Hypokalemia
Hyperkalemia
Hypocalcemia
Hypercalcemia
Hypophosphatemia
Hyperphosphatemia
Hypomagnesemia
Hypennagnesemia
Acidosis
Alkalosis
HYPONATREMIA
Hyperglycemia, by osmotically shifting water
into the intravascular space, will decrease the
serum sodium (Na) 1.6 mEq/L for each

100 mEq/dl increase in serum glucose greater than
100 mEqldJ. If the Na is decreased out of proportion to
the expected decreased owing to hyperglycemia alone.

another osmolar substance may be present or true hyponatremia may coexist.
Increased anion excretion can cause increased
electrolyte and water loss. Metabolic alkalosis is
the most frequently associated condition. Any
of the causes of metabolic alkalosis may be present (see
Alkalosis). Bicarbonate is present in any urine with a
pH greater than 6.1 in the absence of urea-splitting
organisms.
II
A Jow serum osmolality implies a relative or

absolute water excess and overhydration of the
extracellular fluid compartment. The totalOOdy
Na (TBN.), however, may be normal, increased, or low.
Hyponatremia is the most common electrolyte abnor
mality in hospitalized patients.
Useful clinical clues to determine the patient's

volume status include orthostatic blood ressure and pulse changes, the moistness or the
mucous membranes, the presence or absence of axillary
perspiration, skin turgor, jugular venous distention, and
the presence or absence of a hepatojugular reflux.
Disorders in which the kidneys perceive a decreased "effective arterial volume" cause avid
Na reabsorption by the kidneys. Effective arte
rial volume is synonymous with renal perfusion. The
decreased MeffectivevolumeMmay be due to decreased
cardiac output in the case of congestive heart failure, or
II
82 Acid-Base and Electrotyte Disorders
Sodium excretion at the level of the individual

nephron is increased when total kidney glomerular filtration rate (CFR) is dt.'Creased.The ability of each nephron to increase the percentage of filtered Na, along with tubular inability to reabsorb much
of the filtered Na, accounts for the increased urinary
Na concentration seen in renal failure. Increased ADH
is released in this setting, contributing to the hyponatremia.
LABS
to the loss of plasma volume into a third space, such as

the massive ascites that may be seen with hepatic cirrhosis. Increased antidiuretic hormone (ADH) is released
in this setting and leads to the hyponatremia_
Hyponatremia
Psychogenic polydipsia is usually seen in females with a history of psychiatric or eating

disorders. \Vhell water intake is greater than
I l..Aar,the kidney's ability to excrete free water is exceeded and hyponatremia results. TIle urine is maximally dilute and urine osmolality is low.
Common iatrogenic causes of hyponatremia include the administration of hypotonic intrave

nous solutions, excessive water intake by per
sons on sodium-restricted diets, tap water enemas, and
the use of large amounts of distiUed water for irrigation
during prostatic or bladder surgery.
The syndrome of inappropriate [secretion of]

ADH (SlADH) is the result of either a defect
in the osmoregulation of ADI-I or the secretion
of ectopic ADH or ADHlike substances. There are
many causes of SIADH, but pulmonary infections, oat
ceU carcinoma of the lung, and some central nervous
system (eNS) lesions are the most common. SIADH
should be considered in the euvolemic, hyponatremic
patient when other causes of impaired water excretion
have been eliminated.
1m
Various drugs impair water excretion by releasing ADH or potentiating the action of ADH in
the distal tubule. Drugs most commonty associated with hyponatremia include chl0'l>ropalllide and
other sulfonylureas; nonsteroidal anti-inflammatory
drugs; opiates; barbiturates; cyclophosphamide; vincristine; haloperidol; tricyclic antidepressants; clofibrate;
nicotine, both inhaled or delivered transdermally; carbamarine; and high doses of acetaminophen.
II
Several mechanisms have been implicated in

the hyponatremia associated with hypothyroid.
ism. Increased ADH levels, as well as enhanced
reabsorption of Na and water in the proximal tubule,
occurs with hyp:>thyroidism. Avid sodium retention is
not seen unless the patient is also volume-depleted.
Urinary sodium concentration is, therefore, usually
greater than 20 mEqIL.
III
Glucocorticoids have an important function in

the normal control of ADH release. Patients
with isolated glucocorticoid deficiency may have
a profound impairment in water excretion. The hyponatremia and increased ADH levels are corrected with the
administration of physiologiCamounts of cortisol.
Hyponatremia in the setting of extrarenal volume loss is the result of the stimulation of ADH
release. Water excretion is impaired even in the
presence of avid sodium reabsorption by the kidney.
II
III
II
When the kidney is the source of abnormal

fluid and electrolyte losses. sodium reabsorption
may be impaired even in the presence of vol
ume depletion and hyponatremia.
~
The combination of decreased Na reabsorption

due to the lack of mineralocorticoid and the
impaired water excretion resulting from decreased glucocorticoid levels (see . o. 12) accounts for
the hyponatremia seen \vith adrenal insufficiency.
Diuretic use is the most common cause of hyponatremia in the volume-depicted patient. Sodium is lost by impaired renal tubular reabsorption, whereas water excretion IS impaired by both ADH
secretion and the decrease of fluid delivery to the diluting portions of the nephron. lIyponatremia is most
common with the thia7ide djuretics.
II
Salt-losing nephritis is most <"'OlIllnonly

seen in
advanced forms of renal disease with the CFR
less than 10 mVmill. Medullary (:ystic disease,
polycystic disease, obstructive nephropathy, analgesic
nephropathy. and chronic p)elonephritis are the most
commonly associated conditions. Salt w.astingoccurs because of tubular d)'sfunctioll, whereas water excretion is
impaired by the same mechanism seen in other forms
of renal failure (see No.6)
II
HyperosmoIa< hyponatremia
"Mannitol
Pseudohyponatremta
-1
2
{
lso-osmola,
hyponatremia
r Hype'll_
Bicarbonaturia
Hyperlipkjemia
Hyperproteinemia

Cirrhosis
Nephrotic syndrome
G.,;fta;n-Bemi
syndrome
Head trauma
Intracranial bleeding
Hyponatremia
(s",
< '35 mEqIL)
Mass
P_-
Measure
serum
osmolality
(Sosm)
Merlingltls
PostoplpairVemotion
la_
Tumo<
SIADH
Drugs
True hyponatremia
Stroke
eNS lesions
--f
Pancreas
-{
Lung
Oat cell carcRJma

B~
Duodenum
carcinoma
AIDS
Hypothyroidism
Viral pneumonia
Glucocorticoid deficiency
Reset osmostat
EmoOOnaI
Pulmonary processes
stress
Aspergillosis
Pneumonia
Tuberculosis
Palo
Bronchogenic carcinoma
Abscess
Postdlu'etic
Glless
Extrarenalloss
the'apy
Glsuction
~pane,eamiS
Vomiting
Third space loss
Diant>ea
Traumatized muscle
Excessive
Rerlal loss 17
Cecil Chapter
102
Sait.losing nephri:--L
49
Bums
Mannitol
Ketonuria
Bicarbonaturia
Harrison Chapter
sweating
=::::~~:...
':
Skinloss----~ [
-----I[
MetabolicaJluUosis
Renal tubular acidosis
Oisorden
Hyponatremia 83
HYPERNATREMIA
II
Hypematremia
always represents a state of hyperosmolality. The serum osmolality can be calculated using the following fonnula:
(1.95)(PN + P,) + BUN/2.8+ glucose/lB

=
calculated
mannitol, alcohol, and ethylene glycol.
associated
with a urine to
plasma osmolality ratio of greater than 0.7, the

total body Na is usually low, with the hypematremia a result of a free water deficit.
The hypematremia
The slight increases in serum Na seen in Cushing's disease and primary hyperaldosteronism,
although common, are rarely of clinical signifi-
cance.
If urine to plasma osmolality ratio is less than

0.7, the total body Na is normal or slightly
elevated.
The hypernatremia
results from a
deficit of free water.
osmolality
where PSa is plasma Na and PK is plasma potassium. If

the measured
osmolality
deviates
by more than 10
mOsm from the calculated osmolality, the source of the
unmeasured
osmolality must be sought. Examples of
commonly
unmeasured
osmolar substances
include
In the disorders
II
often associated
with hyper-
catabolic states such as severe hums is second-
ary to the osmotic diuresis caused by the pro

duchon of excess urea. Hypercatabolic
patients, along
with those patients receiving the protein hydrolysate
contained in hyperalimentation
solutions, may develop
hypematremia
unless sOOium and free water are adequately replaced.
In the disorders in which the urine or plasma
osmolality is variable, the urine Na concentration is usually greater than 20 mEqIL. Urine
Na in this range is usually associated with normal or
increased TBN
84 AcicJ.Base and EJectrotyte Dlsorden Hypematremia
II
Polydipsia, the excessive intake of water, causes

expansion and dilution of the extracellular fluids. As serum osmolality falls, ADH is suppressed and hypematremia
can result. Primary polydipsia may result from an abnormality
in the osmolar
regulation of thirst but more commonly is associated
with psychiatric disorders.
Central diabetes insipidus is a primary failure

of ADH production in the pituitary gland. Although approximately 50% of the cases are idiopathic, central diabetes
insipidus has several known
causes. Disorders associated with central diabetes insipidus include trauma, a primary tumor in the sellar area
(pinealoma, craniopharyngioma,
and metastatic disease,
most commonly from breast and lung), infections of the
CNS (Guillain-Barre
syndrome and syphilis), granulomatous diseases (sarcoidosis, tuberculosis,
and Wegener's granulomatosis),
histiocytic diseases, vascular events
associated with sickle cell disease, aneurysms, cerebral
vascular accidents, and postpartum
necrosis (Sheehan's
syndrome). Ra.rely, central diabetes insipidus can occur
during, or as a sequela of, infections of the CNS.
Osmoreceptor
ablation can occur when a lesion
involves the area of the hypothalamus
where
the osmoreceptors
are located. Many lesions
involving this area of the hypothalamus have been implicated, including granulomas,
hydrocephalus,
vascular
occlusion, tumors, and degenerative disorders.
11
Congenital nephrogenic
diabetes insipidus is a
rare Xlinked disorder in which the distal tubule
is unresponsive to ADH. The mechanism of the
AD H resistam,.'e is not known but may represent an
abnormality of ADH-mediated
cyclic adenosine monophosphate.
II
Acquired
nephrogenic
diabetes
insipidus
is
most commonly associated with renal diseases
such as polycystic disease, chronic pyelonephri.
tis, and ureteral obstruction.
Other causes of acquired
diabetes insipidus include direct drug effects on the
renal tubules and collecting system as seen with alcohol,
lithium, demeclocycline.
sulfonylureas,
amphotericin,
iodinated dyes, colchicine, fluorinated anesthetics, and
various antibiotics, as well as sickle cell disease, multiple
myeloma, amyloidosis,
sarcoidosis, and Sjfigren's disease. Dietary abnormalities such as decreased NaCI and
protein intake may add to increased Na concentration.
Hypercalcemia
and hypokalemia of any cause as well as
hypothyroidism
has been associated with hypcmatremia.
II
The hypematremia
associated with paroxysmal
atrial tachycardia
appears to be caused by a
primary suppression
of ADH release with a
resultant water diuresis.
Extrarenal Josses
--f
Excessive sweating
Diarrhea
Respiratory loss
Mannitol
Renal losses
--f
Osmotic diuresis ----~

Diuretics
Glucose
Hypercatebohsm
InterstiUal renal disease
Idiopathic reset osmostal
Hypematremla
(Na > 145 mEqIL)
Measure spot
Urine/plasma
Osmolality (U/P Osm) and
Urine Na (U )
Exogenous
Hypertonic NaHC03 infusion

Hypertonic NaCI infusion
Hypertonic dialysis
Cushing's disease
Hormonal --{
Excessive water intake with decreased ADH (water diuresis)
Central diabetes insipidus (Ol)

Osmoreceptor
ablation
Hypodipsia secondary to CNS lesion

Nephrogenic diabetes InsipiduS----
11
10 [ Congenftal or familial
Acquired
Paroxysmal atrial tachycardia

Pregnancy (rare)
Cecil Chapter
Harrison Chapter
102
49
AcidBase and Electrotyte Disorders
Hypematremia
85
HYPOKALEMIA
II
Elevated renin production resulting in elevated

aldosterone levels will cause hypokalemia by
increasing renal secretion of potassium. Malignant hypertension, renovascular hypertension,
and reninsecreting tumors are the most common disorders
associated with elevated reoins.
Increased
aldosterone
production
of any etiol-
ogy can cause hypokalemia by enhancing distal

tubular secretion of potassium. The hypokalemia can develop, however, only if distal fluid delivery
is adequate. Disorders associated with increased aldosterone production such as congestive heart failure, cirrhosis, and nephrotic syndrome may also cause decreased renal perfusion, and the hypokalemia may not
occur until diuretic therapy increases distal tubule
fluid delivery.
Pseudohyperaldosteronism,
or Liddle's syndrome, has all the clinical manifestations of aldosterone excess, including hypertension, metabolic alkalosis, and hypokalemia as a result of renal
potassium wasting. The etiology, however, is tubular,
with hyperabsorption of sodium (Na) and volume expansion with resulting hypersecretion of potassium and H" .
II
Hypokalemia is commonly associated with renal

tubular acidosis (RTA). In proximal RTA, the
potassium loss is due to increased delivery of
Na and HC03 ~ to the distal tubule. In distal RTA,
increased potassium secretion is due at least in part to
decreased H" secretion and the need to maintain cationic balance. Hyperaldosteronism
is also seen in this
disorder and may contribute to the hypokalemia.
:.
II
Protracted vomiting is a common cause of hypokalemia. The potassium loss, however, is not
from the loss of gastric Ruid itself. Because
gastric fluid contains only 5 to 10 mEqIL of potassium,
massive losses would be necessary to deplete the body's
potassium stores. Vomiting can, however, cause volume
contraction that stimulates aldosterone production and
the development of hypochloremic metabolic alkalosis.
Both of these factors increase the renal excretion of
potassium (see Nos. 2 and 12).
Bartter's syndrome, a disorder of uncertain etiology, consists of muscle weakness, polyuria,
metabolic alkalosis, potassium wasting, and elevated renin in the absence of hypertension. The syn.
drome occurs most commonly in children. Although
86 Acid-Base and Electrolyte Disorders
Hypokalemia
the mechanism of the disorder is uncertain, increased

aldosterone and increased urinary prostaglandins appear
to playa role.
Hypokalemia is seen commonly in association
with magnesium (Mg) depletion. The mechanism is not known. Like the hypocalcemia seen
with Mg depletion, the hypokalemia cannot be corrected until the Mg is repleted.
Diuretics, whose site of action is proximal to

the sites of potassium secretion in the distal
tubule, may cause profound potassium wasting.
Several factors enter into the mechanism of potassium
loss. These factors include increased delivery of Ruid to
the distal tubule, volume contraction with stimulation
of aldosterone secretion, and the metabolic alkalosis
seen with volume contraction (see No. ] 2).
Several drugs have been associated with hypokalemia. The most common of these are the
semisynthetic penicillins such as carbenicillin,
piperacillin, and ticarcillin. The hypokalemia is caused
by the delivery of large quantities of Na and nonreabsorbable anions to the distal tubule. The aminoglycosides, most notably gentamicin, can also calise renal
potassium wasting. Intracellular potassium depletion in
the renal tubule is thought to playa part in the mechanism of nephrotoxicity of these drugs.
1m
Hypokalemia can be seen in certain forms of

both acute and chronic leukemia and is most
commonly associated with lysozymuria.
III
Osmotic diuresis, most commonly associated

with glycosuria, may cause profound potassium
wasting and hypokalemia. The hypokalemia is
secondary to increased delivery of fluid past the distal
tubular potassium secretory sites, thereby increasing p<r
tassium loss. Diabetic ketoacidosis may be associated
with a potassium deficit of as much as 200 to 300 mEq.
The acidosis and insulin deficiency may Illask this den
cit, but severe life-threatening
hypokalemia may develop when treatment is begun if potassium is not adequately repleted.
II
Alkalosis may cause mild hypokalemia by shifting potassium from the extracellular to the intracellular space. The effect is not nearly as
profound as that seen with the hyperkalemia associated
with acidosis. Respiratory alkalosis by itself causes little
change in the serum potassium.
III
Hypokalemic periodic paralysis is an IIncom

mon and usually familial disorder. Sporadic
cases have also been described, and there appears to be an oc-casional association with thyrotoxicosis.
Episodes of paralysis due to a rapid redistribution of
potassium into the cells can be precipitated by various
factors known to have a direct or indirect effect on
potassium balance. These include carbohydrate-rich
foods, insulin, glucose, (3-adrenergic agonists, adrenocorticotropic hormone (ACfH). and some mineralcx.'or
ticoids. During an attack, plasma potassium may fall to
1 to 2 mEqlL. Diazoxide, propranolol, spironolactone.
and acetamlamide
have been shown to abort attacks.
III
Although the kidneys are efficient at {.'onserving

potassium, prolonged decreased intake of potassium will lead to total body potassium depletion
and hypokalemia. Protein- and caloric-poor diets will
also be lacking in potassium. True starvation and de
creased intake secondary to psychological causes (anorexia nervosa) may lead to profound potassium dcple.
tion. Elderly patients with limited access to food or
the inability to prepare balanced diets may he<:ome
potassium-depleted,
hence the name "tea and toast syndrome."'
:.
II
Geophagia, a form of pica most common in the

southern United States, may lead to profound
hypokalemia. In this syndrome, large quantities
of red clay are ingested. The red clay binds potassium
in the intestine and prevents adequate absorption .
II
Perspiration contains a high concentration

of
potassium. Chronic loss, as seen with routine
vigorous exercise and work in hot environments,
can lead to excessive loss of potassium, especially if the
fluid is replaced with solutions containing low or no
potassium. Hypokalemia of mild-to-moderate
degree
has been reported in women during the peri menopausal
period if Rushing with heavy perspiration is extreme.
Replacement fluids high in potassium, such as certain
juices or sport's drinks, Illay prevent this problem.
II
III
Large amounts of potassium can be lost in diarrheal stools. The stool water itself may be high
in potassium. In addition, the volume contraction may increase renal potassium losses (see No.5).
Villous adenomas, which constitute 2% to 12%

of colonic tumors, are commonly associated
v.-ith hypokalemia. Potassium concentration
in
Cecil Chapter
Malignanthypertensioo
102
Renovascularhypertension
Renin-secretingtumor
Harrison Chapter
Primaryhyperaidosteroolsm
3 [ PseudohyperaJdosteronism
Cushing'ssyndrome
Renal_
AJkak>o;, -{
:::-::':
StarvatlOl1
Extrarenalloss -16
-:t
SkInlosses
15
AmphoteriCin
Druga----+Carbenollolone
Fanconrssyndrome 9 Antibiotics--{
Semlsynlheticpenicillins
10
Leukemia
Aminoglycosldes
11
Osmoticdiuresis
Levodopa
Treatmentof megaloblasticanemia
Leukerma
Increasedcell uptake
DecreasedIntake ~
Diuretics
Mg depletion
Familialperiodicparalysis
Bariumpoisoning
14
Bartter'ssyndrome 8
1
13
Intracellular-extraceUular
shifts
HyperaJlmentabOll
ji-agonlstdrugs
Insulin
-;,1
~-adrenerglcactivity
Stress
CoronaryISCMfTlia
Tea and toast syndrome

Anono ""...,..
Geophagia
18
Deliriumtremens
ZoIlo"96,-EII"""
'ynd""""
VIllousadenoma
Laxativeabuse
Lossof gastncfluid
GastroinlestlOalloss;:;L
17 Diarrhea
Islet cell tumor

19
Ureterosigmoidostomy
LowergastrolOtestlOalllstulas
the secreted mucus may be as high as 80 mEqIL. Volumes of diarrhea may reach 1 to 3 Uday. This direct
loss of potassium, along with the volume contraction
seen in this disorder, leads to the hypokalemia.
lEI
is now an uncommon
urinary diversion procedure in which the ureters
are implanted in an isolated portion of the sigmoid colon. Secretion of potassium and bicarbonate into
the lumen of the sigmoid loop leads to both metabolic

acidosis and hypokalemia. The now more common ileal
loop allows for a more rapid transit time of the urine in
the loop of bowel and less potassium loss.
Acid-Base and Electrotyte Oisorders Hypokalemia 87
HYPERKALEMIA
PseuclohyperkaJemia is caused by the in vitro

release of potassium from leukocytes, platelets,
or red blood cells. The potassium is released
when the walls of these potassium-rich cells rupture

during the clotting process, which occurs after the blood
has been collected. If pseudohyperkalemia is suspected,
plasma potassium should be measured. Under Donnal
circumstances, there should be no more than a
0.3 mEqfL difference between serum and plasma potas-
metabolic acidosis. Metabolic acidosis associated with

mineral acids such as chloride, phosphate, and sulfate
causes a greater shift of potassium out of the ceUs than
do organic acids such as lactate or the keto acids. This
effect is caused by the impermeability of the cells to
the mineral anions, forcing a greater shift of potassium
out of the ceUs in order to maintain electrical neutrality.
The profound hyperkalemia that can be seen in diabetic
ketoacidosis is more a reflection of the insulin de6ciency
(see No.5) and the hypoaldosteronism (see No. 15)
than the actual acidosis.
sium.
Hyperkalemia from increased dietary potassium

in the absence of renal insufficiency or hypoaldosteronism is rare. The administration of high
doses of the potassium salts of various antibiotics such
as potassium penicillin, or the treatment of hypokalemia
with oral or intravenous potassium, has, however, been
associated with life-threatening hyperkalemia.
The release of potassium from endogenous

sources is more likely than increased dietary
intake of potassium alone to cause hyperkalemia. Large quantities of potassium may be released
from the hemolysis of transfused red blood cells. A
large potassium load can be avoided by using blood that
has been stored a short time or saline-washed prior to
transfusion.
The relationship between acidosis and hyperkalemia is well known and until recently was believed to be relatively constant, with potassium
rising 0.6 mEqIL for each fall of 0.1 pH unit. It is now
knov.rn,however, that the type of acidosis, the duration
of the acidosis, and the anion associated with the elevated H ->- concentration are important factors influencing potassium concentration. Respiratory acidosis has a
much smaller elTect on serum potassium than does
88 Acid8ase and Electrolyte Disorders Hyperkalemia
Insulin has great importance in the maintenance of potassium homeostasis. When insulin
secretion either is inhibited chemically with somatostatin or is absent in type I diabetes mellitus, both
basal serum potassium and serum potassium after a
potassium load rise. Hyperkalemia may occur in the
setting of insulin de6ciency alone, but a variety of other
factors contribute to the hyperkalemia associated with
diabetes. These factors include acidemia during episodes of ketoacidosis, hypertonicity associated with elevated blood glucose, diabetes associated renal insufficiency, and the selective hypoaldosteronism that can be
seen with diabetes mellitus.
The digitalis glycosides have been associated

with life-threatening hyperkalemia when taken
in toxic amounts. The hyperkalemia is thought
to be due to inhibition by digitalis of the cellular uptake
of potassium. Although hyperkalemia is a consistent
finding in severe digitalis intoxication, therapeutic digitalis levels have little elTect on serum potassium.
The muscle relaxant and paralY7ingagent succinylcholine may cause mild hyperkalemia in normal patients because of increases in the ionic
permeability of the muscle cells with consequent movement of potassium into the extracellular space. In many
neuromuscular disorders, however, severe hyperkalemia

may develop after administration of drugs such as succinylcholine.
The treatment of metabolic alkalosis with arginine or lysine hydrochloric acid (He!) may
cause severe hyperkalemia. Patients with impaired renal function appear especially susceptible. The
etiology of the hyperkalemia is thought to be due to
movement of potassium from the intracellular to the
extracellular space caused by the amino acids themselves rather than the actual change in pH.
The hyperkalemia associated with heparin administration is due to impaired aldosterone production. Heparin acts directly on the adrenal
zona glomerulosa. The synthesis of aldosterone is impaired by heparin's inhibition of IS-hydroxylase activity.
The hyperkalemic effect of heparin may be seen within
2 to 4 days after its initiation. The new low-molccularweight heparins may diminish this effect.
II
The hyperkalemia seen with the angiotensinconverting enzyme (ACE) inhibitors is multifactorial. Decreased aldosterone synthesis, as well
as a derangement of the tubular potassium secretory
mechanism, has been implicated. Severe hyperkalemia
in the absence of impaired renal function is rare.
\Vhether or not the newer angiotensin II receptor antagonists will diminish this elTect has not yet been determined.
Hyperkalemia has occasionally been observed

following the use of nonsteroidal anti-inRammatory drugs (NSAIDs). The inhibition of certain prostaglandins may inhibit aldosterone production
as well as altering renal hemooynamics and reducing
GFR. The effect is reversible within 1 to 2 weeks after
discontinuing the drug.
(continued
on page 91)
HyperkIleml.
<5,. > 5.5 mEQIl.)
Exogenous potassium intake
[Diet
Potasslum-contalnlng medICations
Endogenous potassium release
---t
Hemolysis of stored blood

GI bleeding
Catabolic state
Exercise after ,6-bloctters

Tissue
Rhabdomyolysis
release -{
Tumor lysis
Hemolysis
Hypercalcemic
periodic paralysis
Drugs -
Cecil Chapter
Harrison Chapter
102
49
Digitalis intoxication
Succinylcholine
Arginlnellysine HCI
Heparin
10
ACE inhibitors
11
Nonsteroidal
anli-inflammatory
drugs (NSAIOsl
Acid-Base and Electrolyte Disorders
Hyperkalemia 89
HYPERKALEMIA (Continued)
II
Acute oliguric renal failure is usually associated

with hyperkalemia. The hyperkalemia is due to
a combination of interrelated factors. First, the
GFR usually approaches zero, causing decreased potassium filtration. Second, the markedly decreased GFR
decreases exchangeable sodium and Auid delivery to the
distal tubule where potassium is secreted. Third, if the
cause of the acute renal failure is tubular damage, there
is a reduction in the number of tubular cells available
for potassium secretion. Finally, most of the patients
with acute renal failure also have increased tissue catabolism, releasing more potassium into the extTaceUular
space.
Hyperkalemia is unusual in chronic renal failure

until the GFR approaches 10 to 15 mVmin. At
this level of eFR, there is inadequate delivery
of Auid to the distal tubular sites of potassium secretion.
Acute potassium loads, however, can cause lifethreaten
ing hyperkalemia even with moderate renal failure. Patients with interstitial nephritis or diabetic nephropathy
may develop hyperkalemia at a higher GFR because of
more extensive tubular damage or associated hypoaldosteronism.
Hyperkalemia
Hypoaldosteronism is usually associated with a

renin defiCiency. most commonly occurring in
the elderly and in patients with diabetes melli
tus. A significant proportion of patients with evidence
of hypoaldosteronism, however, have no detectable reduction in renin production. These patients have a se
lective decrease in aldosterone production because of a
generalized adrenal insufficiency, as seen in Addison's
disease, or an alteration in some portion of the synthetic
pathway for aldosterone. such as deficiencies in
C-ll.deoxycorticosterone hydroxylase.
III
.,
II
Renin deficiency is usually a result of damage

to the juxtaglomerular cells. The damage may
be due to the sclerosis accompanying aging or
destruction of the cells seen in interstitial nephritis.
Hydronephrosis is also a common cause of decreased
renin production. and hyperkalemia may be a presenting sign of this condition. The hyperkalemia often
associated with diabetes mellitus is partially due to the
high frequency of decreased renin production causing
hypoaldosteronism.
II
A number of drugs may decrease renal tubular

secretion of potassium independent of any effect on aldosterone production or action. Tri
amterene and amiloride are potent inhibitors of potas
sium secretion. These drugs are usually combined with
other diuretics to prevent excessive potassium losses.
The use of these drugs in the setting of renal insufficiency or hypoaldosteronism may lead to life-threatening hyperkalemia.
III
Several drugs may cause hyperkalemia by reductions in plasma renin activity and aldoste
Several primary renal diseases, as well as certain

systemic diseases with renal involvement, may
cause a primary defect in the secretion of potassium. The exact mechanism of the defect is not certain
but may involve reduced tubular sensitivity to aldosterone as well as an increased tubular absorption of chlo-
rone. Several or the drugs may also change
ride ion.
II
renal hemodynamics or alter prostaglandin synthesis.

Cyclosporine, a widely used antirejection drug, is typical
of drugs with these effects. ACE inhibitors, especially
in the setting of the type IV RTA seen in diabetes, may
lead to serious hyperkalemia. Heparin-induced. hypkalemia is common and may be lessened by the use of
newer low.molecular-weight heparin.
12
I
(continued
r Acute
Renal failure -----:;:;L

13
Chronic
Glucocorticoid
Angiotensinogen
from
page 89)
defICiency
defICiency
-{
Uver failure
decreased
Aging
Volume
15
expansion
Drugs
Renin deficiency
Inactive renin
Diabetes
potassium
Check
serum
excretion
(U. < 20 mEq/L)
creatinine
(Sc.)
Angiotensin-converting
enzymedeficiency
-{
Interstitial
Drug inhibition
Idiopathic
mellitus
nephritis
Hydronephrosis
AIDS
Defective
angiotensin
receptor
Defective
aldosterone
synthesis
Adrenal
insufficiency
{
local
synthetic
Medullary
sponge
defect
kidney
Drug effect
Sickle cell disease
Inadequate distal tubular delivery of Na

Primary
renal secretory
Renal transplant
defect
Obstructive
Amyloid
~
Cecil Chapter
Harrison
Chapter
Systemic
nephropathy
deposition
lupus erythematosus
102
49
Hyperkalemia
91
HYPOCALCEMIA
Approximately 40% of the total calcium (Ca) in
the serum is bound to proteins, with 80% to 90%
of this ea bound to albumin. A decrease in serum
albumin will decrease the amount of protein-bound
ea
and therefore the total Ca. An approximation of this effect
can be obtained by assuming a 0.8 mg/ell change in serum
Ca for each 1 gldl change in albumin ooncentration. Globulins have a much smaller effect. A change of 1 gldl in
globulin concentration will change serum ea concentration by approximately 0.12 mWdl. Changes in pH can also
affect protein binding by Ca. A change of 0.1 pH unit
will change protein-bound Ca by 0.12 mWdl.
II
Ionized h)'lXlCllicemia is most commonly seen in

the setting of resuscitation of trauma patients
in the emergency department.
The etiology is
multifactorial and includes administration
of large volumes of crystalloids and citrated blOCMi products, as well
as iodinated contrast dye and hypeTVentilation therapy
for severe head injury. The incidence of ionized hypocalcemia in this setting is unclear, but it should be suspected
when refmctory hypotension or electromechanical
dissociation occurs. Ionized hypocalcemia may also be seen
during blood component pheresis procedures when the
donor is given too little C'".alciumto counteract the effects
of citrate used during the procedure.
Parathyroid hormone (ITH) is a single-chain
polypeptide of 84 amino acids 'With a molecular
weight of 9500. Biologic activity resides in the
N-terminal
portion consisting of the amino acid sequence 1-34. The ITH effect on kidney and bone is
mediated through the activation of adenylate cyclase,
'With the subsequent
formation of cyclic adenosine 3',
5'-monophosphate
(cyclic AMP). Several mdioimmunoassays are available to measure ITH. These include
assays for the Nterminal and carboxy or Cterminal,
as
well as the whole molecule. Measurement
of the Cterminal portion or the whole molecule appears to be
best correlated 'With clinical disorders of PTH except in
renal failure. With renal failure, the Cterminal, or inac
tive fragments, accumulate, and measurement
of the Ntenninal is necessary for an accurate measurement
of
active PTH.
The most common cause of hypoparathyroidism

is the surgical removal of one or more parathyroid glands because of an adenoma or hyperplasia. Damage to the glands can also occur during thyroid
or other extensive neck surgery. The usual postoperative
fall in serum Ca is temporary if it is related to suppres-
92 AcldBase and Electrolyte Disorders
Hypocalcemia
sion of the parathyroid glands from the previous longstanding hypercalcemia,

or if rapid remineralization
of
bone occurs, as 'With the hungry bone syndrome (see
No. 17). In these cases, serum ea usually will not fall
below 8.5 mg/dI, and the hypocalcemia does not last for
more than 7 to 10 days. Prolonged hypocalcemia or a
more profound decrease in serum Ca is indicative of
possible permanent
hypoparathyroidism,
and appro
priate treabnent
should be started. Infiltrative diseases
of the parathyroid
glands such as amyloidosis, hemochromatosis related to thalassemia or Wilson's disease,
and metastatic
cancer may also cause hypoparathyroidism. Idiopathic hypoparathyroidism
begins either in
childhood as a sexlinked recessive disorder or in adolescence as an autosomal recessive disorder. H ypoparathy.
roidism has also been associated with adrenal insufficiency and has been described
in association
with
pernicious anemia. Aminoglycoside
antibiotics and certain cytotoxic agents may also directly suppress production of ITH.
Vitamin D (vit D) is present in may plants and
as 7-dehydrocholesterol
in the skin of humans.
Skin exposure to ultraviolet radiation converts
the 7-d.ehydrocholesterol
to cholecalciferol (vitamin D3),
the primary endogenous
source of vitamin D. The
shorter duration of sunlight exposure in extreme northern
and southern latitudes may reduce serum vitamin D
levels. Vitamin D3 is then metabolized to 25-hydroxyvitamin D3 (calcifediol) in the liver. The calcifediol undergoes enterohepatic
circulation and is further metabolized
in the kidney to 1,25-d.ihydroxyvitamin D3 (calcitriol) via
the enzyme I.hydroxylase. CaJcitriol is the most biologically active fonn of vitamin D. Biochemical properties of
vitamin D include increased absorption of Ca and PO .
in the intestine and possibly increased mineralization of
bone. Production of calcitriol is increased by PTH, a
low ea diet, and hypophosphatemia.
There is a marked
reduction in the production of calcitriol in advanced renal
failure. Calcitriol also exists in the 24, 25-dihydroxy fonn,
but its significance is unclear.
Malabsorption
of vitamin D may be a result
of a reduction of intraluminal
bile salts, rapid
intestinal transit time, or mucosal disease in the
gastrointestinal
(GI) tmct. In each of these cases there
is decreased vitamin D absorption, and increased fecal
loss of the 25-hydroxyvitamin
0 derived from enterohepatic circulation. Clinical conditions associated 'With
malabsorption
of vitamin D include gastrectomy, tropical and nontropical sprue, chronic pancreatitis,
biliary
cirrhosis, Ia.~tive abuse, and intestinal bypass.
II
Increased
metabolism
'With a shortened
half
life of vitamin 03 and 25-hydroxyvitamin
D is
thought to be the result of microsomal enzyme
induction in the liver secondary to the use of anticonvul
sant drugs. Increased metabolism causes a more rapid
turnover of vitamin D along 'With production of certain
inactive forms of vitamin D.
Ethanol (ETOH) may act to reduce vitamin 0

levels via poor nutrition and hepatic dysfunction.
The decreased levels of vitamin D in nephrotic

syndrome have been attributed
to the loss of
vitamin D-binding
globulin in the urine. The
clinical significance of h)'lXK=a1cemia in this setting is unclear.
1m
Decreased production of vitamin D and subsequent hypocalcemia

are common in liver disease, because the liver is the site of the conversion of vitamin 0 into one of its active forms.
II
Advanced
renal failure with GFR less than
25 mVmin is associated 'With d(."Creased production of the 1,25-dihydroxy form of vitamin D.
The exact mechanism of this decreased production
is
not well understood
but is probably related to the decrease in renal mass. The availability of oral I.25-dihydroxy vitamin D has helped to prevent much of the
bone disease associated with renal failure.
II
The bone disease seen ",>jth vit D-dependent

rickets is a result of a deficiency in the 1hydroxylase enzymc that metabolizcs 25-hydroxyvitamin D3 to the more active fonn 1.25-dihydroxyvitamin D3. Pharmacologic
doses of vitamin D or small
doses of the I ,25.dihydroxy fonn of vitamin 0 are effective in treating this disorder.
In pseudo-idiopathic
hypoparathyroidism,
hypocalcemia is thought to be due to production
of an abnonnal
ITfH molecule or cleavage of
the PTH prohormone
at an incorrect site. The h)'fMlCalcemia responds
to thc administration
of exogenous
ITH. The elevated levels of PTII in this disorder are
secondary to the hypocaleemia.
III
Pseudohypoparathyroidism
is a rare inheritable
disease consisting of the somatic manifestations
of mental retardation, short stature, brachydactyly, exostosis, and "clCpressionless face:' Biochemical
abnormalities
include hypocalcemia and hyperphosphatemia. The disorder can take two forms. Type IA has
:.I
Reduction in protein-bound calcium only
Nutritional defICiency
Vit D resistance type I
Malabsorption
7t
Hypocalcemia
(Sc. < 8.4 mgIdI)
Increased metabolism -
Anticonv\Jlsants
ETCH
Glutethimide
Accelerated loss
_________
.~[ Nephrotic syndrome

.
Billaryclrrhosls
10 ~ Uve, d;",.",
Decreased production -11
Renallailure
12
Vit D-depenclent rickets
13
Pseudo-kllopathlc
14
Pseudotlypoparathyroidism
hypoparathyroklism
Vit D resistance type II

Acutealkalosls
Cecil Chapter
Harrison Chapter
Hyperphosptlaterma
18
Hypomagnesemia
17
Hungry bone syndrome
18
Acute pancreatitis
19
Drug effects
264
Rhabdomyolysls
354
both the somatic and biochemical

abnormalities,
whereas type 18 presents with only the biochemical
abnormalities. The mechanism of the biochemical abnormalities is thought to be due to end-organ unrespcm
siveness to PTH secondary to a presumed failure of
renal and bone adenylate cyclase stimulation. There is
no response to exogenous PTH administration.
PTH
levels are again increased owing to hY}XlCUlcemia.
II
15
The mechanism for the reduction in serum ea

with hyperphosphatemia
is unknown but is pas
sibly deposition of CaP04 in bone and soft tissue. Either the endogenous release or the increased
intake of P04 can be associated with decreases in serum
Ca. A product of serum Ca and P04 greater than 70 is

associated with an increased risk for the precipitation of
CaP04 in the tissues.
II
The hypocalcemia associated with hypomagne

semia arises from a combination of PTH suppression and skeletal resistance to the effects of
PTH. The hypocalcemia will usually not respond to
treatment until the magnesium level has been restored
to normal.
II
The mechanism of the hypocalcemia seen in

the hungry bone syndrome is the same as that
described in the section on hypophosphatemia
(see page 96).
lEI
Both the precipitation of intra-abdominal

Ca
soaps and the sup ression of PTH are thought
to be responsible ~r the hypocalcemia, at times
profound, seen in acute pancreatitis.
:
Several drugs, including colchicine, estrogen,

ntamidine, ci latin, and doxorubicin, have
ken
associate1
with hypocalcemia.
80th
mithramycin and calcitonin have been used therapeutically for their calcium-lowering effects. The expanded
use of biphosphonate
in the treatment of osteoporosis
has been associated with occasional hypocalcemia. A
decreased ionized Ca may be seen following transfusion
of large amounts of citrated blood.
Hypocalcemia. 93
HYPERCALCEMIA
II
Average
dietary
In
intake
of Ca is 900 mg, with

only 30% to 35% of this ea absorbed in the
small bowel. There are both active and passive
components
to absorption;
the active component
requires vitamin D. Between 150 and 200 mg of
are
absorbed from the CI tract. This absorption presents
the extracellular fluid with 150 to 200 mg of
per day.
Because there is no net gain or loss of bone
under
nonnal circumstances,
renal excretion is approximately
150 to 200 mWday. Ninety-eight percent of the filtered
load of
is reabsorbed. Sixty percent to 70% of
is
reabsorbed in the proximal tubule, 20% to 25% in the
loop of Henle, and 5% to 10% in the distal tubule,
where absorption is influenced by PTH. ea reabsorption
by the renal tubule is enhanced by PTH and metabolic
alkalosis and inhibited. by metabolic acidosis and phosphate depletion. Malignancy and primary hyperparathyroidism account for 60% of all causes of hypercalcemia.
ea
ea
ea
ea
ea
The effects of albumin concentration

on serum
Ca are described On page 92. In diseases with
increased paraprotein production, such as multiple myeloma, there may be sufficient elevation in the
Ca-binding protein to produce an increase in the total
serum Ca, although ionized Ca is nonnal.
Primary hyperparathyroidism
is seen most commonly in women over 60 years of age. Eighty
percent of patients have a single parathyroid
adenoma. Hyperplasia. multiple adenomas, and the rare
parathyroid
carcinoma account for the remainder
of
cases. Apart from the multiple endocrine
neoplasia
(MEN) syndromes described below, several disorders,
including sarcoidosis,
Hashimoto's
disease, some malignancies,
medullary
sponge kidney, and Cushing's
syndrome, have been associated with primary hyperparathyroidism.
Laboratory 6ndings in primary hyperparathyroidism
may include hypercalciuria,
low or normal inorganic
phosphate
level,
normal
alkaline
phosphatase
(in the absence of overt bone disease), a
PTH level inappropriately
high for the level of serum
Ca, and elevated urinary cyclic AMP (cAMP) excretion.
MEN 2, parathyroid hyperplasia is associated

with medullary carcinoma of the thyroid, and
pheochromocytoma.
MEN 2 is also inherited as
an autosomal dominant trait.
Isolated adult hyperparathyroidism

is a rare disorder with poorly understood
inheritance.
MEN syndromes must first be eliminated before the diagnosis can be made.
Familial hypocalciuric
hyperparathyroidism
is
an autosomal dominant disorder with onset at
an early age, hypocalciuria,
occasional hypermagnesemia, and a benign course.
Lithium-induced
hypercalcemia
is a benign
condition with hypercalcemia
thought to be due
to decreased entry of Ca into the parathyroid
cells, thereby altering the set-point for PTH release. It
is reversible by discontinuing
the drug.
Increased PTH with subsequent

hypercalcemia
can be seen in the re<.'Overy phase of acute renal
failure due to rhabdomyolysis.
1m
Tertiary hyperparathyroidism
describes the development of autonomous
hyperparathyroidism
following a prolonged period of se<.'Ondary hyperparathyroidism
with its associated parathyroid hyperplasia. Several cases have been described
in celiac
disease. Far more common is the secondary hyperparathyroidism seen in chronic renal failure. This hyperparathyroidism is probably a result of hypocalcemia, hyperphosphatemia,
and altered
vitamin
D metabolism.
Hypel'"Calcemia may occur for varying periods of time
following correction of the renal failure with recovery
or renal transplant.
The persistent
hypercalcemia
of
tertiary hyperparathyroidism
is due to the now autonomous function of the parathyroid glands.
II
The effects of vitamin D intoxication may last

for months after the discontinuation
of the vita
min D. The effect probably results from high
levels of 25-hydroxyvitamin
D. which has a half-life of
10 to 20 days .
same increase in vitamin D has been seen

granulomatous
disorders such as tuberculosis,
sis, histoplasmosis,
and coccidioidomycosis.
II
III
In hyperthyroidism,
hypercakemia
is <.'Ommon
and PTH is suppressed. The cause of the hypercalcemia is thought to be increased bone resorption secondary to the effect of thyroid hormone.
The hypercalcemia
associated with adrenal insufficiency is partially attributable
to volume
contraction
and increased Ca-binding protein.
There may also be enhanced
renal tubular and GI
absorption of calcium due to the loss of the suppressive
effect of glu<.'tX:Orticoids on vitamin D.
~
Although
the hypercaleemia
associated
with
pheochromocytoma
is usually seen \vith MEN
2, isolated hypercalcemia
and pheochromocytoma have also been described. Tumor prodm;tion of
PTH and stimulation of PTH secretion are the probable
mechanisms.
II
The hypercalcemia
associated \vith immohili'l~ltion occurs in patients with high bone tumover,
usually children and patients with Paget's disease. Immobilil'..atiun may also contribute to the hypercalcemia associated with malignan<.j' and the ostcomala<.'ia of renal
failure.
The
mechanism
of the
hypercalcemia
is not clear, but the PTH is usually low.
II
Causes of malignancy-associated
hypercalcemia
include ectopic PTH production;
PTH-related
peptide; direct bone invasion by tumor; immobilization; prostaglandin
effects; osteoclast-activating
factor, including interleukin-l
(I L- I), tumor necrosis
factor (TNF), IL-6, and insulin-like growth factor: and
the release of vitamin D-Iike substances.
II
Hypervitaminosis
A is associated with increased
bone resorption,
nephrocalcinosis,
and renal
failure. Vitamin A doses of 50,000 to lOO,()(X) U/
day have been reported as causing this syndrome.
:
11
The hypercalcemia seen with the administration

of thiazide diuretics is partially due to volume
contraction with an increase in Ca-binding protein, but increased renal tubular reabsorption of calcium
is also a factor. Patients with hyperparathyroidism
or
patients undergoing vitamin 0 therapy are particularly
at risk for the development
of severe hypercalcemia
with the administration
of thiazide diuretics.
Ninety percent of patients with MEN type 1

have hyperparathyroidism
secondary to parathyroid hyperplasia. MEN I is also associated with
pituitary and pancreatic
islet tumors, including
Zollinger-Ellison syndrome. MEN 1 is inherited as an autosomal dominant trait.
94 Acid-Base and Electrotyte
Disorders
Hypercalcemia
II
Up to 25% of patients with sareoidosis have

hypercalcemia.
Etiologies of the hypercalcemia
include intestinal hyperahsorption
of Ca as well
as elevated levels of 1,25-dihydroxyvitamin
D, probably
of nonrenal origin. The granulomatous
tissue itself is
the most likely source of the increased vitamin D. The
in other
beryllio-
Cecil Chapter
264
Harrison Chapter
]54
Parathyrofd adenoma
Sporadic --{
Parathyroid hyperplasia
MENl
Pseudohypercalcemia
Primary hyperparathyroidism
Hereditary
MEN 2
Isolated adult hyperparathyroidism
~ 7
Familial hypocalciuric hypercalcemia
Ectopic
1
Hypercalcemia
ISc. > 10.0 mg/dl)
Miscellaneous causes ~
r Uthium-induced
Recovery from acute renal failure

~
Secondary hyperparathyroidism ~
Malabsorption
Renal failure
Post renal transplantation
Check
intact
Tertiary hyperparathyroidism
PTH
molecule
11
Vii D intoxication
Tumor production of vit D
12
Sarcoidosis
Other granulomatous disease
3
Endocrine
Hyperthyroidism
14
15
Pheochromocytoma
Pancreatic cholera
6
Immobilization
17
Increased bone release
18
~
II
The milk-alkali syndrome, consisting of hypercalcemia, alkalosis, and renal insufficien<.j'. can
occur in both acute and chronic foons. The
intake of milk and absorbable alkali or the ingestion of
large quantities of CaC03 is needed to produce the
syndrome. The alkalosis reduces the renal Ca excretion
so that a combination of increased intake and decreased
excretion produces the disorder.
Malignancy
Hypervitaminosis A
Dialysis osteomalacia
Tamoxifen
19
Thiazide diuretics
20
Milk-alkali syndrome
Disorders
Hypercalcemia
95
HYPOPHOSPHATEMIA
tion is thought to be a direct decrease

PO. reabsorption
rate and stimulation
Hypophosphatemia
is defined as serum phosphate (PO.) below 2.5 mgldl. Approximately
1000 mg of phosphate are consumed daily, with
75% to 90% of the dietary rhosphate
retained by the
kidney. Eighty-five percent 0 the total body PO. resides
in the skeleton, 9% in muscle, and only 0.08% in the
extracellular space. Hypophosphatemia
may be divided
into two classes: moderate hypophosphatemia,
with lev.
cis between 1.0 and 2.5 mg/cll. and severe hypophosphatemia, with levels below 1.0 mgldl. The degree of
hypophosphatemia
may help to differentiate between
etiologies.
II
The fractional excretion of PO., or FEPO., is

the amount of filtered PO. that is not reabsorbed. FEI'O. is calculated using the formula
FEpo.
Unfiltered PO. mglday

Filtered PO. or eFR X O.95(serum PO.)
Renal reabsorption
of PO.
tubular function is altered.
is nearly
complete
unless
Vitamin D-resistant
rickets is a rare sex-linked
dominant disorder in which an isolated defect
in
reabsorption
is present. Small mesenchymal tumors have been frequently
associated with
this disorder and have been shown to alter 1,25-hydroxyvitamin
D3 synthesis or to pnxluce a circulating
PTH-Iike substance. Patients with this disorder develop
severe rickets in childhood.
Ninety percent of filtered PO. is reabsorbed in

the pro~mal
tubule. Any condition affecting
pro~mal tubular function may decrease reabsorption of PO. The most common disorder reducing
PO. reabsorption is Fanconi's syndrome, which is associated with multiple myeloma. heavy metal poisoning.
systemic lupus erythematosus,
Wilson's disease. and cystinosis.
II
POt clearance is increased in almost all conditions associated

with extracellular
volume
expansion. Included among these conditions are
hyperaldosteronism,
high salt diets. SIADH. and saline
infusions. The mechanism of the increased PO. excre-
po.
Severe hypophosphatemia
frequently develops
in the setting of uncontrolled diabetes mellitus,
most commonly when ketoacidosis is present.
Acidosis causes the breakdown
of compounds
within
the cells and allows the liberated inorganic PO. to move
into the plasma. The increased
plasma POt is then
excreted in the urine. Renal POt excretion is enhanced
by the osmotic diuresis caused by the glycosuria and
ketonuria. Owing to the shift of PO. into the plasma,
initial serum PO. levels may appea.r normal and not
reflect the underlying PO. depletion. If the initial serum
PO. is low, severe hypophosphatemia
must be suspected.
II
PTH is the most potent inhibitor of PO. trans

port in the kidney. ITH inhibits pro~mal tubu
lar reabsorption
of PO. by the stimulation of
adenylate cyclase and the pnxluction
of cAMP. Alterations in both the active and passive transport mechanisms for PO. have been found with increased intracellular levels of cAMp, although the exact mechanism of
P'TH inhibition of PO. transport is still unclear.
in the maximum
of ITH release.
8
chronic
nesium
intake
below
Severe hypophosphatemia
can result from the
use of large quantities of PD.-binding antacids
in the treatment
of peptic ulcer disease or
renal failure. These antacids include both maghydroxide and aluminum hydroxide. When PO~
is also inadequate,
serum PO. levels may fall
1 mg/dl and symptoms appear.
Vitamin D and its metabolites playa major role

in PO. absorption in the jejunum. Deficiency
of vitamin D usually results from dietal)' defi
ciency, lack of sun exposure, malabsorption,
or a decrease in the 25-hydroxylation
of vitamin D, as may
occur in liver disease. The most potent stimulator of
PO. absorption is 1,25-dihydroxyvitamin
D3' Vitamin D3
production may be decreased by inadequate delivel)' of
25-hydroxyvitamin
D to the kidney or by renal disease.
1m
hypophosphatemia
seen in up to
hospitalized
for alcoholism is
multifactorial.
Poor oral intake and chronic
vomiting result in decreased intake of PO . Magnesiu~
deficiency is commonly seen in alcoholism and may be
responsible
for the renal POt wasting. Ketonuria and
Hypophosphatemia
The
occasional ketoacidosis cause PO. losses similar to those

seen in diabetic ketoacidosis (see No.7). Initially. serum
PO. may be normal, increased, or low, but the hypophosphatemia
will become apparent once treatment for
acidosis is instituted.
II
Prolonged respiratol)'
alkalosis may cause severe hypophosphatemia.
with serum PO. falling
as low as 0.3 mg/clI. Respiratol)' alkalosis produces a rise in intracellular pH because of the preferential diffusibility of CO2 over bicarbonate.
The rise in
pH in turn activates phosphofructokinase,
increasing
phosphol)'lation
of glucose. This process utilizes extracellular PO. as the source of the phosphorus. The serum
PO. falls and renal excretion of PO. decreases to zero.
Metabolic alkalosis is associated with a much smaller
rise in intracellular
pH. Glycolysis is not accelerated,
and severe hypophosphatemia
does not usually occur.
lEI
The administration of glu<..'ose may cause a moderate decrease in serum PO. levels. Glucose
causes an increase in insulin secretion, which in
turn increases cellular uptake of PO . Cellular uptake
increases primarily in skeletal muscle and in the liver.
Serum PO. rarely falls by more than 0.5 mgldl except
in malnourished
patients or patients with severe hepatic cirrhosis.
II
Hyperalimentation
in malnourished
patients
may result in severe hypophosphatemia
when
adequate
PO. replacement
is not provided.
Malnutrition
alone does not cause hypophosphatemia.
but refeeding with a high calorie substance may force
PO. into the cells. In this setting, muscle PO. as well as
serum POt may fall dramatically
in order to provide
adequate PO. for vihll organs such as the brain and
the heart.
III
In nutritional recovel)' syndrome, severe hypophosphatemia

can occur during refeeding with
only the normally required calories. The syndrome can occur in any patient with underlying proteincalorie malnutrition.
Included in this group are alcoholic
patients, patients with anorexia nervosa, surreptitious
vomiters, and patients with malabsorption syndromes.
~
severe
50% of patients
II
A marked period of diuresis occurs during recovel)' from severe bums. This diuresis may
lead in turn to renal PO. wasting. The change
from a catabolic to an anabolic state may also shift large
amounts of PO. into the cells.
Hyperparathyroidism
Ectopic hyperthyrok:lism
Tubulardefects
-j
6
Acquired
4 [ Fanconi's syndrome
5 [ Volume expansion
Diuretics
Vit D-femstant
Congenital
PeriodICparalysis
7
Ketoacidosis
1
Hypophosphatemia
(s.o. < 2.5 mgldl)
8 ~ Phosphate
nckets
--{
Hypokalemia
'
Diabetic
AIcohofic
binders
Malabsorption
Phosphate deficiency- 9
10
ViI 0 deficiency
Chronic alcoholism
Hyperosmolar
Sepsis
states
.
Respiratory
1
alkalosis
Alkalosis
SaIl ate lsonln

cyf
po
9
Hepatic coma
Heatstroke
Metabolic
alkalosis
lntracellular-extracellular shift
Glucose
administration
Fructose
administratk>n
Hyperalimentation
Nutritional
Recovery
recovery
syndrome
'rom thennal
injury
Insulin
Hormone-mediated
Androgen excess
{
Glucagon
Anovulatory
Cecil Chaptel'"
264
Harrison Chapter
356
Add-Base
and Electrolyte Disorden
hormones
Hypophosphatemia
97
HYPERPHOSPHATEMIA
Hyperphosphatemia, although less common

than hypophosphatemia, can cause a number of
serious clinical problems. Hyperphosphatemia

may contribute to acute renal failure, metastatic extravascular calcification, and cardiac failure.
Neoplasms with extremely high cell turnover
rates or with a large necrotic tumor mass can
release large quantities of PO. into the circulation. Hyperphosphatemia
most commonly occurs in the
early phases of chemotherapy or radiation therapy (see
No.3).
Tumor lysis syndrome occurs after the treatment of certain tumors with radiotherapy or
Several laxatives and PD.-containing

enemas
have been shown to cause hyperphosphatemia.
Children taking laxatives have a higher incidence of severe hyperphosphatemia,
with reported serum PO. levels as high as 15 mg!dJ.
Acidosis of any type may cause

ated PO. from the intracellular
lular space. The rise in serum
offset by increased excretion of PO.
creased pH in the renal tubular lumen.
a shift of dissocior the extracelPO. is partially

because of de-
Diabetic ketoacidosis is a rare cause of hyperphosphatemia. The serum PO. may appear normal or slightly elevated when the acidosis is
most severe, but treatment may uncover severe hypophosphatemia owing to prolonged renal losses. Assuming that the PO. is normal or elevated may lead to
profound hypophosphatemia
if it is left untreated. Subsequent hemolysis and decreased tissue oxygenation
hyperphosphatemia
when the product of ea and PO. is
greater than 70. Increased serum PO. with its concomitant decrease in serum Ca is the major contributor to
the secondary hyperparathyroidism
and consequent renal osteodystrophy seen in chronic renal failure. Control
of hyperphosphatemia
with oral PO. binders such as
aluminum hydroxide and CaCo3, as well as vitamin D
supplementation,
is effective in decreasing
the incidence and severity of osteodystrophy in these patients.
II
H)'p)parathyroidism
decreases the renal excretion of POt. Normally, PTH inhibits the reabsorption of PO. in both the proximal and distal
tubule. In hypoparathyroidism
this inhibitory mechanism is lost and PO. reabsorption increases.
quantities
of PO., uric acid, and potassium
when
treated. Acute renal failure, metastatic calcification, and
life-threatening hyperkalemia may result.
phosphoglycerate)
Normally, renal reabsorption of filtered PO. is

nearly complete. Small increases in serum PO.
or in the quantity of PO. ingested can be excreted by small decreases in the fraction of PO. reabsorbed. For hyperphosphatemia
to develop when PO.
intake is increased, a decrease in renal function with
decreased PO. excretion is usually necessary.
Serum phosphorus
will increase moderately
when the glomerular filtration rate falls below
25 mVmin, provided that intake remains constant. In acute oliguric renal failure, PO. may rise to 8
to 10 mg!dl. When serum PO. is above 12 mg/dl, tissue
breakdown or cell lysis must be suspected. Crush injury
with myoglobin-associated
renal failure and tumor lysis
syndrome are the most common causes of a serum PO.
greater than 12 mg!dl.
II
III
Renal excretion of PO. may occasionally be

overwhelmed when large oral or intravenous
loads of PO. are administered, as in the treatment of hypercalcemia or hypophosphatemia.
1m
III
II
chemotherapy. Acute leukemia, most commonly
the lymphocytic
type, and several of the lymphomas,
most notably the Burkitt's variety, can release large
caused by decreased red blood cell 2,3-0PG (2,3-dimay occur.
Chronic renal failure is the most common cause

of hyperphosphatemia.
In the absence of PO.
binders, serum PO. may increase to 8 to 10 mg!
dl. Metastatic calcification is common in patients with
Hyperphosphatemia
Hyperthyroidism significantly increases PO. absorption in the kidney. Thyroid hormone increases the sodium gradient-dependent
uptake
of PO. by the brush border of the proximal tubule.
An excess of growth hormone may cause hyperphosphatemia by increasing PO. absorption in

the intestine and increasing renal absorption by
a mechanism similar to that of thyroid hormone (see
No. 12).
Hyperthe~mia
may cause h~erphosph~temia
by increasmg the reabsorption of PO. In the
kidney via increased generation of cAMP as
well as by PO. release from tissue breakdown.
~
Tumor calcinosis is the exact reverse of vitamin

O-resistant rickets. In this disorder there is a
tubular defect causing increased reabsorption
of PO.
''''''''''''''''
phosphorusload
Transfusion
Parenteral
Intravenous PO.
PO.Intake
4
Enteral-{
of stored bklod
-{
5
Replacement therapy
IS PO.-contalnlng
laxatives
or enemas
vi! 0 intoxication
Etidtonal&
dlsodlum
Respiratory
acidosis
[ Lactic acidosis
8 [ Diabetic keloacldosls
Redistribution of phosphorus
TIssue ischemia
1
Hyfrphosphatemla
(8,0.::. 5.2 mo'dl)
---.!.r
Decreased filtration ~
Decreased
clearance
10
Acute
Hypoparathyroidism
renal failure
Chronic renal failure
tubular
Multiple myeloma
12
Hoononal --13
Hyperthyrodsm
Acromegaly
Postmenopausal
Volume contraction
Mg deficiency
NonhoJJ11Oflal
Cecil Chapter"
264
Harrison Chapter
356
14
~ 15
Hyperthermia
Tumor calcinosis
Acid-Base and Electrotyte Disorders
Hyperphosphatemia 99
HYPOMAGNESEMIA
Nonnally, 30% to 40% of dietary Mg is ab
sorbed in the CI tract. Absorption can increase
to as much as 80% when dietary Mg is restricted. Poor intake alone is a rare cause of significant
hypomagnesemia,
owing to this inverse relationship between dietary Mg and the absorption of Mg.
When protein-calorie
malnutrition
occurs, the
hypomagnesia is probably a result of decreased
intake as well as increased GI loss of Mg secondary to vomiting and diarrhea.
Selective Mg malabsorption
is a rare, probably
X-linked disorder than can cause profound hypomagnesemia
on normal
diets. I ncreasing
the
Mg intake can overcome the defect and prevent the

clinical consequences.
Approximately 30% of patients with disorders
associated with fat malabsorption develop hypomagnesemia. The serum Mg level roughly parallels the degree of steatorrhea.
Mg probably forms
soaps in the intestinal lumen and is lost in the stool.
Decreasing the dietary intake of fat can help alleviate
this problem.
Oral calcium competes

intestine
for transport
space.
with magnesium in the

into the extracellular
The Mg concentration
of pancreatic fluid, gas
hic secretions, and biliary fluid is between 0.4
and 1.1 mEqlL. Because the amount of Mg loss
needed to produce significant hypomagnesemia
is 1 to
2 mEqlkg of body weight, Mg lost in the colon accounts
for most of the extrarenal causes of hypomagnesemia.
The Mg concentration
of stool water is 5 to
6 mEqIL but can increase to 14 to 15 mEqIL
in severe diarrhea.
Internal redistribution
of Mg is usually seen
when the underlying disorder has also caused
Mg wasting. Causes of redistribution
can include both cellular
and skeletal
Mg mobilization,
allowing the serum Mg to appear normal or slightly
elevated. When treatment of the underlying abnormality
is undertaken,
Mg shifts back into its various storage
pools, causing a rapid fall in the serum Mg. This situation is worsened when there is inadequate
Mg replacement during treatment of the underlying disorder.
100 Acid-Base and Electrotyte Dlsorden
II
rapidly
formed
Hungry bone syndrome usually occurs following

the removal of a parathyroid adenoma or hyperplastic parathyroid
glands. Mg, like Ca, may
shift out of the extracellular
fluid into newly
bone salts.
II
II
The
ting
the
formed with
mechanism of hypomagnesemia
in the setof acute pancreatitis is unclear but may be
formation of Mg fat salts similar to those
Ca in this disorder.
Alcoholism and its treatment are the most common causes of si ificant hypomagnesemia.
The
etiology is multi~torial,
with each of the major
contributors-including
extrarenal losses, renal losses,
and redistribution
of magnesium-playing
a role. Decreased intake, alcohol-induced
Mg malabsorption,
liver
disease, and diarrhea contribute to the extrarenal causes
of the hypomagnesemia.
Secondary hyperaldosteronism
and ketoacidosis can cause severe renal Mg wasting.
Alcohol itself may cause decreased tubular reabsorption
of Mg. Treatment of the decompensated
alcoholic patient usually includes refeeding with high calorie, high
protein supplements.
This refeeding may cause a rapid
shift to Mg from the extracellular
to the intracellular
space, causing severe hypomagnesemia.
II
Selective Mg wasting can occur in both congenital and acquired forms. Congenital Mg wasting
is extremely rare and is associated with nephrocalcinosis,
hypokalemia,
and hypocalcemia.
The acquired form is usually drug-related
(see No. 15).
III
Hypercalciuric
states of any cause are associated with increased Mg excretion. Ca competes
with Mg for reabsorption
in both the proximal
tubule and the loop of Henle. Any syndrome that increases serum calcium, and therefore urinary calcium
excretion, can be associated with Mg wasting. Malignancy, sarcoidosis, hyperparathyroidism,
and vitamin 0
therapy are most commonly associated with this form
of renal Mg wasting. Hypocalcemia
may also be associated with hypomagnesemia,
as is hypoka.lemia. If hypocalcemia and hypokalemia coexist, underlying hypomag.
nesemia should be suspected.
III
~
creased
Hypomagnesemia
Chronic renal tubular acidosis causes increased

bone demineralization
and the consequent hyp.
ercalciuria. This hypercalciuria
may cause inrenal Mg excretion (see No. 13).
II
The drug most commonly associated with renal

Mg wasting is cisplatin. As many as 50% of
patients receiving this drug develop hypomagnesemia. The effect appears to be a direct one on the
renal tubule and may persist for several months after
the drug is discontinued.
Antibiotic-induced.
nephropathy, most commonly seen with the aminoglycosides and
amphotericin,
is also associated with renal Mg wasting.
II
II
III
Interstitial nephritis is usuaUy associated with

administration
of synthetic penicillins, but druginduced interstitial nephritis of any cause can
be associated with renal Mg wasting.
Increased Mg excretion in hyperaldosteronism

is probably secondary to the extracellular volume eKpansion (see No. 21).
Increased PTH is occasionally associated with

hypomagnesemia,
but it is unclear whether this
is due to a direct effect of the hormone or
secondary to the associated hypercalciuria.
:
112
Thiazide diuretics may cause acute or chronic,

mild hypomagnesemia,
due in part to secondary
hypoaldosteronism.
Loop-acting diuretics may
have a profound effect on renal Mg reabsorption
and
are the most com mon cause of hypomagnesemia.
Passive Mg reabsorption
is reduced owing to the direct
inhibition of the sodium-potassium-chloride
transport
system. Osmotic diuretics like mannitol or urea decrease
Mg reabsorption
at the loop in direct proportion
to
the osmotic load. Decreased reabsorption
in the loop,
coupled with increased delivery of Mg to this portion
of the tubule, enhances excretion of Mg. Potassiumsparing diuretics may ~Iso have a significant Mg-sparing effect.
II
II
I
PO. depletion
has been associated with mild
hypomagnesemia
and is probably related to defective tubular Mg reabsorption.
An immediate increase in Mg excretion is seen

with volume expansion. There is a marked re
duction in proximal tubular reabsorption
and a
more modest reduction of reabsorption
at the loop of
Henle. The reduced reabsorption is probably due to an
increased flow rate past these portions of the nephron.
Inadequate intake
-t
Protein-calorie
malnutrition
Decreased absorption
Fat malabsorption
-1
'
Os'
elective Mg mala orptlon
Chronic diarrtlea
Oral calcium
Non-Mg laxative abuse
Nasogaslric suction
GI ~
Ex t rarena I Iosses
Biliary fistula
7
-{
Diarrtlea with inc,reased stool H20

lacatiOO
Other ---{
ThennaJ bums
Treatme,nl of ketoacidosis
i
9
Hungry bone syndrome

Refeedlng after starvation
Hypomagnesemia
(S"'lI < 1 ,5 mEqIl)
8 Redistribution
10
Acute pancreatitis
11
Alcoholism
Myocardial ischemia
Selective Mg wasting
Hypercalciuria
Drug-induced
Primary
Interstitial nephritis
Post-ATN syndrome
Postobstructive
diuresis
Post-transplant
syndrome
Renal loss
~
HY~eraldos.teronjs,m
Hofmonal----::[
Hyperthyroidism
-'19
18
Secondary
{
20
Other
Hyperparathyroidism
Forced diuresis
PO. depletion
K depletion
21
Hypervolemia
Increased ADH
Cecil Chapter
223
Harrison
357
Chapter
Acid-Base and Electrolyte Oisorden Hypomagnesemia. 101
HYPERMAGNESEMIA
II
Mg excretion is dependent upon both CFR and

tubular reabsorption.
Seventy percent to 80%
of plasma Mg is ultrafilterable.
Twenty percent
fluid into the intestine. The mechanisms of the hypermagnesemia

are therefore
both increased absorption
and decreased excretion secondary to intravascular volume depletion (see No.9).
to 40% of the filtered Mg is then reabsorbed in the

proximal tubule, with the remainder reabsorbed
in the
thick ascending loop of Henle and the distal tubule.
With normal dietary intake, urinary Mg exere

tion is usually between 100 and 150 mgt24 hr .
decreased.
Normal renal excretion of Mg can increase rapidly, so that hypermagnesemia
from excessive
intake usually requires
some concurrent
de
crease in renal function.
The hypermagnesemia
associated with MgSO~
ingestion is caused by the combination
of a
large Mg load plus third-spacing of intravascular
II
In hypoaldosteronism,
enhan(:ed tubular reabsorption in addition to the decreased intravascular volume is the mechanism of hypennagnese.
Excretion can be increased to 500 to 600 mg!
24 hr if the intake of Mg is increased. Conversely, a

normal kidney can decrease excretion to as little as 6 to
12 mg/24 hr within a few days after Mg intake has been
4.,
Hypennagnesemia
due to increased CI absorption rarely occurs if the CFR is greater than
15 mVmin. Marked hypermagnesemia
is possible when the GFR is less than {i mVmin (see No.8).
II
Hypermagneselllia
rarely occurs in chronic renal failure until the GFR is less than 15 mVmin.
This is due to the kidney's ability to increase Mg
excretion to up to 30% to 60% of the filtered load.
The dietary restrictions usually placed on patients with
chronic renal failure may also protect against excessive
Mg intake. Oral intake of Mg-containing products in this
setting, however, can cause severe hypermagnesemia.
:
The mechanism for hypermagnesemia

in ketoacidosis is not well understood.
Exchange of
Mg ions for hydrogen ions in the distal tubule
is one possible cause. Another cause may be the decreased Mg excretion seen with the intravascular volume depletion common in this disorder.
Hypennagnesemia
in acute renal failure usually
occurs when excessive intake is not corrected.
The most common sources of increased intake
are Mg-containing
antacids, laxatives, and additives to
hyperalimentation
solutions.
102 Acid-Base and Electrolyte Olsorden Hypermagnesemia
mia.
1m
In hyperparathyroidism,
PTH may act directly
on the distal tubule to increase Mg absorption.
This cause of hypennagnesemia
is unusual because the increased calcium concentration
in the serum
and urine can increase renal Mg excretion, thereby
preventing hypennagnesemia.
II
Decreased
intravascular
volume is associated
with an increase in Mg reabsorption
in the
proximal tubule.
-1
"""""50,
Mg-containing
Increased Mg intake
antacids
Mg-cootalning enemas
Mg administration
during eclampsia
IncreaseQ GI absorption
HyJ*Tl\agnueml.
(Swe > 2.1 mEqIl)
UMgvariable
Dect'eased
HypercataboJic stale
Redistribution ----;[
Diabetic ketoacidosis
excretion
H,poth,,,,,,,,,,m
erCl
> 15 mllmin
Check
Hypocalcemia
In,,,eased Iu,,""" ,eab,mption ~.

Ca
Cecil Chapter
233
Harrison
357
Chapter
Hypoaldosle,onlsm
10
HyperparathyroidIsm
11
HYPOVOlemia
Hypennagnesemia J03
ACIDOSIS
II
Acidosis is the result of the net addition of

hydrogen ion (H"') to the extracellular space or
loss of bicarbonate
(H C03 -) from that space.
H'" may be added by the increased production of strong
acids, an increase in CO2 concentration.
or the addition
of exogenous acid. The equation
demonstrates
how H'" concentration
increases as CO2
increases. Both respiratory and metabolic acidosis may
also occur as part of a mixed acid-base disturbance,
or
as a compensatory
mechanism for a primary alkalosis
(see page 106). The Joss of HC03 - may occur ooth
renally and extrarenally.
The anion gap (AG) is the most useful measurement for differentiating
between the forms of
metabolic
acidosis. The AG is composed
of
those unmeasured anions liberated into the extracellular
fluid when a strong acid is produced and buffered by
HC03 -. The AG is calculated by using the formula AG
= Na+ -(CI+ HC03-). Organic anions, sulfate, and
phosphate are the most common contributors
to the
AG. The normal AG is 10 to 14 mEqIL. Any increase
above 14 represents the abnormal accumulation
of unmeasured anions in the extracellular fluid.
The severe acidosis seen \\lith nonketotic hyperosmolar coma is thought to be due to the accumulation of as yet unknown organic acids. The
measured quantities of lactate and ketones in the serum
do not account for all of the unmeasured
anions usually
seen in this syndrome .
ganic acids produced, but lactic acid may also contribute

to the acidosis and the increased AG. Serum glucose is
usually normal or low. Thirteen percent of patients present with a serum glucose of less than 50 mg/dl.
II
StalVation leads to the production of keto acids

by the same mechanism as diabetic ketoacidosis
(see No.4).
There is also increased hepatic
ketogenesis and decreased tissue breakdown of the keto
acids. The acidosis is usually mild. Serum HC03 - is
rarely less than 18 mEqIL.
II
Methanol intoxication is one of the few causes

of an AG greater than 50 mEqIL. The methanol
is metabolized
by alcohol dehydrogenase
into
formic acid. Formic acid interferes with oxidative metabolism, leading to the accumulation of large quantities
of lactic acid.
Ethylene
glycol ingestion
may cause an AG
greater than 50 mEqIL. Metabolism of ethylene
glycol to glycolic acid and finally to glyoxylic
acid and oxalic acid results in a high AG acidosis.
8:
Lactic acid is the end product of the anaerobic

metabolism of glucose. The major sites of lactic
acid production
are skeletal muscle and the
small intestine. When cells receive inadequate
oxygen
delivery (type A) or oxygen utilization is impaired (type
B), lactic acid is produced in quantities that cannot be
completely metabolized
in the liver. Shock, severe hypoxia (Pao2 < 35 mm Hg), seizures, hepatic failure,
phenformin,
and carbon monoxide intoxication are the
most common causes of lactic acidosis.
1m
Aspirin or other salicylates in large doses may

cause a severe metabolic acidosis. Respiratory
alkalosis is the most common presenting sign in
adults (see No.3, Alkalosis algorithm), but an AG acidosis supelVenes in more than 50% of the patients .
In diabetic
ketoacidosis
the lack of insulin
causes the overproduction
and underutilization
of both glucose and the fatty keto acids 13hydroxybutyrate
and acetoacetate.
These strong acids
dissociate in the extracellular fluid to form H + and keto
anions. The degree of acidosis may be severe, with
HC03 - falling as low as 5 to 10 mEqIL. Elevated glucose concentrations
arc not always present, with apfroximately 15% of patients having a serum glucose 0 less
than 350 mid1.
II
Alcohol-induced
acidosis is usually associated
with binge drinking, poor nutrition, and vomiting. Keto acids are the most prominent
or-
104 AcidBase and Electrolyte Oisorders Acidosis
II
In acute renal failure, the acidosis results from

the kidney's failure to excrete the entire daily
production of endogenous
acid. The body normally produces aboul I mmolJkgtday of acid from the
breakdown of foods and body protein. Add production
may increase owing to infection, increased catabolism,
or tissue injury. In chronic renal failure, titratable acid
excretion is impaired and the AG is increased by the
accumulation
of sulfate, phosphate,
and other organic
acids.
Several other drugs and chemicals can be associated with AG acidosis. These include phenformin, isoniazid in high dosage, chloramphenicol,
sodium azide poisoning, hydrofluoric acid exposure, and
inorganic sulfur sometimes used in certain folk remedies.
The accurate measurement

of urinary pH re
quires that the sample be taken in the early
morning when urine is maximally acidified. The
sample should be placed under oil to prevent the loss
of dissolved CO2 and the resultant increase in pH.
III
Renal tubular acidosis (RTA) may involve de

feets in either the proximal or distal tubule. In
the proximal tubular form (type 2), the proximal
tubule is unable to reabsorb the filtered HC03 -. Increased HC03 - is delivered to the distal tubule, where
much of the He03 - can be reabsorbed. Serum HC03rarely falls below 15 mEqIL. In the distal tubular form
(type I), the distal tubule is unable to seerete H+. The
H C03 - may fall to extremely low levels, often below
15 mEqlL. Both of these forms of RTA are commonly
associated with other tubular defects. Proximal RTA
is most commonly associated with cystinosis, multiple
myeloma, amyloidosis,
medullary cystic disease, and
heavy metal toxicity. Distal RTA is most commonly associated with hypercalcemia,
lupus nephritis, medullary
sponge kidney, renal transplant
rejection, and toxicity
from amphotericin
B and lithium. There are also idio
pathic forms of both proximal and distal RTA.
:.l
II
Diarrhea is the most common form of nonnal

AG met~bol.ic acidosis: ~he collcen.lration
of
HC03 - III diarrheal flUld IS usually higher than
in serum. Patients with inflammatory or infectious colitis
may lose up 10 20 L of fluid per day. Each liter of fluid
may contain up to 50 mmol of HC03-.
II
Hypoaldosteronism
may cause an acidosis similar to Ihat of distal RTA (see No. 14). Both H+
and potassium secretion are reduced, leading
to a hypercalcemia
metabolic acidosis. Patients with
hypoaldosteronism
may, however, achieve a urine pH of
less than 5.5. A form of this syndrome associated with
hyporeninism
is commonly seen in diabetes mellitus.
II
these
HC03
Amino acid solutions commonly used for intravenous hyperalimentation

may contain 0
'c cations in excess over organic anions. Met~sm
of
cations produces
H +. The H + is buffered
by
- and a hyperchloremic
metabolic acidosis develops.
Decreased alveolar-capillary
gas exchange
Hypoventilation due to eNS depression
Respiratory acidosIs
Anatomic abnormalities
Neuromuscular weakness
Airway obstnJCtion
Nonkelolic hyperosmolar coma

Ketoacidosis
associated
with hyperglycemia
[ Diabetic ketoaciclosis without hyperglycemia

5 [ Alcoholic ketoacidosis
Starvation
7 M"hanol in,,,,,,",,,
8
Ethylene glycOl ingestion

Paraldehyde
9
MetabolIC acidosis
lactIC acidoSIs
10
Salicylate intoxication
11
Renal faiture
12
Other drug/chemICal
IngestIOn

Interstitial nephnlis
Obstructive uropathy
'l
Carbonic anhydrase inhibitors
oi
13
GI loss of HC03
.""o.
pa~creatiC fistula
Amon exchange resins
,.t
CaCI;t'MgCI2 ingestion
Miscellaneous causes
17
Hypoaldosteronism
Hyperalimentation
Addition of Hel
Cecil Chapter
Harrison Chapter
102
50
Add-Base and Electrolyte Disorders
Acidosis 105
ALKALOSIS
Alkalosis is defined as an excess of total body
bicarbonate (HC03 -) or a deficit of total body
hydrogen ion (H -+-). Alkalemia is de6ned as a
serum pH greater than 7.45. Although this algorithm
will deal with the differential diagnosis of primary alkalosis, alkalosis may also be one of the body's compensatory mechanisms
in the setting of acidosis or may be
part of mixed acid-base disorder.
Acute decreases in PC02 will be accompanied

by sim~Jtaneous decreases. in the HCO~ - concentratIon. The He03 - will fall approXImately
1 to 3 mEqIL for each 10 mm Hg fall in PC02 in accordance with the laws of mass action. In more chronic
fonns of decreased. PC02, the HC03 - concentration
will
fall approximately 2 to 5 mEqIL for each 10 mm Hg fall
in PC02 hut will rarely fall below 14 mEqIL.
II
Salicylates stimulate the medullary respiratory

centers directly, causing increased
respiratory
drive. Respiratory alkalosis is usually the earliest
clinical sign. Metabolic acidosis will eventually supervene as the intoxication becomes more severe (see No.
10, Acidosis algorithm). Respiratory alkalosis is a more
common presenting sign in adults than in children.
A variety of mechanisms contribute to the respira
tory alkalosis that commonly occurs with hepatic
failure. These mechanisms include hypoxemia related to pulmonary shunts, increased progesterone levels
(see No.6), increased ammonium levels, and increased
intra-abdominal pressure due to ascites.
II
With sepsis, endotoxins

liberated
by many
gram.negative
organisms probably cause respiratory alkalosis by direct stimulation
of the
medullary respiratory centers.
An increased progesterone
level may directly
stimulate
the medullary
respiratory
center,
causing respiratory alkalosis. Increased progesterone levels may be the result of increased production
occurring in pregnancy or decreased metabolism as occurs with hepatic insufficiency (see No.4).
II
Acute mountain
sickness may be seen following
ascent to altitudes above 8000 ft by persons
usually residing at sea level. The resultant hypoxemia stimulates hyperventilation

and respiratory alkalosis. Pulmonary and cerebral edema may also occur with
this syndrome.
106 Acid-Base and Electrotyte Disorders
Alkalosis
The respiratory alkalosis that occurs following a

pulmonary embolus is due to hypoxemia, bronchospasm, and the stimulation of intrapulmonary stretch receptors.
8
9
If serum HC03 - rises above 28 mEqIL, the

PC02 will. rise 0.~5 to 1.0 mm Hg f~r each
1 mEqIL mcrease III HC03 - concentration.
1m
Metabolic alkalosis requires two phases. The alkalosis must be generated by either the net addition of HC03 - (or its metabolic precursors such
as citrate, acetate, or lactate) or the net loss of H +.
These events can occur either intra- or extrarenally. The
resultant pH increase is rapidly corrected unless other
factors allow the second phase or maintenance
of the
alkalosis to occur. Factors that maintain the alkalosis
include volume depletion, potassium depletion, and fr'
eralocorticoid excess. Each of these factors inhibits the
kidney's ability to either excrete HC03 - or retain H+.
j-
II
Loss of gastric acid as a result of vomiting or

gastric suction is the prototype of the genera
tion and maintenance
of metabolic alkalosis.
H + and chloride are lost in the gastric fluid. These
losses lead to generation
of increased HC03 - in the
serum and generation of the alkalosis. The consequent
volume depletion causes increased aldosterone production and the avid reabsorption
of sodium by the kidney.
The lack of reabsorbable
chloride, resulting from its
previous loss from the stomach, allows HC03 - to be
reabsorbed with the Na +, thus maintaining the alkalosis
even after GI losses have stopped.
II
The administration
of large quantities of nonreabsorbable
anions, usually in the fonn of sodium salts of penicillin or carbenicillin, can lead
to metabolic alkalosis by enhancing distal tubular acid
and potassium secretion. Increased secretion is due to
delivery of large quantities
of sodium past the distal
secretory sites. Delivery of large quantities of sodium to
the distal tubule without chloride will, in addition, enhance distal tubular reabsorption
of H C03 - .
III
Bartter's syndrome
is a rare disorder usually
seen in children, associated with increased renin and aldosterone
production,
hypokalemia,
hypertrophy of the juxtaglomerular apparatus, and nonresponsiveness

of the vascular system to angiotensin II.
The metabolic alkalosis is probably due to the hypokalemia (see No. 14) and the hyperaldosteronism
(see
No. 16).
III
Although metabolic alkalosis is almost always

present with potassium depletion, the mechanism is unclear. There is some evidence that
potassium
depletion
directly increases distal tubular
HC03 - reabsorption.
~
II
II
Diuretics lead to metabolic alkalosis by causing

volume depletion and loss of chloride (see No.
11).
Hyperaldosteronism,
or an excess of any other
mineralocorticoid,
generates metabolic alkalosis
by enhancing distal tubular H + secretion. The
alkalosis is maintained
by increased reabsorption
and
generation of HC03 - resulting from the increased exchange of sodium for secreted potassium and H +.
II
Ingestion of substances with potent mineralocorticoid activity may cause metabolic alkalosis
via the mechanisms
described above (see No.
16). These substances include certain forms of licorice,
carbenoxolone,
chewing tobacco, and some nasal sprays.
Liddle's syndrome is a rare disease in which an unidentified mineralocorticoid
is produced.
II
:
Renal artery stenosis may cause metabolic

losis by increasing renin and aldosterone
duction (see No. 16).
alkapro-
Bibliography
Brenner BM: Brenner and Rector's The Kidney. 6th ed.
Philadelphia, WB Saunders, 2000.
Glassock RJ: Current Therapy in Nephrology and Hypertension 1984-1985. St Louis, Mosby-Year Book, 1984.
Kurtzman
NA, Batlle DC: Acid-base disorders.
Med
Clin North Am 67:4, 1983.
Ueu TA, Grasmeder
HM, Kaplan BS: An approach to
the evaluation and treatment of microscopic hematuria. Pediatr Clin North Am 38(3) 579-589, 1991.
Rose BD: Clinical Physiology of Acid-Base and Electrolyte
Disorders. 4th cd. New York, McGraw-Hill, 1994.
Schrier RW; Renal and Electrolyte Disorders. Boston,
Little. Brown, 1986.
Schrier RW, Briner VA: The differential
diagnosis of
hyponatremia.
Hosp Praci 29:32--38, 1990.
Stein JH: Nephrology:
The Science and Practice of
Clinical Medicine. Vol. 7. New York, Crone & Strat
ton, 1980.
Taylor HB: Difflcult Diagnosis
2. Philadelphia,
WB
Saunders, 1992.
Chemoreceptor
stimulus
____
~[
Hypoxia
Hypotension
Psychogenic hyperventilation
Salicylate ingestion
Hepatic failure
Sepsis
Respiratory alkalosis
Central stimulus
Brain stem lesion

Pregnancy/progesterone
Encephalitis
-i
7 L Acute mountain sickness
Pneumonia
Intrathoracic receptor stimulus
1
Alkelosls
(pH> 7.45)
Pneumothorax
Pulmonary embolus
Pulmonary fibrosis
.._~
===----r
GI fluid loss
Postdiuretic syndrome
Vomiting or gastric suction

Chloride diarrhea
Villous adenoma
Cystic fibrosis
_~
Decreased eHective arteriat volume
CHF
Cirrhosis and ascites
Severe bums
10
Metabolic alkalosis
Nonreabso~able an=--t'ons
Alkali administration
H?OJ administration
MIlkalkall syndrome
Hypercalcemia
Antacids in renal failure
Rebound after organic acidosis

Hypoproteinemia
13
Bartter's syndrome
Mg depletion
14
K depletion
15
Diuretics
Correction 01 chronic hypercarbia
Other mineralocorticoids
Cecil Chapter
102
Cushing's syndrome/disease
18
Harrison Chapter
Renal artery stenosis
50
Alkalosis 107
Signs and symptoms:
Bleeding
Lymphadenopathy
Splenomegaly
Labs:
Anemia
Microcytic anemia
Normocytic anemia
Hemolytic anemia
Immune hemolytic
anemia
Aplastic anemia
Macrocytic
Vitamin
anemia
Bit
delldenC)'
FoliC acid deficiency

Myelodysplastic
syndromes (MDS)
(refractory anemia)
Polycythemia
Pancytopenia
Neutropenia
Neutrophilia
Monocytosis
Lymphocytosis
Eosinophilia
Thrombocytosis
Thrombocytopenia
Dysproteinemia
SIGNS AND SYMPTOMS

BLEEDING
Bleeding occurring spontaneously
or for a prolonged period following trauma indicates abnormal hemostatic
mechanisms.
A history of the
type of bleeding experienced is the most helpful clue to
the diagnosis of the source of a bleeding problem. Delayed, prolonged
bleeding or significant
deep tissue
bleeding (muscle and soft tissue hematomas,
hemarthroses) suggests a coagulation
cascade abnormality.
Skin and mucosal bleeding manifested as petechiae and
purpura
suggest a platelet abnormality.
A thorough
medication history as well as a family history of abnormal bleeding may also provide important
information
regarding platelet dysfunction or coagulation defects.
II
Initial tests of coagulation

include a platelet
count, prothrombin
time (PT), and partial
thromboplastin
time (lYIT). Other tests that are
usually performed
simultaneously
include thrombin
time (IT), fibrinogen level (Factor I), and a visual microscopic exam of the peripheral blood smear. Clotting
factor levels can be drawn if indicated by abnormal
coagulation tests (see No.9).
Bleeding time is the time needed for platelet
plug formation to stop bleeding caused by a
shallow incision made on the forearm under
standardized
conditions. Platelet plug formation does
not require clotting factors, and is therefore
normal
108 Hematologic
Disorders
Bleeding
with coagulation factor deficiencies, except for von Willebrand's disease (see No. 18). Bleeding time is prolonged due to a decreased number of platelets, or platelet dysfunction.
II
If all tests of the hemostatic

mechanism
are
normal, the most likely source of abnormal
bleeding is a vessel defect or nonthrombocytopenic bleeding.
Vascular defects, although common,
usually do not result in serious bleeding problems.
~
In hereditary hemorrhagic telangiectasia (OslerWeber-Rendu

disease), multiple fragile telangiectases appear on the skin, mucosae, and gastrointestinal tract. The telangiectases are responsible for
abnormal bleeding. The disorder is transmitted
as an
autosomal dominant trait.
The nonallergic purpuras are a mixed group of

disorders in which vascular abnormalities
result
in purpura. Many are due to the poor dennal
vascular support. as in senile purpura, Cushing's disease,
drug-induced
purpura (treatment with corticosteroids),
scurvy. and the inherited connective tissue disorders.
Many mechanisms
have been proposed to explain the
bleeding abnormality that accompanies the dysproteinemias. Proposed mechanisms include perivascular deposition of paraproteins or interference of clotting proteins
owing to hyperviscosity. In the latter case, platelet and
clotting tests may be altered. Infections are well established as a source of nonthrombocytopenic
purpura,
especially meningococcemia
and subacute bacterial endocarditis.
Infection-related
purpura is thought to be
due to vasculitis secondary to vascular microemboli.
Allergic purpura, also known as Henoch-Schon

lein purpura,
is a non thrombocytopenic
purpura in which a vasculitis is the cause of the
purpura. Renal failure may be a serious sequela of the
disorder. This condition is primarily a disease of children. The cause is unknown but is thought to be an
allergic response to a foreign antigen.
4
II
Platelet dysfunction
can be cogenital
or acquired. The acquired disorders are more com
mon by far. The two categories can most easily
be differentiated
by history. The cause of abnormal
:
platelet function in uremia is unclear. It is thought

a dialyzable low-molecular-weight
inhibitor of platelet
function is present in uremic plasma. Drug-induced
platelet dysfunction
is probably the most commonly
seen abnormality clinically. The most commonly implicated drugs are aspirin and prostaglandin
inhibitors.
Other drugs responsible for platelet dysfunction include
anesthetics,
carbenicillin,
dextran and hydroxyethyl
starch (plasma expanders), dipyridamole,
ethanol, and
sul6npyrazone.
Of course, a full history will uncover
those drugs, such as the new antiplatelet drugs, which
are given speci6cally
to reduce platelet aggregation
and clotting.
Bleeding disorders
associated with abnormal
coagulation are accompanied
by abnormalities
of the PI' and PT"T. The PT measures clot
formation via the extrinsic pathway and tests for Factors
VII, X, V, II, and I. The P1T measures clot formation
via the intrinsic pathway and tests for all factors except
Factor VII. These tests often overlap, because an isolated deficiency of Factor VII is rare. If the IT is
prolonged
but all other tests are normal, Factor VII
deficiency is implicated. The hereditary form of Factor
VII deficiency is a rare autosomal dominant condition.
A prolonged PT is more commonly due to deficiency of
the vitamin K-dependent
synthesis of Factor VII. The
vitamin K-dependent
factors are synthesized in the liver
and include Factors II, VII, lX, and X. Vitamin K
deficiency, severe liver disease, or vitamin K antagonists
(warfarin) will result in a decreased level of these factors. In these conditions there is usually a prolongation
of both the IT and PTT.
1m
Circulating anticoagulants are antibodies to specific clotting factors. Although circulating anticoagulants
are not usually associated
with
bleeding, they can cause a prolongation
of the lYIT.
Antibodies to Factors I, V, VIII, lX, X, XI. and XIII
have been found. Antibodies can be found in patients
with a normal coagulation system, in patients with a
congenital factor deficiency (with a history of multiple
transfusions), or as part of an autoimmune disease such
as systemic lupus erythematosus
(SLE). Antibodies to
Factor VIII are the most common, occurring in up to
10% of patients with hemophilia A as well as in patients
with SLE.
Hlredrtary hImorfhaglC tlllngllclisia
4 Nonltlrombocytopemc
purpur
asculal disorders
II
NOOIller~ purpure
Anlrgic putpIlra (Henocn-5chOn1eIn)

Autoeryttlrocyte sen5/lMty
BlMdlng
Common patl'lway atlnOnTlllity

(Factors I,ll, II, X)
-E
AtlflOrmaJconUiClfeClOf
Abnormal
(Fac'Ofllllll,
IX. XI, XII)
(InlnnslCpl.th
ay)
EOrculaling 1Ohlbit0<
-j1
Faclor 11111
deree!------19
Hemophilia B
Fetlor IX C1erect
--{AcqUlfOO--{
20
FaCIo<Xl d,ree!
InlrinSICsystem d,recl
Cecil Chapter
Harrison
Chapter
HIlgeman Factof XII

High molecular wefgtll k1nioogen
FIIlcherprlklJlekrl,n
l'
HemoptH.
,. A
\Ion W.llebrano'sC1IMlSe
NephrollCs~rome
Orc:ulallng irlhibitO<
18]
60
Hematolocic
Dlsorden
8k"(.'(lin~ 109
BLEEDING
(Continued)
Disseminated intravascular coagulation (Ole) is

a complex interaction of the blood coagulation
system in which thrombin is activated and fibrinogen and other clotting factors are consumed. Fi
brio degradation products act as anticoagulants. Although the exact mechanism initiating ole is unknown,
gram-negative septicemia, subacute bacterial endocarditis, certain neoplasms, anaphylaxis, liver failure (with
resulting impaired clearance of activated anticoagulant
factors), shock, snake venoms, bums. and obstetric complications have all been associated with Ole.
II
The vitamin K-dependent factors (II, VII, lX,

X) are synthesized in the liver. Vitamin K is a
fat-soluble vitamin produced by the nonnal gut
Aora. Only very small stores of vitamin K are nonnally
present in the body. Any interference with the absorption or action of vitamin K will result in decreased
synthesis of its dependent clotting factors. Malabsorption, prolonged use of oral antibiotics, liver failure, or
the use of vitamin K antagonists (coumarins) may result
in prolonged PT and PTT.
Heparin inactivates thrombin (Factor lIa), and,
to a lesser degree, Factors lX, X, Xl, and XlI.
Both the PT and PIT are affected by heparin,
although the PTT is the best measure of heparin effect
in nonnal therapeutic use.
II
110 Hematologic Disorders
Bleeding
III
Liver disease results in impaired coagulation,

not only by decreased hepatic protein synthesis
but also by increased plasma proteolytic activity.
The latter is probably due to the decreased clearance
of proteases from the circulation by the liver.
J
II
Factor VIII deficiency is the mosl common

clotting factor dencient.')' and can be diagnosed
with a Factor VIII assay. Hemophilia A (Fm;tor
VIII deficiency) is inherited as a sex-linked recessive
disorder (70%) or may occur as a spontaneous mutation (30%).
II
III
II
111
Fibrinogen (Factor I) levels can be specifically

assayed to determine the presence of a congenital fibrinogen disorder. Both afibrinogenemia
and dysfibrinogenemia are inherited as autosomal recessive disorders. Dysfibrinogenemia refers specifically to
the fact that the fibrinogen functions abnonnally in
these patients, and the fibrinogen level may be normal
or low. Acquired disorders in which fibrinogen functions
inadequately include hepatic insufficiency, DIC, and
heparin administration.
If the PTf is prolonged and the PT nonnal,

there is an abnormality of one of the factors of
the intrinsic pathway (XlI, XI, IX, VIII). An
abnonnality or deficiency of any of three "contact" factors is manifested only as abnormal laboratory results
without an associated bleeding tendency. These contact
factors are factor XII (Hageman factor), pre kallikrein
(Fletcher),
and high-molecular-weight
kininogen
(HMWK). Contact factor abnonnalities are usually inherited, and levels of these factors can be assayed.
Deficiencies of factors VIII, IX, and XI account for the
majority of inherited bleeding disorders.
Von Willebrand's disease is a Factor VIII deficiency, although it presents clinically like a
platelet disorder. The basic defect is the lack of
the von Willebrand component of Factor VIII, which
results in decreased platelet adhesiveness. Most cases
of von Willebrand's disease are autosomal dominant
with variable pcnetrance, although there is a rare autosomal recessive type.
:
Hcmophilia B, or Christmas disease, is onI)'

20% as prevalent as hemophilia A. If the Factor
VIII assay is normal, the likely diagnosis is deficiency of Factor IX. Factor IX can also he assayed. In
the nephrotic syndrome, Factor IX can be lost in the
urine. causing an acquired Factor IX deficicll(:y.
Deficient.y of Factor XI is less t.'OIllJllOlIth;lJI

Factor IX deficien<.yand C"dUSCS a mild to mIXlcrate hemophilia. It is an autosomal dominant disorder occurring most commonly in people of J<.-'Wish
origin.
II
Purpura Simplex
Mechiinalpurpura
Senile purpura
Cushing', disease
Connective tissue disordelli
HereditaryhllTlOl'rhaOic::telangiect.aSiil
" Nonlt1rombocylopenic
'Nonallergic
purpuraIVascular disorders
purpura
S'"NY
AllergIC pulpUra (H.~.SchOnlein)
ONg-lnduced
Dysp'olainem'as
Inf.chons
Auloerythrocyte sensitivity
Impaired adhesion
Schamberg', dlSeilse
lmpalredaggregatiorl
Abnormal plltelet factO( III
{
Congenital
"granular
platelets
Platelet dysfunction
Polycylhem'i1 vera
Myeloicl metaplasia
Uremia
-{
MVllopfolilefallVldiSOrdelli
Acquired
lIvef disease
{
Decreased ~telets
<100,OOOt'mm
Thrombocytopenia _ see page 159
Factor VII deliciency

(exlrinsicpathway)
--f
-E"CU"ItIUkemll
tChroll~
granulocy1lCleukemia
Essent.al thrombocytopenia
<lNg.
Multiple myeloma
Macroglobulinemia
n. __
' -[
..
J .,l.'nemll.
Vitamin K defiCiency (inct. Ofal anticoagulants)

Con~ital
liver disease
C'rculatingarnieoagulanlS
ilnlaction
Obstetric compIicallOf'lS
DIsseminated intravascular co8gulatoon (0. Ie)
Trauma/shod:.
Malignancy
M.1absofJllion
Translusoon reactions
er.1.nllb'Qllea:
Vitamin K defioency -{
Oral anhCOagulaf\ls
Common pathway abnormality

(Fac1Ot'1Il,II, v, Xl
HepaM
HernontlagO(:dIsease o! ltle newborn
Hepatic dystunetion (>90'% dysfunction)
rAbnofmaI
contact ractof
Abnormal
(Fact~ VIII. IX. Xl. XU)
(IntonsO(:pathway)
Intrin$ie s}'litem defect
H8~n
Fador XII
High molecular Welghl kimnogen
Fletcher prelcallekrein
-f
-j
17
19
Factor VIII detect --------,

Factor IX detect --{
Hemop/'l,lia B
Acquired ----[
"
CorC'U18,.,ng
,nhobrlor
HemophIlia A
.
Von W,llebran(fs d,sease
NephrotIC syndrome
Ctrculatlng mh,b'lOf
20
Cecil Chapter
Harrison Chapter
Factor XI detect
18]
60
Hemtologic Disorders
Hl..t!lll.c:
III
LYMPHADENOPATHY
II
The etiology of lymphadenopathy depends on

whether an enlarged lymph node is an isolated
finding or generalized adenopathy exists. There

is, however, overlap among diseases causing localized
and generalized lymphadenopathy.
Lymphadenopathy
is
considered generalized
if there is enlargement of the
cervical, axillary, and inguinal nodes. Painful adenopathy
is more likely due to an inflammatory
condition,
whereas nonpainful adenopathy
is more likely due to
infiltration of the node with tumor.
If generalized
adenopathy
is present, a thorough history and physical examination are crucial to diagnosis. Further laboratory studies are
obtained based on the clinical indications. A complete
blood count (eBG), including a peripheral blood smear,
is one of the most useful initial tests. The presence of
atypical lymphocytes may indicate a viral illness, e.g.,
mononucleosis.
Immature leukocytes present on CBC
point toward leukemia, and leukocytosis indicates infection. Anemia often accompanies
connective tissue diseases, e.g., SLE. Ultimately, excisional biopsy of a lymph
node (for histologic exam and culture) may be necessary
if the tests performed as indicated by history and physi.
cal examination are nondiagnostic.
Lymph node excision
is the standard for diagnosis (see No. 11).
II
Malignant cells may rarely be found in the circulation in patients with lymphoma.
Hypersensitivity
reactions can result in lymph
node enlargement.
Hypersensitivity
to drugs,
such as the hydantoins (e.g., phenytoin),
may
result in a generalized
lymphadenopathy
known as
"pseudolymphoma."
Anemia, mild leukocytosis, and occasionally eosinophilia can occur in serum sickness.
112 Hematologic Disorders Lymphadenopathy
The most common cause of generalized adenopathy is infection. Acquired immunodeficiency

syndrome (AIDS) is a common cause of generalized adenopathy and should be a strong diagnostic consideration in any patient with generalized
adenopathy
and risk factors for AIDS. Common communicable
diseases such as measles, rubella, mumps, and chickenpox
are frequently associated with generalized lymphadenopathy. Other common infectious etiologies of generalized
adenopathy include infectious mononucleosis
(both Epstein Barr virus and cytomegalovirus), toxoplasmosis, and
bacterial,
rickettsial,
fungal, and other viral diseases.
Clues to diagnosis include the presence of fever, skin
rash, and atypical lymphocytes on CBe. Depending on
the clinical situation, further testing, including appropriate cultures, a serologic test for syphilis, heterophile
antibodies, antibody tests for toxoplasmosis, a chest radiography, and skin tests (purified
protein
derivative
[PPD]), may reveal the source of infection.
II
Hyperthyroidism
may be accompanied
by gen
eralized lymphadenopathy,
splenomegaly,
and
lymphocytosis.
The changes revert to normal
when the euthyroid state is attained.
Generalized
lymphadenopathy
is commonly
found with sarcoidosis,
although mediastinal
and hilar nodes are most frequently involved.
Although bilateral hilar adenopathy
is characteristic
of
sarcoidosis, tuberculosis and coccidioidomycosis
should
also be considered.
Asymmetric
hilar adenopathy
is
more commonly seen with metastatic carcinoma, nonHodgkin's lymphoma, and nodular sclerosing Hodgkin's
lymphoma. Hilar adenopathy is rarely seen with bacterial or viral pulmonary infections.
8:
Localized adenopathy is common in both infection and malignancy. Localized adenopathy due
to metastatic disease is usually firm or hard
on palpation, whereas adenopathy

due to infection is
commonly tender. Again, careful review of the history
and thorough physical exam are critical to diagnosis.
Adenopathy
that is seemingly localized may truly be
generalized but have one prominent group of nodes.
Localized lymph node enlargement
may be due
to lymphoma or metastatic disease. The location
of the enlarged node is critical to the diagnosis
of metastatic disease. For example, an isolated supraclavicular node on the left (Virchow's node) may be the
only clue to an intra-abdominal
neoplasm. Isolated axillary nodes would indicate breast carcinoma, and cervical
nodes indicate carcinoma of the head and neck. With
isolated node enlargement
and no evidence for local
inflammation
or infection, an excisional biopsy of the
entire node is important for diagnosis. A lymph node
biopsy should also be performed in both localized and
generalized
lymphadenopathy
if the diagnosis is in
doubt.
II
Any group of lymph nodes that provides drainage to an area of recurrent

trauma, skin inflammation,
or vaccination
is subject to inflammation and enlargement.
For example, epitrochlear
nodes can be enlarged in a patient who does manual la
00'_
II
In 40% to 60% of patients who undergo lymph

node biopsy, the biopsy is not diagnostic and
only a reactive hyperplasia is found. If the biopsy is nondiagnostic
and other nodes are palpable,
repeat biopsy should be performed.
If repeat biopsy is
nondiagnostic
and lymphoma is a strong consideration,
abdominal laparotomy may be necessary. Several studies
have shown that 25% to 60% of patients with initially
nondiagnostic
lymph node biopsies were found to have
lymphoma, carcinoma, connective tissue diseases, or infection on close follow-up and rebiopsy.
~lymphoma
lymphOfelicular disease ~
leukemia
SLE
Rheumatoid arthritislSUU's disease
Dermatomyositis
Connective tissue disease --{
Autoimmune hemolytic anemia

Generalized lymphadenopathy
Serum
Hypersensitivity reactions -{
sickness
Drugs (hydantoins)
Acute
CBC
-{
Infections ------~[
Chronic
noonsl
Atypical TB
TB
Syphilis
AIDS
Hyperthyroid.~sm
, Hypoadrenalism
Endocrine -~-
Hypopltuitansm
Whipple's disease
Cystic hygroma
,[ lymphangioma
Conllenital----Sarcoidosis
lymphadenoj)8thy
Miscellaneous -----
Mar na
IQ
ncy
--{
EKfoliative dermatitis
Im~unoblastic lymphadenopathy
lipId storage diseases
lymphoma
.
Metastatic disease
sypnms
Infections
Granuloma inguinale
lymphogranuloma venereum
localized lymphadenopathy
Cecil Chapter
Harrison
Chapter
Tularemia
TuberculosiS
Cat-scratch fever
Kawasaki's disease
Dermatitis
10
local inllammallon~
Vaccination
11
Reactive hyperplasia
Trauma
178
61
Hematologic ~isorders Lymphadenopathy. 113
SPLENOMEGALY
Although splenomegaly may be the first sign of
disease. an enlarged spleen may not be clinically
significant. A palpable spleen is not always an
enlarged spleen. Several studies have revealed a 2% to
6% prevalence of a palpable spleen in a large series of
healthy patients. although no etiology could be discov
ered in 25% to 41% of those patients. In a large series
of nonnal coUege students, spleens were palpable in
approximately 3% of those examined. A third of these
patients continued to have palpable spleens at 3 years'
follow.up examination without associated disease.
114 Hematoloa1c
Disorders
Splenomegaly
If a young person with a palpable spleen has an

otherwise normal history and physical exam,
and a normal CBe, it is likely that the spleen
is normal and the splenomegaly is idiopathic (see No.
l). Splenic imaging (see No.3)
may not confirm splenic
enlarsement or may show a displaced spleen. If splenomegaly is confirmed but the etiology is uncertain, the
patient should be [oUawed closely and reexamined peri.
odica1ly.with further testing as indicated by changes in
the patient's history or physical exam.
Spleen size can be evaluated by a variety of

methocls. including computed tomography (CT)
scan, radionuclide spleen scan, ultrasonography.
and magnetic resonance imaging (MRI). Ultrasonography is probably the most accurate, low-cost, noninvasive
technique available to image the spleen. If splenic imaging is normal, the spleen is probably nonnal. Splenic
imaging is useful to confirm splenic enlargement but
will also uncover causes of splenic displacement or
space...occupyingsplenic lesions.
Renal
OispW:ement by extrinsic masses -{
~~n:atic
Ovanan
Displacement
-{
Metastases
....
Displacement by IntrinsICmasses -{
1 Splenornegllly
Hamartoma
TI\Ie cysts
False cysts
True splenomegaly -------------------(uniform splenic enlargement)
Cecil Chapter
Harrison Chapter
(continued on
page 117)
176
61
Hematolocic Disorders
SplenomegAly
115
SPLENOMEGALY
(Continued)
The term hypersplenism has been used to desig.

nate the concept that the spleen is proclucing
hematologic abnormalities via an exaggeration of
its normal activities. Hematologic abnormalities due to
hypersplenism include anemia, leukopenia, and thrombocytopenia. In many cases of splenomegaly, a -pseudoanemia" is a result of increased total plasma volume and a
normal red blood cell mass that is sequestered in the
enlarged spleen. Primary hypersplenism refers to a state
in which no underlying disease can be discovered.
Chronic congestive splenomegaly. known as

Banti's syndrome, consists of splenomegaly,
pancytopenia, portal hypertension, and gastroin.
testinaI bleeding. Any condition that causes portal hypertension can cause Bano's syndrome. Underlying
causes of portal hypertension include portal or splenic
vein thrombosis or compression, as well as intrahepatic
processes such as Laennec's cirrhosis (irreversible cir
rhosis). The portal hypertension is responsible for the
increased incidence of gastrointestinal (GI) bleeding
and splenomegaly. The enlarged spleen, in turn, may

cause pancytopenia.
II
Splenic hyperplasia is thought to be due to an

increase in workload placed on the spleen. The
spleen hypertrophies in response to increased
work of removal of abnonnal blood cells from the ci.rculation. The abnormal cells may have intrinsic defects or
may be cells coated with antibody. The clUef causes of
splenic hyperplasia include various forms of anemia and
many autoimmune disorders. In some cases, splenic hy.
perplasia is a result of extramedullary hematopoiesis. Dj
agnosis is apparent upon appropriate hematologic testing.
Splenomegaly
7
8:
A benign generalized lymphoid hyperplasia is
the source of splenomegaly that may be seen in

Graves' disease.
Splenomegaly is often the result of infiltrative
diseases, including Gaucher's disease, NiemannPick disease, and amyloidosis. The spleen can
be infiltrated by leukemic cells and lymphoma. Occasionally, the enlarged spleen may be the presenting site
of lymphoma. In Hodgkin's disease, palpable splemr
megaly is usually indicative of more advanced disease.
Histologic confirmation of suspected splenic disease
may ultimately require fineneedle biopsy or splenectomy for diagnosis.
Splenomegaly is commonly associated with
acute inAammatory processes, usually in response to an increase in the activity of the
immune functions of the spleen. Chronic infections
causing splenomegaly may mimic a primary hematologic
disorder. The clinician must have a high suspicion of
infection to make an accurate diagnosis. Blood.cultures
and appropriate serologic testing for infectious agents
will aid in diagnosis.
1m
Felty's syndrome is defined as splenomegaly

and leukopenia associated with rheumatoid arthritis in adults. Splenomegaly may precede the
development of leukopenia by many years.
Primary hypersplenism
Clm.osl'
Portal vein thrombosis/compression
Congestive
-{
Splenic vein thrombosis/compression

Congestive heart !ailure (CHF)
lytic
(continued from
pags 115) ---
4
Hypersplenism
HyperplastIC ---
ChronIC anemias ----
PernICIOUsanemia
ThalassemIa
:::::::'
My.'~'h""
Graves' disease
{
ThrombotiC thrombocytopenIC purpura (TTP)

CryptogenIC
ExtrameduUary hematopoieSIS
Gargoylism
Lymphoma
Leukemia
Secondary hypersplenism
Inlillrative-----4
Histiocytosis X
Gaucher's disease
Niemann-Pick disease
AmyloidosiS
Type 1 hyperlipidemia
HIV
InfectIOUS mononudeoSIS
Septicemia
Acute/subacute
InfectIOUS
SplenIC abscess
-{
Subacute bactenal endocarditis (SSE)

Viral hepatitis
Inflammatory
~=::::SiS
-1
______ + ChronIC...InfectIOUS
Malaria
HISlopiasmosis
~~~=:o:nital)
SchIstosomiasis
SLE
Other inflammatory
Cecil Chapter'
Hamson
Chapter'
178
,~o
Felty's syndrome
Sarcoidosis
~ Beryllium disease
61
HemOltologic Disorders
Splenomegaly. 117
blood cells are micr<X:ytic if the MeV is low and macrocytic if the MCV is high.
LABS
MCHC=mean
ANEMIA
II
Red. blood cell indices are calculated with automated equipment
and include
corpuscular
where Het is hematocrit and RBC is red blood cells
(x 10'/1'-1).Normal range MCV ~82 to 98 8. The red
Anemia
the average
weight
of henwglobin
in the red
blood ceU. To calculat"
tion. The MCHC caIculates the weight of hemogWbin

per volume of red blood cells. To caIculat"
MCH = HgbIRBC
MCHC ~ HgbIHct
where Hgb is hemoglobin
Disorders
concentra-
the following;
MCV ~ mean =P"'cular volume. The MCV

represents the average size of the red blood ceU. To calculate,
118 Hematolocic
hemoglobin
MCH = mean corpuscular hemogWbin. The MOl represents
and Het is hematocrit.
Nor-
mal range MCHC ~ 32 to 34 yd!. CeUs are hypochroif the MeHe is low and hyperchromic if the
MCHC is high.
mic
where Hgb is hemoglobin and RBC is red blood cells

(x 10'/1'-1).Normal range MCH = 27 to 34 pg per cell.
MeH reflects both the size and hemoglobin
concentra-
tion of the red blood cells. Low MCH indicates hypochromia, microcytosis,
or both.
MIcrocytic anemia ---+ See page 120
Anemia
(Hct<411 M)
(Hct<38 F)
MCV82-98
NormocytiC anemia ---+ See page 122
Macrocytic
Cecil Chapter
Harrison Chapter
anemia
---+ See page
124
159
59
Hematolotlc Disorders Anemia 119
Microcytic Anemia
In hereditary spherocytosis, the MeV is usually
normal (normocytic) or slightly decreased (microcytic), and the MCHC is increased to 35 to
40 glill. Hereditary spherocytosis is usually classified as
a normocytic hemolytic anemia (see No. 10, Hemolytic
Anemia). Almost all other hemolytic anemias are normocytic, normochromic.
Cow's milk is a poor source of iron. Infants fed

primarily cow's milk are prone to iron deficiency anemia.
Frequent
pregnancies
ment. Frequent
blood
plete iron stores.
increase
donation
iron requiremay also de
Except in infants and rapidly growing children,

iron deficiency
anemia
is most commonly
caused by chronic blood loss. Menstruation
is
the most common cause of chronic blood loss in premenopausal
women, and GI blood loss is the most
common cause of chronic blood loss in men and postmenopausal women.
II
Iron deficiency anemia is the most common

cause of microcytic. hypochromic
anemia. Of
ten anemia is detected
by a low hematocrit
before the MeV becomes low enough to indicate microcytosis. I fon deficiency should yet be considered
as a
cause of anemia even in normocytic anemia.
Total iron binding capacity (TIlle) is a measure
of serum transferrin content. Serum iron is decreased in both iron deficiency anemia and in
anemia associated with chronic disease. In iron deficiency, TI Be is usually increased.
The anemia of
chronic disease is usually associated with a decreased
TIBe. The relationship between iron and TrBe can be
expressed
as percent transferrin
satumtion
such that
normally approximately
30% transferrin
is saturated
with iron. In iron deficiency, the transferrin saturation
is usually less than 15%.
Measurement
of serum ferritin also provides a
reliable estimate of iron stores. In nonnal persons, ferritin
reflects the size of body iron
stores. A decrease in plasma ferritin to less than 10 n'll
ml is strongly indicative of iron deficiency. Some individuals with iron deficiency anemia, however, may have
serum ferritin levels up to 50 nglm!.
Dietary deficiency is a rare cause of iron deficiency anemia. However, dietary iron absorption can be decreased
due to dietary calcium
and phytates (in cereals), which complex with iron and
decrease its absorption.
Vitamin C promotes iron absorption, probably by allowing reduction of ferric iron
to the ferrous form, which is more readily absorbed.
120
Hematologic Olsorden Anemia
Iron deficiency may result from hemoglobinuria

and hemosiderinuria
resulting from severe intravascular hemolysis. Serum lactate dehydrogenase (LDH) is usually increased in iron deficiency ane
mia associated with hemolysis. Hemolysis is usually a
nonnocytic anemia (see No.4, Nonnocytic Anemia).
1m
Examination
of the stool for occult blood is
critical in the investigation
of iron deficiency
anemia. CI blcxxl Joss may be intermittent,
re
quiring the testing of several stool specimens for occult
blood over a prolonged period of time. In the absence
of another source of bleeding, the CI tract may require
evaluation even when stool tests for occult blood are
negative. Iron deficiency in men and postmenopausal
women is most often due to GI blood loss.
II
II
Iron deficiency anemia associated with hemodialysis may be due to treatmentrelated

blood
loss (e.g., trapping of blood in the dialyzing
equipment).
An increase in plasma ferritin may indicate increased iron stores. Various other conditions
can result in increased plasma ferritin without
coexistent iron overload. These other conditions include
increased metabolism, inAammation, liver or kidney disease, tissue damage, and neoplastic disease. In order to
diagnose iron overload based on increased plasma ferritin, these other causes must first be excluded.
111
Plumbism,
or lead poisoning,
causes anemia
primarily
by inhibiting
several enzymes im
portant to heme synthesis. Lead may also cause
hemolysis. Examination of the blood smear characteristically reveals basophilic stippl;ng of the red blood cells.
Plumbism usually results in a nonnocytic, hypochromic
anemia, although it may also cause a microcytic anemia.
II
Sideroblastic
anemias are a heterogeneous
group of disorders with the common feature of
ringed sideroblasts
in the bone marrow. The
anemia is caused by an enzymatic defect in the synthesis
of heme. Sideroblasts
are red blood cell precursors
that contain nonheme iron granules. With sideroblastic
anemia, hypochromic
cells can be found among relatively nonnal cells so that a "partial hypochromia" exists.
Diagnosis requires examination of bone marrow aspirate
stained for iron.
~
II
II
Isoniazid is an inhibitor of pyridoxal kinase and

may cause a pyridoxine-responsive
sideroblastic
anemia (vitamin BlI).
Anemia associated with chronic inflammatory

conditions
is usually normocytic,
normochromic, but the smear may have a mixed population of cells-including
hypochromic
red blood cells.
(see Nos. 10-13, Normocytic Anemia).
II
Hemoglobinopathies
can be classified broadly
into two categories: (J) Inherited structural alteration in one of the globin chains. This category includes sickle cell anemia and related disorders.
The hemoglobinopathies
in this group may also be microcytic anemias but are usually nonnocytic.
Electrophoresis is the test of choice to define globin chain
abnormality. (2) Inherited defects in the rate of synthesis of one or more of the globin chains. This category
includes the thalassemias.
Thalassemia
minor is 90%
probable if significant microcytosis is found to accompany minimal anemia. Over 350 different abnormal hu
man hemoglobins
have been described. (see No. 13,
Hemolytic Anemia).
Microcytic hyperchromic anemia
---1 Hereditary
spherocytosis
..
Teenagers
Decreased dietary Intake -;L
6 Infants
-----r
~
Microcytic
anemia
(MCV<82)
FelTlBC < 10%,

ferritin < 10 ngIml
Impaired absorption
Iron deficiency
Malabsorption
Gastrectomy
Sprue
~
7
Increased requirements
Rapldgrowtl1
Pregnancy
Bk>oddonation
--1
Surgery/phlebotomy
Menstruation
Blood loss
2 Microcytic hypochromic anemia
Intravascular hem~is
10
Chronic GI blood loss
11
Hemodialysis
Sports anemia
13
Blocked heme synthesis ~
r Lead
Pyrazinamide
Neoplasms
12 Fe>150mgfdlor
nonnal50-150 mgfdl,
fenitin > 200 ng/ml
Cecil Chapter
Harrison Chapter
[ Hereditary
14
Sideroblastic anemia -
15 [ Isoniazid
16
Chronic inflammatory states
17
Hemoglobinopathies -[
Pyridoxine responsive
Sickle cell & related disorders

Thalassemias
159
59
Anemia 121
Normocytic
Anemia
Reticulocytes are red blood cells newly released

from the bone marrow. The reticulocyte count
is obtained by noting the number of reticulocytes per thousand red blood cells--expressed as percent reticulocytes. Normal values are 0.5% to 1.5%. The
reticulocyte count is dependent upon the total number
of red blood cells in circulation; therefore, the total
number of reticulocytes varies with diiTerent hematocrits. A correction factor based on a nonnal hematocrit
of 45% can be used. to calculate the corrected reticulocyte count:
Percent corrected reticulocyte count

percent reticulocyte count X patient hematocrit/45
An elevated reticulocyte count anemia indicates

increased marrow production of red blood cells.
TIle reticulocyte count is a good indicator of
adequate marrow function. Since reticulocytes are
larger than normal red blood ceUs, the MCV can be
elevated when a large number of reticulocytes are pres
eot. Therefore, anemia with increased red blood cell
production may be initially classified as macrocytic. Ex
aminatioll of the peripheral blood smear (see No.3)
should allow detection of the large number of reticula-cytes and lead to correct diagnosis.
Visual examination of a smear of the peripheral

blood quickly reveals whether increased mar
row activity is due to destruction of red blood
cells by hemolysis or to blood loss.
There are a number of laboratory tests useful

establishing or confirming the presence of
4 inhemolysis:
(1) Examine the blood smear. Review of the smear may reveal red blood cell fragments
or the characteristic shape of cells found in some hereditary membrane abnormalities. Spherocytes, fragmented
red blood cells, and spiculated red blood cells are im
portant findings. (2) Unconjugated or indirect bilirubin
is elevated in patients with hemolysis. The serum level
of conjugated bilirubin remains within normal limits,
unless there is coexistent liver disease. (3) Haptoglobin,
an a. globulin that binds to the protein (globin) in
hemoglobin, is decreased or absent due to the release
of globin from the lysed red blood cells. (4) Urine
122
Hematologic Disorders Anemia
hemoglobin is found when the absorptive capacity of

the renal tubule has been exceeded. Normally, the hemoglobin is bound to haptoglobin and is not filtered by
the kidney, but once the haptoglobin.binding capacity
has been exceeded, hemoglobinuria occurs. These abnormalities usually occur only with severe hemolysis.
flammatory diseases associated with this anemia include

inflammatory bowel disease, SLE, and rheumatoid arthritis. Tuberculosis, chronic abscesses, and chronic osteomyelitis can be associated with anemia of chronic
disease. The anemia improves when the condition re
mits.
II
II
A normal or decreased reticulocyte count may

indicate inadequate bone marrow response to
anemia, although a reduced reticulocyte count
is not always due to a primary marrow disturbance.
Causes of a dilutional anemia include rapid infusion of intravenous fluids and venipuncture
proximal to the site of infusion of intravenous
fluids.
Myelophthisic marrow refers to bone marrow
that has been infiltrated-usually by tumor or
granuloma, although marrow infiltration can
also occur with lipid stomge diseases. Tumor infiltration
may be by metastatic solid tumor or by cells indigenous
to the marrow as with myeloma or leukemia. Invasion
of bone marrow by metastatic tumor inhibits erythropoiesis and thrombopoiesis, but neutrophil production may
be nonnal or increased.
Aplastic anemia refers to a bone marrow that is

acellular or hypocellular, resulting in a
pancytopenia-i.e.,
anemia, neutropenia, and
thrombocytopenia.
In red blood cell aplasia, a cytotoxic antibody is

directed against an early red blood cell antigen,
causing a selective failure of the production of
the erythroid elements of the bone marrow although
other marrow cell lines are normal. Red blood cell
aplasia is associated with autoimmune diseases such as
rheumatoid arthritis and SLE.
1m
A normocytic anemia that is usually mild and

gradual in onset is characteristic of anemia of
chronic disease. Red blood cell production failure is the cause of this anemia. Anemia of chronic
disease is associated with chronic inflammation, chronic
infection, malignancy (not necessarily metastatic to
bone), or post-traumatic or post-surgical. Chronic in
Anemia of chronic liver disease is associated

with any advanced liver disease, commonly alcoholic liver disease. Alcohol directly suppresses erythropoiesis, and blood loss is common in
alcoholic patients. Jnadequate intake and impaired utili
zation of folate and a shortened red cell life span also
contribute to the anemia in alcoholic patients.
II
In anemia associated with chronic inflammation, the extent of the anemia is roughly proportional to the duration and severity of the in
flammatory process. Chronic infections, collagen.
vascular diseases, and neoplasms are all classified in this
group. Neoplastic disorders alone can cause anemia,
but commonly anemia develops via a variety of other
mechanisms with neoplasms-e.g.,
blood loss (colon
cancer), invasion of bone marrow (myelophthisis), and
suppression of hematopoiesis by chemotherapy or radiation therapy.
II
The low red blood cell production associated

with uremia is due to inadequate secretion of
erythropoietin. Other factors that may contribute to the anemia associated with renal failure include
hemolysis. dialysis-related blood loss, and CI bleeding.
II
Thyroxine, glucocorticoids, testosterone, and

growth hormone all affect hematopoiesis. Patients with myxedema have an increased incidence of pernicious anemia. Hypothyroid patients also
often develop iron deficiency anemia. Anemia associated
with endocrine failure may be corre<:tL><.I
with hormone
replacement.
:.I
II
In early iron defiden<.." anemia, the peripheral

red blood cells may remain normocytic (MeV
is usually in the low normal range), hut examination of the bone marrow reveals nuxlcmte erythroid
hyperplasia. Marrow stains for iron are decrea.'ied or
absent (see Microcytic Anemia).
Blood loss
Anemia with increased
red blood cell production
Red blood cell destruction -
,
HypoplaSUl
Hemolytic anemia -+ See page 124
r Aplastic anemia -+ See page
----gL
Red blood cell aplasia
-f
Myeloma
6 Dilutional anemia
Indigenous cells
Intrinsic
Myek>phthisicl
marrow -7 infiltrative
disease
disease
Lymphoma
leukemia
Gaucher's
Upid stors
ge
disease {
disease
Niemann-Pick disease
Congenital dyserythropoietic anemias
Inadequate marrow
production
10 Anem,ia ~f
Harrison Chapter

Chronic inflammation
chronIC disease 13
~
14
15
Cecil Chapter
11
12
=1
Malignancy
Collagen-vascular disease
Chronic renal insufficiency
Chronic infection
Endocrine disorders
Earty iron deficiency
159
59
Anemia 123
Hemolytic Anem;a
II
If absolute reticulocytosis
is present (see Nos.
1, 2, Normocytic Anemia), hemolysis must be
confirmed before proceeding with further evaluation, because blood loss and marrow failure are far
more common causes of normocytic
anemia than is
hemolysis. The visual examination
of the peripheral
smear is critical (see No.3,
Normocytic
Anemia). A
series of tests will help confirm the presence of hemolysis (see No.4, Normocytic Anemia). LDH is liberated
from lysed red blood cells and will be elevated in hemolytic anemia. Indirect or unconjugated
serum bilirubin
is elevated with hemolysis. Haptoglobin
levels are de-
creased because hemoglobin released from lysed red

blood cells will fonn a complex with haptoglobin.
Hemoglobin and hemosiderin can be detected in the urine.
These tests should be used to confirm the likelihood of
hemolysis prior to further testing. Further evaluation
must be directed by the clinical setting, e.g., the presence of sickle cells on peripheral
smear exam in a
young black patient should preclude the need to order
a Coombs' test.
II
The direct Coombs' test is a test in which human red blood cells are placed in contact with
rabbit or goat antihuman
serum globulin reagent. The red blood cells are subsequently
evaluated
for the presence of agglutination.
If the red blood cell
surface is coated with 19G, agglutination
is induced by
the anti-IgC-containing
reagent and a positive test occurs. The 'gM antibody reacts most efficiently with red
blood cells in the cold, and has therefore been tenned
cold agglutinin disease. The direct Coombs' test will
usually not detect 19M-coated red blood cells owing to
the decreased affinity of the IgM from the surface of
the red blood cell at
In IgM-mediated
immune
hemolytic anemia, the direct Coombs' test will usually
be negative. In IgM-mediated
disease, complement
(C3
and C4) can usually be detected via a non-Coombs'
test.
3rc.
A positive direct Coombs' test indicates the

presence of antibodies in the patient's serum
directed against his own red blood cells.
Anemia
A negative direct Coombs' test indicates that

hemolysis is usually unrelated
to an immune
mechanism,
although
about 10% of patients
with autoimmune
hemolytiC anemia have a negative
direct Coombs' test. Nonimmune
causes of hemolytic
anemia include agents that physically damage red blood
cells and abnormalities
intrinsic to red blood cells resulting in hemolysis.
Hemoglobinopathies,
including sickle cell anemia and thalassemia, can also result in hemolytic anemia. 1n sickle cell anemia, the abnormally
shaped
cell
is rapidly
cleared
by the
reticuloendothelial
system. Thalassemia
is a hereditary
anemia in which there is a quantitative
decrease in
synthesis of one or more of the globin chains, resulting
in unbalanced globin chain synthesis. In the thalassemias, red blood cell destruction results from the precipitation of the abnonnal hemoglobin
(fonning Heinz bodies) and the increased osmotic fragility of the red blood
cells. The hemolysiS is most severe in a-thalassemia
ma-
jor.
Fibrin deposition is the primary cause of the

red blood cell fragmentation
that occurs in microangiopathic
hemolytic anemia.
A variety of infectious agents may be associated

with severe hemolysis, some by parasitization of
the red bloOO. cell, others by indirect action as
is seen with clostridial infections.
Chemical agents such as benzene and copper

can have a direct hemolytic effect on the red
blood cell. The hemolysis seen in Wilson's disease is thought to be due to copper toxicity.
8
9
Hypersplenism
erwise nonnal
nomegaly).
may result in hemolysis of othred blood cells (see No.4. Sple-
1m
The shape of the red blood cells in spur cell

anemia accounts for their entrapment
and destruction
by the reticuloendothelial
system.
Spur cells occur most commonly in patients with severe cirrhosis.
II
Paroxysmal nocturnal hemoglobinuria

(PNH) is
an acquired intracorpuscular
red blood cell defect with a markedly increased sensitivity to
complement-mediated
hemolysis. Clues to diagnosis in
c1ude decreased leukocyte alkaline phosphatase and he
mosiderinuria.
Either a Ham's test or a sucrose hemolysis test can be used to diagnose PNH. Ham's test is too
insensitive to detect all patients with PNH. The sucrose
hemolysis test is more sensitive but is less specific (see
No.5, Pancytopenia)
II
Hereditary spherocytosis, elliptocytosis, and stomatocytosis are all autosomal dominant disor+
ders in which the poor defonnability of the red
blood cell membrane allows for red blood cell destruction by a nonnal spleen.
II
III
1ntemal red blood cell disorders are caused by

red blood cell enzyme defects and hemoglobinopathies. Both result in premature
red blood
cell destruction.
Glucose-6.phosphate
dehydrogenase
(G6-PD)
is an important enzyme employed by the red
blood cell to protect itself against oxidant stress.
G-6-PD deficiency is inherited as an X-linked trait and
is found in 10% to 15% of American blacks. Hemolytic
anemia arises in G-6-PD deficiency only when the individual is exposed to environmental
stress such as drugs
or infection. Examples of drugs that can cause hemolysis
in G-6-PD-deficient
patients include antimalarials (pri+
maquine, chloroquine).
sulfonamides and sulfones (dapsone), antihelmintics,
analgesics (including aspirin, although
aspirin
can be given in moderate
doses),
nitrofurans, chloramphenicol,
vitamin K analogues, and
fava beans. Upon oxidation, the hemoglobin
tends to
precipitate in the red blood cell, forming Heinz bodies.
~
3 Positive
direct
Coombs'
test
Immune herTlOfyticanemia -+ See page 126

5
Hemoglobinopathy
Sickle cell anemia

Thalassemia
Radiation
Physical
agents
Abnormal
vessel
Eclampsia
Allograft rejection
wall
Hemangiomas
March hemoglobinuria
.
MechanlCSl trauma - 6
Insect
Animal agents {
Microangiopathic
he~ytic
anemia
DIG
Thrombotic
thrombocytopenic
purpura
ArtifICial heart valves

stings
Idiopathic
Snake bites
Bartonellosis
Infectious agents (nonimmune)
Hemolytic uremic
syndrome
Malaria
Disseminated carcinoma
Clostridia
leishmaniasis
Negative
direct
Coombs'
test
Babesiosis
Extensive bums
Extreme temperat~
8
Chemical agents
Hypersplenism
Membra~.
_
abnormalities
10
11
12
Benzene
L Lead
Copper (Wilson's disease)
Spur cell anemia

Paroxysmal nocturnal hemoglobinuria
Hereditary spherocytosis
Hereditary ellipocytosis
Hered~ary
Hereditary stomatocytosis
Hereditary pyropoikilocytosis
Abnormal
internal
red blood
ceil
~
Enzyme deficiencies
structure
Cecil Chapter
Harrison Chapter
159
Immune hemolytic anemia

(10% negative direct Coombs')
Pyruvate kinase deficiency
------:-.:1 Congenital erythropoietic porphyria

14
G-6-PD deficiency
-+ See page 126
59
Hematologk:: Disorders
Anemia 125
Immune Hemolytic Anemia

Immune hemolytic anemia (autoimmune hemo-
lytic anemia) describes a group of disorders

in which the body produces antibodies against
antigens on their own red blood cell membranes,
leading ultimately to the lysis or destruction
of the red
blood cell. The antibodies IgG and IgM are the'autoantibodies, along with complement
fixation, that cause
hemolysis.
Immune hemolytic
anemia is most com-
monly caused. by IgG.

The direct Coombs' test h Coombs') is a test
in which human red blood cells are placed in
contact with rabbit or goat antihuman
serum
globulin reagent. The red blood cells are subsequently
evaluated for the presence of 3Wutination.
If the red
blood cell surface is coated with IgG, agglutination
is
induced by the anti-IgG-containing
reagent and a positive test occurs. The IgM antibody reacts most efficiently with red blood cells in the cold, and has therefore been termed cold agglutinin disease. The direct
Coombs' test will usually not detect IgM-coated
red
blood cells owing to the decreased affinity of the IgM
from the surface of the red blood cell at 3T'G In
IgM-mediated
immune hemolytic anemia, the direct
Coombs' test will usually be negative. In IgM-mediated
disease, complement
(C3 and C4) can usually be detected via a non--y Coombs' test.
Isoimmune hemolytic disease of the newborn,

or erythroblastosis
fetalis, is a hemolytic disorder caused by transplacental
maternal antibodies directed against fetal red blood cells. Most cases are
due to anti-Rh antibodies.
II
The division of the hemolytic

anemias into
warm and cold varieties is based on the optimal
temperature
of antibody reactivity with the red
blood cell surface. Wann immune hemolytic anemia is
due to an IgG antibody that reacts with the red blood
cell surface optimally
at 37C. The IgG-coated
red
blood cells are then destroyed by splenic macrophages.
The majority (40% to 50%) of these cases are idiopathic.
In cold autoimmune
hemolytic anemia, IgM autoantibodies interact with the red blood cell membrane optimally between 0 and JOOC (see No.7).
"4
There are three types of drug-induced

autoimmune hemolytic anemias: the hapten type, the
autoimmune
type, and the innocent bystander
type. In the hapten type, antibody is produced against
the drug, not the red blood cell membrane.
However,
the antibody-drug
complex has an affinity for the red
blood cell surface, resulting ultimately in red blood cell
destruction.
The antibody mayor may not fix complement. Penicillin is an example of the hapten type of
hemolytic anemia. In the autoimmune
type, patients
produce antibodies against their own red blood cells
and not against the drug. The most characteristic
drug
in this group is methyldopa
(Aldomet). The innocent
bystander type of hemolysis is due to the generation of
activated complement components by the drug-antibody
complexes. Quinine, sulfonamides,
and phenothiazines
are examples of drugs that induce this type of hemolytic anemia.
Anemia
If a Coombs' test is negative, a non-"Y Coombs'

test should be performed
to screen for cold
autoimmune
hemolytic anemia, caused by IgM.
A non-"Y Coombs' test uses a reagent containing antibodies directed toward human complement
(C3 and
C4). A non-"Y Coombs' test relies on the fact that (.'omplement usually remains bound to the red blood cell
membrane
at 37"C, despite the fact that IgM will not
remain bound at that temperature.
II
Less eommon than warm immune hemolytic

anemia, cold immune hemolytie anemia is due
to an IgM complement-fixing
antibody
that
binds to the red blood cell optimaUy at 4C but rapidly
dissociates from the red blood cell at increased temperatures. Cold agglutinins are present in normal serum but
at such low titer that they are of no clinical concern. In
certain disorders, cold agglutinin titers may range from
1:1000 to 1:100,000. Antibody attachment to red blood
cells during transient temperature
decrease (as happens
when blood Hows through fingertips, ears, and nose)
can activate the complement
sequence and cause red
blood cell lysis. The IgM may dissociate from the red
blood cell as the cell returns to a wanner temperature,
but the complement
remains bound, causing continued
red blood cell destruction
via the macrophages of the
reticuloendothelial
system.
A rare cause of cold immune hemolytic anemia

is paroxysmal cold hemoglobinuria
(PCH). The
antibody is an unusual IgG antibody, not IgM.
Although this antibody was originally found to be present in syphilis, it is now more frequently
found in
children with viral infections.
Lymphocytic
leukemia
Acute (ALL)
Chronic (elL)
Hodgkin's
Lymphoma
---
I[ Non-Hodgkin's
Previous transfusk>ns
Transfusion
reactions
Pregnancy
Multiple
myeloma
Thymoma
lsoimmune
hemolytic
disease of the newborn
Ovarian
Idiopathic
tumors
tumors
Carcinoma
Warm autoimm~ne
hemolytic
anemIa
Infections
-1
MYCOPlasm.8 (esp. P
neumonia)
~ Collagen-vasculardisease
TuberculOSIs
Immune
hemolytic
Nonmalignantdisorders
anemia
-------
Drugs
-1
;~~ee~~tl~~~
Cytomegalovirus
:onUcleoSiS
Ulcerativecolitis
Chronic
activehepatitis
Immunodeticiencysyndromes
Rheumatoid
arthritis
Thyroid
disorders
IdIopathIC
Neoplasms
-1
Cold agglutininS
7 hemolyt)C
Cold autoImmune
anemia
6
-{
Infections
Connectrve
tissue disease
--f --{
ParoxysmsI cold hemoglobrnemla
Spontaneous
Congenrtal
Syphlhs
Viral
Acquired
Warm autoimmune
hemolytic anemia
Cold autoimmune
hemolytic anemia
~--------------~1~59~
Cecil Chapter
Harrison Chapter
59
Hematologic Disorders Anemia 127
Aplastic
Anemia
Aplastic anemia refers specifically to patients

with a bone marrow that is acellular or replaced
with fat due to hypoplasia of the erythroid,
myeloid, and thrombopoietic ceU lines. Destruction of
all these cell lines is thought to be secondary to injury
or destruction of a common pluripotential stem cell.
The pancytopenia of aplastic anemia must be differentiated from pancytopenia due to marrow replacement.
with aplastic anemia are found to have hemolytic anemia with complement-sensitive red blood cells similar
to those in PNH (see No.9, Hemolytic Anemia).
Drugs and chemicals causing marrow aplasia
can do so in either a dose-related or an idiosyncratic fashion. Agents that will predictably produce marrow depression with calculated dosing include
antineoplastic agents (alkylating agents and antimetabolites) and ionizing radiation. The degree of aplasia varies
among individuals but in general is dose-related. Withdrawal of the drug usually allows for marrow recovery,
although aplasia may sometimes be irreversible.
II
Direct examination of the peripheral smear and

bone marrow are important to determine the
source of bone marrow dysfunction. In severe
aplasia, not only is the bone marrow aspirate "empty"
but the prognosis of the disease depends upon the
presence of two of the three following factors: (1) an
The most common drug causing aplastic anemia
absolute neutrophil count (ANC) of less than 5OOIml;
is chloramphenicol. Chloramphenicol can cause

(2) a platelet count of less than 20,OOOIml; and (3) a
both a dose-related marrow aplasia and an idioreticulocyte count of less than 1% or an absolute reticu- syncratic marrow aplasia. Idiosyncratic chloramphenicol
locyte count of less than 40,OOO/mi.
marrow suppression may appear long after the drug has
been discontinued.
Approximately 50% of all cases of aplastic anemia in the UOited States are of unknown etiology. Some of these cases may be due to environBenzene-induced marrow aplasia is usually remental toxic exposures.
versible. Pancytopenia can occur many years
after actual benzene exposure. although in most
cases marrow depression appears shortly after exposure
Aprroximately one fourth of patients with PNH
4~ wil develop aplastic anemia during the course and appears to be related to dose and duration of the
exposure. Benzene exposure can also cause leukemia.
of their disease. Five percent to 10% of patients
II
128 Hematologic Dlsorden
Anemia
II
Ionizing radiation causes marrow aplasia in a

dose-related manner. Patients exposed to large
amounts of ionizing radiation in laboratory or
nuclear reactor accidents sufTer from damage to the
bone marrow and intestines. If these patients can be
supported for 3 to 6 weeks, the surviving stem cells may
be the source of bone marrow regeneration.
:
Aplastic marrow that develops during pregnancy may recover after the fetus is born. It is
thought that an inhibitor of hematopoiesis may
be present during gestation.
1m
Aplastic anemia may appear as hepatitis resolves. It is thought that the aplasia is due to a
direct efT<.."Ct
of the virus on the bone marrow,
possibly via an immune mechanism.
Miliary tuberculosis has been reported to cause

aplastic anemia, but in most cases causes bone
marrow dysfunction rather than true aplasia.
II
Constitutional aplastic anemia is the term used

to describe the group of patients with congenital marrow aplasia with or without associated
visceral and bony abnormalities. The prototype is Fanconi's anemia in which a familial marrow aplasia is
accompanied by multiple congenital abnormalities.
There is a high incidence of late development of leukemia in those patients who survive the aplasia.
Cecil Chapter
159
Harrison Chapter
59
Chloramphenicol
Benzene
Alkytating
agents
Dose-related
Antimetabolites
Acquired
Idiopathic
Paroxysmal
Chemical
Mitotic inhibitors
noctumal
-1
hemoglobinuria
aplastic anemia
Immunologically
mediated
and physjcal
agents
--;{
Pancreatitis
Pregnancy
Inorganic
DnJgs
=:n
Chloramphenicol
Phenylbutazone
Idiosyncratic
reactions
Sulfa drugs
Viral
10
Methylphenylethylhydanloin
Viral hepatitis
Gold compounds
Bacterial
1
Apla.tic
anemia
------11
Infections
Check peripheral smear,
perform bone marrow
asp;llltion and biopsy
Organic arsenicals
Miliary tuberculosis
Insecticides
MononocIeosis
'2
Fancon,'s
Inhented
aplasttc anemia
(Epst91n-Barr
anem
DyskeratosIs
arsenicals
Undane
..
Metabolic
Anthracydines
ACE inhibitors
VIruS)
Amantadine
HrV/AIDS
congenita
Familial aplastic anemias
AmegakaryocytlC
thrombocytopeOla
Others
-i
-i
Myelodysplastic
Paroxysmal
syndromes
noctumaJ hemogk)binuria
Hairy cell leukemia
Primary bone marrow disease
lymphoma
Myelofibrosis
Myelophthisis
Pancytopenia with
cellular bone marrow
1DS
Systemic
o:-~_
..
ry to systemIC dIsease
Macrocytic
lupus erythematosus
anemia
(B1Jf~te
deficiency)
Alcoholism
Infection
~
Infections
Q fever
Hypersplenism
Legionnaires'
disease
Mycobacteria
Starvation
--
Anorexia
nervosa
Anemia 129
Macrocytic
Anemia
The term macrocytic refers to an MCV greater

than 98. The term megaloblastic
refers to the
large red blood cells that result from an unbalanced growth of the cells caused by impaired DNA
synthesis in the nuclew. while cytoplasmic
RNA and
protein synthesis proceed normally. Because DNA syn.
thesis is impaired, there is more time for ceD growth
between cell divisions, resulting in larger cells. The
terms macrocytic
and megaloblastic
are often interchanged because macrocytic anemias are most often
associated with a megaloblastic morphology in the bone
marrow. Not all macrocytic anemias are megaloblastic.
The most common causes of a macrocytic, normochromic anemia are liver disease, alcoholism,
and vitamin BII or folate deficiency. Both BIt
and folate deficiencies
demonstrate
identical
blood
smears and marrow changes so that further clinical
information and diagnostic studies mwt be undertaken
to discover the cause of the macrocytic anemia. Combined deficiencies of BII and folate are not unoommon.
Often the underlying cause of BII and folate deficiency
is the same. An MCV above 110 is more predictive of
vitamin deficiency, and the likelihood of a Bit or folate
deficiency i.ncreases proportional
to the MCV. An MCV
greater than 130 is associated with a deficiency in BIt,
folate, or both almost 100% of the time.
Normal folic acid levels are 2 to 14 nwml, but

remember that individual labs will pUblish the
normal ranges for that particular lab. Sources
of folate include fruits, vegetables,
liver, kidney, and
yeast. The average diet contains 200 to 700 1J.g. with a
daily requirement
of 50 J.Lg.The body storage p::>ol is 5
to 10 mg folate. Folate is labile and can be destroyed
by cooking the foods that contain it.
II
>10%
A low MCHC 32)

may indicate a sideroblastic anemia in which a defect in the synthesis
of heme results in hypochromia.
Sideroblastic
anemias are most commonly microcytic, hypochromic
anemias. but they can be macrocytic, with the MCHC
often not decreased. Many times a "partial hypochromia" is seen in which a hypochromic population of
cells is mixed with a relatively normal cell population.
Bone marrow examination reveals a number of abnormalities, including erythroid hyperplasia with megaloblastic changes. The most diagnostic abnormality is the
presence of ringed sideroblasts in the bone marrow, as
is demonstrated
with iron stains.
130 Hematoloeic Disorders
Anemia
Normal Bli levels are 160 to 930 PWml, but

remember
that individual labs will publish the
normal ranges for that particular lab. The dietary sources of vitamin BIt are primarily animal protein
(dairy foods, fish, meat). The average diet contains 3 to
30 IJ.g of Blih but the daily requirement
is only 0.6 to
1.2 ILg. Body stores are large (5000 to 11,000 ILg), so
that depletion is unlikely solely on a nutritional basis,
except in strict vegetarians.
Thyroid
function
tests
should also be measured at this point becawe
more
than 50% of patients with hypothyroidism
demonstrate
an associated. macrocytic anemia.
Bit de6ciency is almost always due to malabsorption, because dietary intake is usually more
than adequate for the body's requirement.
Reticulocytes
are larger than normal red blood
cells and may raise the MCV to the macrocytic
range when reticulocytosis
is marked (e.g.,
to 20%).
If the bone marrow is megaloblastic, then de6ciency of Bit or folate must be considered even
if respective serum levels are normal.
II
Administration
of BII and folate and noting the
clinical response of the hematocrit
win help
differentiate
between a Bit or folate de6ciency
and a refractory anemia.
II!I Lack
of response to Bit or folate administration

de6nes the refractory anemias.
Hypothyroidism
2 Macrocytic hypochromic anemia
812 deficiency ---+ See page 132
1
Macrocytic
anemia
(MCV> 98)
4
3 Macrocytic
normochromic
anemia
Check Bl2
and folate
levels, TFTs
(nl B" 160-930 pgfml)
(nl folata 2-14 nglml)
6 Folic acid defICiency -+
See page 134
Hemolysis
Posthemorrhage
Antimetabolite administration
Folate defICiency ....... See above

B,z defdency
--+
See above
Myelodysplastic
....... See page 136
syndromes (MDS)
Cecil Chapter
Hamson Chapter
159
59
HematolOKic Dlsorden
Anemia
131
Vitamin Bn Deficiency
Normal BI:! absorption depends on binding to a
gastric juice protein, "intrinsic factor," so that
70% of dietary BIz is absorbed. Intrinsic factor
is derived from the parietal cells of the fundus of the
stomach. After binding to intrinsic factor, BIz is absorbed primarily from the distal ileum by attaching to
specific receptor sites on the ileal mucosa. Optimal BIz
absorption requires pancreatic enzymes as well. The
pancreatic enzymes act by degrading "R proteins" that
bind Eli and compete with the binding by intrinsic
factor, thereby reducing BIz absorption. Once absorbed,
B12 is carried in plasma by transcobalamins (TCs), which
are Bl2-binding proteins: Tel, hTCII, and TCIIl. Tell
binds nearly all absorbed or injected B12 and is therefore
the true transport protein, moving BIz from the site of
absorption to the site of storage. TCl is responsible for
B12 transport from storage sites and is in equilibrium
with tissue stores.
II
The test of choice to evaluate B12 absorption is

the Schilling test. There are three parts to the
Schilling test designed to help define the cause
of malabsorption. In the first part, radioactive Ba in a
dose of 0.5 to 2.0 f.Lgis given orally. Two hours after
oral B12' 1000 f.Lgof nonradioactive BI2 is administered
parenterally. This is a "flushing dose"; Le., the intramuscularly administered
BI2 will block storage of orally
administered
Bl2 and cause any absorbed radioactive
Bl2 to be excreted in the urine. The urine is then
collected for the 24- to 72-hour period following the
oral B12 dose, and the amount of radioactive B12 is
measured. The amount of BI2 excreted represents the
amount of Bl2 absorbed. In normal persons, 7% to 22%
of the initial oral radioactive B12 is excreted in the urine.
Error can be due to inadequate collection of urine or
to prolonged urinary excretion of B12 caused by de
creased renal function. If Bl2 excretion is low, the second part of the test can be performed. Part 2 of the
Schilling test entails giving intrinsic factor along with
the oral B]2' Part 3 entails repeating the Schilling test
after a course of tetracycline therapy to reduce intestinal
bacterial overgrowth.
A normal Schilling test indicates that there is

an increased requirement or inadequate dietary
intake of vitamin B12
II
~
Vitamin Bl2 (cobalamin) is derived from animal

products in the diet, due to the production by
microorganisms. Plant products do not provide
132 Hematologic Disorders Anemia
B12' which is why strict vegetarians

can suffer from Bl2
deficiency. Commercial vitamin supplements are now a
major source of B12 in the diet. Inadequate
dietary
intake is a rare cause of 812 deficiency, because dietary
intake usually exceeds daily requirements.
Rarely, a
purely dietary deficiency can be seen in infants whose
entire diet consists of breast milk (usually from strict
vegetarian mothers), in alcoholic patients with poor dietary intake of all nutrients, and in strict vegetarians
who ingest no animal protein.
TCll deficiency is a rare autosomal recessive

trait in which BI2 is absorbed orally but cannot
be transported and stored. Bl2 is absorbed and
lost to the urine due to lack of Tell. These patients
can survive when given pharmacologic but not physiologic doses of Bu.
With gastrectomy, intrinsic factor is absent because the parietal cells have been resected.
However, even if B12 therapy has been overlooked following gastrectomy, a megaloblastic anemia
will not become apparent for 5 to 6 years, because body
stores are large. On the other hand, partial gastrectomy
rarely results in a significant decrease in 812 absorption.
A 8]2 de6ciency after partial gastrectomy is probably
due to partial excision of parietal cells as weD as to
atrophy of the remaining gastric mucosa.
The most common cause of Bl2 deficiency in

adults is pernicious anemia, which is malabsorption of B]2 due to inadequate intrinsic factor.
Pernicious anemia refers specifically to defective secretion of intrinsic factor by the gastric mucosa. Pernicious
anemia occurs in two fonns-a
common adult type in
which lack of intrinsic factor is associated with gastric
atrophy and a deficiency of many other gastric secretions and a rare congenital form in which only intrinsic
factor is lacking while other components of the gastric
juice are normal. Pernicious anemia is usually seen in
persons of northern European descent and usually occurs after the age of 40. An 'exception is its occurrence
in young black women. The congenital form of the
disease is autosomal recessive; the adult form has been
found to be familial, but the pattern of inheritance
remains in doubt. Parietal cell antibodies, intrinsic fac
tor antibodies, and thyroid antibodies have all been
demonstrated in the serum of some patients with pernicious anemia. If thyroid disease has not previously been
investigated (see No.1,
Abnormal Thyroid Function
Tests), thyroid function should be evaluated at this

point. Approximately 25% of patients with pernicious
anemia have concomitant hypo- or hyperthyroidism.
Anti-intrinsic
factor antibodies
may also be
found in patients without pernicious anemia.
There is an increased frequency of anti-intrinsic
factor antibodies in patients with diabetes mellitus, thyroid disease, thyrotoxicosis, Hashimoto's thyroiditis, hypogammaglobulinemia,
vitiligo, rheumatoid arthritis,
and gastric carcinoma.
A normal Schilling test fonowing tetracycline

therapy indicates that B 12 absorption has been
inhibited by bacterial overgrowth. The tetracycline decreases bacterial growth, allowing increased Bli
absorption
to normalize the Schilling test. Bacterial
overgrowth
can occur in several diseases, including
"blind loops" created surgically, and scleroderma, in
which bacterial overgrowth occurs secondary to stasis.
1m
I
Diseases involving the terminal ileum can decrease B12 absorption, because the terminal ileum is the site of selective Bli absorption.
B12 malabsorption
in chronic pancreatic insufficiency is thought to be secondary to a lack
of pancreatic enzymes needed to degrade the
complexes of Bwbinding proteins (R proteins). These
proteins are found in saliva, gastric juice, and bile and
compete with intrinsic factor for the binding of B]2'
Familial selective malabsorption

(the Imerslund-Griisbeck
syndrome) is a rare inherited
disease in which ileal B 12 absorption is impaired
whether it is bound to intrinsic factor or not. It is
characterized by the onset in childhood of a megaloblastic anemia along with persistent proteinuria thought to
be due to an associated renal tubular defect.
lEI
Malabsorption
of Bl! observed in carriers of
the fish tapeworm Diphyllobothrium latum is
probably due to a competition
between the
worm and the host for dietary B]!. In patients with
anemia, the worm has been found to lodge in the
jejunum, proximal to the site of B12 absorption, enabling
the worm to bind Bl2 before it reaches the site of
normal ileal absorption. In patients without anemia, the
worm has been found in the ileum. D. latum is a
common parasite of freshwater fish, and human infestation ensues after ingestion of inadequately
cooked
whitefish.
-f
-f
Inadequate dietary intake
Increased requirements
-4
Breast-ted infants
Alc0hoiiCs
Strict vegetarians
Prugnancy
Cancer
Hyperth,-sm
Transcobalamin
Impaired utilization
II deficiency
___
Nitrous oxide administration
1
Vitamin
2
Bla deficiency
(8" < 160 pglmI)
Inadequate
intrinsic factor
~[TotaJ
Postgastrectomy
Partial
Pernicious anemia----~[
Anti-IF antibody in gastric secretions
CongeMaJ
Adu'
. _.~NeopIastic
infiltration
Gastric mucosal injUry--rlrradialion

lye ingestion
Transplacental anti-IF antibody
_______
Congenital
PMoon
part II
Schining
(oral 812
~[ AbsenilF
Nonfunctional IF
Small bowel diverticulosis
1
-i
Anastomoses and fistulas
+ IF)
Bacterial overgrowth
"blind loop"
Blind loops and pouches

Strictures
Scleroderma
Achlorhydria
Ileal ,esection
Sprue
Malabsorption
Regional ileitis
11
ChroniCpancreatic insufficiency
12
Familial selective malabsorption
[Colch"'ne
-----~[PAS
Neomydo
-----
Cecil Chapter
Harrison
Chapter
Fish tapeworm Diphyllobothrium
latum
159
59
Hematoloalc Dlsorden
Anemia 133
Folic Acid Deficiency
II
]n patients with folate deficiency. both serum

and red blood cell folate levels are decreased.
In patients with BI2 deficiency, serum folate
levels tend to be elevated and can even be greater
than the upper limits of normal, so that with combined
deficiencies, serum folate levels may be normal but the
red blood cell folate level will fall. Therefore, red blood
cell folate levels should always be measured in addition
to serum folate levels. In contrast to BI2 stores, folate
stores can be depleted within 4 to 5 months.
Decreased folate intake is by far the most common cause of folic acid deficiency. Folate-de6clent diets are those that lack fresh, green vegetables. Folate deficiency can occasionally be seen in
diets containing a large amount of vegetables when the
folate has been destroyed by cooking.
134 Hematologic
Dlsorden
Anemia
Folate deficiency seen in alcoholic patients results from a combination of factors. Inadequate
folate is due not only to inadequate dietary
intake but also to a disordered folate metabolism seen
in cirrhosis. Cirrhotic patients have impaired ability to
store folate in the liver and have excessive urinary loss
of folate.
Folate deficiency is common in patients taking

oral contraceptives and the anticonvulsants phenobarbital and phenytoin. The source of this
deficiency has not been determined but is thought to
be due to folate malabsorption. Sulfa salatine can also
inhibit folate absorption.
Pregnancy is a common cause of folate deficiency. Pregnancy-related folate deficiency is

due to the combination of decreased folate
body stores and a 5- to lO-fold increase in folate requirement, especially in the last"trimester.
_
Folate deficiency seen in association with oremia is due to the loss of folate with dialysis.
Folate deficiency is seen as a complication of a

variety of hematologic disorders characterized
by rapid cellular proliferation: sickle cell anemia, PNH, acquired autoimmune hemolytic anemia, thalassemia, hereditary spherocytosis, drug-induced hemolytic anemia with G-6-PD deficiency, myelofibrosis,
sideroblastic anemia, leukemia, and multiple myeloma.
Impaired folate utilization is caused by dihydrofolate (DHF) reductase inhibitors such as methotrexate and aminopterin. Folinic acid administration can counteract the actions of DHF reductase
inhibitors by bypassing the inhibited enzyme.
__________
2
--l[
3
Inadequate dietary intake
Infants
Alc0hoiics
Steatorrhea
Spn>e------------~
TropO:a'
NontropICal
Gastrectomy
Jejunal bypass/resection
Impaired absorption
Drugslfollc acid lnhibitors----------~

DIabetes mellitus
Phenytoin
Phenobarbital
Oral contraceptives
Whipple's disease
Leukemlallymphoma
Amyloid
~ Scleroderma
1
Folic .cld derldency
2~mr)
P"ONlncy
Hyperthyroidism
Inlaney
Exfoliative
Skin diseases ------------~.
Increased requiremElflts------------i
Uremia with dialysis
dermatitis
PSOriaSis
Malignancy
Alcoholism
7
8
Impaired metabolism -------
Cecil Chapter
Harrison
Chapter
- ---
-- .
Rapidcell tul'l"lOVer
DHF reductase Inhibitors
OHF reductase deficiency

Formlmlnotranslerase deficiency
Mell',,""""'"
Triamlerene
Pyrimethamine
Trimethoprim
Other enzyme deficiencies
159
59
Anemia 135
Mye/odysplortlc Syndromes (MDS)
II
Myelodysplastic syndromes (MDS), formerly
known
as refractory
anemias,
are a diverse
group of hematologic disorders in which hematopoietic stem cell abnormality leads to peripheral blood
cytopenia. MDS are defined loosely by cytopenias that
are associated with an abnormal-appearing bone marrow. MDS usually present as a macrocytic anemia with
a cellular bone marrow including adequate numbers
of progenitor cells. An abnormality in progenitor cell
differentiation leads to the anemia and varying degrees
of pancytopenia.
Antimetabolite drugs that block DNA synthesis
are commonly used in the treatment of various
neoplasms and can cause a megaloblastic anemia. Included in this group are drugs that interfere
with DNA synthesis without being readily reversed by
simultaneously administered folic or folinic acid.
136 HematolORk Disorders
Anemia
Hereditary orotic aciduria is a rare disease in

which pyrimidine metabolism is defective, resulting in megaloblastic anemia. Associated features include growth retardation and orotic aciduria.
(Refractory Anemias)
The unexplained disorders are a small group in

4 which megaloblastic transformation of red
blood cells occurs and the changes are unresponsive to therapy with Bit or folate. These disorders
have not been associated with any enzyme defect or
deficiency.
Thiamine-responsive anemia is thought to be

due to a rare defect in a thiamine-dependent
enzyme involved in DNA synthesis.
Di Guglielmo's syndrome (also known as

erythremic myelosis or erythroleukemia) is a
disease in which erythrocytes are primarily involved in a "leukemic" myeloproliferative process. Di
Guglielmo's syndrome is associated with severe refractory megaloblastic anemia.

In a number of disorders, no underlying defect
can be identified. The megaloblastic changes
are unresponsive to treatment, and all current
modes of therapy are considered investigational. Because an understanding of the biologic defect is lacking,
this heterogeneic group of disorders has been classified
into different subtypes on the basis of clinical characteristics and marrow morphology. These categories include
refractory anemia without ringed sideroblasts; refractory
anemia with ringed. sideroblasts; refractory anemia with
excess blasts; and refractory anemia in transformation.
Pyridoxine-responsive anemia is thought to be

due to a poorly defined enzymatic defect in
which pharmacologic doses of pyridoxine overcome this defect and reverse the anemia.
8:
Metabolic inhibitors (antimetabolite drugs)
---i
[ Azathioprine
Purine inhibitors -------~[
6-Thioguanine
Pyrimidine inhibitors -------6-Azauridine
Thyrnidytale inhibitors-------5-Fluorouracil
DNA inhibitOl"S--------
1
MyelodyaplaaUc
syndromes
(MOO)
Inborn
errors of metabolism
------3
&Mercaplopurine
Hydroxyurea
Cytosine arabinoside
Severe Iron deficiency
lesch-Nyhan syndrome
Hereditary oroticaciduria
Enzyme deficiency ----------,
Fonniminotransferase deficiency
[ Methyltranslerase defICiency
Thiam;_.ne"""
Unexplained disorders
~
OJ Guglielmo's erytl'\foteukemia
Nonresponsive anemia
Pyridoxine-responsive
anemia
Chronic myelomonocytlc leukemia (CMMLl
Cecil Chapter
175
Harrison Chapter
110
HematoJOKk Disorders
Anemia. 137
POLYCYTHEMIA
II
Polycythemia is an increase in the absolute

number of circulating red blood cells, usually
indicated. by an elevated hematocrit. The hematocrit may be elevated without an absolute increase in
the number of red blood cells in conditions in which
plasma volume is decreased. Confirmation of a true
increase in red blood cell mass is made by measuring
the red blood cell mass with radioactive chromium
(SICr). Hematocrits in the range of 60% or greater
almost always represent true erythrocytosis, whereas
hematocrits in the 50% to 55% range may be due to
plasma volume contraction.
A normal red blood cell mass in the presence
of an elevated hematocrit can be due to a loss of
plasma volume, which may occur with diarrhea,
vomiting. sweating, or diuresis. GaisbOCk'ssyndrome, or
stress er;throcytosis, is seen in active, anxious persons
whose hematocrits are elevated. These patients usually
are male with a high frequency of smoking, obesity. and
hypertension. It is likely that the combined effects of
smoking, obesity. and hypertension are the source of
the red blood cell and volume changes that result in an
apparent erythrocytosis.
The definitive test for diagnosing the group of

diseases associated with secondary erythrocytosis is the arterial oxygen saturation test. The
O2 saturation must be interpreted with caution, however, because approximately 10% of patients with polyC)1:hemia vera (PCV) will also have reduced oxygen
saturation in the 88% to 92% range.
In diseases associated with hypoxia, increased

red blood cell mass is a compensatory response.
Via this mechanism, oxygen-canying capacity to
the tissues is increased. Hypoxia associated with pulmonary diseases manifested by ventilation, perfusion, or
diffusion defects can cause polycythemia. Prolonged periods at altitudes greater than 5<XlOft may also cause
polycythemia secondary to decreased oxygen saturation.
Erythropoietin levels may be increased in this setting,
but only until equilibrium is reestablished.
Congenital heart disease associated with right~

to-left shunting may produce erythrocytosis.
Trans-position of the great vessels, persistent
truncus arteriosus, ventricular septal defect with pulmonary hypertension. and tricuspid atresia are the most
common anomalies associated with right-to-Ieft intracardiac shunting.
Polycythemia
Mechanical factors may decrease pulmonary oxygenation and result in a secondary erythro~
C)1:osis.In the pickwickian syndrome, decreased
alveolar oxygenation is due to massive obesity causing
hypoventilation. Nonobese patients can also hypoventilate due to decreased respiratory drive secondary to a
decrease in carbon dioxide sensitivity in the respiratory
center of the brain stem. The decreased ventilatory
drive may be congenital. idiopathic. or a result of disease of the respiratory center such as vascular thrombosis, encephalitis. or bulbar poliomyelitis.
The partial pressure of oxygen at which the

saturation of hemoglobin is 50%, known as the
PliO.can be measured to detennine the affinity
of hemoglobin for oxygen. Increased oxygen affinity of
hemoglobin results in a reduced PliO.Abnonnal hemoglobins with increased affinity for oxygen cause tissue
hypoxia by failure to release adequate oxygen at the
tissue level. TIssue hypoxia leads to a secondary increase
in erythropoietin level and subsequent polycythemia.
Arterial P02 and O2 saturations are nonnal in this setting. At least 45 hemoglobin variants with increased
oxygen affinity have been found.
Methemoglobinemia occurs when the heme

iron is oxidized to methemoglobin and becomes
incapable of binding oxygen. Less than 1% methemoglobin is present in nonnal persons but can increase markedly with exposure to certain drugs or toxins. Hereditary methemoglobinemia is a mild disorder
caused by the presence of hemoglobin M or by a deSciency of methemoglobin reductase. Acquired methemoglobinemia can be severe and can be seen in patients
receiving nitrite or nitrate preparations, including so
dium nitrite, amyl nitrate, nitroglycerin, nitroprusside.
and silver nitrate. Other drugs capable of causing methemoglobinemia include sulfonamides. lidocaine aniline
dyes. phenacetin. and acetanilid .
Carboxyhemoglobinemia occurs with inhalation

of carbon monoxide in cigarette smoke or after
inhalation of carbon monoxide from other
sources. All smokers, and nonsmokers with unexplained
secondary erythrocytosis. should have their carboxyhemoglobin levels measured. Nonnally, nonsmokers have
less than 1% carboxyhemoglobin, and smokers' levels
range from 5% to 10%. Carbon monoxide replaces oxygen in the heme molecule and increases the heme
affinity for oxygen. Increased oxygen affinity by the
heme molecule results in tissue hypoxia and is the
source of the erythrocytosis.
1m
Sulfhemoglobinemia is due to the irreversible

oxidation of hemoglobin by certain drugs and
chemicals. The oxidized heme is incapable of
binding oxygen. The drugs most commonly causing this
fonn of altered hemoglobin are acetanilid, phenacetin,
and the sulfonamides. Sulfhemoglobinemia is uncom~
mon despite widespread use of these drugs.
III
Polycythemia may be due to the autonomous

production of erythropoietin by a neoplasm. A
remission of the polycythemia has been observed after the tumor has been resected and may recur
when the tumor recurs.
II
An increased erythropoietin Ie.vel has been

found in association with non-neoplastic renal
disorders such as polycystic kidney disease and
hydronephrosis. However, polyC)1:hemiais seen in fewer
than 2% of patients with non-neoplastic renal disease.
II
The polycythemia that accompanies endocrine

disorders-especially
endocrine tumors-is
thought to be secondary to an increase in erythropoietin levels. The erythrocytosis may be due to an
inappropriate secretion of erythropoietin by the tumor.
Hydrocortisone and other oorticosteroids can
cause a mild generalized stimulation of the
bone marrow. The polycythemia that occurs in
Cushing's disease is often accompanied by an increase
in the number of granulocytes and platelets as well.
II
The erythropoietic activity of androgens is wellknown. Androgens can be successful in treating

some fonns of refractory anemia and are probably the source of the polycythemia that accompanies
androgen therapy for other conditions.
II
The diagnosis of PCV is made primarily by

excluding other causes of increased red blood
cell mass, as well as utilizing the criteria for
diagnosis established by the Polycythemia Vera Study
Group as follows:
Polycythemia vera is diagnosed if 0), (2), and (3)
are present:
(1) Red blood cell volume >36 mllkg in males or
>32 mllkg in females
(2) Arterial O2 saturation >92%
(3) Srlenomegaly
I splenomegaly is absent, then two of the following can substitute for (3):
(a) Thrombocytosis >400,OOO/mm3
=.,= ~
Putmona'Y
AV
Cavernous
Putmona
'Y
1
Po/ycy1homIo
(Hd > Sol""
Seoondaoye<y1h-
Red cell mass

Inc oed
(m:> 36 mVKg)
(f:> 32 rnVKg)
-{
hemangioma
(COPD)
Luno """'"
Higholtitude
heart diseaSe
Alveolar hypoYentilation -{
R .... l
stu'lts
0besiIy _n
Nonobese
Essential
syndrome)
hypererythropoietinemla
_Variants
Abnonnal_
Inherited
~-{_
II Cattox)'heulogloblnemia
function
10~1elTI1a
Pheoctuomocytoma
Endocrine dtson:Iers
Cecil Chapter
174
Harrison Chapter
III
(b) Leukocytosis>
12,OOOImm3 (in the absence
of fever or infection)
_______
Adrenal adenoma
15
Androgen therapy
'_"o[ PoIycy'lhemia
17
These criteria are more specific than sensitive.
so that
(e) Leukocyte alkaline phosphatase> 100
early cases of PCV may not meet all of the criteria.

Over time a secondary cause of polycythemia may be
(d) Serum Bll >900 pglml or serum

protein >2200 pglml.
discovered,
criteria.
Bll-binding
:1
Ovarian tumor
14
or the disease
may progress
to meet these
vera
Idiopelt'Uc familial eryttvocytOSlS
II
Idiopathic familial erythrocytosis is a mre l.'ondition in which no hemoglobin

abnonnality
has
been found. A primary increase in erythropoietin has been found in some cases and may represent a
variant of PCV.
Hematololic Disorders Polycythemia
139
PANCYTOPENIA
Pancytopenia is defined as a pronounced reduction in the number of red blood cells, white
blood cells, and platelets in the peripheral circulation. Pancytopenia is not a separate disease entity
but describes a group of clinical Bndings that are secondary to a variety of diseases. Aplastic anemia is the
most common cause of pancytopenia.
with marrow fibrosis include carcinomas, SLE, rheumatoid arthritis, and chronic myelogenous leukemia.
Bone marrow biopsy (versus aspiration alone)

allows for differentiation among the disorders
resulting in peripheral pancytopenia. If a hypocellular marrow is discovered, the cells must be examined
carefully. Abnormal cells will be present if the marrow is
infiltrated with neoplasm or granulomas or if a metabolic
disorder or fibrosis is present. At times it may be difficult
to distinguish between aplastic anemia and leukemia.
Leukemia may be characteri7..edby striking ffiarTO\Y
hypocellularity and pancytopenia, making a diagnosis difficult.
The presence or absence of other features such as circulating immature cells and splenomegaly may suggest a
myerophthisic disorder rather than pure aplasia. Splenomegaly is absent in aplastic anemia.
Myelofibrosis may be primary (idiopathic) or

secondary to a variety of underlying inflammatory conditions. Diseases commonly associated
] 40 Hematologic Disorden Pancytopenia
Miliary tuberculosis can result in marrow hypocellularity by the replacement of marrow con
tents with granulomas. In some patients with
miliary tuberculosis, the marrow will be nonnocellular;
therefore, bone marrow biopsy material should be rou
tinely cultured for tuberculosis during the investigation
of pancytopenia. The presence of widespread tuberculosis with pancytopenia may be coincidental to an underly~
iog lymphoma, leukemia, or other blood dyscrasia.
If no abnonnal cells are identified in a hypocellular marrow biopsy specimen, PNH should be
excluded before a diagnosis of aplastic anemia
can be made. PNH is a rare, acquired hemolytic anemia
in which red blood cells, white blood cells, and platelets
are destroyed by a complement-mediated process. The
bone marrow may be profoundly hypocellular or may
be hyperplastic. Ham's test is very specific for diagnosis
of PNH but is too insensitive to detect all patients with
PNH. The sucrose hemolysis test is much more sensi
tive than Ham's test but is less specific, because it may
be positive in some patients with myeloproliferative
disorders, Both tests depend on the detection of hemolysis of the red blood cell that results from activation of
complement pathways. In addition, the urine should be
examined for the presence of hemosiderin if the diagnosis of PNH is suspected. If hemolysis is severe, the
sucrose hemolysis test may be negative and the presence of urine hemosiderin will be an important clue to
the diagnosis of PNH. A decreased level of leukocyte
alkaline phosphatase is a further clue to a diagnosis of
PNH but is also nonspecific.
Hypersplenism refers to the clinical disorder in
which the spleen produces hematologic ahnor
malities via an exaggeration of its nonnal activities, A hyperactive spleen can cause a peripheral pancytopenia by destroying normal circulating red blood
cells, white blood cells, and platelets, The pancytopenia
associated with sarcoidosis is usually a result of hypersplenism.
II
SLE is commonly associated with anemia,

thrombocytopenia, and leukopenia. The leukopenia is usually mild, The simultaneous depression of red blocxl cells, white bl<XXl cells. and platelets
is unusual, occurring in fewer than 5% of patients with
SLE.
va Iody sp Iastic. syndromes
Marrow infiltration
Hematologic malignancies
--I
Lymphoma
Leu~mia
Multiple myek>ma
Agnogenic myeloid metaplasia

______
--E
LNonhema,ologic
[
malignanctes [ cNarcioblasnoma
eur
toma
Idiopathic
Secondary
Myelopthisis
4E
TB
Sarcoid
Fungi
E
Perlorm sucrose
hemolysis test
and check for
urine hemosiderin
1
Pancytopenia
Negative hemolysis test

and no urine hemosiderin
Positive hemolysis
urine
hemosiderin present
test or
..
diseases
Lipid storage
Osteopetrosis
Marble
Aplastic anemIa --
bone disease
See page 128
Paroxysmal nocturnal hemogk>binuria

MyelodysplasUc syndromes
Perform
sucrose
Overwhelming infection/AIDS
5 hemolysis test
and check for
urine hemosiderin
6
Negative hemolysis test
and no urine hemosiderin
neffective hematopoiesls
7
Hypersplenism
Sarcoidosis
SLE
Croon's disease
Vitamin B12"'fo1ate deficiency
Akoholism
Cecil Chapter
160
Harrison Chapter
110
Hematolocic
Disorders
Pancytopenia
141
NEUTROPENIA
Neutropenia is defined as an absolute neutroI phil count (ANC) of less than 15OOlmm3.The
ANC is the product of the percentage of neutrophils and the total white blood cell count. Agranulocytosis refers to a severe neutropenia, with less than
500 cells per cubic miUimeter.
A thorough
history
may be the
most
helpful
"test" in the differential diagnosis of neutropenia. Drugs and viral infections are the most
common causes of acute neutropenia. The presence of
splenomegaly may direct investigation toward diagnosis
of diseases in which there is destruction of neutrophils.
II
Felty's syndrome is characterized by rheumatoid arthritis. splenomegaly. and neutropenia.

Splenomegaly may precede the neutropenia by
many years. Even after splencetomy, the neutropenia
may recur (see also No. 10, Splenomegaly).
Many viral, bacterial, and rickettsial diseases

result in neutropenia. Viral and rickettsial diseases include influenza, measles, chickenpox,
rubella, infectious hepatitis, HIV infection or AIDS,
yellow fever, dengue fever, sandfly fever, and Colorado
tick fever. [n viral infections, there is often a lymphopenia accompanying the neutropenia. Infectious mononucleosis may be accompanied by splenomegaly and neutropenia. Most bacterial infections are accompanied by
a granulocytosis. However, some bacterial infections
may be associated with neutropenia. Typhoid fever,
paratyphoid fever, tularemia, and occasionally brucellosis may be accompanied by a decrease in the number
of neutrophils. Neutropenia can also occur in patients
with overwhelming bacterial infection (septicemia), in
patients with disseminated tuberculosis, and in debilitated, infected patients. Neutropenia in these settings is
associated with a poor prognosis.
history should reveal the ingestion or exposure to those drugs, chemotherapies, or ionizing
radiation that may cause neutropenia. Some
142 Hematologic Disorders Neutropenia
agents consistently produce marrow suppression if given

in sufficient doses (dose-related), whereas other agents
produce leukopenia as an idiosyncratic reaction (see No.
5, Aplastic Anemia). Examples of the former include
ionizing radiation, benzene, nitrogen mustard, colchicine, the antimetabolites, and anthracyclines. Examples
of the latter include phenothiazines, anticonvulsants,
antithyroid drugs, sulfonamides, antihistamines, certain
antimicrobial agents such as chloramphenicol and sulfa
drugs, and tranquilizers.
Examination of the bone marrow is useful in
determining whether the neutropenia is due to
abnormal or decreased marrow production or
to increased peripheral destruction of neutrophils. Hypocellular marrow can be found with immune injury to
the white blood cells, drug-related marrow suppression
(see No.5), aplastic anemia, AIDS, viral infections,
mycobacteral infections, and hereditary neutropenias.
Normal or increased marrow cellularity can be associated with leukemia, lymphoma, megaloblastic anemia,
AIDS, myelodysplasia, hypersplenism, acute infection,
peripheral blood neutrophil injury, sequestration, or in
creased utilization.
If the number of neutrophils and neutrophil

precursors is increased in the marrow, the neu
tropenia may be due to abnormal marrow release of cells or to pseudoneutropenia. Pseudoneutropenia is caused by a shift of neutrophils from the
circulating pool to the marginal pool. The marginal
pool of neutrophils is the group of neutrophils that are
"marginated" along blood vessel walls and in the spleen.
Pseudoneutropenia is rare and should not be considered
until more common entities have been investigated.
II
Severe deficiencies of BIt and folate cause inef

:
fective hematopoiesis. The number of neutrophil precursors in the bone marrow is increased, but most of the precursors fail to mature. The
cells that do mature and are released from the marrow
are abnormally large and hypersegmented.
II
Familial neutropenia is an autosomal dominant

disorder. Many paticnts dic in carly childhood
as a result of infection.
1m
Cyclic neutropenia is a disorder in which neutropenia recurs every 20 to 30 days and lasts
for seveml days. During the neutropenic period,
the patient may develop stomatitis and infections. There
may be an accompanying monocytosis. The etiology is
unknown.
II
Chronic idiopathic neutropenia, or chronk be

nign neutro nia, is presulll<..>d10 be an ac
qui red disoC:S:r.Patients have neutrophil <"'OllOls
below lOOOlmm3but tend 10 have few infections. The
neutropenia is thought to be due either to the increased
peripheral destruction of cells or to a dcfecl in the
release of neutrophils from the marrow. Myelokathexis
refers to morphologically abnormal mature Ileutrophils
that are not released from the marrow. Lazy leukocyte
syndrome refers to apparently normal nculrophils with
defective marrow release.
II
Severe neutropenia is observcd in Kostmanll's

disease. The disease is thought to be recessively
transmitted. Mature neutrophils are rare 011
marrow examination, although neutrophil pr<.."Cursors
are
increased, indicating matumtion arrest or destruction of
cells while still in the bone marrow. Most palients die
of infection while they are young.
lEI
If the marrow examination is normal, an autoimmune mechanism for the neutropenia mllst
be considered. The detection of autoimmunc
neutropenia is difficult because of the lack of reliable
tests for antineutrophil antibodies. In a significant num
ber of patients, neutropenia will remain unexplained.
These patients must be followed closely and reevaluated
at frequent interv.us to establish a diagnosis.
Collagen-vascular disorders
:If Felty's
L
syndrome (RA)
Systemic lupus erythematosus (SLE)
Banti's syndrome
Hypersplenism
Gaucher's disease
Congestive splenomegaly (hepatic cirrhosis)
Infections
1
Neutropenia
2
(ANC < 1500/mm3 nonblacks
ANC < 14001mm3 blacks)
-r
t ~~~:;::
:;:~-I
A_H_~_s_t_iU_.S
Spirochetal
Protozoal
Immunosuppressiveagents
Cyt~toxic agents
Anti-inflammatory
agents
Antimalarials
Antibiotics
Chemical
and physical agents
Antihistamines
Drugs
Analgesics
Chemotherapy
Anticonvulsants
Ionizing radiation
Antithyroid agents
Diuretics
Cardiac drugs -{
Aplastk:
anemia
Myelodysplastic
(see p. 128)
Oral hypogtycemics
syndromes
Acute leukemia
Myelophthisic disorders
1
1
Pseudoneutropenia
Tumor
Granuloma
. Fibrosis
Severe malnutrition
Congenital disorders
AIOO
~
Idiopathic immune neutropenia
Cecil Chapter
Harrison Chapter
Antiarrhythmics
Antihypertensives
Familial neutropenia
10
11
12
Cyclic neutropenia
Myelokathexis
Chronic idiopathic neutropenia {Lazy I kocyt
~
e
Kostmann's neutropenIa
syndrome
Unexplained neutropenia
62
Hematoloalc Disorders
Neutropenia.
143
NEUTROPHILIA
Neutrophilia is defined as an absolute neutrophil count (ANC) of greater than 1O,0CI0 neutrophils per cubic millimeter. The ANC can be
determined by multiplying the total white blood cell
count by the percent neutrophils.
Leukocytosis (increased total white blcxxl cell

count) is a nannal response to many noxious
stimuli. Increases in the number of neutrophils
can be a physiologicresponse or can be an autonomous
abnormal proliferation of granulocytes. The history and
physical examination arc the most helpful in determining whether neutrophilia is physiologicor autonomous.
as well as fibrosarcomas and liposarcomas, have been

implicated in the production of a humoral neutrophiliainducing substance. Surgical e-xcisionof the bulk of
some tumors has been associated with the fall in the
neutrophil count, which lends further support to the
existence of a humoral neutrophil-stimulating substance.
A variety of drugs and loxios. including digitalis.
lead, mercury, and benzene, may result in neutrophilia. Lithium has been used therapeutically
to stimulate neutrophil production in the neutropenic
patient.
II
The administration or overproduction of corti

costeroids, as occurs in Cushing's disease,
causes a granulocytosis. The neutrophilia that
occurs with corticosteroid administration is due to an
increase in the release of granulocytes from the bone
marrow, as well as a decrease of clearance of granulo.
cytes from the circulating blood pool.
:
pseudoneutrorhilia refers to the state in which

the neutrophi count rises although there is no
increase in granulopoiesis. The apparent neutrophil increase results when the marginal granulocyte
pool quickly reenters the circulating granulocyte pool.
This granulocyte pool is made up of neutrophils that
are "marginated" along the sides of small blood vessels
and sequestered in the spleen. Stimuli such as epineph
rine, vigorous exercise, anesthe-o;ia,
paroxysmaltachycardia, and hypcrthennia can cause these cells to "demarginate" and join the pool of circulating granulocytes.
II
Neutrophilia following splenectomy is most

likely due to the addition to the circulating
granulocyte pool from the large marginal granulocyte pool that nonnally resides in the spleen (see
No.3).
Acute bacterial infection is the most common

cause of neutrophilia. Other organisms that may
cause neutrophilia include fungi, spirochetes,
viruses, and parasites.
1m
Elevated neutrophil counts without infection

are a frequent accompaniment to inflammation.
The granulocytosis that may occur with uremia
or gout is secondary to inflammatory conditions associated with severe azotemia and crystal deposition. Granulocytosis that accompanies ketoacidosis should arouse
suspicion of an underlying infection or inflammatory
condition that may have precipitated the ketosis. The
neutrophilia seen with the injection of various venoms
is probably related to the severity of tissue necrosis.
II
The granulocytosis that accompanies a variety

of malignant neoplasms may be due to several
mechanisms. Most commonly, neutrophilia occurs when a rapidly growing neoplasm outgrows its
blood supply and undergoes necrosis. In addition, some
tumors may produce a humoral substance that can cause
leukocytosis.Carcinomas of the breast, lung, and kidney,
144 Hematologic
Disorders
Neutrophilia
II
When the history and physical examination faiJ

to reveal a robable etiology for granulocytosis,
the possibitty of autonomous neutrophil production should be examined. Bone marrow examination
may reveal a primary hematologic disorder such as
chronic myelogenolls leukemia (CML). In an early
stage, CML may be difficult to diagnose without bone
marrow examination.
The mechanism for granulocytosis that is seen

with acute hemorrhage is unknown but is
thought to be due to several factors. With hemorrhage, there is evidence for a shift of neutrophils from
the marginal to the circulating pool, as well as an increase in the release of neutrophils from the bone marrow. In cases in which the hemorrhage is into a body
cavity and is painful, it is thought that the neutrophilia
is also due to the demargination of neutrophils resulting
from epinephrine and adrenocorticosteriod release.
Granulocytosis is often seen, perhaps as an

"overshoot" phenomenon, when the marrow is
recovering from agranulocytosis.The same phe.
nomenon is seen during treatment for megaloblastic
anemia.
II
Without directly i?vading the bone marrow,

solid tumors may cause neutrophilia by secre
ting neutrophil-stimulating growth factor. This
phenomenon is known as a paraneoplastic syndrome
(see No.6).
III
The differentiation of a leukemoid reaction

from a clonal myeloid neoplasm is an important,
yet often difficult task. A leukemoid blood picture is one in which there is a profound neutrophilia
that may suggest the diagnosis of leukemia, hut the
disease does not progress. A leukemoid reaction may
be secondary to multiple diseases, including acute and
chronic infections (pneumonia, meningitis, diphtheria,
tuberculosis), or due to toxins such as mercury poisoning; malignant disease, including bone metastases, mul
tiple myeloma, myelofibrosis, and Hodgkin's disease;
or severe hemorrhage. A leukemoid reaction can be
manifested in several ways: (1) a leukocytosisof unexpected magnitude w;th respect to the unde,lying disease; (2) immature or abnonnal cells in the blood regardless of the total number of white blood cells; or (3)
an abnormal number of immature or abnonnal cells in
the bone marrow.
A number of examinations may be used collectively
to aid in differentiating the leukemoid reaction from
clonal myeloid neoplasms, as well as distinguishing
among the neoplasms themselves. The Philadelphia
(Ph') chromosome. although not specific fm CML. is
present in approximately 90% of patients with CML.
PhI is also occasionally present in patients with idiopathic myelofibrosis, acute myeloid leukemia (AML),
and acute lymphoblastic leukemia (ALL). The chromosome is never present in patients with the leukemoid
reaction. Auer rods are a useful finding for distinguishing AML from the leukemoid reaction. These granules
are seen in AML and in the blast phase of CML.
Down's syndrome may be associated with a unique
leukemoid reaction in which the blood and bone marrow findings are indistinguishable from those of AML.
The leukemoid reaction appears to resolve spontaneously in these patients. It is unclear whether these
patients can truly be diagnosed with AML with longterm spontaneous remission or if the picture is consistent with a leukemoid reaction. The picture is confusing
because there is a high rate of ALL and AML in
Down's patients as well.
~
~:;::~zures
Eplnephnnelstress
3
Pseudoneuirophilia
Smoking
Ovulatlonlpregnancy
Infection
Inflammation
Physiologic
neutrophilia
------1
Extreme temperature
Familial coIcI urticana
----1
Rheumatoid
Metabolic
arthritis
---------[
Vasculitis
Diabetic ketoacidosis
Bums
Tissue necrosis
Uremla
Gout
Gangrene
Colitis
Myocardial
-i~:~Xin
Infarction
Neoplasms
ith'
Drugsltoxins
Heavy metals
Chemicals
[ Cushing's disease
Endocrine/metabolic
Neutrophilia
2
(ANC > 10,000 cellslmm3)
disorder [ Thyroid storm

Lactic acidosis
Hemolytic .nem,.
9
HematologIC abnormalities
Post-splenectomy
10
Hemorrhage
11
Recovery from agranulocytosIs
~12
ParaneoplastlC
MegaJoblastlC anemia WIth treatment
Pnmary hematologIC dIsorder
~4
16
13 Autonomous
neutrophilia
Chronic IdIOpathIC neutrophilia
~o:~~ep
Cecil Chapter
Harrison
Chapter
See above
syndromes
Leukemoid reactIOn
Polycythemia vera
InlectlOl"l
Toxins
-15
CarCInoma
Neoplasms
Severe hemorrhage
Down's syndrome
Acute myeloid leukemIa

Idlopath,c myelofibrosIs
ChronIC myeloid leukemia
172
62
See above
Hematololle Disorders Neutrophilia
145
NEUTROPHILIA
(Continued)
II
Examination of bone marrow that has been in

filtrated by carcinoma cells can present a diagnostic dilemma, because the cells cannot always
easily be distinguished from leukemic cells. Leukoer}1.hroblastosisis a condition in which a large number of
both mature and immature neutrophils appear in the
blood along 'N'itha large number of nucleated, abnormal
red blood cells. Metartatic cancer, Bbrosis, leukemia.
146 Hematoloalc Disorders Neutrophilia
and granulomas are responsible for bone marrow invasion, known as myelophthisis, and a leukoerythroblastic
reaction.
II
II
Breast and prostatic carcinomas are the two

most likely tumors to infiltrate the bone marrow
and result in a neutrophilia.
A nondiagnostic marrow examination presents

a diagnostic dilemma if other sources of neutrophilia have been excluded. There have been
rare reports of chronic idiopathic neutrophilia in' which

high neutrophil counts have been observed and have
persisted without discovery of the underlying cause. It
is unlikely that thorough history, physical exam, and
bone marrow exam would not reveal the SOtirce of
neutrophilia, but the patient without a clear diagnosis
at this point should be followed closely and reexamined
at intervals.
Pseudoneutrophll~
=::::
-1
Smoking
OYUlatiotv'pregnancy
Extreme temperature
Infection
lnftammation
:::~---1 1
---1
Familial
cdd urticaria
Vasculffis
TIssue necrosis
Physiologlc
_"ia
Colitis
----1
~=
.-.
Bums
Gangrene
Gout
u "rdtalinlarction
'",Neoplasms
Uthlum
Digoxin
OrugsIl:oxins
Endotoxin
Heavymeta!:s
ChemIcals
[ Cushing's disease
Neutrophilia
(ANe>
10,000 cellslmm3)
Endocrine/metabolic disorder --[
Thyroid storm
lactlc acidosis
HemolytIc anemia
1R
9
Hematologlc abnormalities
PostspIenec1omy
10
11
Hemorrhage
Recovery from agranulocytosis
12
paraneoplastlc
u-,"lobIastic
16
~~p
Cecil Chapter
Harrison Chapter
See above
Infection
syndromes
4leukemoid
Primary hematologic disorder
Chronic idiopathic neutrophilia
anem~ with treatment
reacOOn--
~
15
ToxIns
Neoplasms
pofycythemla vera
Severe hemorrtlage
Carcinoma
Down's syndrome
Acute ~
leukemia
IcOopalhlcmyelofobrosis
Chronic myeloid leukemia
172
62
See above
Hematolock Disorders
Neutrophilia
147
MONOCYTOSIS
Monocytosis
is an absolute
monocyte
count
above 7501mm3 and is associated with a variety
of hematologic and inflammatory processes. By
itself. monocytosis is not diagnostic of any particular
disease entity. Monocytosis is secondary to hematologic
diseases in about 50% of patients, collagenvascular
diseases in 10% of patients, and associated with malignancies in approxi mately 8% of patients. Because monocytes and neutrophils are thought to be derived from a
common progenitor cell, their regulation is closely related. Monocytosis is often accompanied
by a neutro-
philia.
2
clinical
A CBe may be abnonnal in both hematologic

diseases and inflammatory
processes. The nature of the abnonnality and the constellation of
6ndings will determine
the need for a bone
Monocytosis
marrow examination.
The CBe abnormalities
may be
more profound with hematologic
disorders and more
subtle or absent with inAammatory conditions.
Monocytosis
has been observed
in approxi
mately 25% of patients with Hodgkin's lymphoma.
Associated abnormalities
of the CBC may provide clues to diagnosis. Because monocytosis is
due most commonly to a hematologic
abnormality, subsequent
bone marrow aspiration and biopsy
may be diagnostic. Monocytosis may be marked in pa.
tients with CML. Monocytosis is common in preleuke.
mia.
A monocytosis often accompanies

granulomatous diseases, because monocytes are the source
of tissue macrophages. Tuberculosis is the most
common infectious cause of granulomas
and may be
accompanied
by a monocytosis. Approximately 20% of
patients with subacute bacterial endocarditis (SBE) have
an associated monocytosis.
Neutropenia
is often accompanied. by monocytosis. The term leukopenic infectious monocytosis has been used. to refer to the condition
of agranulocytosis with accompanying
monocytosis. Reports have indicated that an increased number of monocytes heralds recovery from agranulocytosis.
II
II
A variety of GI disorders have been associated

with monocytosis including the granulomatous
disorder, regional enteritis (see No.6).
Chronic high-dose corticosteroid administration

leads not only to neutrophilia
but to a monocytosis as well.
Myeloid metaplasia
Monocyllc
l..e1Jkemia------------_
Multiple myeloma
Lymphocytic
Granulocytic
Preleukemla
'~Ag""'UIocy1OS~
Hematologic disorders
Neutropenia------------
Cyclic neutropenia
Chromc granulocytopema
of chi5dhood
Familial neutropenia
___________
.~[ Hodgkin" ~mp/1oma

Non-Hodgkin s lymphoma
Malignant histiocytosis
Polycythemia vera
Hemolytic anemia
Idiopathic thrombocytopenic
purpura (lTP)
Post-splenectomy
Hypochromic
anemias
~ Subacute bactenal endocan!ill. (SBE)

Tuberculosis
Infection
Syphilis
Mononucleosis
Sarcoidosis
-1
Rheumatoid arthritis
Systemic lupus erythematosus
Autoimmune disease
Temporal arteritis
Polyarteritis nocIosa
Polymyositis
Malignancy
sPrue
GI disorders
NontrOptCaI
[
Inflammatory bowel disease --{
Corticosteroid administration
Cecil Chapter
Harrison Chapter
~[TropicaJ
Ulcerative colitis
Regional enteritis
172
62
Hematologic
Disorders
Monocytosis
149
LYMPHOCYTOSIS
II
The nonnal lymphocyte count varies with age.

but in the adult lymphocytosis is defined as an
absolute lymphocyte count of greater than 4000
lymphocytes per cubic millimeter. Absolute lymphocytosis is much less common than the relative lymphocytosis
that may accompany granulocytopenia
and many viral
infections.
Lymphocytosis
is due most commonly
to
acute viral infection and rarely bacterial infection.
II
Another major clue in the differential diagnosis

of lymphocytosis is the presence of atypicallymphocytes on examination of the blood smear. As
many as 5% to 10% of lymphocytes may appear atypical,
or pleomorphic, on the nonnal blood smear. A marked
increase in atypical lymphocytes
is associated with
ISO Hematologic Disorders Lymphocytosis
mononucleosis
(regardless
tivity, infectious hepatitis,
sis.
II
of etiology), drug hypersensitransfusion, and toxoplasmo-
Infectious mononucleosis
is a common cause of
lymphocytosis
in teenagers and young adults.
Symptoms may be mild or severe and include
fever, fatigue. pharyngitis,
lymphadenopathy,
and lymphocytosis. Splenomegaly may be present in as many as
40% of patients with infectious mononucleosis
and may
even lead to splenic rupture.
Mononucleosis
can be
caused by several different viruses, the most common
of which is Epstein-Barr
virus (EBV). Other organisms
implicated
in infectious
mononucleosis
include cytomegalovirus (CMV), herpes simplex type 2, rubella, Toxoplasma gondii, and adenovirus. Only EBV will yield a
positive heterophile antibody test, although 5% of EBV-
induced mononucloesis
negative.
may be heterophile
antibody-
The post-transfusion
syndrome consists of atypical lymphocytosis in association with fever and
splenomegaly. CMV has been implicated as the
cause of this ~yndrome and appears to be transmitted
via the leukocytes in the donor blood.
With the exception of perhlssis, acute haetcrial

infections rarely C'duse lymphocytosis. Acute infectious lymphocytosis
is another acute infectious cause of lymphocytosis in which no atypical lymphocytes are present, helping distinguish this entity from
infectious mononucleosis.
Acute infectious lymphocytosis is largely asynlptomatic, occurs in children and young
adults, and is thought to be virally transmitted.
lymphadenopathy
-----rr
Chronic lymphocytic leukemia (eLL)

lymphoma
Infection
ON
"
enomega'l
--[
Chronic lymphocytic leukemia (ell)

Hairy ceilleukemi8
(HeLl
Infectious mononucleoSIS (EBV)
Lymphocyto.l.
(>4000 tymphslmm3)
Infectious mononucleosIs (CMV)

Phenytoin
Drug hypersensitIVity ----~
p-Ammosallcyhc
acid
Infectious hepatitis
Post-transfusion
syndrome (CMV)
-1

Acute lymphocytic leukemia (All)
Hematopoieticdisorders
MultIplemy.aloma
Non-HocIgku,.s lymphoma
Hairy cell leukemia (HeL)
---i
Acute inlectious lymphocytosis
Acut8LP9rtUSSIS
Inlection
Cecil Chapter"
Harrison Chapter
Viral
Chronic
--f
Tuberculosis
Secondary syphilis
Brucellosis
172
62
Lymphocytosis.
151
EOSINOPHILIA
Eosinophilia is defined as an absolute eosino-
II
phil count greater than 350 eosinophils per cubic millimeter of blood. The absolute eosinophil
count is determined
by multiplying the total white blood
cell count by the percenl eosinophils. The most oommon causes of eosinophilia
are allergic reactions and
parasitic diseases. Hypereosinophilic
syndromes are accompanied
by the highest eosinophil counts, which
helps distinguish these syndromes from other disorders.
Most causes of eosinophilia can be uncovered with a
thorough history and physical exam, with further diagnostic tests as indicated to confirm likely etiology.
Normal range of eosinophils in the peripheral
blood is up to 350 cells per cubic millimeter of
blood. Eosinophilia is classified as mild, moderate, or severe, depending on the number of eosinophils
present. Mild eosinophilia is arbitrarily defined as 35J
to lS00/mm3; moderate eosiniphilia
as )500 to 5000/
mm3; and severe as greater than SOOO/mm3 Eosinophil
counts are often highest with parasitic infections, but
there is a great deal of overlap among the various causes
of eosinophilia with respect to the degree of elevation
of the eosinophils. The algorithm reveals general guidelines to distinguish
between
the categories,
but the
diagnosis rests with the clinical manifestations
of a particular disease rather than the absolute number of eosinophils.
Drug allergy is perhaps

the most common
source of eosinophilia.
Drugs commonly causing eosinophilia include erythromycin
estolate,
sulfonamicles, chlorpropamide,
para-aminosalicylic
acid,
imipramine, nitrofurantoin,
procarbazine,
gold, iodides,
and methotrexate.
A contaminant
found in L-tryptophan
preparations
was found, in 1989, to be responsible for
the eosinophilia-myalgia
syndrome characterized
by eosinophilia, myalgia, fasciitis, and peripheral neuropathy.
Asthma is commonly accompanied
hy an eosinophilia,
ranging from 400 to lOOO/mm3. However, if asthma is
exacerbated by acute bacterial infection or complicated
by infection, the eosinophilia will be absent. A charac
teristic of acute bacterial infection is eosinopenia,
and
eosinophilia has been described as a favorable prognosis
in the resolution of acute infections.
Addison's disease may be accompanied

by a
mild eosinophilia.
Of interest, the eosinophil
count falls with the administration
of corticosteroids in any patient.
Eosinophilia
Eosinophilia has been reported in up to 40% of

patients undergoing
irradiation for carcinoma,
most commonly in patients with intraabdominal neoplasms.
A significant proportion
of immunodeficiency
states are accompanied
by eosinophilia. These
disorders
include Wiskott-Aldrich
syndrome,
hyper.IgE syndrome, Job's syndrome, and selective IgA
deficiency. These syndromes
may include cutaneous
manifestations,
primarily eczema.
Eosinophilia has been reported to accompany a

wide variety of neoplasms. In general, eosinophilia is present when there is wide dissemination of the tumor, or if tumor necrosis is present.
Eosinophilia
may accompany
Hodgkin's
lymphoma,
non-Hodgkin's
lymphoma, or T-cell lymphomas (mycosis fungoides). Carcinomas of mucin.secreting
epithelial
cell origin are most likely to be accompanied
by eosinophilia. Examples of these tumors include carcinoma
of the colon, pancreas, lung, and cervix. Leukemias
associated with eosinophilia include T-cell leukemia (Sezary syndrome),
acute lymphoblastic
leukemia,
and
CML. In CML, the massive increase in the number of
mature white blood cells may increase the absolute
number of eosinaphils,
but the percentage
of eosino
phils may not be increased.
Collagen-vascular
disease is sometimes accompanied by an increase in the number of eosinophils. Eosinophilia
occurs in 10% to 12% of
patients with rheumatoid
arthritis and tends to occur
primarily in patients with long-standing
severe disease.
Polyarleritis
nodosa (PAN) had been reported to be
accompanied
by eosinophilia,
but it appears that the
eosinophilia is seen in a distinct subset of patients with
PAN. TIle subset of patients with allergic granulomatosis, or Churg-Strauss
syndrome, exhibit asthma, PAN,
and hypereosinophilia.
Wegener's granulomatosis
has
also been reported to be accompanied
by hypcreosinophilia.
II
Various skin disorders

are accompanied
by
marked eosinophilia, most consistently urticarial
pemphigoid and pemphigus vulgaris. Other skin
diseases that may be accompanied
by eosinophilia include exfoliative dermatitis,
pityriasis rosea, leprosy,
granuloma
faciale, ichthyosis,
pruritus
secondary
to
jaundice, lymphomatoid papulosis, eosinophilic cellulitis
(Wells' syndrome), and eosinophilic fasciitis (Shulman's
syndrome).
Erythema multiforme and erythema nodosum are reaction patterns on the skin that may be
secondary to a variety of drugs, viral infections, and
even coccidioidomycosis
(erythema nodosum). Dennatitis herpetiformis
has often been reported to be accompanied by eosinophilia, but the eosinophilia is mild and
only occasionally present.
1m
A case for hereditary eosinophilia can be made

if (I) there is a significant level of eosinophilia;
(2) there is familial incidence with more than
one generation being affected; and (3) other recognized
causes of eosinophilia are absent. Hereditary hypereosinophilia is rare. Idiopathic hypereosinophilia
is a diagnosis of exclusion and must be distinguished
from the
idiopathic hypereosinophilic
syndrome. in the latter, a
marked elevation of eosinophils is accompanied
by organ dysfunction, presumably due to direct deleterious
effects of the eosinophil.
~arked e~~i":ophil~a usually a~mpanies

invasIve parasItic mfectlons and a vanety of primary
skin disorders (see No.9). Despite high parasite
loads, the eosinophil count rarely exceeds 25,000 eosinophils per cubic millimeter and is probably the highest
with trichinosis. Even if the eosinophil count is markedly elevated (i.e., >50,OOOImm3), skin diseases, parasitic infections, neoplasms, and collagen-vascular disease
must still be excluded prior to the consideration
of
the hypereosinophilic
syndrome. The hypereosinophilic
syndrome is a diagnosis of exclusion (see No. 13).
II
Dramatic and prolonged eosinophilia accompanies metazoan parasitic infections.

Protozoan
parasitic infections are less likely to be accompanied by a significant eosinophilia unless the parasite
load is high and tissue invasion occurs. Tropical eosinophilia had been classified as a pulmonary eosinophilia,
although now it is recogni7..ed to be due to filarial infestation.
The criteria for defining the idiopathic hypereosinophilic syndrome are as follows; (I) persistent eosinophilia
of at least 1500 eosinophils
per cubic millimeter for at least 6 months; (2) lack of
evidence
for parasitic,
allergic, or other recognized
causes of eosinophilia; and (3) signs and symptoms of
unexplained
organ system dysfunction
related to the
eosinophilia.
It should be stressed that organ system
dysfunction
may also be seen in patients \vith other
forms of eosinophilia.
Eosinophilia-myalgiasyndrome
DNgS --Allergic
:::i
Allergic rhinitis
[ Bronchopulmonary
Addison's disease
Asthma------
aspergillosis
Irradiation
Urticaria
Churg-Strauss syndrome
Neoplasms
leukemias
:::.-!=
Oysproteinemias
Collagen-vascular
cisease
-{
1
Eosinophilia
(>350
Kimura's di=::-{ase
Allergic granulomatous
angiitis (Churg--Strausssyndrome)
Vasculitis
Hypervisc::osity
Rheumatoidarthritis
Wegener's granulomatosis
vasculitis
Eoslnophiticlasciitls
eosImm')
EosinophilicgaslrCleflteritis
GI disease -{
Inflammatorybowel disease
Eosinophilicperitonitis
Ef)'thema nodosum
Erythema multiforme
Scabies
Urticar\a
Skin disorders
Idiopathiceosinophilia
Hereditary eosinophilia
11
Bullous pemphigoid
Pemphigusvulgaris
Mycoses fungoidesl8ezary's syndrome
Herpes gestalonis
VtSCerallarva
Pruritic urticarial papules and plaques of

pregnancy (PUPP)
mign>ns
Isospora
P
itiv
andP
12 Parasitic {
infections
Protozoa
belli
Dientamoeba
fragllis
Helminths
Toxocsrs
Echinococcus
StrongyfokJes
"""'' ' ' '
--qs
13~ Idiopathic hypereosinophilic
14
CIleckCXA
T""'*'<>sis
Pulmonary infiltrates
Allergic
with eomophilia
Irradiation 16
Eosinophilic leukemia
Neoplasms
Fungal disease
Harrison Chapter
172
AJ\ergicgranulomatosis
----L Coccidioidomycosis
Collagen-vasculardisease
Cecil Chapter
LOftier'ssyndrome
Eoslnoptlilic pneumonia
Aspergillosis
GI disease
62
Eosinophilia. 153
EOSINOPHILIA
(Continued)
III
A
Pulmonary
infiltrates with eosinophilia
(PIE)
refers to a group of disorders characterized
by
peripheral eosinophilia and pulmonary infiltrates. The term does not imply etiology. and overlap is
great. For example, tropical eosinophilia, which is now

known to be due to filariae. has been classified as a
pulmonary eosinophilia because the clinical features include pulmonary infiltrates and peripheral eosinophilia.
The pulmonary eosinophilias comprise a diverse group
of disorders and are usually secondary to other underlying abnormalities,
including fungal infections, parasitic
infections, neoplasms, and drugs. The pulmonary eosinophilias also include umer's syndrome, prolonged pul.
154 Hematoloa1c Disorders Eosinophilia
monary eosinophilia,
asthma,
pulmonary
and allergic granulomatosis
eosinophilia
with
(Churg-Strauss).
tomer's syndrome is distinguished

from other
pulmonary eosinophilias and the idiopathic hypereosinophilic
syndrome
on the basis of a
short, benign clinical course. It is characterized
by fleeting pulmonary infiltrates and eosinophilia, with resolution within 3 weeks.
II
TIle diagnostic criteria for eosinophilic

leuke
mia include the following: (1) pronounced,
per
sistent eosinophilia
associated with immature
forms either in the blood or bone marrow; (2) greater
than 5% blast forms in the bone marrow; (3) tissue

infiltration by immature eosinophils; and (4) an acute
clinical course of several months accompanied
by anemia, thrombocytopenia,
susceptibility
to infections, or
hemorrhage.
Of note, a marked elevation of serum vitamin Blt has been found in patients with eosinophilic
leukemia but is also seen in patients with the idiopathic
hypereosinophilic
syndrome.
Allergic
=-f
Drugs ---
Eosinophilia-myalgia syndrome
Allergic rhinitis
Asltlma -----~
Addison's disease
Irradiation
Urticaria
ImmUnodefi=1Cncy
states
lymphomas
Carcinomas
Neoplasms
Leukemias
Bronchopulmonary
aspergillosis
Churg-Slrauss syndrome
Dysprotelnemlas
Mild/moderate
elevation
(905 35O-5OOOImm3)
Kimura's dl~ase
8
1
Eosinophilia
(>350 eostmm3)
Collagen-vascular
-{
dISease
Allergic granulomatous
angIItis (Churg-Slrauss syndrome)
Vasculitis
HypeMSCOSity
Rheumatoid arthrttls
vasculitis
Wegener's granulomatOSIS
EosinophilICfasclltis
Eosinophilic gastroenteritis
GI disease
-{
Innammatory bowel disease

Eosinophilic peritonitis
Erythema nodosum
Erythema multifonTl8
Scabies
,.
Unlca""
Skin diSOf'ders
Bullous pemphigoid
Idiopathic eoslnophllia
Pemptllgus vulgaris
Hereditary eosinophilia
Mycoses fungoidestSe:zary's syndrome
11
Herpes gestatonis
Visceral larva
migrans
Pruritic urticarial papules and plaques of

pregnancy (PUPP)
Skin disorders
(See above)
Check stool
f()(OandPx3
Trichinosis
'sospora
Positive
and P
12
Parasitic
infections
{ Protozoa. {
belli
Toxocara
Dientamoeba
fragllis
Echinococcus
Helminths
13!
14
Allergic
Irradiation
16
Neoptasms
Cecil Chapter'
172
Strongyloides
Idiopathic hypereosinophilic
syndrome
~5
lOftier's syndrome
Pulmonary infiltrates
Eosinophilic pneumonia
with eosinophilia
Allergic granulomatosis
Eosinophilic leukemia
Fungal disease-----
Collagen-vascular disease
~
Aspergillosis
Gl disease
Hamson
Chapter'
62
Hematologic Olsorden
Eosinophilia
155
THROMBOCYTOSIS
II
Thrombocytosis
is defined as a platelet count
greater than 4OO,OOO/mm3 of blood. Thrombocytosis can occur in three forms: (I) autonomous or primary thrombocytosis,
also known as throm
bocythemia; (2) a transitory or physiologic elevation of
platelets; and (3) secondary or reactive thrombocytosis.
An increase in the number of platelets can translate
clinically into a tendency toward bleeding or thrombosis, or the patient may remain asymptomatic.
A number
of other laboratory
abnormalities
may accompany
a
marked increase in the number of platelets. These abnormalities

include pseudohyperkalemia
(see No. I,
Hyperkalemia),
as well as elevated levels of acid phosphatase, zinc, uric acid, phosphorous, and lactacte dehy-
drogenase (LDH).
Primary thrombocytosis.
or thrombocythemia,
is a diagnosis of exclusion. Thrombocythemia
is
diagnosed when there is a marked increase in
3
the platelet count, usually exceeding 1 X 1()8/mm , and
no other associated
disease is present.
The platelet
count may be elevated for months or for years. The
white blood cell count is increased
in over 90% of
patients with thrombocythemia,
but is usually normal in
patients with secondary thrombocytosis.
Splenomegaly,
usually absent in reactive thrombocytosis,
is found in up
to 80% of patients with thrombocythemia.
Bone marrow
examination will reveal a marked increase in the number
of megakaryocytes.
There are five diagnostic criteria
for essential thrombocythemia
that help distinguish this
disorder from PCV and myeloid malignancies
such as
Thrombocytosis
CML, (1) a platelet count greater than 6x W'IILI persisting without an indentifiable
underlying cause; (2) a
normal total red blood cell mass; (3) iron present in the
bone marrow or response to oral iron therapy; (4) an
absent collagen fibrosis on bone marrow biopsy; (5) an
absent Philadelphia
chromosome;
and (6) absence of
conditions associated with secondary thrombocytosis.
Transitory thrombocytosis
is due to the mobili
zation of performed
platelets, not to a true
increase in platelet production. Platelets are re
leased from a pool thought to be stored in the lung
vasculature
and spleen. Transitory thrombocytosis
oc
curs most frequently following exercise, with stress, and
with epinephrine
release or injection.
An elevated platelet count is usually an isolated

abnormality
in transitory
thrombocytosis
and
the remainder of the CBC is normal. An abnor
mal CBC would indicate that thrombocytosis
is related
to an underlying disorder, and the abnormality would be
dependent
upon the nature of the underlying disease.
Reactive thrombocytosis
is due to a true in
crease in platelet production. The platelet count
rarely exceeds IOS/mmJ in secondary thrombocytosis. Reactive thrombocytosis
is secondary to a variety
of inflammatory
and infectious diseases, although the
mechanism responsible for stimulating platelet produc.
tion is usually unknown. The platelet count may return
to normal levels if the underlying
disorder
can be
treated. I f other oomponents
of the blood count are
abnormal, the thrombocytosis

may be secondary to an
associated hematologic abnonnality such as anemia or
JXllycythemia vera. Plasma fibrinogen level is useful to
help distinguish
between myeloproliferative
disorders
(MPD) and reactive thrombocytosis due to malignancy

and inflammatory and infectious diseases. Plasma fibrin
ogen is an acute phase reactant and will be elevated with
reactive thrombocytosis,
usually to levels of greater than
5 gIL, but will usually remain low in MPD. If the histol)'.

physical examination, and blexxl examination do not provide enough information to make a diagnosis, a bone
marrow examination should be performed. Bone marrow
examination may reveal leukemia or myelofibrosis.
Splenectomy
may result in platelet oounts as
high as l()6/mmJ of blexxl. Increased numbers
of platelets can be seen within the first few days
after splenectomy
but will return to normal within
weeks to months postoperatively.
Vincristine may interfere with platelet regula

tion of thrombopoiesis
and specifically stimulate
platelet production, resulting in thrombocytosis.
II
One to 2 weeks after the withdrawal of a drug

causing thrombocytopenia,
such as methotrex
ate or alcohol, a rebound thrombocytosis
can
occur. A rebound
thrombocytosis
has also been obselVed once therapy has begun for vitamin Bit defi
ciency. Thrombocytosis
has been observed, perhaps as
a "rebound" phenomenon,
after prednisone therapy for
idiopathic thrombocytopenic
purpura.
:
Primary thrombocytosis ---
Essential thrombocythemia
Childbirth
3
T<llnsitO<y --{
thrombocytosis
(physioklgic)
Exerase
Stress
Epinephrine
Leukemla (CML)
Multiple myeM>ffi8
Myeloproliferative
-{
disorders
Myelofibrosis
Polycythemia rubra vera
Postoperative
-4
Splenectomy
Stress
Ca<cinoma
Malignancy
Lymphoma
Acutehemonllage
Iron deficiency anem~'
Osteomyelitis
Hemolytic anemia
Tuberculosis
Infectious disease
Acute rheumatic fever
7 [ Vincristine
Drugs----
Inflammatory
Bacterial infections
Post drug
_
Subacute bacterial
endo", ditls (SSE)
Cirrhosis
Sarcoidosis
Ulcerative colitis
Regional enteritis
Cecil Chapter
174
Harrison Chapter
III
Polyarteritis nodosa (PAN)

Temporal arteritis
Wegener's granulomatosls
Hematoloalc
Disorders.
Thrombocytosis
157
THROMBOCYTOPENIA
The normal platelet
count is 150,000 to
400,OOOImm3, usually determined

by automated
equipment. An estimate of the platelet count
can be detennined.
however. by examination
of the
peripheral blood smear. \\lith a nannal platelet count,
more than 10 platelets should be visible in each oil
immersion
field. Thrombocytopenia
is defined as a
platelet count below lSO.<XXVmm3. Spontaneous
bleed
iog is uncommon with platelet counts greater than
40,0<X>but is often severe when the platelet count falls
below lO,OOOImm3,
Once
thrombocytopenia
is confinned.
a com-
plete history and physical examination will supply the greatest amount of infonnation to discriminate among the diagnostic possibilities.
In every
158 Hematoloak
Olsorden Thrombocytopenia
adult patient, a drug. related etiology must be considered and an extensive drug history obtained. History of
illnesses for which cytotoxic agents and ionizing radiation have been used must be known. A history of recent
transfusion,
blood contact with extracorporeal
equipment, or recent hemorrhage with massive transfusion is
also important.
Splenomegaly
and petechiae
are the
most useful physical findings.
II
II
Examination of the peripheral blood smear will

help to diagnose pseudothrombocytopenia
by
demonstrating
platelet aggregations
or giant
platelets that are not counted by automated equipment.
Defective maturation of megakaryocytes occurs

with megaloblastic anemia (vitamin BIt or folate
deficiency)
as well as with severe iron defi-
ciency. Bone marrow examinalion may reveal a nonnal

number of megakaryocytes,
but they can be decreased
or absent in severe cases.
The administration
of cytotoxic agents is a COmmon cause of marrow injury leading 10 Ihrombocytopenia.
Other drugs thai can cause marrow injury resulting in thrombocytopenia
include gold,
sulfonamides,
ethanol, thiazides, and eslrogens.
The megakaryocyte is often a site for viral repli.

cation with subse<luent decrease in megakaryocyte maturation. Viral infe<.1ions associated with
thrombocytopenia
include measles (including measles
vaccination), inAuenza, rubella, mononucleosis.
dengue
fever, Thai hemorrhagic fever, IIIV infection, and A IDS.
~
Pseudothrombocytopenia
PlateleVgranulocyte
rosettes
Platelet agglutinins
Giant
megakaryocytes
Defective maturation
------r
---.IB12deficiency
Folate deficiency
',on def~;ency-i
Drugs
Chemicals
Injury
Marrow
Ionizing radiation
Infection
Decreased platelet
production
Congen".,
1
Thrornbocytopenl8
150,000
p1ateletslmfTl3)
Marrow failure
-{
Acquired
Decreased thrombopoiesis
Decreased number
megakaryocytes
Marrow infiltration
---t
Decreased number of
platelets on smear
Thrombopoietin
Mega~lastic
Ineffective
thrombopoiesis
-{
Amegakaryocytic
-E
Megakaryocytic
-{
anemia
anemia
Aplastic anemia
Cyclic
of
anemias
Fanconi's anemia
-{
thrombocytopenia
Myelofibrosis
Lymphomalleukemia
Carcinoma
(metastatic)
deficiency
01 Guglielmo's Syndrome
Myelodysplastic
syndromes(MDS)
Autosomal dominant thrombocytopenia
~~:~i
--
MayHeggJin anomaly
WiskottAldrich
syndrome
Normal or increased
number 01 megakaryocytes
Cecil Chapter
Harrison
Chapter
184
60
Hematol0llc Disorders
Thrombocytopenia.
159
THROMBOCYTOPENIA
(Continued)
I n conditions associated with hypersplenism

there can be splenic sequestration of platelets
and decreased platelets in the peripheral circulation. Normally 70% of platelets are circulating and
30% are in the spleen. If splenic enlargement occurs.
the balance may be altered so that up to 80% of the
platelets are stored in the spleen, with marked reduction
in the number of circulating platelets. Platelets are
stored but not destroyed by an enlarged spleen. The
sequestration of platefets secondary to hypothermia is
thought to be due to.rlatelet aggregation. The platelet
count returns to norm as body temperature normalizes.
In immune thrombocytopenia, antibodies cause

platelet destruction or premature sequestration
and removal from the circulation by the spleen
and reticuloendothelial system. Immune destruction of
the platelets may be accompanied by immune destruction of red blood cells as well. Examining the blood
smear for evidence of hemolysis is most useful in the
differential diagnosis of the immune thrombocytopenias. In isoimmune neonatal thrombocytopenia, maternal
antibodies are directed. against the platelet antigen (PLA
1) on the platelet surface. These antibodies are passed
transplacentally to destroy fetal PLA I-<x>ntainingplate
lets. This disorder is very rare because 98% of the
population have platelets with PLA 1 on their surface.
Immune thrombocytopenia caused by drugs is

in some cases due to the drug acting as a hapten, binding to a plasma protein to form a
primary antigen. The resultant immune complexes have
a high affinity for the platelet membrane and are responsible for platelet destruction. The drugs most commonly implicated in this form of thrombocytopenia
160 Hematoloeic
Olsorden
Thrombocytopenia
include quinidine, quinine, and sulfonamides. Antilymphocyte globulin (ALG) causes thrombocytopenia because of its reactivity with platelet surface antigens. The
severe thrombocytopenia that is sometimes seen with
heparin therapy is due to heparin-induced antiplatelet
antibodies.
III
Thrombocytopenia can occur in many autoim mune diseases. The thrombocytopenia accompanying anaphylaxis is thought to be due to
immune complexes binding with platelets. The platelets
are then cleared from the circulation by the spleen.
Autoimmune disorders associated with platelet antibodies and thrombocytopenia include rheumatoid arthritis,
Graves' disease, Hashimoto's thyroiditis, myasthenia gra
vis, and SLE. Lymphoreticular disorders and infections
are also associated with thrombocytopenia, although the
evidence for antiplatelet antibodies is less certain. Some
lymphoreticular disorders associated with thrombocytopenia include tuberculosis, CLL, some lymphomas, sarcoidosis, and Hodgkin's disease. An important member
of the group of immune thrombocytopenias is idiopathic
thrombocytopenic purpura (rTP). ITP is not accompanied by hemolysis. Lack of hemolysis helps distinguish
this disorder from thrombotic thrombocytopenic pur
purn (TIP) (see No. 14). Post-transfusion thrombocytopenia occurs in some patients who are PLA I-negative
(see No.8). Antibodies to PLA 1 are formed by the
transfused patient and are thought to result in the formation of immune complexes that aggregate on the
platelet surface, resulting in platelet destruction .
4
II
Washout thrombocytopenia occurs when plate

lets are lost by massive hemorrhage. Platelet
loss with extmcorporeal devices is due to sequestration and consumption of platelets in the blood
pump and tubing, as can occur with cardiopulmonary
bypass.
4
II
Drugs cause a decrease in platelets by immune

mechanisms (see No.9) or by direct toxicity of
the drug to platelets. Ristocetin and heparin
cause a decrease in the number of circulating platelets
by promoting platelet aggregation.
II
Evans' syndrome is a disease in which autoantibodies are directed against the red blood cell
and the platelet. Evans' syndrome is a Coombs'positive hemolytic anemia, which win distinguish Evans'
syndrome from ITP. SLE is often accompanied by
thrombocytopenia. Destruction of platelets in SLE is
due to antiplatelet antibodies.
III
The hemolytic-uremic syndrome occurs primarily in infancy and may be a variant of TIP. This
syndrome is characterized by hemolytic anemia,
thrombocytopenia, and acute renal failure. In contrast
to TIP, neurologic dysfunction is rare.
;,
II
In DIC, thrombocytopenia is thought to be

due to platelet consum tion. In DIC, thrombin
aggregates platelets ana reduces the circulating
platelet count. An increased amount of platelet associ
ated IgC is found in greater than 50% of thrombocytopenic patients with DIC, however, such that platelet
destruction may be partially immune-mediated.
4
II
TIP is characterized by the triad of thrombocytopenia, hemolytic anemia, and neurologic

changes, TIP is usually accompanied by fever
and renal failure. The etiology is unknown, but the
thrombocytopenia is due to consumption by diffuse
thrombosis. TIP has been considered the prototype
of the nonimmunologic causes of thrombocytopenia,
although an immunologic mechanism may be involved
in its etiology.
Hereditary thrombocytopenia
8p1e
.
SequestratiOn
__
Hypothermic anesthesia
-{
Venous stasis
Bum'
Thrombocytopenia
Alloantibodies --{
8
Immune
--{
Drug,
-10 [Autoimmune
Autoantibodies
due to maternal ITP
lsoimmune neonatal thrombocy'lopenia
diseases
idiopathic thrombocytopenic
purpura (ITP)
Platelet lOss or destruction

11
(continued from
page 159)
examine
peripheral blood
smear lor
hemolysis
Nonimmune
WaShout thrombocytopenia
loss ---{
Platelet injury -
Immune platelet dealruction
-j
13
Autoantibodies
--f
Drugs (directloxiclty)
Splenic hamartoma
Consumption
Alloantibodies --
,.
ExIracorporeal circulation
--E
Fat embolism
Renal vein thrombosis
Erythroblastosis fetalis
Drug,
SLE
Evans' syndrome
swan_Ganz
catheter
Subacute bacterial endocarditis (SBE)
Platelet injury
Prosthetic valves
Vatvular stenosis
Thrombotic endocarditis
Nonimmune platelet destruction
Renal transplant rejection

Inlection/sepsis
Toxemia 01 pregnancy
Hemolytic-uremic syndrome
Disseminated intravascular coagulation (DIG)
Cecil Chapter
184
Thrombotic thrombocytopenic purpura (TTP)

Cavernous hemangioma
Harrison
Chapter
60
Primary pulmonary hypertension
Hematologic Olsorden Thrombocytopenia
161
DYSPROTEINEMIA
II
Dysproteinemia
refers to the group of disorders
that occurs secondary to an abnonnal clone of
immunoglobulin-secreting
plasma cells derived
from B cells. Other commonly used terms for dysproteinemia are plasma cell dyscrasias, gammopathies,
paraproleinemias,
immunoglobulinopathies,
and monoclonal gammopathies.
Dysproteinemia
is diagnosed by
the identification
of a homogeneous
immunoglobulin
"spike" on serum protein electrophoresis
(SPEP). An
elevated serum globulin or a low anion gap is the usual
clinical clue.
Examination of the Ixme marrow may reveal

plasmacytosis with abnonnal clones of plasma
cells that may invade the adjacent bone. The
definitive diagnosis of multiple myeloma, heavy chain
disease, and Waldenstrom's
macroglobulinemia
rests on
the demonstration
of this plasmacytosis. Benign gammapathies are not characterized
by the extensive bone
marrow involvement, and the marrow is usually nonnal.
II
In order to identify the class of immunoglobulin

responsible
for the monoclonal
spike, or M
component, on the SPEP, a serum immunoelectrophoresis (IEP) must be performed.
The M component can be made up of the immunoglobulins
IgC,
IgM, IgD, IgA, and IgE; light chains alone; or heavy
chains alone. The heavy and light chains that compose
the immunoglobulins
are often synthesized in unequal
amounts by the neoplastic clone of {.'ells. Usually the
light chains are in excess and can be excreted in the
urine due to their low molecular weight. The monoclonal light chains that are found in the urine in association with plasma cell neoplasms are known as Bence
Jones proteins. Urine dipstick analysis will not detect
Bence Jones protein. Bence Jones protein can be detected only by a special technique in which the protein
demonstrates
certain solubility
characteristics
upon
heating and cooling of the urine. A urine protein electrophoresis (UPEP) is perhaps the best method to demonstrate the presence of Bence Jones protein.
Macroglobulinemia
is characterized
by IgM as
the M component on IEP. Primary macroglobulinemia, or Waldenstrt>m's macroglobulinemia,
is due to a primary plasma cell dyscrasia. Bence Jones
proteinuria accompanies Waldenstrt>m's macroglobulinemia in approximately
10% to 30% of the patients. The
diagnosis of Waldenstrt>m's macroglobulinemia
is made
162 Hematologic Disorders Dysproteinemia
in the presence of typical clinical signs and symptoms

of hyperviscosity
caused by circulating
IgM, an IgM
concentration
greater than 3 gldl, and evidence of a
substantial number of plasma cells and plasmacytic lymphocytes on bone marrow examination. Typical clinical
features of Waldenstrom's
macroglobulinemia
include
fatigue and bleeding manifestations,
as well as neurologic symptoms, primarily due to hyperviscosity.
The diagnosis of multiple myeloma is based
on the demonstration
of marrow plasmacytosis,
evidence of clone invasiveness (e.g., lytic bone
or soft tissue lesions), and a significant M component
on SPEP. IgG is the M component
in greater than 50%
of the cases of myeloma. IgA is the M component
in
25% of cases and free light chain in 20% of cases. IgM,
IgD, and IgE are the M components
in fewer than 5%
of cases of multiple myeloma.
The frequency
of the class of immunoglobulin
reo
sponsible for myeloma pamllels the relative frequency
with which the immunoglobulins
are found in the blood
normally. In addition, 1% of patients may have plasma
cell tumors that produce two or more monoclonal proteins, the so-called biclonal gammopathies.
The most
common biclonal gammopathy
is combined
IgG and
IgA, which occurs in about 30% of these cases.
Fewer than 1 % of the patients in whom myeloma is
suspected clinically but laboratory confirmation is lacking probably have light chain myeloma with removal of
the light chain by the kidney. Myeloma may be difficult
to. diagnose if any light chain myeloma is present because of the lack of a prominent
monoclonal spike on
IEP. Two thirds of the patients with IgC or IgA myeloma are also found to have Bence Jones protein in
their urine. Bence Jones protein may be detected in
fewer than 50% of patients with light chain myeloma.
Bence Jones protein may also be detected in the urine
of patients with primary amyloidosis and in approximately 20% of patients with macroglobulinemia
(see
No. 10).
Secondary macroglobulinemia
refers to a macroglobulinemia
occasionally
found with lymphoma, carcinoma, and infectious and other inRammatory conditions. IgM levels are much lower than
those seen in Waldenstrom's
macroglobulinemia.
Previously knoym as benign monoclonal gammopathy, monoclonal gammopathy of unknown

significance (MGUS) denotes the presence of
IgM as the M component on IEP without the diagnostic
features
of macroglobulinemia,
myeloma.
or other
plasma cell disorder. The disease may not be benign,
as man)' of the patients develop macroglobulinemia
or
myeloma over time. Patients with MGUS have lower
quantities of IgM in their serum than do patients with
multiple myeloma, and Bence Jones protein is absent
from their urine. Bone maTTOW examination
usually
demonstrates
less than 5% plasma cells. MGUS can be
detected
in approximately
1% of the population over
the age of 50 and in 3% of the population over 70 years
of age. If initial investigation of IgM component leads to
the diagnosis of MGUS, the patient should be followed
without treatment
at intervals of 3 months
the IEP
being repeated with each examination.
If th~ quantity
of the monoclonal IgM increases by more than 50% on
repeat fEP, then a complete
reevaluation.
including
bone marrow examination, should be performed. Previous studies of MGUS have shown that approximately
60% of patients continue to have stable protein levels
over a 5-year pericxl of follow-up. Approximately
11%
of patients with MCUS go on to develop macroglobulinemia, myeloma, or amyloidosis.
Indolent myeloma <x.'curs in about 5% of patients with criteria diagnostic of myeloma but
\vith a more indolent course. Bence Joncs proteinuria is absent.
1m
Amyloidosis is a complex of disorders in which

K and
>.. light chain immunoglobulin
components are deposited
in various body tissues.
Most dysproteincmias
that are associated
with light
chain secretion call also be accompanied
by amyloid
deposition. I EP detects an M component in only about
50% of patients "vith primary amyloidosis, but 90% will
have detectable
Bence Jones protein in their urine. If
amyloidosis is associated with myeloma, the IEP will
detect an M component
in about 75% of the patients.
The diagnosis of amyloidosis requires the demonstration
of amyloid on tissue biopsy.
Heavy chain disease is a rare condition caused

by the secretion of the heavy chain. or heavy
chain fragment,
of an immunoglobulin
by a
clone of neoplastic cells. Heavy chain synthesis corresponds to the five subc1asses of immunoglobulins.
The
presence of heavy chain protein in the urine cannot be
detected
by the solubility tests used to detect Bence
Jones protein, hut UPEP will reveal the presence of
heavy chains.
WaJdenstrOm's macroglobulinemia
Multiple myeloma
5 Multiple myeloma
Gamma chain disease
6 Heavy ctl8in disease
Mu chain disease
Alpha chain disease
Delta chain disease
~carcinoma
Malignancy
lymphoma
-{
Inflammallon
-E
Cold agglutinin disease

Mi,ed cOY<>;lklbulinemia
SjOgren's syndrome
Reevaluate
Monoclooal gammopathy
unknown
slgnlficance
of
(MGUS)
Repeat serum IEP at 3 mos.
Indolent myeloma
Lichenmyxedemalosus
Gaucher's disease
10
Cecil Chapter
181
Harrison
114
Chapter
Miscellaneous
Cirmosislliver
Primary amyloidosis
Sarcoidosis
Hype'gemmagklbullnemia
C3'cinoma
disease
Hematologic Disorders Dyspmtein~lllia 163
Bibliography
Beck WS: Diagnosis of megaloblastic anemia. Annu Rev
Med 42,311-322, 1991.
Bimdon NI, Pentecost )0, Coakley )R, et at An expert
system to diagnose anemia and report results directly
on hematology fanns, Comput Biomed Res 29:1626, 1996.
Djulbegovic B, Hadley T, Joseph C, A new algorithm
for the diagnosis of polycythemia. Am Fam Physician
44(1),1l~120, 1991.
Elias), Dauth ), Senekal )C, el ai, Serum beta-2-microglobulin in the differential diagnosis of monoclonal
gammopathies. S Af, Med ) 79,65Q...S53,1991.
Farley PC, Foland J: Iron deficiency anemia. Postgrad
Med 87(2),89, 1990.
Finazzi G, Budde V, Michiels JJ: Bl~n~
time and
platelet function in essential thrombocythemia and
other myeloproliferative syndromes. Leuk Lymphoma
22(1),71-78, 1995.
164 HematoloJic Disorders.
Dysproteinemia
George )N, Raskob CK Idiopathic thrombocytopenic

purpura: diagnosis and management. Am J Moo Sci
316(2),87-93, 1998.
Coerg C. Schwerk WB. Coerg K: Splenic lesions: $000graphic patterns, followup, differential diagnosis. Eur
) RadioI13,59-66, 1991.
Goodman KI, Salt WB: Vitamin B11 def1cienq. Postgrad
Med 88(3),147, 1990.
Imbert M: Adult patients presenting with pancytopenia.
Hem'lol PathoI3(4),159-167, 1989.
Keisu M, Ost A: Diagnoses in patients with severe
pancytopenia suspected of having aplastic anemia.
Em) Haemalol 45,11-14, 1990.
Majer RV:Which tests are most useful in distinguishing
between reactive thrombocytosis and the thrombocytosis of myeloproliferative disease? Clin Lab
HaematoI13:9-15, 1991.
Moses PL, Smith RE: Endoscopic evaluation of iron
deficiency anemia: A guide to diagnostic strategy
in older patients. Postgrad Med 98(2):213-224,

1995.
Mmphy S, Polycythemia vera. Dis Mon 38(3),1992.
Roskos RR, Boxer LA: Clinical disorders of neutropenia.
Pedial Rev 12(7),208-212, 1991.
Rothenberg
M: Eosinophilia.
N Engl J Med
338(22),1592-1600, 1998.
Ruggenenti P, Remuzzi G: Thrombotic thromlxx:ytopenic purpura and related disorders. Hematol Dnrol
Clin North Am 4(1),219-231, 1990.
The American Society of Hematology ITP Practice
Guideline Panel: Diagnosis and treatment of idiopathic thrombocytopenic purpura: Recommendations
of the American Society of Hematology. Ann Intern
Med 126,319-326, 1997.
Wheby MS (ed): Anemia. Med Clio North Am
76(3),1992.
Gamma
He
. d
avy cham l58ase
chain disease
Mu chain disease
Alpha chain dsease
Delta chain dIsease
Can:;noma
Malignancy
1
Dysprol~nemll
-{
-f
-f
Inflammation
Lymphoma
Cold aggMinin disease
MI,ed ayog_'namla
S;6gren'.
syndrome
Monoclonal gammopathy of
Unknown signiflcance (MGUS)
Repeat serum IEP at 3 mos.
II
Indolent myeloma
Uchenm,,_matoou,
Gaucher's disease
10
Cecil Chapter
181
Harrison
114
Chapter
Miscellaneous
Cirrhosislliver
disease
Primary amyloidosis
Sarcoidosis
Hype'llammagiobullnamla
Ca,",noma
Hematofoetc Disorders
Dysproteinemia 165
1:1 Neurologic
Disorders
or partial herniation,
lumbar puncture
should never
be delayed if bacterial meningitis is suspected. Human
immunodeficiency
virus {HIV)-associated
meningitis is
now a well-recognized
entity. It may occur in the setting
of other viral or bacterial meningitides or may represent
may involve compression of the nerve by vascular structures. The syndrome has also occurred following viral
infections, and rarely, secondary to a gasserian ganglion
tumor. Neuralgia of other cranial nerves, including the
glossopharyngeal
and occular nerves, oc-curs oc'CaSionally.
SIGNS AND SYMPTOMS
the effect of HlV itself
HEADACHE
Migraine headaches are a common fonn of vascular headache (see No. ) 1). Most are not associ
ated with focal neurologic findings, but occasionally ocular motor palsy, as well as other focal neurologic
defects, may occur. A few studies have revealed ischemic
changes in the involved area of the brain. A rare familial
fonn of complex migraine is associated \\lith aphasia,
confusion, and hemiparesis or hemiplegia.
Exposure to many chemicals and dnlgs has been

associated \\lith headache. Chemicals most frequently associated with headache include benzene, nitrates. tyramine, monosodium glutamate, carbon
monoxide, insecticides, and lead. Drugs, including oral
contraceptives, nitrates (nitroglycerin), indomethacin, C'alcium channel blockers, caffeine, and alcohol. have also
been associated \\lith headaches. Sudden \\Iithdrawal of
any of these drugs may lead to headache. An example of
a \\Iithdrawal headache is that which occurs with chronic
aspirin ingestion. Many aspirin products t'Ontain a large
amount of caffeine. When the individual suddenly stops
taking aspirin (and therefore C'dfTeine), headache ensues.
The cause of the headache is usually an alteration in
blood flow to cranial stru(.tures.
Signs and symptoms:

Headache
Vertigo
Dementia
Altered mental
Seizure
status
Headache may be the most common of all physical symptoms. In the United States, it accounts
for over 40 million physician visits per year. The
severity, onset, and location of the pain may give useful
clues to the diagnosis. Only the bony structure of the
head and the brain parenchyma are not richly supplied
with pain-sensitive ncnre fibers. Headache may therefore
originate from irritation to nny of the other structures of
the head and neck. The most severe pain originates from
the arteries, cranial nelVCS, and dura mater.
Almost all of the life-threatening

etiologies of
headache cause sudden or rapid onset of pain.
Acute-onset headache is defined as pain with
an onset of less than 1 week, but often it occurs only
minutes to hours prior to the patient's seeking medical
care. Headaches may be also considered acute if there
is a sudden change in the pattern or severity of a
chronic headache. Due to the possibly senous nature of
the acute-onset headache, a thorough and often urgent
evaluation should be undertaken.
Even in this setting,
however, fewer than 5% of headaches have lifethreatening causes, and fewer than 15% are the result of
serious neurologic disease.
II
Focal neurologic findings are signs or symptoms

referable to one area of the central nervous sys.
tern with relative sparing of other functions. The
abnormality most commonly involves motor or sensory
functions, but more subtJe changes in balance, memory,
and other cognitive functions must also be sought.
Most fonns of bacterial meningitis are associated with other systemic symptoms such as fever, altered mental status, and nuchal rigidity.
Viral, fungal, and certain opportunistic
infections of the
meninges may present with only acute-onset headache
in the early stages. Although computed
tomography
(Cf) scanning prior to lumbar puncture is desirable to
rule out the possibility of increased intracranial pressure
166 Neurologic: Disorders
Headache
Thrombosis
of any of the major dural sinuses
may occur spontaneously or as a result of infection. Spontaneous
thrombosis is usually associated with pregnancy, puerperium,
collagen. vascular disorders (most notably systemic lupus erythematosus),
malignancy. and oral contraceptives.
Infection of the
dural sinuses usually occurs through direct extension of
infection through a sinus wall or a draining vein or via
venous embolization. Although any of the dural sinuses
may be involved, the large paired lateral, cavernous,
and petrosal sinuses are affected most often. Anyone
of these conditions is potentially life-threatening
and
should be suspected in any person \\lith a sudden deterioration following sinus infection.
Cranial arteritis occurs most commonly in patients over the age of 60 years. Any of the
large cranial arteries may be involved, but the
temporal artery is the most common site of inflammation. The pain is usually intense and localized to the
temporal of fronto.occipital
regions of the head. There
may be tenderness
to palpation as well as firmness
over the affected artery. Temporal arteritis is strongly
associated
with polymyalgia
rheumatica
and, if untreated, may result in occlusion of the retinal arteries,
followed by pennanent
blindness. The erythrocyte sedimentation rate is invariably elevated, at times to greater
than 100 mmJbr.
The cranial neuralgias result from a sudden and

excessive discharge from the involved cranial
nerve. Trigeminal neuralgia or tic douloureux is
the most common fonn of cranial neuralgia. The disorder
1m
Extracranial (systemic) infections an' a l.'ommon

cause of headache. Up to 40% of acutc-onset
headaches may be due to extracranial infection.
Generalized
viral infections, as well as bacterial infections involving any other areas of the body. have oc>en
associated
with headache.
Other systemic symptoms
such as fever, lethargy, and anorexia may be prominent.
Migraine headache is a well-defined disorder of

severe headache
that can be associated \\lith
generalized neurologic symptoms. These symptoms may include visual aurae, hemianoptic visual loss,
vertigo, and taste and smell abnonnalities.
Occasionally,
ataxia and generalized
sensory abnormalities
lllay also
occur. At times, the symptoms may be more focal (see
No.5). Typical attacks of migraine may have up to four
phases. The first phase is a prodrome lasting up to 24
hours that is associated with mood changes, drowsiness,
and loss of appetite. The second phase consists of the
neurologic symptoms. The third phase bebrins as the
neurologic symptoms subside and consists of a severe
headache, usually involving one of the frontotemporal
regions of the head. The headache may be accompanied
by photophobia,
nausea, vomiting. and noise intolerance. The headache may last from 4 hours to several
days if not treated. The 1st. or postheadache. phase

consists of a feeling of exhaustion,
and occasionally
ten-
Tumor
Subdural
hematoma
Intracranial
bleed
Acute hydrocephalus
Cerebral
edema
Brain abscess
Subdural
empyema
Pseudotumor
cerebri
Meningitis
Encephalitis
1
Headache
Complex
Cluster
Subarachnoid
migraine
headaches
bleed
EncephalHis
Meningitis
[ Bilateral
6
subdural
hematomas
Dural sinus thrombosis

Sinusitis
7 Cran~1 arteritis
Glaucoma
Neuralgias
Arteriovenous
New onset migraine
malformation
Sedrale
Chronic hydrocephalus
<50
mm/hr
Musculoskeletal
Drug/chemical
Extracranial
infections
Posl-lrauma
Benign exertional
Temporomandibular
joint syndrome
Hangover
demess of the scalp. The etiology of the migraine headache is unclear, but alterations
of blood flow over the
cerebral cortex have been noted. The migraine attacks
can mimic many other serious neurologic disorders, and

these disorders must be excluded before the diagnosis
can be made.
Cecil Chapter
Harrison
454
Chapter
15
Headache.
167
VERTIGO
Vertigo is the sensation of rotary movement.
The patient may feel either that he or she is
turning OT that the environment
is turning. Ver
tigo is usually accompanied by nausea and visual distur-
bances. Vertigo implies a disorder in the vestibular apparatus. This disturbance

may be in the vestibular
labyrinth itself or in the central nervous system. Injury
or disease in any of these areas will cause an imbalance
in the symmetry of the impulses from the right and left
vestibules and result in vertigo. The vertigo may be
continuous
or intennittent,
and this finding may be
useful in the differential
diagnosis. Dizziness is any
nonrotary sense of disequilibrium.
Dizziness is not a
labyrinthine phenomenon.
II
Although much can be learned from a skilled

neurologic examination, electronystagm
phy
(ENG) is a useful test in the diagnosis
ders of balance. ENe is a battery of tests that consist
first of a recording of tracking gaze, as well as vertical,
spontaneous,
and optokinetic nystagmus. Abnormalities
in this portion of the test are consistent with a central
nervous system origin for the vertigo. A second part of
the test evaluates positional nystagmus, and the third
part tests caloric response of the inner ear. Abnormalities in these last two portions of the ENe are associated
with labyrinthine disorders, or positional vertigo. A normal ENe eliminates true vertigo. The patient is more
likely unable to differentiate vertigo from dizziness.
Zfilisor-
A formal audiogram should be performed

on
any patient with vertigo and evidence of hearing
loss. Audiometry tests the ability to sense
tones via both air and bone conduction. The loss 0 the
ability to hear only selected tones is most consistent
with certain forms of ototo~city. A more complete hear-
168 Neurololic Disorder'S Vertigo
Fure
ing loss in one ear in association with vertigo may

indicate nerve damage through entrapment
or replacement by tumor. Further evaluation, including cr scanning, is necessary in this setting. The brain stem evoked .
response may also be useful in further evaluating the
magnitude of the hearing loss and differentiating
between disorders of the cochlea, eighth nerve. and brain
stem lesions.
The most common tumor affecting the cerebropontine angle is an acoustic neuroma. A high
index of suspicion is necessary to make the
diagnosis while the tumor is small. An acoustic neuroma
must be suspected in any patient with total or severe
one-sided hearing loss. a depressed caloric response on
ENe,
or an abnormal
brain stem evoked response.
Early diagnosis is extremely important, as the prognosis
for large or advanced tumors is poor.
Meniere's disease is a common disorder affecting mainly middle-aged

persons and occurs in
about 10% of all patients with vertigo. The
disease is manifested
as periods of episodic vertigo,
many times accompanied
by severe nausea, blurred vision, and at times shortness of breath. The vertigo is
usually accompanied
by fluctuating
hearing loss and
tinnitus. Meniere's disease may be progressive.
with
attacks becoming more frequent. Occasionally progressive disease will result in permanent
damage to the
inner ear.
Ototo:tic agents can be associated with hearing

loss and occasionally with vertigo. The agents
most frequently
implicated
include alcohol,
heavy metals, carbon mono~de, the aminoglycoside antibiotics, furosemide,
quinine, cisplatin, and aspirin.
Among these groups, the aminoglycosides
are potentially the most damaging to the vestibular and cochlear
sensory ceUs. The ototoxicity of the aminoglycosides

appears to be related to elevated peak serum levels.
Furosemide
has been associated with severe vertigo.
The rapidity of the intravenous administration of furosemide is thought to be associated with its ototoxicity.
Temporomandibular
joint neuralgia,
or TMJ
syndrome. is frequently associated with dizziness and tinnitus. The joint itself is tender to
palpation. Joint radiographs are wually diagnostic.
Benign positional vertigo (BPV) is the most

common cause of vertigo. BPV is a disorder
consisting of sudden attacks of vertigo related
to changes in position. There is no associated tinnitus
or hearing loss. The vertigo is brought on by placing
the diseased ear in a dependent
position. Nystagmus
toward the affected ear is invariably present. The disorder is self-limited, usually resolving in several months,
but may last up to a year.
True vertigo occurs in up to one third of patients with multiple sclerosis. Nystagmus is almost always present and creates an abnormal
ENe. The onset of the disease is usually between 20
and 50 years of age and should be suspected when
central-type
vertigo or visual disturbances
are noted in
this age group. Magnetic resonance imaging (MRI) may
demonstrate
findings consistent with this diagnosis, but
there is no single diagnostic test available.
1m
seventh
hearing
seen in
external
Herpes zoster may affect the geniculate ganglion

(the Ramsay Hunt syndrome) in the petrous
portion of the temporal bone. Severe otalgia and
nerve paralysis may occur. TInnitus, vertigo, and
loss may also be noted. Herpetic lesions may be
the distribution of the seventll cranial nerve, the
ear, or the tympanic membrane.
1
Vertigo
2 Check
electronystagmography
(ENG)
Posterior TIA
Hyperventilation
Functional
Acoustic
Glomus
ENG
abnormal
syndrome
disorder
neuroma
tumor
Temporal
bone fracture
Tumor of middle ear

Meningioma
labyrinthine
vertigo
3
Barotrauma
Meni~re's disease
Ototoxic agents
Acute labyrinthitis
Vestibular
neuronitis
Temporomandibular
[TMJ ."""orne)
joint neuralgia
Chronic otitis media

Syphilis
8
Benign JXl5itionai vertigo

Labyrtnthine concussion
Multiple sclerosis
Meningioma
Hemangioma
AN ma"ormation
Central (eNS) vertigo
Intracranial
aneurysms
Posteriorlbrain
Vertebrobasilat
stem stroke
insufficiency
Herpes zoster oticus (Ramsay Hunt syndrome)

T emporallobe
Granulomatous
Cecil Chapter
Harrison
Chapter
517
epHepsy
meningitis
Migraine
headaches
Cerebral
vasculitis
20
Neurologic Dlsorden
Vertigo 169
DEMENTIA
Dementia
is an acquired condition in which
mental capacity is diminished. Dementia is not
a diagnosis, but a symptom of an underlying
disorder. Dementia may affect memory. language, cognition, spatial orientation, or personality. Usually several
of these functions are impaired. Dementia is a global
phenomenon
and should be distinguished
from focal
defects such as aphasia or amnesia. Dementia
should
also be distinguished from acute confusional states that
last only hours or days. Dementia may affect as many
as 15% of people over the age of 65 as well as a smaller
percentage
of younger persons. As many as 50% of
these patients may have treatable metabolic or structural causes for the dementia.
Focal neurologic findings are signs or symptoms

referable to one area of the central nervous
system with relative sparing of other functions.
The abnormality most commonly involves motor or sensory functions, but more subtle changes in balance,
memory, and other cognitive functions must also be
sought.
Brain imaging can now be performed

utilizing
several modalities. The suspected
underlying
condition should govern the choice of available
techniques. cr scanning has become the standard for
the evaluation of structural lesions within the brain and
ventricles. M RI may be more reliable for certain subtle
changes in white or gray matter, as seen in lacunar
syndromes and multiple sclerosis. N~ techniques like
positron emission tomography (PET) may help to delineate many metabolic disorders.
Multiple sclerosis may be one of the causes

of early-age dementia. The dementia is usually
accompanied
by other clinic-o:alsigns involving
scattered areas of the brain as well as the optic nerve
and spinal cord. TIle age of onset is between 15 and 50
years. MRI has been shown to be a sensitive tool suggestive of the diagnosis by revealing typical areas of demyelination, but may not be diagnostic.
Pick's disease is often

common Alzheimer's
cause of the similar
prominent
motor symptoms.
confused with the more

disease (see No. 12) beform of dementia
with
The dementia
of Pick's
170 Neurologic Disorders
Dementia
disease is caused by a degeneration

of the temporal and
frontal lobes. Aphasia may be a prominent
symptom.
The CT scan will reveal enlarged temporal horns and
frontal atrophy. There is no known treatment and the
progression is rapid.
1m
The chronic forms of meningitis

are usually
caused by indolent infections. Fungal infections,
especially those caused by Cryptococcus and
Coccidioides, are associated with various forms of dementia. Tuberculosis, sarcoidosis, and carcinomatous forms of
meningitis are also commonly associated with dementia.
II
II
II
II
Normal-pressure
hydrocephalus
is a chronic
condition in which there is a slow accumulation
of cerebrospinal
fluid (CSF) and enlargement
of the ventricles. The pressure in the CSF is nonnal.
The etiology of nomlal pressure hydrocephalus
is unclear, as is its clinical significance. Many patients with
this nonobstructive
or communicating
form of hydrocephalus have a syndrome of dementia,
psychomotor
retardation, unsteady gait, and urinary incontinence.
As
many as 5% of {lOOpJe over the age of 60 may have
demonstrable
hydrocephalus
on CT scan, and many of
these patients are asymptomatic. The reversibility of this
disorder with ventricular shunting procedure is unclear.
Progressive
supranuclear
palsy can resemble
Parkinson's disease, but it has a less prominent
tremor, and ophthalmoplegia
is present.
Dementia occurs late in the course of the disease, but
there is a more rapid decline in mental capacity than in
patients with Parkinson's disease. No effective treatment
is known.
AIDS dementia is composed of a combination
of changes in ~ition,
motor skills, and bebavior. It is thought to be the result of direct
infection of the brain with the AIDS virus. The dementia has a slow onset and may progress for months to
years. As the disease progresses, leg and arm weakness
may develop, along with urinary and fecal incontinence.
Tremor and myoclonus may also develop. The disease
may progress to complete mutism and render tbe patient completely helpless. This form of dementia must
be distinguished
from the more treatable causes of dementia associated with AIDS such as infection (see No.
10) medication effects, and depression.
Systemic lupus erythematosus,

as well as otber
forms of vasculitis, may cause an acute cerebritis leading to dementia. The exact mechanism
of the dementia
is not known. The development
of
dementia in patients with vasculitis should be 'treated
emergently.
Drugs may be the most frequent cause of de~

mentia. Both therapeutic
and toxic chemicals
may cause dementia. The drugs most commonly
associated with dementia include the major tranquilizers, antidepressants,
minor tranquilizers, narcotics, anticonvulsants, antihypertensives,
digoxin, and anticholin~
ergic
drugs,
as well as certain
antibiotics
and
antineoplastic
drugs. The dementia-producing
effect of
any of these drugs is more profound in the elderly.
Toxic chemicals known to produce dementia include
the heavy metals, organic solvents, and insecticides. Use
of these drugs, alone or with alcohol, can mimic Alzheimer's disease. A thorough drug history is critical because
this cause of dementia occurs often and is treatable.
Alzheimer's disease is the most common illness
producing dementia. It is thought to affect as
many as 3 million people in the United States
alone. Alzheimer's disease begins insidiously, with fail.
ure of recent memory a prominent
early symptom.
Emotional lability and nominal aphasia may be severe.
Primary motor and sensory functions are spared early
in the disease, but apraxia and incontinence may appear.
The etiology is unknown, but viral diseases, genetic
predisposition,
and neurochemical
disorders have all
been implicated. The pathologic changes seen in brain
tissue consist of senile f.laques, granulovacuolar
degeneration, and neurofibril ary tangles. The disease is progressive with eventual loss of most cognitive function.
Alzheimer's disease is a diagnosis of exclusion, as only
histologic examination of the brain tissue at autopsy is
diagnostic of the disease.
Depression may cause a syndrome virtually indistinguishable

from dementia.
Depression
is
most difficult to diagnose in the elderly. in
whom the common complaints of sadness, helplessness,
insomnia, and weight loss may not be obvious. A thorough psychiatric evaluation is necessary when 110 other
cause of the "dementia"
can be found. Many patients
with even profound
depression
can be successfully
treated and returned to a functional status.
Tumor
Subdural hematoma
Cerebral oontuslon
Lacunar stroke
Multiple sderosis
Huntington's
ChOrea
Pick's disease
Normal-pressure
Multi-infarct
hydrocephalus
dementia
Pernicious
[ Par1dnson's disease
1
Dementia
OIlvoponlocerebellar
anemia
Syphilis
7 [ Progressive supranuclear palsy
Uremia
degeneration
Hyperlhypocalcemia
Hyperlhypomagnesemla
HyperltlypOthyroidism
Hepatic encephalopathyfaJcoholism
Cushing's
disease
Addison's disease
8
AIDS encephalopathy
Mercury
Heavy metal intoxication
ILead
Aluminum
Progressive
multifocalleukoencephalopathy
Acute meningitis
Chronic meningitis
limbic
encephalitis
Carcinomatosis
Jakob-Creutzfeldt
disease
Whipple's disease
Poslconcussk>nal
12
13
Cecil Chapter
Harrison
Chapter
449
26
Alzheimer's
syndmme
disease
Depression
Senile dementia
Wernicke's
encephalopathy
Neurologic Olsorden Dementia 171
ALTERED MENTAL STATUS

Altered mental status is defined as a decrease
in the level of consciousness. The change in
mental status is acute, appearing over minutes
to days. The changes may be brief, lasting for minutes
to hours, or sustained. A decrease in the level of consciousness is usually classified into three levels of
severity-delirium, stupor, and coma. Delirium is confusion and a reduction of awareness. The level of wakefulness is not usually abnormal. Delirium is most often
caused by a metabolic brain disorder rather than by
trauma or intracranial lesions. Stupor is an unarousability that can be overcome only by vigorous or direct
noxiousstimuli. The most severe form of altered mental
status is coma. In coma. the patient is unarousable to
even the strongest external stimuli. Consciousness is
controlled mainly in the ascending reticular activating
system, a group of neurons extending from the pons to
172 Neurol~c
DilOf"den;
Altered MenIal Status
II
the thalamus. Conditions affecting consciousness must

Extreme changes in body temperature can
involve the entire brain (metabolic) or the brain stem
cause decreased levels of consciousness. Core
temperatures greater than 4O.5Cor less than
either directly or indirectly. The more depressed the
level of consciousness, and the longer the condition 32"C are associated with altered mental status. Hyper.
continues, the worse the prognosis. Several severe {>sy- thennia may be caused by extremely high fever or
chiatric conditions may mimic any of these states (see heatstroke. Heatstroke is caused by exposure to ex
tremely high ambient temperatures, usually accompa
No.9).
nied by some fonn of impaired bodily heat reduction
Carbon monoxidepoisoning can be acute and is mechanisms. Drugs that impair sweating, such as anti
eas;ly delected by history. if obtainable. or the cbolinergics, phenothiazines, ablockers, and antihistacherry-red Rush of the skin and mucous mem mines, may contribute to the development of heatbranes. Chrome carbon monoxidepoisoning is less easily stroke. Hypothennia is usuallyassociatedwith metabolic
detected but is seen in a substantial percentage of pa- causes such as sepsis, hypoglycemia, uremia. hepatic
tients presenting with altered mental status. This fonn of failure, adrenal insufficiency, and hypothyroidism. $e.
chronic carbon monoxide exposure usually is the result vere brain injury or spinal cord transection can also
of faulty indoor heating systems or indoor cooking using cause rrofound hypothennia. Certain drugs, such as
charcoal fuel. A carboxyhemoglobinmeasurement should ethano and phenothiazines, as well as thiamine defibe included in any arterial blood gas (AIlC) determina- ciency (see No.8). have also been associated with hyp<>tion when evaluatingaltered mental status.
thennia.
II
Subdural hematoma
Intracranial bleed
1
Attered mental statu.
Infection
--f
Pneumonia
Urinary tract infection
Sepsis
Hyperthermia
Hypothermia
Hyperlhyponatremia
Hyperlhypomagnesemia
Hyperlhypocalcemia
Metabolic abnonnaJity
Hyperlhypoglycemia
Uremia
Hepatic failure/encephalopathy
Sepsis

Cecil Chapter
Harrison
Chapter
469
24
Neuroloak Disorders Altered Mental Status
173
ALTERED MENTAL STATUS (Continued)

Brain stem herniation is the most ominous
4 cause of altered mental status. Increased intracranial pressure resulting from space-occupying
mass lesions or generalized cerebral edema may cause
downward displacement of the diencephalon. This displacement causes compression of the midbrain into the
tentorial notch (central herniation) or compression of
the uncus against the midbrain in the tentorial notch
(uncal herniation). Herniation can also be caused by
removal of CSF when intracranial pressure is increased.
Therefore, except in extreme circumstances (such as
the suspicion of bacterial meningitis), lumbar puncture
should be performed after the cr scan in patients
with altered mental status. Clinical signs of herniation
include a rapidly decreasing level of consciousness, sighing, yawning, and periodic respirations. Pupils may
shrink to pinpoint size at first. Later one or roth of the
pupils may dilate. Unless rapid treatment is undertaken,
permanent brain damage or brain death is inevitable.
11
Any lesion that directly affects the midbrain

region may cause decreased levels of consciousness. These lesions may include rare tumors of
174 Neuroloalc Dlsorden Altered MentalStatus
the brain stem, ischemia, and degenerative diseases of

the central nervous system. Patients who are awake
but unable to respond may have a form of "Iockedin" syndrome. In this condition, all descending motor
pathways are blocked, usually by an infarction or hemorrhage at the base of the pons. The patient may be
completely aware of all extemal stimuli but may be able
to communicate only by eye movements.
Drugs may be the most common cause of altered mental status. Sedatives, ethanol, tranquilizers, and all of the narcotics are frequent
causes of altered mental status. Many other drugs, including tricyclic antidepressants, lithium, steroids, anticonvulsants, heavy metals, cardiac glycosides, cimetidine, salicylates, and amphetamines,
have been
implicated in decreased levels of consciousness. The
random drug screens performed on blood and urine
detect only a small percentage of those drugs that may
cause an alteration in mental status. It is important to
obtain a complete drug history when possible in order
to obtain specific drug levels not included in the routine
screen. Numerous toxins, including certain pesticides,
methanol, ethylene glycol, and cyanide, are also causes
of altered mental status.
Many forms of vasculitides can affect the {:erebral circulation. The most common occurs with
systemic lupus erythematosus. Periarteritis nodosa, temporal arteritis, granulomatolls vasculitis, druginduced vasculitis, and isolated Ya'iculitisof the central
nervous system are among other fOrolSof vasculitis that
affect the central nervous system. The mechanism by
which the altered mental status occurs is probably due
to ischemia and inRammation with subsequent cerebral
edema.
Deficiencies of thiamine (vitamin BI) (causing

Wernicke's encephalopathy), niacin, pyridoxine,
vitamin BIt, and folate are associated with altered mental status.
8:
Certain severe psychiatric diseases can be virtually indistinguishable

from stupor and
coma. Catatonic states and severe hysterical
conversion reactions may also mimic stupor and (:oma.
Catatonia may be a manifestation of severe vegetative
depression. Many patients with severe depression may
be diagnosed with paranoid schizophrenia.
4
5
Spontaneous subdural
Herniation
Brain stem lesion
hematoma
(continUBd
from psg8 173)
7 Cerebral vasculitis
Petit mal seizure

Temporal lobe seizure
Postictal state
Cecil Chapter
Harrison
Chapter
469
24
Neurofoak Dlsorden Altered Mental Statm 175
SEIZURE
Seizures are more frequent than is commonly
thought. Approximately 1% of the population
has an active seizure disorder, and as many as
10% of the population will sufTer at least one seizure
during their lifetime. Seizures may be classified by the
area of the brain that is involved. Generalized seizures
have no specific focus, whereas partial complex seizures
may emanate from a local area of the brain. The specific
area of brain involved, i.e., the temporal lobe, may
determine the actual manifestation of the seizure. The
etiology of any seizure is related to a lowered threshold
for seizure, as seen in trauma, toxic reactions. sleep
deprivation, stress, or anatomic abnormalities; to genetic
traits leading to primary epilepsy; or to some combination of the two.
Seizures associated with hypertensive crisis are

an extremely ominous sign. This complication
is associated with markedly elevated diastolic
pressures (usually greater than 140 mm Hg), as well as
other manifestations of malignant hypertension. These
176 Neurolosic Disorders Seizure
manifestations may include papilledema, retinal hemorrhages, renal failure, and congestive heart failure. The
onset of seizures may reflect a hypertensive stroke or
an intracranial hemorrhage.
with nonketotic hyperglycemia. Seizures rarely occur in

diabetic ketoacidosis.
Hypocalcemic seizures are rare and occur when

ionized calcium is less than 2.5 mg/loo m!.
Cause of hypocalcemia of this severity include
renal failure. acute pancreatitis, hypoparathyroidism, severe hyPOmagnesemia, and vitamin D deficiency (see
Hypocalcemia).
Both hypo- and hypematremia have been re

ported to cause seizures. Seizures appear to
be more common with serum sodium below
115 mEqIL than with sodium levels above 160 mEqIL.
The rapidity (less than 24 hours) with which either
condition develops or the rapidity with which it is cor
rected may be more important in the causation of seizures than the actual sodium concentration.
Hypoglycemia is the most common cause of

metabolically induced seizures. U to 7% of
patients with symptomatic hypogl;,cemia will
have at least one seizure episode. The seizures tend to
be generalized rather than focal, and they usually occur
when the hlood glucose is less than 30 mydJ. Hypoglycemic seizures occur more frequently with the use of
insulin than with oral hypoglycemic agents. Generalized
seizures may also occur in as many as 25% of patients
Seizures associated with cardiac events are related to cerebral hypoperfusion associated with
low output states or arrhythmias. Although the
resting electrocardiogram (EKC) may not reveal transient arrhythmias, certain Bndings associated with some
of these arrhythmias may be evident. These include
Wolff-Parkinson-White syndrome, abnormal Q-T intervals, and high-degree atrioventricular blocks. A 24hour
Holter monitor study may be used when indicated to
gain further information.
Subdural
Intracranial
hematoma
bleed
1
Seizure
2 Hypertensive
encephalopathy
Hypocalcemia
Hyper"'ypogtycemla
HypoIhypematremia
Hypomagnesemia
Hypoxia
Renal failure
Cecil Chapter
484
Harrison Chapter
365
(continued
on page
179)
SciZllrt>
177
SEIZURE
(Continued)
EpiIe,psyis a genetic seizure dis~rder without

assOCIated structural or metabolic abnormalities. Most of the epilepsies have their onset
during childhood, but first seizures may occur at any
time. Most of the epilepsies have a distinctive pattern
on electroencephalogram (EEG). including brief high.
amplitude electrical discharges followed by a slower
wave, referred to as a spike and wave pattern. Either
focal or generalized seizures may be seen, and they
involve not only motor abnormalities but verbal, auditory, sensory, and autonomic phenomena as well.
Psychogenic seizures may be manifested in

ways that have psychological significance to the
patient. They should be suspected in any reported seizure that does not result in even minor injury
to the patient, or when the seizure pattern does not fit
any known anatomic pathways. Any bizarre behavior
may be an epileptic event, so the diagnosis of psy_
chogenic seizures may only be made when the symp_

toms fit those described above and no abnormalities
are found on the EEG. Psychogenic seizures are not
responsive to antiepileptic medications.
II
Idiopathic disorders may include seizure-like

episodes and at times are distinguishable from
true seizure disorders only by sophisticated testing. These disorders may include systemic disorders
such as hyperventilation, intermittent porphyria, pheochromocytoma, or dystonic drug reactions. Other neurologic disorders such as dyskinesia and some forms of
migraine may be difficult to distinguish from true seizure disorders.
178 Neurologic
Disoniers
Seizure
II
Syncope is associated with a transient global

cerebral hypoxia. ]f the hypoxia is severe, the
syncope can be associated with clonic movements and misidentified as a seizure, and is known as
convulsive syncope.
Bibliography
Cohen NL, The dizzy patient. Update in otolaryngology
I. Med Clin North Am 75(6), 1991.
Coldman 1., Bennett JC (eds.), Cecil Textbook of Medi
cine. 21st ed. Philadelphia, WB Saunders, 2000.
Mahler ME, Cummings JL, Benson DF: Treatable de.
mentias. West J Med 146:705-712, 1987.
Mondell BB: Evaluation of the patient presenting with
headache. Med Clin North Am 75(3), 1991.
Plum F, Posner IB: The Diagnosis of Stupor and Coma.
2nd ed. Philadelphia, FA Davis, 1972.
Taylor RB: Difficult Diagnosis 2. Philadelphia, WB
Saunders, 1992.
(continued from page 177)
EpIlepsy
Migraine
Psychogenic
Idiopathic
Syncope
Cecil Chapter
484
Harrison Chapter
365
Neuroloak Dlsorden Seizure 179
III Endocrine
Signs and symptoms:
Amenorrhea
Hirsutism
Labs:
Abnormal thyroid
function tests
Hyperlipidemia
Hypoglycemia
Thyroid nodule
Thyroid
Disorders
enlargement
SIGNS AND SYMPTOMS

AMENORRHEA
Amenorrhea is the absence of menses. Primary
amenorrhea is the absence of menses in a phenotypic female by the age of 17. Secondary
amenorrhea
is the absence of menses for 3 months or
more in a previously menstruating female. Oligomenorrhea refers to menstruation that is infrequent and irregu-
lar.
Pregnancy
is the most common
physiologic
cause of amenorrhea. Despite the most forceful
assertions of virginity, a pregnancy test should

always be the first test performed in an investigation of
secondary amenorrhea.
Trophoblastic
growths include hydatidiform
mole, invasive
mole (chorioadenoma
destruens), and choriocarcinoma.
These growths
are accompanied
by unusually high titers of human
chorionic gonadotropin
(HCG).
Once pregnancy has been excluded as a cause

of amenorrhea, the serum prolactin level should
be measured, particularly if amenorrhea
is accompanied
by galactorrhea.
Hyperprolactinemia
is a
common cause of secondary amenorrhea,
occurring in
15% to 40% of women without galactorrhea and in 80%
to 97% of women with galactorrhea.
Prolactin secretion
can be induced by a variety of factors, including drugs,
physical or psychological stress, and pituitary adenomas.
The higher the serum prolactin level, the more likely
the presence of a pituitary adenoma. The presence of a
pituitary adenoma is almost certain if the serum prolactin level is greater than 300 nglml.
Secondary
amenorrhea
can be the earliest
man-
ifestation of thyroid dysfunction. Thyroid func-
tion tests (TITs) should include measurement

of free thyroxlne (T4) index and thyroid-stimulating
hormone (TSI-I) to determine
whether hypothyroidism
is
Amenorrhea
due to pituitary or thyroid dysfunction (see the Abnormal Thyroid Function Tests algorithm). With hypothyroidism due to thyroid dysfunction, thyrotropin-releas.
ing honnone (TRH) will be elevated and is responsible
for a mild prolactinemia.
Thyroid honnone replacement
should return menstrual function and prolactin lev~ls to
normal. Serum prolactin level should be reassayed after
thyroid replacement
has been achieved. If the prolactin
level remains elevated despite adequate thyroid hor
mone replacement,
further investigation is in order (see
No. 13).
Adequacy of endogenous
estrogen production
and ovulation can be evaluated by measuring
estrogen levels or administering
progesterone.
The progesterone challenge is perfonned by administer~
ing 100 mg of progesterone
in oil intramuscularly,
or
10 mg of medroxyprogesterone
acetate orally daily for
disorder may also be hirsute (90%), overweight (50%),

have acne (50%), and show signs of virilization 25%).
Prolactin levels may be mildly elevated in up to 30% of
patients with PCG.
If estrogen levels are nonnal but no withdrawal
bleeding is observed with progesterone
admin~
istration, the history becomes important to de~
termine the presence of uterine anomalies responsible
for outflow tract abnormalities.
Ashennan's syndrome is
secondary amenorrhea
due to the destruction
of the
endometrium
and the development
of intrauterine
synechiae. The most common cause of Asherman's syndrome is uterine curettage, which may occur during the
course of a therapeutic
abortion. Infection is another
cause of intrauterine
scarring and synechiae formation.
II
High estrogen levels in the setting of secondary

amenorrhea
may indicate the presence of ovar
ian or adrenal tumors autonomously
secreting
androgens or estrogens or both. Secretion of androgens
such as androstenedione
provides a substrate for peripheral conversion to estrogen. The high levels of androgen
or estrogen result in amenorrhea
because of the sustained negative feedback effect on the hypothalamicpituitary control of the ovaries. Androgen produced by
ovarian or adrenal tumors may be sufficient to allow
peripheral production of estrogen but may not result in
signs of virilization.
Ovarian failure results in low estrogen levels.

The etiology of the ovarian failure can be determined by measuring the hypothalamic
hormones FSH and LH. Normal levels of FSH and LH
vary with the menstrual cycle, but postmenopausal
values provide the basis for comparison
in amenorrhea.
Postmenopausal
serum FSH values are 20 to 110 miU/
mll24 hr, and serum LI-I values are 20 to 80 mIU/mV
24 hr (where mIU/ml = milli-International
Units per
milliliter). Elevated
levels of FSH and LI-I indicate
that ovarian failure is primary. A karyotype should be
performed on any woman with primary Qvarian failure
to rule out a sex chromosome
abnormality, especially if
ovarian failure occurs before the age of 35. Accelerated
follicular atresia \vith subsequent
ovarian failure can
occur in patients with Turner's syndrome (XO chromosome abnonnality).
Thirty percent of women \vith the
presence of a Y chromosome
may be phenotypically
female without any signs of viriliz.1.tion. The possibility
of malignancy is high in patients with Y chromosome,
so that all gonadal tissue must be removed. Buccal
smears are an inadequate means of evaluating k:u)'otype
owing to the presence of mosaicism in this tissue.
Polycystic ovary disease (PCO), also known as

Stein-Leventhal
syndrome,
is a disorder
in
which the ovaries are enlarged, with numerous
follicular cysts and thecal hyperplasia.
High levels of
androstenedione
are produced by these ovaries. Levels
of luteinizing hormone (LH) are increased, but folliclestimulating hormone (FSH) is normal or decreased. In
addition to secondary amenorrhea,
women with this
Premature ovarian failure is deflncd as amenorrhea associated with elevated levels of gonadotrophins prior to age 40. Premature
ovarian
failure may be due to premature
menopause,
Savage
syndrome (insensitive ov,u;es), or follicular atresia due
to toxic exposure such as radiation, chemotherapy.
or
infection. Surgery and autoimmune
disease may also
cause follicular depletion and ovarian failure.
10 days. Withdrawal bleeding will occur 3 to 5 days

after progesterone
has been discontinued if endogenous
estrogen levels are adequate to stimulate endometrial
growth, and the amenorrhea
is due to anovulation. If
estrogen levels are low or withdrawal
bleeding does
not occur, the underlying problem is low endogenous
estrogen production.
Normal estrogen levels vary with
the nonnal cycle phase but will be less than 10 J-Lgl24hr
if endogenous estrogen production is low.
II
Pregnancy
GestaUonal trophoblastic tumors
-{
Tumors
Adrenal
Ovary
Lactation
Estrogen Ieve{
nonnaIIno
withdrawal
~ing
Polycyslic ovary disease
Trauma
-f
(peO)
Ashennan's syndrome
Hysterectomy
Infection
------.r
Gonadal
dysgenesis~
Tumer's syndrome
Y chromosome
Amenorrhea
~:I
9Prema,ure
menopause
, ,
Premature Savage syndrome Radtatlon
11 o~arian
failure
Toxic exposure
Surgery
:IChemotherapy
LViral
Autoimmune disease
Hypothalamic amenorrhea
Athletes
Nutritional deprivation
Extreme stress
(psychogenic stress)
12 Drugs
13
External radiation
Hyperproiactinemia
ldiopalhic
hyperprolactinemia
Cecil Chapter
PilUilary
adenoma
Craniopharyngioma
250
Pituitary lesion
Harrison
Chapter
52
Sheehan's syndrome
Inf'll
I'd'
-[
I ra lve lsease
TB
Empty sella syndrome
Sarcoid
Infarction
Endocrine Disorders
Amenorrhea 181
AMENORRHEA
(Continued)
Oral contraceptives, progestogens, synthetic estrogens, and TRH may directly stimulate pitu
itary lactotrophs and cause hyperproJactinemia.
Other drugs induce hyperprolactinemia by decreasing
dopamine synthesis, which in turn decreases prolactin
inhibition. Examples include mcyclic antidepressants,
opiates, anorexiants, monoamine oxidase inhibitors, phenothiazines, and thioxanthenes. Prolactin levels usually
are no greater than 100 nglm! when hyperprolactinemia
is drug-induced.
182 Endocrine Dlsorden
Amenonhea
III
Pituitary adenomas are a common cause of hyperprolactinemia (see No.4), and the sella must
always be evaluated when prolactin levels are
increased. In addition, in women with secondary ovarian
failure (Le., hypothalamic-pituitary dysfunction), the
sella must also be evaluated to rule out a pituitary
lesion. Evaluation of the seUa is most easily accom
plished by computed tomography (Cf) or magnetic resonance imaging (MRI).
III
Hypothalamic amenorrhea can result from a

variety of stresses. Amenorrhea has been well
documented in runners and ballet dancers, as
well as in patients with anorexia nelVOsaand nutritional
deprivation. Any stress, including surgical or physical
trauma, as well as emotional and psychological stress,
can result in amenorrhea. Serum prolactin levels arc
usually elevated with stress as well.
:.I
Pregnancy
Gestational
7
trophoblastic
tumors
-{
Tumors
Adrenal
Ovary
Lactation
Estrogen
level
Polycystic
ovary
(peO)
disease
normaVno
withdrawal
bleeding
Trauma
Asherman's
syndrome
L Hysterectomy
Infection
1
Amenon11ea
Gonadal
----.r
Turner's
dysgenesis
Y chromosome
~;~
,premeture
Premature
11ovarian
syndrome
menopause
Savage Syndrom~ Radiation

Toxk:exposure
Chemotherapy
failure
Surgery
Autoimmune
Viral
disease
Head injury
Tumor
Anorexia
Hypothalamic
amenorrhea
Athletes
Nutritional
deprivation
Extreme stress
(psychogenic
12 Drugs
13
External
Hyperprolactinemia
stress)
radiation
Idiopathic
hyperprolactinemia
P~uitary edenoma
Craniopharyngioma
Pituitarylesion
Cecil Chapter
Harrison Chapter
250
Sheehan's syndrome
Infilt
t" d"
_
I ra lve lsease ~
Empty sella syndrome
TB
Sarcoid
Infarction
52
Endocrine Dlsorde"
Amenorrhea 183
HIRSUTISM
Hirsutism is defined as tennina] hair growth
occurring on the body and face of a woman in
a pattern that is typical of the hair growth in
men. It is important to know the normal distribution of
terminal hair growth in women, because terminal hair
on the upper back, shoulders, upper abdomen, and ster
num is distinctly abnormal, whereas terminal hair on the
10000r
abdomen, around the areolae, and even on the
face may be normal. In addition, the division between
normal and abnormal hair growth in a woman is not
exact. because there are major variations in the normal
pattern due to race. Therefore, family histol)' and appearam,.'e of family members is very important in the
overall evaluation of a patient with hirsutism. A family
history of hirsutism does not rule out an endocrine cause
of abnormal hair growth, however. An evaluation should
be perfonned even in these patients, because familial or
idiopathic hirsutism is a diagnosis of exclusion. An<fro..
gens are resIX>nsiblefor tenninal hair growth in sex
honnone-responsive hair follicles. In women, the adrenal glands and the ovaries are equally resIX>nsiblefor
androgen production. The adrenal androgens (dehydroepiandrosterone [DHEA), DHEA sulfate, and anc:lrc?
stenedione) do not produce an androgenic effect on the
hair follicles directly but do 50 by peripheral conversion
to testosterone and its metabolites (e.g., dihydrotestosterone, or DHT). Testosterone and androstenedione are
secreted by the ovary. Androstenedione from the ovary,
as from the adrenals, must be converted to testosterone
to exert an androgenic effect.
The most important honnonal measurement in

the evaluation of hirsutism is the free serum
testosterone level. The bound fraction of testos
terone is biologically inactive so that, although the total
measured level of testosterone may be elevated, no
conclusions can be made relative to hirsutism if the
unbound portion is not measured. If the measurement
of free testosterone is not readily available, the ratio of
testosterone to sex hormone-binding globulin can iden
tify an abnonnality in hirsute women. A majority of
hirsute women can be demonstrated to have an increased
level of serum testosterone. Measurement of DHEA
sulfate can be done simultaneously but is a nonspecific
test in the evaluation of hirsutism (see No.5).
Exogenously administered androgenic agents

are a common cause of hirsutism. Women athletes may be reluctant to reveal the use of
anabolic steroids.
Hirsutism
Cushing's disease results from hypersecretion of

adrenocorticotropic honnone (ACfH). Clinical
features include diabetes, amenorrhea, hypertension, centripetal obesity, hirsutism, and acne. Cushing first described the disorder secondary to basophilic
adenoma of the pituitary, but any ACTH-secreting tumor can produce this disease. ACTH can be produced
ectopically by a number of tumors, including small cell
lung carcinomas, pancreatic islet cell tumors, and carcinoid tumors. In patients with Cushing's disease, only
about 50% have elevated plasma cortisol levels. Therefore, the 24-hour urinary free cortisol is the most reliable test to identify adrenal hyperactivity.
Although measurement of DHEA and DHEA
sulfate is often recommended as a screening test
for the detection of an adrenal carcinoma. the
best test for detection of an adrenal tumor is an abdominal CT scan. Extremely high levels of these hormones
may be present with adrenal tumors, but the levels of
these hormones may be elevated in a variety of other
disorders, including Cushing's disease, polycystic ovary
disease, ovarian tumors, and idiopathic hirsutism. Similarly, a pelvic examination and pelvic ultrasound are the
most sensitive measures to identify an ovarian neoplasm.
Both benign and malignant adrenal neoplasms
can produce androgens and cause hirsutism.

Adrenal carcinomas, however, are usually inefficient in their production of steroid hormones and can
grow to large size before they produce enough androgen
to cause hirsutism.
Ovarian tumors are uncommon causes of androgen production resulting in hirsutism. SertoliLeydig cell tumors account for half of all ovarian virilizing tumors but make up less than 0.2% of
all ovarian tumors. Most ovarian tumors resulting in
hirsutism are benign and well differentiated. Most granulosastromal cell tumors are feminizing and rarely
cause hirsutism.
Congenital adrenal hyperplasia (CAH) is associ
:
ated with hirsutism because androgen overproduction is the result of the overactivity of the
adrenals necessary to maintain nannal cortisol secretion.
The virilizing forms of CAH are caused by either 21hydroxylase deficiency, ll.hydroxylase deficiency, or 311hydroxysteriod dehydrogenase deficiency. The most
common cause of CAH is the 21-hydroxylase deficiency,
but its incidence is estimated to be only I % to 10%
among women \vith hirsutism. 21-Hydroxylase defi
ciency is inherited as an autosomal recessive trait and
may present as PCO. The best way to diagnose any
II
7
II
of these enzyme deficiencies is to perform an ACTH

stimulation test and measure the steroid precursor just
prior to the enzyme defect in the adrenal steroidogenic pathway.
Increased prolactin secretion is often associated
with increased levels of DHEA and DHEA sulfate. Prolactin has been found to augment the
ACTH-induced secretion of these l'A!O hormones by the
adrenals and is therefore thought to have a direct effect
on the adrenal glands. The increased levels of these preandrogens are responsible for the associated hirsutism.
Hyperprolactinemia is the most common mani
festation of pituitary hyperfunction. In addition
to prolactin-secreting adenomas, causes of nonphysiologic hyperprolactinemia include pharmacologic
agents such as Aldomet (methyldopa), reserpine, phenothiazines, estrogens, and narcotics. InBammatory or infiltrative diseases, such as sarcoidosis and histiocytosis,
hypothyroidism, renal failure, and hepatic cirrhosis, as
well as idiopathic hyperprolactinemia, may cause elevated prolactin levels. The sella must always be evaluated when prolactin levels are increased.
PCO is a diagnosis of exclusion. peo accounts
for 30% of all the di oses of hirsutism and is
the leading cause ofar:rsutism in women. The
clinical features of this disorder include hirsutism
1m
(>90%),
obesity (50%), virilization 25%),
and acne
50%). The etiology of PCO is poorly understood

and has been associated with insulin resistance and
hyperinsulinemia. In addition, mild elevations of prolactin levels have been found in up to 30% of patients with
PCO, which may explain, in part, the increased androgen levels in these women. peo is diagnosed on the
basis of the constellation of clinical findings, which include the aforementioned symptoms, as well as menstrual irregularity, elevated gonadotropin (LH or FSH)
levels, and polycystic ovaries detected by pelvic ultrasound examination.
Hirsutism for which no abnonnality is found
can be diagnosed as idiopathic hirsutism. Idiopathic hirsutism accounts for only 10% of all
hirsutism and is a diagnosis of exclusion. These patients
have excessive male-pattern hair grow1.h,which can be
mild or diffuse and severe; normal menstmal cycles;
and normal semm testosterone. Because it is the local
conversion of androgens to OHT by Sa-reductase that
is responsible for the end-organ response (hair growth)
to androgens, it has been h)1lOthesized that the hirsutism in these patients may be due to an increase in
Sa-reductase activity in the skin.
II
Testoslerone
Oenez"
ACTH
Drug-induced hirsutism
Metyrapone
Anabolic steroids
Progestins
Adrenal
carcinoma
Androgen-producing tumors (adenomas)
{
Adrenal tulTl()(
Granulosa-stromal celllulTlOfS
Sertoll-l.eydig cell tumors
AntIenobIaslomas
Ovarian tumor
~
Hilar cell tumors
21-hydroxyiase defidency
l1-hydroxylase defidency
~roxysteroid
Idiopathic hyperprolactinemia
dehydrogenasede_
Pituitary adenoma
ONgS
Sarcoidosis
Polycystic ovary disease (peO)
Polycystic ovary disease (PCO)
Cecil Chapter
255
Ana,;"
12 Idiopathic hlrsuti
13 Hypertrichosis
Congenital
Harrison Chapter
Hypertichosis is androgen-independent
53
hirsu-
tism. In androgen.independent
hair growth,
there is an increase in the nonsexual hair of the
body. Androgen-dependent hairs arc those hair growth

areas where men usually bec..:ome hirsute after adoles-
cenee. The growth of hairs that are not unique to men,
e.g., the eyelashes and eyebrows, are androgen-independent hair follicles. Hypertrichosis can be localized or
generalized and often is more vellus than terminal hair
growth. Nonandrogenic drugs, the porphyrias, a variety
Cydo,ponn
Porphyrias
Phenytoin
Malignancy
Nonandrogenic drugs
Oiazoxide
Minoxidil
Chlorobenzene
Penicillamine
Psoralens
of congenital syndromes (including the fetal alcohol

syndrome), and malignant tumors can be associated
\'lith diffuse hair growth.
Endocrine Disorders
Hirsutism 185
THYROID
NODULE
Although most solitary thyroid nodules are benign, the discovery of a thyroid nodule requires
investigation to role out the possibility of malignancy. In addition, even if a thyroid nodule is identi6ed
to be a benign lesion, its function and growth are important to identify and follow. A hyperfllnctioning autonomous benign nodule may lead to thyrotoxicosis.
Thyroid nodules occur in 1% to 5% of the adult popula-
tion, and are four times more common in women than
in men. The incidence of single thyroid nodules that are

malignant is estimated to be between 0.1% and 0.2%.
II
Although many tests have been proposed for

the initial evaluation of a thyroid nodule, a needle aspiration biopsy is the most informative
and cost-effective initial test if it is performed by an
experienced operator. Needle aspiration biopsy is indicated because open biopsy of the thyroid presents unnecessary risks to important neck struchtres, especially
because most solitary nodules are benign. Many other
"first tests" have been suggested to rule out thyroid
carcinoma, including TFTs (carcinomas are usually
poorly functioning, so TITs are usually normal), radioiodine thyroid scan (most thyroid nodules are "cold" on
scan), and ultrasonography (cystic lesions are less likely
to be cancerous). All of these tests are nonspecific,
however, because hyperfunctioning lesions ("hot" nodules) can be cancerous, "cold" nodules are often benign,
and cystic lesions may occasionally be cancerous. All of
these tests can add information in the evaluation of
thyroid nodules but are of limited usefulness because
they do not accurately differentiate between benign and
malignant lesions.
Needle aspiration biopsy is most useful if cytology is interpreted as definitely benign or definitely malignant, which can be done for 60% to
80% of the patients. In the other 20% to 40%, however,
cytology is not as clear, and approximately one fourth of
patients with thyroid nodule aspirates of unclear cytology will ultimately be found to have thyroid malignancy.
A suspicious aspirate should therefore be considered a
positive result and be followed by open biopsy of the
thyroid. Papillary carcinoma of the thyroid is the most
common type of thyroid carcinoma and carries the best
prognosis. Approximately 50% to 60% of thyroid carci
nomas are papillary or mixed papillary. follicular carcinoma. Another 25% of malignant thyroid nodules are
186 Endocrine Disorders Thyroid Nodule
follicular carcinoma. Needle aspiration biopsy may not

always distinguish between a benign follicular adenoma
and follicular carcinoma. Because these lesions can be
well differentiated, only the presence of capsular and
vascular invasion will indicate that the lesion is malignant and is found on open biopsy. Undifferentiated
carcinoma accounts for 15% and medullary carcinoma
for 5% of thyroid carcinomas. Metastatic carcinoma to
the thyroid is rare, as is lymphoma involving the thyroid,
but they can also be identified by needle aspiration bi
opsy.
If the needle aspiration biopsy is inadequate
or equivocal, benign disease is a diagnosis of
exclusion (see No.3). Sampling error can occur,
especially when the nodule is large. Numerous samples
from various areas of a large nodule must be performed
before a nodule can be considered benign. Risk factors
that would direct the clinician toward surgical interven
tion with an equivocal needle aspiration cytology include
any history of prior head and neck irradiation (e.g.,
acne, thymic enlargement, tonsillar enlargement), male
sex (malignant nodule is twice as likely in men), age
under 20 or over 60, family history (medullary carci
noma), palpable Iympb nodes, or a hard, fixed nodule
on palpation. Patients with risk factors for thyroid carcinoma should undergo surgical removal and histologic
diagnosis of the nodule, rather than simply periodic
follow-up examinations.
In patients with negative needle aspiration results and no risk factors for thyroid carcinoma,
imaging techniques may be helpful in evaluating the thyroid nodule. If a radioiodine scan is performed, a nonfunctioning or cold nodule is more likely
carcinoma (thyroid carcinoma is not very efficient at
trapping iodine and synthesizing thyroid hormone),
whereas a functioning or hot nodule is less likely to
be carcinoma. tJkewise, with ultrasonography, a cystic
nodule is less likely to be carcinoma, although cystic
degeneration can occur in any mass, including carcinoma. Because imaging techniques are poor predictors
of malignancy, close clinical observation and repeat needle aspiration biopsy are necessary until a definite diagnosis is made.
If thyroid scan reveals a cold nodule, needle

aspiration biopsy is negative, and risk factors for
thyroid carcinoma are absent, a repeat needle
aspiration biopsy is indicated prior to open biopsy. If a

second aspiration biopsy is negative, then suppression
of the nodule should be undertaken by administering
thyroid honnone. If the nodule increases in size despite
suppression, open biopsy is indicated.
A warm nodule is a nodule that functions the
same as the surrounding thyroid tissue. A hot
nodule is a hyperfunctioning nodule. Most
functioning nodules are benign. Both hot and warm
nodules can be followed clinically without treatment if
the patient remains asymptomatic. Functional suppression of the nodule can be attempted by administering
thyroid hormone. If the nodule increases in size despite
suppression, or the patient remains hyperthyroid, treatment is indicated.
II
Most solitary thyroid nodules are benign adeno~

mas. Ninety percent to 95% of thyroid adenomas are nonfunctioning and exist as asymptomatic neck masses. With growth, these lesions may rarely
cause problems secondary to compression of other neck
struchtres. Functioning follicular adenomas usually do
not cause hyperthyroidism unless they are greater than
3 cm in diameter.
:
A colloid nodule is a mixed cystic-solid area

that results from cycles of hyperplasia followed
by involution of a thyroid lobule. The nodule
may contain areas of necrosis, fibrosis, and hemorrhage,
but it mainly consists of large colloid-filled follicles lined
by typical cuboidal epithelium. A colloid nodule can
form clusters leading to a multinodular goiter.
lEI
Owing to its anatomic location, a parathyroid

adenoma can present as an apparent thyroid"
mass. Parathyroid adenomas presenting as neck
masses are extremely rare.
Multinodular goiters may contain hyperfunctioning and hypofunctioning areas, visible a" hot
and cold nodules on thyroid scan. If risk factors
for thyroid carcinoma are rresent (see No.4), surgical
intervention is necessary. I a single cold nodule continues to enlarge despite absence of risk factors, needle
biopsy of that nodule may be adequate to determine
the presence or absence of malignancy.
Papillary carcinoma
Thyroid carcinoma
:-{
Metastatic carcinoma
Lymphoma
1
Thvrold nodul.
Follicular carcinoma
Undifferentiated
carcinoma
Medullary carcinoma
Thyroid carcinoma
Tllyroid carcinoma
Benign nodule
(see
8
9
10
11
Cecil Chapter
339
Harrison
331
Chapter
Thyroid adenoma
Colloid nodule
=---1
Parathyroid adenoma
Goiter
Hematoma
Thyroiditis
Hyperplastic lobe
belOW)
Microlollicular
Macrofollicutar
Embryonal
Oxyphil
Endocrine Disorders
Thyroid Nodule 187
THYROID ENLARGEMENT
An enlarged thyroid can be diffusely enlarged
multinodular (multincxlular goiter), or
partially enlarged (single thyroid nodule). Enlargement of the thyroid suggests nothing about the
thyroid's function, because an enlarged thyroid can be
hyperfullctioning (hyperthyroid), normal functioning
(euthyroid), or hyporunctioning (hypothyroid). The evaluation of an enlarged thyroid is undertaken principally
to dctennine the thyroid function and metabolic status
and to evaluate for the presence or absence of malig-
(goiter),
nancy.
II
Lithium ingestion may cause thyroid enlargement but is most often associated with hypothyroidism. Thyroid hormone replacement can
cause iatrogenic hyperthyroidism if the replacement
dose is too rligh. Thyroid hormone is often ingested by
patients (usually women) as a method of weight controL
Many times, tllyroid hormone is ingested surreptitiously,
and any history of exogenous thyroid ingestion is denied.
Thyroid function tests, along with the history
and physic'll examination, are very useful clues
to the di3gnosis of an enlarged thyroid. Despite
thyroid gland enlargement, however, most of these thyroid diseases may be accompanied by varying degrees
of hypcr-, hypo-, and euthyroid states at various times
during the course of the disease. Hashimoto's thyroiditis, for example, often presents as hypcrthyroidism but
ultimately results in hypothyroidism. Hashimoto's auto.
immune thyroiditis is the most common cause of hypothyroidism. Thyroid function can be determined by
measuring TSH and the free T. index and free triiodothyronine (T3) index (referred to in the algorithm as
Mindiccs").l11e combination of these measurements can
help to determine the source of the thyroid gland dysfunction. (Scc 190.) (Abnormall11yroid Function Tests
algorithm.)
Thyroid carcinoma is a rare cause of hyperthyroidism. Most thyroid carcinomas are nonfunctioning so that the patient is euthyroid despite
thyroid enlargement. Thyroid enlargement, therefore, is
more often due to tumor infiltration and growth than to
hypcrfundioning thyroid tissue.
~
188 Endocrine ~isorders
Thyroid Enlargement
Acute thyroiditis is rare. The condition is due

to bactcrial infection of the thyroid gland, and
thyroid function tests are usually normal. Clinical symptoms include an enlarged, tender thyroid and
fever.
II
early Hashimoto's disease (see No. 11) and to Graves'

disease. Subacute lymphocytic thyroiditis can be differentiated from Craves' disease on the basis of the low
radioactive iodine uptake, and from Hashimoto's disease
by a low anti microsomal antibody titer (see No. II).
Graves' disease (diffuse toxic goiter) is the most

common cause of goiter and hyperthyroidism.
It is an autoimmune disease in which a serum
immunoglobulin (antibody) acts to stimulate thyroid
function. Clinical features of Craves' disease (also
known as Basedow's disease in most of Europe) include
symptoms of hyperthyroidism, a diffusely enlarged thyroid gland (goiter), exophthalmos with symptoms of
burning, itching, and tearing, and pretibeal dermopathy.
Hashimoto's thyroiditis, also known as chronic

lymphocytic thyroiditis, is an autoimmune disease of the thyroid gland. Hashimoto's disease
is the most common thyroid disorder in the United
States. It most often presents with a painless palpable
goiter, usually initially euthyroid but ultimately almost
always hypothyroid. In 5% to 10% of patients, Hashimoto's disease presents with hyperthyroidism, which
must be distinguished from Craves' disease. Most often
the serum free T. index.is low and the TSH is elevated,
but the diagnosis is based on the demonstration of
circulating antimicrosomal antibodies, which are present
in approximately 95% of patients with the disease. Approximately 50% to 60% of patients also have circulating
antithyroglobulin antibodies in their serum as well. Radioactive iodine uptake may be normal, low, or increased in Hashimoto's thyroiditis.
Rarely, trophoblastic tumors can stimulate thyroid gland h)1>ertrophy and hyperfunction via
secretion of large amounts of HCG. HCG has
some biologic cross-reactivity with T5H and can stimulate the thyroid gland directly.
The jodbasedow phenomenon refers to hyperthyroidism induced by iodine supplementation.

Most patients with this phenomenon are patients with underlying Crave's disease who are given
iodine in sufficient amounts to provide substrate for the
diseased gland's overproduction of thyroid hormone.
II
II
Riedel's thyroiditis is a rare disorder of unknown etiolo in which the thyroid gland is
gradually infifP:ated by a sclerosing fibrous infiltration, ultimately resulting in hypothyroidism and a
finn, enlarged gland.
II
II
1m
III
Subacute granulomatous thyroiditis (de Quer

vain's thyroiditis) presents as a painful thyroid
enlargement, often with systemic symptoms of
fever, malaise, and chills. It occurs more commonly in
women (3: 1), usually in their third to fifth decades of
life. Although the etiology is unknown, the condition
usually follows a viral infection by several weeks. Histologically, the thyroid gland is infiltrated with lympho.
cytes, ncutrophils, and multinucleate giant cells characteristic of granulomas.
Subacute lymphocytic thyroiditis, in contrast to

de Quervain's disease, is a painless thyroiditis
with hyperthyroidism, thyroid gland enlarge~
ment, and histologic lymphocytic infiltration of the thyroid gland. The etiology of the disorder is unknown but
is thought to be an autoimmune mechanism. The features of subacute lymphocytic thyroiditis are similar to
Endemic goiter refers to thyroid enlargement

found in a large fraction of the population,
usually caused by environmental influences.
Most commonly a result of iodine deficiency. the disorder is now very rare in the United States as a result of
the iodinization of salt. l11e thyroid enlargement is due
to hypersecretion of TSH, which occurs in response to a
decreased production of thyroid hormone, especially T.
Sporadic goiter is presumed to be due to an
enzymatic defect in one of the steps of thyroid
hormone production, leading to low thyroid
hormone levels and elevated levels of serum T5H.
~
Pituitary adenoma may secrete TSI-I autonomously without sensitivity to negative feedback
regulation.
Dietary iodine excess

Lithium
Jodbasedow phenomenon
Thyroid hormone ingestion
Thyroid carcinoma
Euthyroid goiter
Graves' disease (diffuse toxic goiter)
Thyroid carcinoma
Plummer's disease
(toxic multinodular goiter)
Acute thyroiditis
Toxic uninodular goiter

Trophoblastic tumor --{
Choriocarcinoma
Hydatidiform mole
Testicular embryonal carcinoma

8 Jodbasedow phenomenon
....
9 de Quervain's thyroiditis
FactitIouS hyperthyroicftsm
(subacute granulomatous thyroiditis)
Struma ovani
10
Thyroicfitis
Subacute
Subacute lymphocytic thyroicfitis
1
Thyroid
enlargement
(goiter)
Suppurative thyroiditis
Hashimoto's disease
Chronic 11 (chronic lymphocytic thyroicfitis)
~1 Riedel's struma
Radiation-induced
(See algorithm for thyroid

nodul., pegs 187)
13
Endemic-{
gofter
Iodine deficiency
Environmental goitrogen
14
Sporadic goiter
[ Uthium ingestion
Chronic thyroiditis -{
Cecil Chapter
239
Harrison
331
Chapter
15 TSH
excess
Hashimoto's thyrooitis
Riedel's thyroiditis
[ Pituitary tumor (adenoma)

Pituitary insensitivity
Endocrine Disorders.
Thyroid Enlargement.
189
LABS
ABNORMAL THYROID FUNCTION
TESTS
Thyroid function may be assessed as part of a
routine chemistry panel even in the absence of
any clinical signs of thyroid abnonnality. Thyroid dysfunction can be difficult to recognize clinically
when the disorder is early or mild or when the patient is
elderly. The prevalence of clinically inapparent thyroid
disorders in elderly women makes this subgroup a popu
lation in which thyroid testing is an important adjunct
to the history and physical examination. A free T~ index
(Fr.!) is the most commonly used means for screening
for thyroid abnormalities. The index is a measurement
that takes into account the amount of thyroxine-binding
globulin (TBG) and the number of binding sites on
TBG available to bind T. The index corrects for falsely
elevated levels of measured T 4 seen in conditions with
increased TBG, such as pregnancy or estrogen administration, and falsely low levels ofT4 with decreased levels
of TBG as occurs in cirrhosis of the liver. In 5% of
cases with hyperthyroidism, the T4 level is within the
reference range and only the T3 level is elevated. This
condition is known as T3 toxicosis and can be confirmed
by measuring the total T3 level. T3 toxicosis can represent mild or early hyperthyroidism and can occur with
any cause of hyperthyroidism.
An elevated Fl41 indicates possible hyperthyroidism, but hyperthyroidism must then be confirmed by measuring the free T3 index (FT3I).
Hyperthyroidism is confirmed if both the FT41 and the
FT31 are elevated.
II
Measuring the TSH level helps to establish the

source of hyperthyroidism. If hyperthyroidism
is primary (due to primary thyroid gland dysfunction), the TSH level will be low. An ultrasensitive
assay that is used to detect TSH is available: high.
sensitivity TSH (HS-TSH). The accuracy and availability
of the HS-TSH may preclude the use of the TRH
stimulation test (see Nos. 11 and 12).
II
Thyroid carcinoma is a rare cause of hyperthyroidism, because thyroid carcinoma makes thyroid hormone inefficiently. Occasionally a large,
well-differentiated thyroid carcinoma can make sufficient thyroid hormone to result in clinically apparent
hyperthyroidism.
:.l
190 Endocrine
Dlscrden
The most common cause of hyperthyroidism is

Graves' disease. The disease is due to the presence in the circulation of abnonnal thyroidstimulating globulins. The measurement of thyroid.
stimulating immunoglobulins (TSls) can confirm the
diagnosis of Graves' disease (see No.6, ThYTOidEnlargement algoritllm).
Toxic multinodular goiter is a cause of hyperthyroidism, usually occurring in an elderly patient
with a long history of goiter. The onset of hyperthyroidism is gradual and is due to growth of nodules
within the goiter. Some of these nodules may eventually
become autonomous in their secretion of thyroid hormone.
Human chorionic gonadotropin (HCG) has a
slight biologic cross-reactivity with TSH. Rarely,
trophoblastic tumors such as hydatidiform mole
and choriocarcinoma, as well as embryonal carcinoma
of the testis, can secrete HCG in large enough quantities to result in hyperthyroidism.
Thyroiditis may result in the release of excessive
amounts of thyroid hormone and cause hyperthyroidism. Examples include inflammation following treatment with irradiation or 131
I therapy, and
chronic lymphocytic thyroiditis.
Thyroid hormone replacement therapy of hypothyroidism can result in iatrogenic hyperthyroidism if the replacement dose is too high.
When hyperthyroidism is due to surreptitious ingestion
of thyroid hormone, serum thyroglobulin levels and radioactive iodine uptake will be low.
Struma ovarii refers to the presence of thyroid
tissue in an ovarian teratoma or dermoid tumor
that may produce excess amounts of thyroid
hormones.
If the FT41 is elevated but the FT3I is within
the reference range, hyperthyroidism is not excluded, but the possibility of a nonthyroidal
illness (NTI) as the source of thyroid function abnormalities must be investigated. At times, a hyperthyroid
patient with an NTI will have this constellation of lab
findings despite the presence of hyperthyroidism. The
clinical settings will determine the need for further
investigation. In general, further testing can be deferred
until the patient nas sufficiently recovered from a nonthyroidal illness. In some instances, however, a TRH
stimulation test can be used to clarify borderline thyroid
function tests. The TRH test is most useful when the
FT41 and the FT31 levels are equivocal and hyperthyroidism is suspected, or when the FT411evei is low and
II
Abnonnal Thyroid Function Tests
TSH is not clearly elevated. A rise in TSH after TRH

stimulation excludes the presence of hyperthyroidism
and efTectively explains the constellation of lab abnormalities as due to the nonthyroidal illness (see No. 19).
Some drugs, such as high-dose propranolol, umiodarone, and radioiodinated contrast agents, can inhibit the
conversion of T4 to T3 so that the FT4I will be elevated
and the FT31 will be low.
The TR H stimulation test is performed by injecting 400 to 5OO ..g of synthetic TRH and
measuring the TSH level just prior to injection
and at 30 minutes after injection. Normally the TSH
rises to 5 to 25 ~IU/ml at 30 minutes after TRH injection. If hypothyroidism is present and is due to thyroid
gland dysfunction, the TSH response is markedly increased. In secondary hypothyroidism, TSH will not
rise, or a delayed rise will be seen. Even mild hyperthyroidism eliminates the TSH response to TRH. In addition, glucocorticoids, somatostatin, and dopamine inhibit TSH secretion and blunt the TSH response to
exogenously administered TRH.
If the FT4I is decreased or in the low normal

range, hypothyroidism is suspected but must be
confirmed by measuring the serum TSI-I level.
An Fi3I is not helpful in this setting. because the value
will be within the reference range in lip to 20% of
patients with hypothyroidism. The combination of a low
FT41 and an elevated TSH (>20 mlUIL) is diagnostic
of primary hypothyroidism.
The most common cause of hypothyroidism is
:.l
Hashimoto's thyroiditis, also known as chronic
lymphocytic thyroiditis or autoimmune thyroiditis. The exact nature of the autoimmune disorder is not
known. Transition from the hypothyroidism of autoimmune thyroiditis to hyperthyroid Graves' disease has
been described.
III
II
Antithyroid drugs used for the treatment of

hyperthyroidism can result in hypothyroidism.
Drugs such as lithium can block the release of
thyroid hormones and result in hypothyroidism. Iodine
can inhibit release of thyroid hormone as well and can
occasionally cause hypothyroidism. Other agents that
may rarely cause hypothyroidism include resorcinol,
para-aminosalicylic acid, phenylbutazone, and cobalt.
II
The second most common cause of hypothyroidism is iatrogenic hypothyroidism resulting

from the destruction of the thyroid by surgical
procedures, radioactive iodine, or radiation treatment of
hyperthyroidism.
Secondary hyperthyroidism-pituitary
neoplasm
Thyroid hormone resistance

Dysalbuminemic
hyperthyroxinemia
4~ThYrO;d
carcinoma
5
Graves' disease (toxic diffuse gofter)
Toxic multinodular goiter (Plummer's disease)

Toxic uninodular goiter
1
Abnonnal thyroid
function testa
(FT .I measured)
Trophoblastic
tumor
Thyroiditis
11 FT311oworin
normal ran
10
,Iatrogenic
Drug-indUced
Factitious
Strumaovarii
Iodine administration
Pituitary neoplasms
Substernal goiter
Psychiatric illnesses
Endemic bone deficiency

Spontaneous
14
Hashimoto's
thyroiditis
Primary hypothyroidism
15
rUthlUm
DruQs,----_[lodide
Riedel's thyroiditis
Antithyroid agents
16 latrogenic,-----------cAadioactive
17 de Quervain'sdisease
iodine
Ionizingradiation
Congenital thyroid abnonnalities

Discontinuing
Surgical ablation
(absence)
thyroid replacement therapy
Y
EUth <Oid---1'
sick~rom.
::::~ronin.
Drugs
Furosemide
Heparin
Salicylate
Subnormal T 3 binding
Irradiation
p..
(
nd)
nuitary seco ary -{
Cecil Chapter
239
Hamson Chapter
331
20 Hypothyroidism
-{
Tumor
~ita~sm
(Sheehan'ssyndrome)
Infinrativ8dIsease
Hypothalamic
(tertiary
Tumor
Inflnrative disease
rf
Irradiation
Endocrine Dlsorden
191
ABNORMAL THYROID
TESTS (Continued)
II
FUNCTION
Subac~te thyroiditis (de uervai,o's thrroiditis)

is a dIsease of unclear etIology m whIch transient hypothyroidism may be present for periods of 1 month to 1 year. Also known as subacute
granulomatous thyroiditis, it often follows an acute viral
infection by several weeks. Although adenovirus. CQXsackievirus, and influenza virus have all been implicated,
the precise cause remains unknown. Permanent hypothyroidism is rare with this disorder.
II
:
The halflife of T4 is 6 days. When thyroid

replacement
is discontinued
in a hypothyroid patient, the FT4I falls rapidly but the TSH
level may remain within the reference range for 4 to

6 weeks.
lEI
Euthyroid sick syndrome refers to abnormalities

of thyroid function tests associated with nouthyroidal illness. In the setting of an acute illness,
a low T~with a normal or slightly elevated TSH may be
due to the acute illness rather than to true thyroid
disease. The tests should be repeated once the illness
has resolved. If the diagnosis of hypothyroidism is
strongly suspected in the setting of equivocal laboratory
values and nonthyroidal illness, a TRH stimulation test
can be helpful in establishing a diagnosis (see Nos. 11
and 12).
II
Pituitary and hypothalamic (secondary and tertiary) causes of hypothyroidism are rare. Lesions that would produce secondary or tertiary
hypothyroidism would interfere with other endocrine
functions as well, so the clinical setting and the presence
of other signs and symptoms of endocrine dysfunction
should be present before further laborcltory evaluation
is performed. A TRH stimulation test will add valuable
information to determine the presence of secondary
hypothyroidism (see No. 12). In primary hypothyroidism, the TSH rise is exaggerated. (>25 I-LIU/ml)with
TRH stimulation. In secondary or tertiary hypothyroidism, the rise in TSH may be delayed., blunted, prolonged, or absent after TRH stimulation.
Secondary hyperthyroidism-pituitary
neoplasm
Thyroid hormone resistance

Dysalbuminemic hyperthyroxinemia
'~Thyrokl carcinoma
5 Graves' disease (toxic diffuse goiter)
6 Toxic multinodular goiter (Plummer's disease)
Toxic unlnodular goiter
proprano
DrugSl
7 T rophobIastlc tumor
""
Amiodarone
~-F=
Iodine contrast
11
1
Abnormal thyroid
function tests
(FT I measured)
StI\lma ovari!
Iodine administration
Substernal goiter
Endemic bone deficiency

Spontaneous
Hashimoto's thyroiditis
Prtmary hypothyroidism
15
Drugs--
UthI
.r 100:
.---
Riedet's thyroiditis
16
17
[Antithyroid
agents
latrogenic'
rSurg)cal ablation
----'[Radioactive
kxtine
de Quervain's disease
Congenital_
lonlzlng radiation
abnOm1aIltles
(absenCe)
Discontinuing thyroid replacement therapy
EuthY-----1S~S~n>M
::~;ne
Drugs
Furosemide
Heparin
Salicylate
Subnonnal T:) binding

Irradiation
Pituitary (secondalY)
-{
Hypothyroidism
-{
Cecil Chapter
239
Hamson
III
Chapter
Tumor
Hypopituitarism (Sheehan's syndrome)
Hypothalamic (tertiary~
Tumor
InfiltraUve disease
Irradiation
Endocrine
Disorders
193
HYPERLIPIDEMIA
Hyperlipidemia is defined as an increase in the
concentration of plasma triglycerides, cholesterol, or both. Hyperlipidemia can be discovered
inadvertently, because measurements of triglycerides
(TGs) and cholesterol (chol) are included in many routine blood panels. Blood must be obtained from patients
after a 12- to 14-hour fast, however, because postprandial
chylomicronemia can increase TG levels substantially.
The cutoff points for diagnosing hyperlipidemia are
largely arbitrary, because the distribution of lipoprotein
concentrations in the population is continuous. The importance of the diagnosis of hyperlipidemia lies in the
fact that there is a positive correlation between plasma
cholesterol levels and the prevalence of coronary artery
disease (CAD). Hypercholesterolemia is defined as the
90th percentile of the population distribution, separated
by age and sex. Hypertriglyceridemia is defined by values
in the upper 5% of the distribution. The prevalence of
genetic disorders increases at higher cutoff points. The
hyperlipidemias have been classified most commonly on
the basis of lipid phenotype. This classification has been
outlined and described as types I through V based upon
lab findings independent of genetic or pathophysiologic
mechanisms. The primary hyperlipidemias can also be
classified on the basis of genetic mechanisms. Manage
ment of hyperlipidemia depends primarily upon which of
the blood lipids are elevated (either TGs or cholesterol),
regardless of the genetic or phenotypic subtype. Therefore, these classification schemes are not of practical
significance in the diagnosis and treatment of the hyperlipidemias. The lipoprotein profile for an individual can
change with time and will change as other diseases are
superimposed.
194 Endocrine Disorders Hyperlipidemia
If hyperlipidemia is discovered inadvertently,

testing should be repeated on a fasting blood
sample. The basic testing that should be perfonned includes total cholesterol level, TG level, and
high-density lipoprotein (HDL) level. Low-density lipoprotein (LDL) levels can be estimated from the fonnula
LDL=total serum cholesterol-HDL-TGIS

although the TG level must be less than 4()() mydl
for this estimation to be accurate. The level of LDL
cholesterol is important to know, because increased levels of LDL are associated with increased incidence
of atherosclerosis. High levels of HDL cholesterol are
correlated with a decreased prevalence of atherosclerosis. The combination of these tests should provide
enough information to detennine the abnonnallipoprotein type. Electrophoresis will also identify verylowdensity lipoprotein (VLDL), chylomicrons, LDL, and
HDL levels. However, even with electrophoresis it may
not always be possible to distinguish between the primary and secondary causes of hyperlipidemia. Primary
byperlipidemias have a genetic basis, and the molecular
defect is known in at least five of these disorders. Secondary hyperlipidemias are due to systemic diseases in
otherwise normolipemic persons. Secondary causes of
hyperlipidemia must be sought and treated on an individual basis before the diagnosis of a primary disorder
can be made. In addition, it is possible for an individual
to have a primary disorder upon which a secondary
disorder is superimposed. In such cases, the abnonnal
lipid profile due to the systemic disorder can alter the
lipid profile of the primary disorder.
Elevated TG levels are due to increased chylomicrons or increased VLDL levels. In general, patients with TG levels of less than
1000 mg/ill rarely have chylomicronemia, and the pres
ence of chylomicronemia suggests that the patient did
not fast. Patients who have eaten a large dinner accompanied by a large amount of alcohol will manifest a
transiently high fasting TG level. If chylomicronemia is
absent, serum TG levels are correlated with elevated
VLDLTGs.
II
Familial lipoprotein lipase (LPL) deficiency is

classified as type I hyperlipidemia. It is characterized by grossly lipemic fasting plasma with
elevated chylomicrons. The disease is rare and manifests
its symptoms in childhood. Symptoms include eruptive
xanthomas of the skin, recurrent episodes of pancreatitis
and abdominal pain, hepatosplenomegaly, and lipemia
retinalis. A deficiency of the activator of LPL, apolipo.
protein C-II(apoC.II), results in a similar syndrome.
~
The most common but most poorly defined

pattern of hyperlipidemia is the so-called polygenic hypercholesterolemia. The term refers to
a group of patients with increased levels of total cholesterol with LDL above the 90th percentile for the population, but without a well-defined mode of inheritance.
It is thought that environmental influences (primarily
dietary) superimposed on a permissive genetic background are responsible for this disorder. This lipid disorder probably accounts for 80% to 90% of the individuals
with a type II lipid profile.
Secondary
Increased
hypenipidemia
----f
Hypergammaglobulinemla
Diabetes mellitus
with SLE (type I)
Drugs
chylomicrons
Primary
1
Hyperlipidemia
> 200 mgldl,
> 250 mgldl)
4[
hypenipidemia
Faml1lallipoprotein
Familial deficiency
lipase deficiency (type I)

of apoc.lI (type I)
Elevated TGs,
elevated c~sterol
(chol
TGs
Elevated cholesterol
(> 200 mgIdl),
normal triglycerides
Acute
Secondary
inlerminent
Renal failure
hypercholesterolemia
Obstructive liver disease

Hypothyroidism
Cecil Chapter
206
Harrison Chapter
341
hypercholesterolemia
(AlP)
Anorexia nervosa
Dysgammaglobulinemia
-{
Primary
porphyria
type lIa
d
5
Familial hypercholesterolemia
Familial combined hypenipidemia
Polygenic hypercholesterolemia
Endocrine Disorders
Hyperlipidemia 195
HYPERLIPIDEMIA
(Continued)
fn the absence of chylomicronemia, hypertriglyceridemia can be attributed to elevated levels of VLDL. However, if an increased level of
VLDL is responsible for hypertriglyceridemia. there will
be an increase in the cholesteror level as well, because
VLDL contains both cholesterol and TCs. This combination of findings defines type IV hyperlipidemia.
Drugs such as alcohol, estrogens, diuretics, and

a-blocking agents may elevate levels of TGs,
but the effect is usually mild unless these drugs
are superimposed on a genetically hyperlipidemic patient. Oral contraceptives can cause hypertriglyceridemia. Estrogen replacement in postmenopausal women
raises the total cholesterol level, but the LDL level is
actually decreased and the HDL level is increased,
thereby possibly decreasing overall cardiovascular risk.
Familial hypertriglyceridemia (FHT) can be

manifested with a type IV lipid profile. The
diagnosis of type IV FHT is suspected when
the TC level is elevated and the total cholesterol level
is mildly elevated. Eruptive xanthomas are uncommon
in type IV FHT. Superimposed disorders, such as diabetes mellitus, obesity, alcoholism, hypothyroidism, or estrogen use, can markedly worsen the lipid profiles in
type IV FIIT.
II
Familial combined hyperlipidemia (FCH) can

manifest itself by a variety of different lipidin>files, most commonly as types lIa, lIb, an IV
Profiles may be different among members of the same
family. In addition, lipid profiles may change in any
individual with time. The disorder is thought to be inherited as an autosomal dominant condition. The diagnosis
of type IV FCH is suspected when the TG level is
elevated and the total cholesterol level is mildly elevated.
196 Endocrine Disorders Hyperlipidemia
1m
Diabetes mellitus is often associated with hypertriglyceridemia. The increase in TGs in

these patients may be due to insulin deficiency
or associated with obesity and hyperinsulinemia.
Marked elevations of TGs, however, should lead to the
suspicion of an underlying familial fonn of hypertriglyc.
eridemia upon which diabetic hypertriglyceridemia has
been superimposed.
II
Type V FHT is usually more severe than type

IV FHT (see No.8). Type V FHT causes elevated levels of cbylomicrons, VLDL, and cholesterol, whereas type rv FHT causes elevated VLDL
and mildly elevated levels of cholesterol. without associ
ated chylomicronemia. It may be difficult to distinguish
the familial fonn of a type V pattern from secondary
causes of this lipid pattern, such as estrogen use, alcohol
use, and diabetes mellitus, but family screening may be
useful. Clinically, patients with type V FHT demonstrate
eruptive xanthomas and recurrent bouts of abdominal
pain or pancreatitis. Superimposed estrogen use, alcohol
excess, and diabetes may decrease the age of onset of
symptomatic disease, which is usually between 20 and
50 years of age. These modifying influences may also
markedly increase the TG levels.
II
Familial dysbetaproteinemia is a lipoprotein

disorder in which levels of total cholesterol and
TGs are elevated to an equal degree. Serum
cholesterol between 300 and 1000 mg/dl may be seen.
Clinically, patients manifest coronary artery disease. pc.
ripheral vascular disease, and xanthomas, including tendon xanthomas of the Achilles and extensor tendons
of the hands. Thberous xanthomas are common. Lipid
electrophoresis will help to identify this abnormal lipoprotein profile in which the pre~ band (VLDL) is
increased. Although the total cholesterol level is elevated, levels of HOL and LDL are low (type III pat
tern). The increase in total cholesterol can therefore be

explained on the basis of the VLOL fraction, which
differs from normal VLDL in that it has an increase in
the ratio of cholesterol to TG content. Concurrent disease such as obesity, hypothyroidism, diabetes mellitus,
and excessive alcohol consumption will exaggerate the
expression of this disorder.
II
Hypothyroidism can cause familial lipoprotein

disorders to become clinically manifest or to
worsen. By itself, hypothyroidism can be associated with a type 11hyperlipedemic pattern. Cholesterol
level may increase as hypothyroidism becomes more
profound.
III
Nephrotic syndrome usually results in increased

levels of TGs and total cholesterol due to increased VLDL and LDL w;th a type lib lipid
profile. These abnormalities are directly related to an
increase in hepatic lipid synthesis. The severity of the
lipid abnormality is directly related to the degree of
hypoalbuminemia and proteinuria.
:.II
II
Familial hypercholesterolemia (FHC) can exist

in two forms with two different lipid profiles,
type IIa and type lIb. In type IIa. LDL cholesterol is increased and TGs are nonnal. In type lIb,
LOL cholesterol and TGs (primarily VLOL) are increased. Both of these disorders are associated with
tendon xanthomas, xanthalasma, premature coronary ar
tery disease, and peripheral vascular disease. Approximately two thirds of the heterozygote patients will demonstrate tuberous or tendon xanthomas during their
lifetime. Total cholesterol levels are usually in the 300
to 500 mg/d1 range for these patients. In contrast, in the
homozygous fonn, cholesterol levels range from 600 to
1200 mg/d1. Clinically, the homozygous form demon
strates xanthomas over the extremities, buttocks, knees,
and palms, in addition to premature atherosclerosis.
Secondary hyperliPidemia--i~[t~-e-s-me-ll-itu-s------l
Uremia/dialysis
Glycogenesis
Upodystrophy
Elevated TGs. VLDL

6 (300-1000 mgJdl),
elevated cholesterol
Type IV primary hyperlipidemia ---------'9il
Secondary hyperlipidemia
---i
Type V primary hyperlipidemia
Secondary hyperlipidemia------j
Type III primary hyperlipidemia-----12
Secondary hyperlipidemia -------,
8[Familial hype~riglyceride~~a
.
Familial combined hyperllpidemta
Diabetes mellitus
Hypothyroidism
Nephrotic syndrome
1_1Familial hypertriglyceridemia
[HYPOthyroidism
Familial dysbetaproteinemia
13~HypothyroidiSm
14 Nephrotic syndrome
Cushing's syndrome
Type lib primary hyperlipidemia -------,
Cecil Chapter
Harrison Chapter
15[Familial hypercholesterol~~ia .
Familial combined hyperhpldemla
341
Endocrine
Oisordel"S
Hyperlipidemia
197
HYPOGLYCEMIA
Hypoglycemia may be a symptom or "diagnosis"
reported by the paoent, may be discovered by
routine blood glucose measurement, or may be
suspected on the basis of the group of signs and symptoms reported by the patient. Hypoglycemia is a measured glucose level lower than the loWerlimit of normal.
In general, it can be defined as a plasma glucose level
of less than 50 mgldl, but it is considered in a patient
with any low glucose level in whom symptoms occur.
All patients with a blood glucose level less than 50 mg!
dl should be evaluated whether or not symptoms occur.
If low blood glucose is discovered by random

glucose measurement but symptoms are absent,
the hypoglycemia may be artifactual. Excessive
numbers of leukocytes or red blood cells may result in
spuriously low whole blood values for glucose. A plasma
glucose level should be normal, however.
Some patients can have an asym\,tomatic hypoglycemia that is not artifactua (see No.2).
These patients may have mild symptoms that
are difficult to recognize or may have a long-standing
hypoglycemia to which they have adapted.
Because the signs and symptoms of hypoglycemia are nonspeci6c, symptomatic hypoglycemia
must be con6nned by measuring glucose levels
at the time the patient compbins of symptoms. Symp
toms include anxiety, palpitations, headache, blurred
vision, irritability, weakness, diaphoresis, nervousness,
drowsiness, fatigue, hunger, and paresthesias. Some of
the symptoms are due to an adrenergic response caused
by the release of epinephrine (e.g., palpitations, nervousness), and some of the symptoms are due to a
neuroglycopenia (e.g., headache, confusion, slurred
speech). There is a triad of conditions known as Whippie's triad that must be demonstrated prior to further
evaluation of hypoglycemia; the patient must be shown
to have symptoms concomitantly with documented hypoglycemia and resolution of symptoms when glucose
or food is administered.
The majority of those who present with a symp.
tomatic hypoglycemia are diabetic patients who
take oral hypoglycemic agents or insulin injections. The most common cause of hypoglycemia in these
patients is the use of the hypoglycemic agent without
an associated sufficient carbohydrate intake. Other
causes of hypoglycemia in these patients include incor
rect dosing (overdosing), strenuous exercise, alcohol intake, and the simultaneous use of potentiating drugs.
198 Endocrine Dlsorden
Hypoglycemia
Commonly used drugs that can potentiate the effect of

sulfonylureas, for example, include barbiturates, salicy.
lates, sulfonamides, and thiazides. Of note, ~-adrenergic
blocking agents (e.g., propranolol) can block the adren
ergic symptoms of hypoglycemia and can be dangerous
when prescribed to diabetic patients because the early
symptoms of hypoglycemia may then go unrecognized.
Occasionally, pharmacy error has led to the dispensing
of an oral hypoglycemic agent when another medication
has been prescribed-the patient experiences hypoglycemic symptoms due to unknowingly ingesting the incorrect medication.
A food tolerance test can be perfomled with a
standard solid or liquid meal rather than the
oral glucose tolerance test. If hypoglycemia can
not be documented, it is important to consider other
causes for the patient's symptoms. Because similar adrenergic responses can occur in many emotional and
psychiatric states, it is important to document true hypo.
glycemia prior to proceeding with further evaluation. A
food-stimulated hypoglycemia, also known as a reactive
hypoglycemia, usually results in adrenergic symptoms.
A fasting (food.deprived) hypoglycemia usually results
in symptoms of neuroglycopenia (see No.4).
Postprandial hypoglycemia (after a food tolerance test), with spontaneous recovery from the
symptoms, is considered to be a reactive (or
food-stimulated) hypoglycemia. Reactive hypoglycemia
may be due to dumping syndrome or may represent a
precursor fonn of diabetes mellitus. Dumping syndrome
can occur post gastrectomy. The hypoglycemia is due to
the rapid dumping of carbohydrates into the intestine
from the stomach, causing an oversecretion of insulin
and resultant hypoglycemia. Very few patients demonstrate idiopathic reactive hypoglycemia. Symptoms occur several hours postprandially and usually resolve
spontaneously. These patients may have an early precur
sor of non-insulin.dependent diabetes.
Serum glucose that does not return to nonnal
spontaneously after a glucose load is usually
indicative of a serious underlying disorder. A
72hour fast (food.deprived hypoglycemia) is performed
to detect a possible insulin-secreting tumor. The fast is
monitored in a controlled environment (i.e., a hospital)
and is usually begun after an evening meal that contains
high glucose levels. The patient is allowed to drink only
water during the subsequent fast. Blood glucose levels,
C peptide levels (see No. 10), and insulin are measured
at baseline and then every 6 hours. When symptoms
are reported, a quick fingerstick glucose test is done to
II
confinn the low blood glucose; then, insulin, glucose.

and C peptide levels are immediately drawn and the
test tenninated. Almost 100% of patients with insuIinoma will develop hypoglycemia within a 72-hour fasting period.
Insulin-producing tumors are nol subject 10 the
usual regulatory feedback mechanism in which
a low blood sugar causes insulin secretion 10
decrease. The best measurement of the relationship
between glucose and insulin is the glucose-insulin mtio,
calculated as follows:
Glucose (mgld!)/insulin (",lU/lll!)

This ratio is usually greater than 2:1. If endogenous
insulin is increased, the ratio is less than 2:I. as usually
occurs with insulinoma. Perhaps more useful to demonstrate relative hyperinsulinemia is a plasma insulin level
that will remain inappropriately high in the prcsen<.'Cuf
hypoglycemia. A plasma insulin level greater than
6 ..
IU/ml is considered the value above which hypcrinsulinemic states are defined.
If factHial hypoglycemia is suspecteJ, a C pepI tide level will be helpful. C peptide is the fragment of endogenously produced proinsulin that
is cleaved off the proinsulin to fonn insulin. If endogenous insulin pr<x:luctionincreases, the level of C peptide
increases in equal amounts. Therefore, when exogenous
insulin is surreptititiously injected, endogenous insulin
prod.uction will be suppressed and blood levels of insulin will be high, whereas blood levels of C peptide "I/ill
be disproportionately low. Because insulin is cleared, by
the liver and C peptide is cleared by the kidneys, C
peptide levels will be elevated in renal failure. C peptide
levels may be elevated when renal failure and insulinoma coexist. Provocative tests are performed to
strengthen evidence for an insulin-secreting tumor.
Tests include the C peptide suppression test, the intravenous (IV) tolbutamide test, and the IV glucagon sup
pression test. The C peptide suppression test documents
excess production of endogenous insulin by demonstrating the lack of suppression of C peptide when IV
insulin is exogenously administered. An IV tolbutamide
test is perfonned over a 3-hour period. Patients with
insulinoma resr,nd to IV tolbutamide with exaggerated
suppression 0 plasma glucose .levels. Plasma insulin
levels are of less use diagnostically with this lest. The
administration of IV glucagon increases blood glucose
with simultaneous release of insulin. If the peak insulin
response exceeds 130 ..
IU/ml, the diagnostic accuracy
for insulinoma is 50% to 80%.
1m
-f
Artifactualhypoglycemia
Unexpalned
Adaptation
Exogenous
-{
hypoglycemicagents
Leukocytosis
Chronicmyelogenousleukemia
Potycythemlarubravera
Insulin
.
Oral hypoglycemlCS
(sulfonylureas)
AsPlrin/acetamlnOPhen
Propranolol
1
Hypoglycemia
Ethanol
.Drugs
Toxins
~
Sulfa drugs
Phenothlazines
Uthlum
Quinine
Disopyramlde
Factitial ingestion
of()(al
hypoglycemics
No hypogtycemi8-f Hyperventilationsyndrome
Other adrenergic
Psychosis
states
Anxiety/depression/neurosis
(sulfonylureas)
Elevated
C peptide and
provocative
tests positive
12t Insulin antibodies
13 Insulinoma
TOOic
(quinine water)
7 Reactive
Postgastrectomy
;-{
hypoglycemia
Eartydiabetes
Idiopathic
Beta cell
hypertrophy
Insulin receptor antibodies
Insulin antibodies
Faetit!sl insulin use
~:r==:al
Hepatoma
Neurofibrosarcoma
Carcinoidtumors
Lymphoma
Othermesenchymal
lumo<s
15NOrHslet
cell tumors
Prolooged
17 Counterregulatory
hormoneabnormality
Cecil Chapter
243
Harrison Chapter
293
exercise
Glucagondeficiency
Starvation
HypopituitarismlACTHdeficiency
Addison'sdisease
Renalinsufficiency
Congestiveheart failure
Hepaticfailure::::--t
Cirrhosis
Pregnancy(pituitary)
Sepsis
Insulinresistance---{
Obesity
Polycysticovary disease
Endocrine
Disorders Hypoglycemia
199
HYPOGLYCEMIA
(Continued)
Oral hypoglycemic agents (often sulfonylureas)
can stimulate proinsulin secretion with C peptide
production. Test results for insuUnoma will not
identify the patient who secretly ingested a sulfonylurea
prior to the test. Therefore, a screen for these agents
must also be performed prior to pursuing further localization studies for insulinoma. Sulfonylurea concentration
can be measured if surreptitious ingestion is suspected.
Insulin antibodies arc almost always formed
after repeated injection of insulin, so that insulin antibodies can also be measured to support
II
the suspicion of exogenously
administered
insulin. Some
patients, however, have developed insulin antibodies

without ever having had an insufin injection.
Insulinoma is rare, occuning in fewer than 1 in
4000 people. The median age at diagnosis is 50,
and the majority of patients with insulinoma are
women (60%). Insulinoma occurs as part of the multiple
endocrine neoplasia syndrome type I (MEN 1), and
these patients are usually diagnosed in their twenties.
The majority of insulinomas are solitary benign tumors
(80%), but some can be multiple or malignant. The
hypoglycemia associated with insulinoma usually occurs
more than 5 hours after a meal. The diagnosis lies with
the demonstration of inappropriately high insulin levels,
while the glucose level is low, but a number of endocrine provocative tests (see No. 10) can also be performed to strengthen the diagnosis. Ultimately, the tumor must be localized anatomically, which can be
achieved with various techniques, including ultrasound
and pancreatic angiography. Insulinomas are usually
highly vascular tumors. If provocative tests are negative
but radiographic evaluation reveals tumor, a non-islet
cell tumor may be present.
Rarely, some patients produce insulin receptor
:I
antibodies that act like insulin agonists and cause
hypoglycemia. Most of these patients have insulin-resistant diabetes, and the insulin receptor antibodies
are thought to be due to autoimmune disease.
Hypoglycemia has been associated with many
different mesenchymal tumors. About 65% of
these tumors are localized to the abdomen, the
most common of which is retroperitoneal fibrosarcoma.
Approximately 35% of mesenchymal tumors are found
in the chest. The etiology of the associated hypoglycemia is multifactorial and may be due to high glucose
utilization by the tumor, interference with glucose regulation, or metastatic destruction of glands such as the
adrenals, to name a few possible mechanisms. In gen-
III
II
Hypoglycemia
eral, measured insulin levels remain relatively low in

relation to the low glucose levels in these non-insulinproducing tumors, unlike the high insulin levels seen
with insulin-producing tumors. Nonpancreatic tumors
may produce an insulin-like growth factor (IGF) that is
responsible for the associated hypoglycemia. Tumors
that have been found to produce IGF material include
fibrosarcoma, neurilemmoma, leiomyosarcoma, mesothelioma, and hemangiopericytoma.
If hypoglycemia cannot be documented during
a 72hour fast, the patient is unlikely to have
hypoglycemia. Fewer than 2% of patients with
insulinoma remain undetected (i.e., do not demonstrate
hypoglycemia) within 72 hours of a prolonged, supervised fast. In addition to a rare undetected patient
with an insulinoma, this group may include nondiabetic
patients who secretly take sulfonylureas or insulin, but
are unable to use it during the supervised fasting period.
Surreptitious use of oral hypoglycemic agents and insulin is most likely to occur in 30 to 40-year-old women
in health-related occupations (e.g., nurses).
Hepatic disease and dysfunction is a common
cause of hypoglycemia because of the liver's role
in glucose homeostasis. The liver is able to maintain nonnaT glucose homeostasis with as little as 20%
of the parenchymal cells functioning. but biochemical
hypoglycemia can occur in a wide variety of diseases in
which the liver is primarily or secondarily involved. The
hypoglycemia rep::uted with congestive heart failure and
sepsis, for example, is likely due to hepatic dysfunction.
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Malo JW, Bezdicek BJ: Secondary amenorrhea. Postgrad
Med 79(3)086-95, 1986.
Margolis S: Diagnosis and management of abnormal
plasma lipids. j Clin Endocrinol Metab 70(4),821825, 1990.
Mavroudis K: Clinical syndromes of secondary amenorrhea. Ann N Y Acad Sci 816:241-249, 1997.
McFarland KF: A clinical approach to amenorrhea. J S
C Med Assoc 81(9),481-483, 1985.
Miller M: Endocrine disorders: New technology allows
quick, accurate diagnosis. Geriatrics 51:52-58, 1996.
MitcheU AI' Krull EA (cds): Hair disorders. Oermatol
Clin 5(3 ,1987.
Nanji AA: Disorders of gonadal function. Clin Lab Med
4(4),717-728. 1964.
Rifkind BM, Levy RI (eels): Hyperlipidemia: Diagnosis
and Therapy. New York, Grune & Stratton, 19TI.
Rittmaster RS, Loriaux DL; Hirsutism. Ann Intern Med
106,95-107, 1987.
Toft AD (ed), Hyperthyroidism. Clin Endocrinol Metab
14(2),1985.
White PC, New MI, Dupont B: Congential adrenal
hyperplasia. N Engll Med 316,1519-1524, 1987.
Williams ED (ed): Pathology and management of thyroid disease. Clin Endocrinol Metab 10, 1981.
Wong, ET, Steffes MW: A fundamental approach to the
diagnosis of diseases of the thyroid gland. Clin Lab
Med 4(4),655-670, 1964.
Artifactual hypoglycemia
Unexplained
-f
Leukocytosis
Chronic myelogenous leukemia
Potycythemia rubra vera
AdaptaUon
Exogenous
-{
hypoglycemic agents
Insulin
Oral hypogtycemlCS(sulfonyiureas)
Asplrinlacetaminophen
Propranolol
1
Hypoglycemia
Ethanol
Drugs
Toxins
Sulfa drugs
Phenothiazines
Lithium
Quinine
Disopyramide
No hypoglvcemi8-f
Other adrenergic
Hyperventilation
states
Anxiety/depressiorv'neurosis
syndrome
Psychosis
Tonic
rl
7 Reactive
hypoglycemia
FactitlaJ ingestion
ofQ(al
hypoglycemics
(sulfonylureas)
(quinine
Elevated
C peptide and
provocative
lests positive
12tlnsuun antibodies
13 Insulinoma
water)
Postga~trectomy
Earty d~betes
Idiopathic
Beta cell
hypertrophy
Insulin receptor antibodies
Insulin antibodies
Factitiallnsulin
use
Re''''P''rilOnea,
fibrosarcoma
Hepatoma
Neurofibrosarcoma
Carcinoid tumors
15 Nonisktl
cell tumors
Lymphoma
Other mesenchymal
tumors
16 No hypoglycemia
Prolonged exercise
Glucagon deficiency
Starvation
High glucose
insulin ratio
Cecil Chapter
Harrison
Chapter
H]
29]
17Counterregulatory
hormoneabnormality
HypopituitarismlACTH deficiency
Ackfison'sdisease
Renalinsuffidency
Congestiveheartfailure
=:-L Sepsis
Pregnancy (pituitary)
Hepatic failure
Cirrhosis
Insulin resistance---{
Obesity
Polycystic ovary disease
Endocrine
Disorders Hypoglycemia
201
1m Skin Disorders
Signs and symptoms:
Pruritus
Urticaria
Purpura
Alopecia
SIGNS AND SYMPTOMS

PRURITUS
Pruritus
is the sensation
in the skin that arouses
the desire to scratch. Itching is the most com-
mall symptom in dermatology; it may be generalized without evidence of skin disease. In the absence
of primary skin lesions. generalized
pruritus can be
indicative of an underlying systemic disorder. Some sys.
ternie disorders, such as diabetes mellitus and cholestasis, can present with localized itching as wen. Most
patients with pruritus do not have a systemic disorder,
however, and generalized
itching is usually due to a
widespread cutaneous disorder.
Pruritus is a rare, nonspecific symptom of underlying malignancy, most commonly pancreatic

or stomach carcinoma. A variety of neurologic
disease can also be associated with itching on rare OC'Casious. The diagnosis is made by examination, which may
reveal focal neurologic findings. Paroxysmal itching has
been reported with multiple sclerosis. Severe pruritus of
the nostrils has been associated with frontal brain tumors.
Notalgia paresthetica
is a form of pruritus in
which itching is localized to an area of the back,
medial to the scapula. Notalgia paresthetica
is
thought to be a variant fonn of peripheral neuropathy.
II
Chronic renal failure is the most common systemic disorder responsible for pruritus. Pruritus
has been estimated to affect as many as 90% of
patients with chronic renal failure on hemodialysis. Almost 50% of the patients are most bothered by pruritus
during or shortly after dialysis. The etiology of the
pruritus accompanying
renal failure is unclear. The pruritus of renal failure has been attributed to secondary
hyperparathyroidism
or to elevated phosphorus
and
magnesium levels. Itching tends to resolve when serum
phosphorus levels are decreased.
and a chest radiograph (CXR).
Cholestatic liver disease is frequently associated

with generalized pruritus. The itching may precede other signs and symptoms of cholestatic
disease. Initially the itching may be localized, limited to
the hands and feet and to areas of pressure, becoming
worse at night. Although the accumulation
of bile acids
in the skin has been implicated in the pathogenesis
of
cholestatic pruritus, bile levels do not always correlate
with the presence or absence of pruritus, or with its
severity. The pruritus that accompanies
benign cholestatic jaundice of pregnancy is most severe in the third
trimester and resolves after delivery. Women who develop cholestatic
jaundice
during pregnancy
are at
greater risk of developing jaundice and pruritus with
use of oral contraceptives
at a later date. Primary biliary
cirrhosis is a disease of unknown etiology. with the
progressive destruction
of the small intrahepatic
bile
Examination of the skin is the best way to determine the presence or absence of primary skin
disease as the cause of pruritus. Lesions secondary to pruritus with subsequent
scratching. such as linear excoriations, lichenification,
and erythema, may be
present and must be distinguished
from the lesions of a
primary skin condition. Atopic dermatitis
is an exception. Atopic dermatitis is recognized by the pattern of
lesions (typically the antecubital
and popliteal fossae)
and the intensity of the itching and scratching. Generalized pruritus deserves initial treatment with emollients
and possibly topical steroids prior to extensive evaluation because xerosis (dry skin) is the most common
cause of generalized pruritus. Persistent pruritus in the
absence of any primary skin lesion requires further
evaluation, including a full history and physical exam
and a series of screening laboratory tests. These tests
include a complete blood count (CBC), an electrolyte
and liver function test (LIT) panel (often referred to as
a chem panel or an SMA (Sequential Multiple Analyzer)
panel, thyroid function tests (TITs), a urinalysis (VA),
202 Skin Discrden Pruritus
ducts. The destruction is thought to be due to an immunologic process. The disease OC'Cursprimarily in women.
Pruritus is usually the initial manifestation
of the disease, and the diagnosis is made when hepatomegaly is
found upon physical examination and abnonnal LITs
are found on an automated
screening panel (SMA).
Like cholestasis of pregnancy, the pruritus may develop
during pregnancy, but in contrast to the cholestasis of
pregnancy, the pruritus in primary biliary cirrhosis continues after delivery.
Rarely, pruritus may be associated with iron
deficiency anemia and resolves \vith effective
therapy. Pruritus has been reported in 15% to
50% of patients with polyt.'ythemia vera. The itching is
usually more severe with temperature
changes, the patient often complaining
of severe itching after showering. Pruritus is also one of the most common cutaneous manifestations
of leukemia.
II
Approximately
6% of patients with Hodgkin's
lymphoma present with generalized severe pruritus without any other symptoms to suggest the
diagnosis. It is unclear whether the presence of pruritus
is a bad prognostic
symptom. but pruritus has been
dropped as a criterion for the B category in classifying
Hodgkin's lymphoma. Itching usually starts on the legs,
is continuous, and is associated with a burning sensation.
:
As many as 8% of patients with thyrotoxicosis

a.re bothered by generalized itching. Itching resolves when the euthyroid state is achieved after
treatment.
Itching associated with hypothyroidism
is
thought to be due primarily to dry skin.
1m
Generalized
pruritus is rare in diabetes mellitus, estimated
to affect about 3% of patients
with this disease. The severity of the itching
does not generally correlate with the severity of the
underlying disease. Localized itching is common in diabetes mellitus and may be associated with secondary
fungal infections of the skin or mucous membranes,
e.g., crural candidiasis.
Xeros~s . --{Scabies
ParasItosIS
Atopic dermatitis
..
PediculoSIS
Urticaria
Folliculitis
Dermatitis
herpetiformis
Bullous pemphigoid
Miliaria
Primary skin disease
Psoriasis
Mycosis
fungoides
Lichen
planus
Lichen
simplex
abscess
Giardia
HIV
Brain
Infection------
chronicus
Allergic dermatitis
Arthropod bites
Prurigo
nodularis
Factitial
dermatitis
IEating
disorders
----~[stress
Delusions
of parasitism
r Hypersensitivity responses
-------[Narcotics
Amphetamines
1
Pruritus
Pancreas
Stomach
-----,
(glucagonoma
syndrome)
Breast
CNS
lesions
1
CVA
Neurologicdisorder
Multiplesclerosis
Notalgia paresthetica
Depression
Carcinoid
Uremia/renal
syndrome
failure
[cocaine
----~[Oral contraceptives
Primary biliary cirrhosis
Chlorpropamide
Extrahepatic biliary obstruction
Drug-related
6 Ob t cf
bT
d'
s ru lve llary lsease --{
Intrahepatic cholestasis of pregnancy

Microcytic anemialFe deficiency
Leukemia
Polycythemia vera
Lymphoma
Hodgkin's
Non-Hodgkin's
Mycosis fungoidesiSezary syndrome
Multiple myeloma
Thyrotoxicosislhyperthyroidism
Hypothyroidism
Cecil Chapter
55
10Diabetes mellitus
Harrison Chapter
519
Skin Disorders
Pruritus 203
URTICARIA
Urticaria is the term used to describe evanescent skin lesions that are edematous (raised),
circumscribed,
erythematous,
and usually in~
tensely pruritic. Inruviduallesions
of true urticaria typically last less than 6 hours and almost always less than
24 hours. Lesions persisting longer than 24 hours suggest the presence of angioedema or urticaria-like dermatoses such as drug eruptions
or vasculitis. Angioedema, related to urticaria and initiated by similar
mechanisms, is due to the extension of edema into the
deep dermis or subcutaneous
and submucosal layers.
Urticaria and angioedema differ mainly in the depth of
edema and may coexist in the same patient. Mediators
of urticaria include IgE, complement,
mast cells, and
basophils, which release histamine and chemotactic factors.
Urticaria can be differentiated

into acute and
chronic forms on the basis of clinical duration.
Even if the etiology of the urticaria is not apparent by initial history and physical examination, extensive
evaluation is unwise because most urticaria clears spontaneously within a few months. Associated symptoms,
such as fever or arthralgias, may warrant immediate
further evaluation, however. In the majority of cases,
further evaluation is warranted only if the lesions are
recurrent for longer than 6 to 8 weeks. The condition
is then known as chronic urticaria. The cause of both
acute and chronic urticaria is rarely uncovered. In fact,
up to 70% of chronic urticaria is idiopathic. Although
idiopathic urticaria is the most common form, it is a
diagnosis of exclusion.
Serum sickness is manifested by fever, urticaria,

lymphadenopathy,
arthralgia, and myalgia. The
reaction occurs 1 to 3 weeks following the administration of the offending agent, usually heterologous
serum. As many as 70% of patients with serum sickness
manifest urticaria. The symptoms are thought to be
due to an immune complex-induced
vasculitis in which
activation of complement may contribute the anaphylatoxins that induce mast cell degranulation.
Urticaria may occur during the prodrome of

acute hepatitis B infection. The urticaria is
thought to represent a necrotizing venulitis due
to complement activation.
Urticaria*like dermatoses are primary skin dis*

orders that mimic urticaria but are distinctive
and diagnostic histologically. A skin biopsy of a
true urticarial lesion shows nonnal skin.
II
Urticaria results from the administration of ra*

dio-contrast media in as many as 5% of patients.
Opiates and antibiotics are other drugs commonly causing urticaria. The mechanism of drug-induced urticaria is thought to be histamine release from
mast cells and basophils. Aspirin, nonsteroidal anti-inflammatory agents, azo dyes. benzoates, and thiazides
are also well-known causes of urticaria, although the
pathogenesis is unclear. Aspirin may exacerbate existing
urticaria without being the etiologic agent of the underlying chronic urticaria.
Urticaria. that occurs after direct contact with a
variety of agents is known as contact urticaria.
Chemicals, arthropod hairs, and stinging nettles
may cause contact urticaria.
204 Skin Disorders Urticaria
Angioedema is edema of the deep dennis and

subcutaneous layers of skin, more often involving mucous membranes such as the lips. Lesions of angioedema, in contrast to those of urticaria,
can last up to 72 hours. Measurement
of the serum
complement levels is helpful in detecting patients with
angioedema. Serum C4 levels can be measured as 'a
screening test. If serum C4 levels are low, further evaluation should include measurement
of Cl, C2, and C3
levels, as well as the levels and function of C 1 esterase
inhibitor protein. Low levels of, or dysfunctional Cl
esterase inhibitor is diagnostic
of hereditary
angioedema, which can be life-threatening. A low Clq level
can be due to a paraneoplastic syndrome that consumes
Clq, causing an acquired angioedema, as occurs in rare
cases with B~celllymphoma.
Chronic urticaria may be a manifestation of a

cutaneous vasculitis, which is a urticaria-like
dermatosis.
The urticaria may be associated
with arthralgia, arthritis, glomerulonephritis,
and abdominal pain* The disorder has' been called the hypocomplementemic-urticaria~vasculitis
syndrome. Skin biopsy will reveal vasulitis on histopathologic exam.
II
Urticaria pigmentosa (cutaneous mastocytosis)

is a condition in which increased numbers of
mast cells are present in the skin. Urticaria is
the result of mast cell degranulation that occurs with
stroking of the skin lesions. Individual lesions of urti*

caria pigmentosa are hyperpigmented and papular when
not urticate. Biopsy is diagnostic by demonstrating collections of mast cells in the dennis.
II
Pressure urticaria may arise immediately or be

delayed 4 to 6 hours after constant pressure
has been applied to the skin. The diagnosis is
suggested by the location of the urticaria: under shoul*
der straps and belts, on the hands after manual labor,
or on the feet after running.
II
Cold urticaria is induced by cold foods or liquids and may be associated with headache, syncope, and wheezing. Cold urticaria may be ac*
quired or inherited as a dominant trait. Cryoproteins
(including cold agglutinins)
can be demonstrated
in
fewer than one third of these patients.
III
Pruritus and urticaria may accompany eX}X)sure

to the sun or an artificial light source emitting
certain wavelengths of light. The diagnosis is
suggested by the distriQution of lesions in light-exposed
areas. Solar urticaria may be a manifestation of systemic
lupus erythematosus
(SLE), erythropoietic
protoporphyria (EPP), or drug photosensitivity.
III
II
:.t
Heat urticaria is rare. The condition is mani*

fested as urticaria at the site of locally applied
heat.
The role of food as a cause of urticaria is difficult to assess. Foods frequently implicated as a
source of urticaria include strawberries, shellfish, nuts, fish, and eggs. It is difficult to establish most
foods as a source of urticaria with any objective certainty, but a dietary log can be used if foods are suspected. Elimination diets can also be helpful.
II
Chronic urticaria is considered idiopathic if no

underlying cause can be found. The roles of
food and occult infection as causes of urticaria
are difficult to assess because the urticaria can be coinci*
dent. Urticaria rarely precedes neoplasia but may be a
presenting sign of lymphoma. The course of urticaria is
u::rredictable,
although most patients experience gradu waning of lesions by 3 to 6 months.
Dental caries
Atopic diathesis
3 Drug sensitivity
4 Contact urticaria
Transfusion reactions
Acute urticaria 5 Serum sickness
6 Acute hepatitis B
Idiopathic
Upper respiratory infection/sinusitis

Mononucleosis
Food ----
Nuts
Shellfish

Subacute cutaneous lupus erythematosus
SjOgren's syndrome
Mixed connective tissue disease
Autoimmune thyroid disease
Chronic urticaria
An9ioedema
Dermal erythema muttiforme
...
Vasculitis
7 Urticane-Ilke
dermatoses
B 11
h" "d
u cus pemp IgOI

Gyrate erythemas
9 Urticarial vasculitis
10 Urticaria pigmentosa/systemicmastocytosis
Psychological
stress
Occult
malignancy
Dermatographism
11 Pressure urticaria
12 Cold urticaria
Physical urticaria--13
Solar urticaria
Cholinergic urticaria
14 Heat urticaria
15 Foods
Aquagenic urticaria
Cecil Chapter
273
Harrison Chapter
310
16
Idiopathic
Sldn Dlsorden Urticaria 205
PURPURA
Purpura is a result of hemorrhage into the skin.
I Purpura includes petechiae, which are purpuric
lesions less than 3 mm in diameter. Ecchymoses
are larger purpuric lesions. Purpura is due to a qualitative or quantitative platelet disorder, a coagulation abnormality, or abnormal or inflamed blood vessels. If the
platelet
count is decreased,
purpura
is likely due to
thrombocytopenia (see Thrombocytopenic algorithm).

If the platelet count and coagulation .tests are
normal, a bleeding time should be determined
to ascertain platelet function. Platelet dysfunc.
tion is common in uremia and can also be responsible
for the purpura accompanying dysproteinemias such as
Waldenstr6m's macroglobulinemia or multiple myeloma
(see Dysproteinemia algorithm).
If tests of platelet number and function are

normal, purpura is due to abnormalities of the
blood vessels. Blood vessels may lose their integrity due to inflammation, which occurs with vasculitis, or to loss of adequate tissue support for the vessel,
as seen in senile purpura. Senile purpura and steroid
purpura are obvious in the appropriate clinical settings
and rarely require biopsy. Senile purpura is commonly
seen on the chronically sun-exposed, sun-damaged dorsum of the hands and forearms. Many elderly patients
ingest daily baby aspirin, which additic;mallyexacerbates
the occurrence of purpura.
Except for the presence of extravasated red

blood cells, a biopsy of a PUluriC lesion will
be othelWise normal in steroi purpura, senile
purpura, and purpura due to trauma. AutoeI)tbrocyte
sensitization syndrome (Gardner-Diamond syndrome) is
thought to be factitial, secondary to self-induced skin
trauma.
206 Skin Disorders Purpura
Hereditary hemorrhage telangiectasia, or OslerWeber- Rendu disease, is an autosomal dominant disorder in which purpura can occur secondary to vascular fragility. A developmental
abnormality of the vasculature results in thin vessel walls
with poor sUf.port and contractility. Mucous membrane
bleeding, inc uding gastrointestinal bleeding, is the most
common clinical manifestation. The disorder is easily
recognized by the presence of numerous telangiectasias,
especially on the mucous membranes.
Amyloid deposition in the walls of cutaneous

6 blood vessels is responsible for their fragility
and subsequent bleeding. Common dennatologic manifestations of amyloidosis include petechiae
and ecchymoses, most commonly on the eyelids and
periorbital region. Minor trauma can cause these lesions, leading to the designation "pinch purpura."
II
Inflammatory change in the walls of blood vessels is known as vasculitis. Leukocytoclastic vasculitis is the term used pathologically to describe a constellation of changes that occur in and
around the blood vessel wall due to inflammation. A
variety of conditions appear as a leukocytoclastic vasculitis histologically, the prototype being Henoch-Schonlein
purpura. Palpable purpura is the clinical lesion that
corresponds to a leukocytoclastic vasculitis histologically.
Purpuric drug eruptions represent a leukocytoclastic vasculitis believed to be due to immune complex deposition in the blood vessels.
Drugs that have been associated with vasculitis include
allopurinol, thiazides, sulfonamides, quinidine, phenytoin, nonsteroidal anti-inflammatory agents, tetracycline,
penicillin, cimetidine, and ketoconazole.
Petechiae and purpura in the setting of acute

infection are manifestations of vasculitis. Although vasculitis may accompany a variety of
bacteremic infections. these skin findings are most diagnostically significant in acute and chronic meningococcemia and rickettsial infections. The presence of
thrombi in the blood vessels is characteristic of the
vasculitis that accompanies infection.
1m
Henoch-Schonlein purpura is the prototype of

leukocytoclastic vasculitis. In this condition, petechiae and palpable purpura are accompanied
by arthralgias, abdominal pain with melena, hematuria
resulting from glomerulonephritis, and occasionally dyspnea with pulmonary infiltrates. Both the skin and systemic manifestations are thought to be due to an IgA
immune complex-induced vasculitis.
II
The cryoglobulins that occur in mixed cryoglobulinemia consist of circulating immune complexes, of which the most common combination
is IgG-IgM. Mixed cryoglobulinemia may occur in association with autoimmune diseases such as SjOgren'ssyndrome, rheumatoid arthritis, and SLE. A leukocytoclastic vasculitis is usually not a feature of monoclonal
cryoglobulinemia.
II
Wegeners granulomatosis is defined by the

triad of necrotizing granuloma of the upper and
lower respiratory tract, necrotizing vasculitis,
and necrotizing glomerulitis. Skin lesions may consist of
papulonecrotic lesions with ulceration in addition to
purpura. These skin lesions are present in about 25%
of patients in the early stage of the disease, and in about
half of the patients when the disease is more advanced.
Platelet
dysfunction-
see page
108
Ehlers-Danlos
Steroid
Platelet
count normal
$enile
syndrome
(type IV)
purpura
purpura
(>100,OOO/mm3)
8
Factitial
(Gardner-Diamond
syndrome)
Waldenstr
Vascular purpura
1
Purpura
Check platelet
count and
coagulation
tests
Thrombocytopenia
see page 158
m's macroglobulinemia
Infection
5[ ::~tary hemorrhagictelanglect8s:
Henoch-Sch nlein purpura
AmyloidosIs
Leukocytoclasbc
Schamberg's
Platelet
count decreased
100,OOOImm3)
Drugs
vasculitis
disease
11
Mixed cryoglobulinemia
12
Wegener's
granulomatosis
Churg-Strauss
syndrome
Urticarial vasculitis
Periarteritis nodosa
Coagulation
.boom.1
Cecil Chapter
Harrison Chapter
tests
(PTIPTT)
Coagulation
abnormality-
see page 108
522
57
Skin Disorders. Purpura
207
ALOPECIA
Alopecia is the term used to describe hair loss.
Most commonly the term refers to seal hair
loss. but it can be used to describe hair Fossin
other body regions. Hair loss secondary to structural
abnormalities resulting in hair breakage are excluded
from this classification of alopecia. The most common
cause of alopecia is male pattern
baldness
(androge-
netic alopecia).
II
The etiology of hair loss cannot always be determined, and the cause of certain alopecias is not
fully understood. The most useful observation
to help establish the diagnosis of alopecia, however, is
the presence or absence of scarring. Scarring is a useful
diagnostic as well as prognostic finding. The presence
of scarring precludes hair regrowth because the hair
follicle has been damaged or destroyed and it can no
longer produce hair.
II
Both malignant and benign neoplasms can be

responsible for follicular destruction and hair
loss. Neoplasm is usually apparent on examination, and a biopsy will establish the diagnosis. At times,
the biopsy will reveal an unsuspected tumor. Metastatic
carcinoma of the skin, although rare, affects the scalp
3% to 8% of the time. Almost half of metastatic tumors of
the scalp, however, are unsuspected at the time of biopsy.
Infection is also apparent on examination, although at times the inflammation is so severe
that the causative organism is difficult to culture
and identify. Severe fungal infections, including kerions
(severe, diffuse scalp inflammation complicating fungal
infection of the hair), can lead to extensive scarring and
hair loss. Viral infections, including herpes, can result
in scarring and hair loss, usually because of the complication of secondary infection.
Discoid lupus erythematosus (OLE) may involve

the scalp with a scarring alopecia. Although scarring alopecia may be seen in SLE, a noncicatricia! alopecia is more commonly seen in this disorder. The
lesions in DLE are usually atrophic and telangiectatic.
Immunofluorescent staining of a biopsy specimen can be
useful when an LE diagnosis is suspected.
II
Follicular mucinosis, also known as alopecia

mucinosa, can lead to a scarring alopecia when
mucin deposition in the outer root sheath
causes follicular destruction. The alopecia is usually reversible and nonscarring. Fifteen percent of patients
over 40 years of age with follicular mucinosis have been
208 Sldn Disorders Alopecia
reported to have concomitant mycosis fungoides, a Tcell lymphoma of the skin.

The presence of scar will be connrmed on biopsy but will be nondiagnostic when the scarring alopecia is due to traumatic destruction of
the hair follicles by mechanical or physical means. History will provide the important clues to diagnosis as
seen after radiation exposure or repeated trauma.
Nonscarring alopecia can accompany both
hyper- and hypothyroidism, as well as hyperand hypopituitarism, and may be either patchy
or diffuse. Most commonly, hypothyroidism is accompanied by a diffuse alopecia that may also affect the lateral
third of the eyebrows. Hair regrowth can usually be
expected once the euthyroid state is reached.
Secondary or tertiary syphilis can be accompanied by a "moth-eaten" scalp alopecia. The lateral eyebrows may also manifest hair loss.
III
R",ely, alopecia can be due to iron deficiency.
Alopecia accompanying SLE is usually nonscarring. In addition to the patches of alopecia that
can occur with SLE, a diffuse nonscaning alopecia can accompany acute disease exacerbations. Approximately 20% of patients with SLE have some degree of hair loss.
When scarring is absent, diagnosis of hair loss
can be established on the basis of patient his
tory and the pattern of the hair loss. Nutritional
denciencies in general can result in a diffuse alopecia, as
has been observed in patients on prolonged inadequate
parenteral hyperalimentation. Hair loss in this setting
may have been due to zinc deficiency, as is observed in
acrodennatitis enteropathica.
Telogen effluvium is a diffuse hair loss that
occurs when the majority of hair follicles have
synchronously entered the telogen (resting)
stage of the hair cycle. Normally, approximately 20% of
follicles are in the telogen stage, resulting in a loss of
less than 50 hairs a day. The anagen (growing) stage of
the hair cycle accounts for the other 80% of the hair
follicles on a nonnal scalp. Hair loss is diffuse and may
not be clinically apparent. The patient usually presents
with the complaint of increased hair loss with sham
pooing, or greater numbers of hair noted in the comb
or brush. The hair loss usually follows physical or emotional stress by 3 to 6 months. Causes include severe
illness, high fever, rapid weight loss, or severe psychiat-
III
ric or emotional stress. The most common presentation

is that of postpartum telogen effluvium, in which
marked hair loss is noted several months post partum.
A similar presentation has been observed in patients
who have discontinued long-term use of birth control
pills or high-dose systemic steroids.
Subconscious frequent hair manipulation may
~ lead to the alopecia found in trichotillomania.
A biopsy may be confirmatory, as distinct
changes can be identified histologically. Histologic features include distorted hair follicles and perifollicular
extravasated blood. Alopecia as a result of traction is
apparent by the pattern of hair loss and the observed
hair style.
Alopecia has been associated with a variety of
hereditary syndromes as either a primary or a
secondary feature. Many hereditary alopecias
are considered to be congenital, although the alopecia
may not be apparent at birth. Progeria is an example of
a hereditary nonscarring alopecia in which there is a
progressive loss of scalp, eyebrow, and eyelash hair in
association with scleroderma-like changes in the ~kin.
Drugs are common causes of nonscarring alope.
cia. The most striking example is the anagen
effluvium that accompanies treatment with chemotherapeutic agents. Antimitotic drugs such as cyclophosphamide, methotrexate, and actinomycin affect the
rapidly dividing cells in anagen hair follicles. Because
anagen hairs are primarily found on the scalp, the hair
loss is usually connned to the scalp. Hair loss is rapid
and diffuse, but regrowth can be expected when the drug
is discontinued. Other drugs that result in hair loss include heparin, warfarin (Coumadin), vitamin A, propranolol, levodopa, lithium, and isotretinoin (Accutune).
Alopecia areata is also a common cause of noncicatricial alopecia. The presence of exclamation-point hairs is a clue to diagnosis. The exclamation-point hair is due to a gradual taper of the
proximal portion of the hair shaft as a result of a follicular insult. The alopecia may be mild or severe, ranging
from coin-sized patches of hair loss in the scalp to a
generalized loss of all body hair, which is known as
alopecia universalis. Alopecia areata is not limited to the
scalp and may occur in patches on the forearm, beard,
or axillae, even if the scalp is not involved. Prognosis
varies with the extent of hair loss and the age of onset.
Poor prognosis accompanies the loss of extensive
amounts of hair or onset prior to puberty. When a
small, stable number of patches is present, spontaneous
regrowth can be anticipated within 6 to 12 months.
III
II
II
II
Basal cell carcinoma (morpheaform)
Squamous cell carcinoma
Neoplasm
Metastatic carcinoma (alopecla neoplastica)

Lymphoma
Adnexal tumors
Bacteriai
Inlec1ioo
-f
Fungal
Protozoan
Systemic disease
M"'.hanical
Trauma
-{
trauma
Bums
Caustic agents
Radiation
Discoid lupus erythematosus

Sarcoidosis
Lichen planus (lichen p1anopilaris)
Scleroderma/morphea
Lichen sclerosus at alrophicus
Necrobiosis lipoidica diabelicorum
Follicular mucinosis
Acne keloidalis nuchae
pseudopelade 01 Brocq
Folliculitis decalvans
AmyloidosIs
Dissecting penlolHculitis of the scalp
Bullous diseases
Hereditary disorders
,
Alopecia
11 SystemiC lupuS erythematosus
(SlE)
[
12
Other nulntlonal deficiency
13
Talogan effluVIum
MalnutrilJoo
Sprue
Zinc deficiency
____
TriCh~tlllomania
Traction alopecia
Hereditary syndromes
Drugs
Cecil Chapter
522
Alopecia areala
Androgens!ic
Harrison Chapter
alopecia
57
Skin Olsol"ders Alopecia 209
ALOPECIA (Continued)
Androgenetic alopecia is the common "malepattern" baldness that results from the combination of androgen level and an afPropriate
genetic makeup. The pattern of this type 0 hair loss
in males is typical and presents as hair loss in the
frontotemp:>ral and vertex areas of the scalp, eventuating in a rim of hair on the posterior and lateral aspects
of the scalp. Androgenetic alopecia occurs in women as
well, although the pattern is one of diffuse hair loss that
begins on the vertex of the scalp. In contrast to men,
women with androgenetic alopecia tend to retain a thin
rim of frontal hair while hair loss progresses on the top
of the head. The presentation of a young woman with
:
210 Sldn Disorders Alopecia
androgenetic alopecia should instigate a search for the

source of excessive androgens, especially if other signs
of virilization are also present. Women with hair loss
beginning at age 50 or older should be considered to
have senile or involutional alopecia, when other causes
of diffuse hair loss (e.g., hypothyroidism) have been excluded.
Bibliography
Cooper KD: Urticaria and angioedema: diagnosis and
evaluation. J Am Acad Dennatol 25,166-176, 1991.
Denman ST: A review of pruritus. J Am Acad Dennatol
14(3),375-388, 1986.
Fitzpatrick TB, Eisen AZ, Wolff K, et aJ., Dennatology

in General Medicine. 3rd ed. New York, McGrawHiII,I987.
Greaves MW Chronic Urticaria. N Engl J Med 322(26),
1767-1772, 1995.
Kitchens CS: The purpuric disorders. Semin Thromb
Hemost 10(3),36; 1984.
Lever WF, &haumburg-Lever G, llistopathology of the
Skin. 6th ed. Philadelphia, JB Uppincott, 1983.
Moschella SL, Hurley Hr Dennatology. 3rd ed. Philadelphia, WB Saunders, 1992.
Olsen EA: Alopecia: Evaluation and management. Prim
Care 16(3),765-785, 1989.
Neoplasm
Basal cell carclnoma (morpheafonn)

Squamous cell carcinoma
Metastatic carcinoma (alopecia neoplastlca)
lymphoma
Adnexal tumors
~BacteriaJ
Infection
Fungal
Protozoan
Systemic disease
Mechanical
trauma
Bums
Trauma
-{
Caustic agents
Radiation
Discoid lupus erythematosus

Sarcoidosis
Uchen planus (lichen planopilaris)
Sclerodennalmorphea
Lichen sclerosus at atrophicus
Necrobiosis 1ipoidica diabeticorum
Follicular mucinosis
Acne keloidalis nuchae
Pseudopelade of Brocq
Folliculitis decatvans
Amyloidosis
Dissecting perifolliculitis 01 the scalp
Bullous diseases
Hereditary disorders
1
Alopecia
11 Systemic lupus erythematosus
(SlE)
rMalnUlrition
12
Other nutritional deticiencyLsPrue
13
Telogen effluvium
Zinc deficiency
Trichotillomania
Trauma -----;.
Traction alopecia
Hereditary syndromes
"'"OS
Cecil Chapter
522
Alopecia areala
Androgenetic
Hamson
Chapter
alopecia
57
Skin Disorders Alopecia. 211
Musculoskeletal Disorders
Signs and symptoms:
Arthralgias and arthritis
Muscle weakness
Low back pain
SIGNS AND SYMPTOMS

ARTHRALGIAS AND ARTHRITIS
II
The differential wagnosis of arthralgias and ar

thritis is broad, encompassing
more than 200
separate entities. The hjstory and physical examination are aimed at defining the nature of the pain
and identifying associated systemic factors that aid in
diagnosis. Factors that must be weighed heavily include
the !lumber, pattem of distribution,
and size of the
joints involved, as well as the presence or absence of
other systemic signs or symptoms.
Whether
pain is
monoarlicular,
oligoarticular,
or polyarticular
and
whether the joint is small or large are important factors
to take into account diagnostically.
When a patient complains of arthralgia (joint
pain), the initial step is to determine
whether
arthritis is also present. The signs of arthritis
(true joint inflammation) include swelling, heat, redness,
evidence of synovial thickening, tenderness upon palpation, and evidence of joint effusion. All joints must be
assessed despite complaints of pain limited to one joint.
If no objective signs of .arthritis are present:

periarticular
pain syndromes
must be considered. Nonarticular or penarticular
pain encompasses a Iargc group of miscellaneous
conditions that
can be diagnosed on the basis of history and physicaJ
pending upon the clinical picture, supportive treatment

can be undertaken
initially, with joint rcst and analgesics. Evaluation with radiographic examination and joint
aspiration is undertaken if symptoms persist or progress.
Joint fluid examination is the most useful test
in diagnosing joint inflammation. Radiologic examination may not be helpful in acute disease
because many of the bone and joint space changes
characteristic
for a particular disease do not occur until
late in the course of the disease. Synovial fluid should
be analyzed for cell count and differential. Normal fluid
contains a small number of mononuclear
white blood
cells, whereas infected joints contain primarily polymorphonuclear white blood cells. The fluid should also be
examined for the presence of crystals and stained for
bacterial, fungal, and acid fast organisms. Measurement
of joint fluid complement
level is rarely diagnostic.
Examination of fluid for the presence of crystals

must be performed
with a polarizing microscope because crystals are difficult to. identify
with bright-field microscopy. The s<xlium urate crystals
of gout are negatively birefringent
and needle-shaped
under the polarizing microscope.
Clinically, gout presents as acute monoarticular
arthritis. The first metatarsophalangeal joint is typially involved, but any joint or
multiple joints can also be affected. Pseudogout
presents in a similar manner to gout \Yith acute monoamcular arthritis, hut the crystals are calcium pyrophosphate.
The calcium pyrophosphate
crystals show positive birefringence under the polarizing microscope. Pseudogout
may occur as a complication of hyperparathyroidism
.
exam.
With ohjective evidence for true joint involvement, other clues obtained from the history and
physical exam should be taken into account. It
may be difficult to determine
whether the arthritis is
due to a primary rheumatic
disease or secondary to
some underlying systemic disease. Although an underly.
ing disorder may already be diagnosed, it must be deterIllined whether the joint symptoms are due to the disease or represent
a separate,
unrelated
problem.
Therefore,
with any new onset of arthritis, joint fluid
should he examined wben possible. The clinical setting
should always he taken illto account prior to invasive
diagnostic procedures
silch ;LS a joillt aspiration
De-
212
Husc:uloskeletal Di50rden ArthralJP:lSand Arthritis
Stains for bacterial, fungal, and acid-fast o.rganisms as well as the corresponding
cultures
should always be performed on aspirated joint
fluid regardless of suspected diagnosis. Septic arthritis
is considered on the basis of cell count and differential,
because white blood cell counts are extremely elevated
(50,000 to "200,000/cm3) and neutrophils
predominate
(>80%). Tuberculous
arthritis results in fewer inflammato.ry cells 25,000),
and the difTerential is variable.
Fungal and acidfast stains are important because fungal
and mYl.'Obact('rial cultures may take many weeks to
grow. Gonococcal arthritis may be missed unless a special medium (modified Thayer.Martin
medium) is used
to culture the joint fluid.
Common causes of pyogenic arthritis include

staphylOCOCCi (acc.'ounting for approximately two
thirds of cases), streptococci
(15% of cases),
pseudomonas
(15% of cases), and pneumococci.
Gramnegative bacillary joint infections are most often seen in
immunocompromised
patients. Gonococcal arthritis can
be polyarticular
early, but later typically affects one
large joint. The initial joint symptoms in gonococcal
arthritis are due to immune complex deposition and can
involve many joints. Aspirated joint fluid at this stage
will be culture-negative.
As the disease progresses, true
gonococcal infection settles, usually into one large joint,
and aspirated joint fluid may reveal the gonococci on
smear or culture. Because gonococcal arthritis is a com
plication of untreated primary gonorrhea, women may
be affected more frequently, as gonococcal infections
may progress undiagnosed
because of the paucity of
symptoms of primary infection in women. A skin rash
consisting of a few periarticular
pustules can be a clue
to the diagnosis of gonococcal arthritis.
II
The white blood cell count and differential will

help differentiate
between inRammatory jo.int
disease and degenerative
joint disease. Markedly elevated white blood cell counts with a predominance of neutrophils
are found in inRammatory joint
disease such as crystalline
arthritis
(gout and pseudogout), infection, and inRammatory conditions of unknown etiology, such as rheumatoid arthritis.
1m
Viral infections most commonly cause arthralgias without true arthritis but can cause transient polyarthritis, whieh usually resolves without sequelae.
Rubella can cause viral arthritis,
and
symptoms may occur even following rubella V"<ll.'Cination.
Varicella, viral hepatitis, infectious mo.nonucleosis, and
mumps are other viral diseases associated with polyar.
thritis. Arthritis as a result of viral joint involvement will
be culture-negative,
and the joint Auid can range from
noninRammatory
to severely inflammatory.
II
Metabolic conditions that result in noninflammatory arthritis

include
alkaptonuria
(och
ronosis), \Vilson's disease, hemochromatosis,
amyloidosis, and acromegaly. Storage disease (Gaucher's)
can also result in a noninRammatory arthritis.
Bursitis (peritendinitis)
Tendinitis
Cellulitis
Fbrositis
Tenosynovitis
_Igk<s
Carpal tunnel syndrotne
Fasciitls
PoIymyalgk<
-.natica
Reflex ~thetic
dystrophy syndrome
Bacterial
_ctens,
Infection
4 ArtIcular pain
-{
Parasitic
Fungal
'0
NOninflammatory arthritis
11
~O':..'",nt
Neuropathic
Traumatic arthntls
MetabolIC arthritis
Degenerative joint disease (osteoarthntis)
Systemic lupus erythematosus (SlE)
-..1![
Spirochetal
Lyme disease
Viral
Syphilis
Reiter's syndrome (postdysenteric)
Psoriatic arthrttis
Ankylosing spoodylltis
Inflammatory bowel disease (IBo)
Sde~
121nflarnmatory arthritis
Cecil Chapter
304
Harrison Chapter
322
Polyarteritis nodose
Rheumatic fever
Infectious endocarditis
SynoviaJlUmors
Hemophilia
Serum sickness
~rsdi88ase
Sarcoidosis
AIDS
FamJlial Mediterranean fever (FMF)
Foreign body synovitis
Arthralgias and Arthritis
213
ARTHRALGIAS AND ARTHRITIS
The inflammatory
arthritides
been identified as crystalline
nature must be differentiated
that have not

or infectious in
on the basis of
detailed history, physical exam, and serologies. Important factors that must be taken into account include
the number, size, and pattern of joint involvement,
the
presence or absen~ of systemic symptoms, and the
subsequent clinical course. Other helpful diagnostic
aids include radiographic examination of both involved
and noninvolved joints and needle biopsy of the synovium, which may be supportive
or diagnostic.
Both
computed
tomography
(CT) and magnetic resonance
imaging (MRO are being used to evaluate joints (such

as the sacroiliac joints) that
clinically. MRI is particularly
synovium.
II
is l.:aused by the spirochete Borfollows infection by

a tick bite. A characteristic
skin rash (erythema
chronicum migrans) can precede the arthritis by several
weeks and can be the hallmark of the disease. If the
rash is identified and the patient treated, subsequent
arthritis may be avoided. Serologic Lyme titers can be
measured if the patient's history is suggestive of a risk
of infection.
Lyme disease
relia burgdorferi. Arthritis
(Continued)
arc difficult to evaluate

useful in visualizing the
214 Musculoskeletal Disorders Arthralgias and Arthritis
III
Rheumatoid arthritis is a chronic systemic rus+

~ ease without known etiology. The disease manifestations are primarily articular. with progressive
symmetric inAammatory destruction
of the peripheral
joints. Systemic manifestations
are rare and diverse and
include pleural effusions. splenomegaly, and peripheral
neuropathy. TIle onset of the disease is usually insidious,
with complaints of fatigue, weakness, myalgia, and morning joint stiffness as t.he initial manifestations.
II
Arthritis may accompany

ulcerative colitis in
approximately
one fifth of patients and affects
approximately
10% of patients with Crohn's disease. Arthritis may also affect as many as 60% of patients with Whipple's disease.
II
can be accompanied
by
an acute polyarthritis
of the large joints. The
polyarthritis
may he migratory and resembles
septic arthritis clinically, but the joint fluid is sterile.
The arthritis is thought to be immunologically
mediated.
II
Bleeding diatheses such as hemophilia result in

recurrent
hemarthrosis
and gmdual joint de+
struction. The diagnosis can he suspected in the
presence of a bloody joint aspiration with a history of
minimal trauma.
Bursitis (peritendinitis)
Tendinitis
Cellulitis
Fibrositis
Tenosynovitis
Myositis/myalgias
Carpal tunnel syndrome
Fasciitis
Potymyalgia rf1eumatica
Renex sympathetic dystrophy syndrome
1
Arthralgl .
arthritis
-{
4 Articular pain
Bactenal
MycobactenaJ
Infection
ParaSitIC
Fungal
Non,nflammatoo)'
a""",,
'iO
11
~~=Eh""
MetabolICarthntls
Degenerative JOInt disease (osteoarthntls)
SystemIC lupus erythematosus (SlE)
___~lyme
Spirochetal ~
Viral
14
15
12 Inflammatory arthritis
11
Cecil Chapter
304
Harrison
322
Chapter
Rheumatoid arthrttis
Reiler's syndrome (postdysenteric)
Psoriatic
arthritis
Ankytosing spondylitis
Inflammatory bowel disease (IBD)
Systemic lupus erythematosus (SlE)
Scleroderma
-[Polyarteritis
16
disease
Syphilis
nodosa
Rheumatic fever
Synovial tumors
Hemophilia
Serum sickness
Beh~el's disease
Sarcoidosis
AIDS
Familial Mediterranean lever (FMF)
Foreign body synovitis
Arthrnlgias and Arthritis
215
MUSCLE WEAKNESS
The diagnosis of muscle weakness is difficult
owing to the diversity of causes and to the fact
that there are no tests that, taken alone, are
diagnostic for a particular disorder. Muscle weakness is
diagnosed by the evaluation of both clinical and laboratory abnormalities. The constellation of abnormalities,
including age of onset, pattern of muscle involvement,
associated systemic symptoms, and clinical course, is the
key to diagnosis. There is considerable overlap among
the various clinical manifestations of muscle disease,
making accurate diagnosis more difficult. Multiple tests
may be necessary to confirm a suspected diagnosis.
Muscle weakness can be due to a primary muscle disorder
or to neurologic
dysfunction.
complete neurologic examination is essential as

part of the history and physical examination. Muscle
pain, however, may prevent full effort by the patient,
resulting in the perception of muscle weakness by the
examiner. Cerebral and upper motor neuron disease is
not difficult to identify, because weakness in these disorders is usually manifested as hemiparesis or other gross
abnormalities. A primary myopathy may be difficult to
differentiate from a neurogenic myopathy when neurologic dysfunction involves the anterior horn cells, the
nerve roots, or the peripheral nerves. A variety of both
clinical clues and test abnormalities helps to distinguish
a neuropathic myopathy from a primary myopathy. In
general, distal limb weakness is likely secondary to a
neurogenic disorder, whereas proximal limb weakness is
more likely myopathic. Muscle fasciculation never occurs in myopathy and is seen primarily with chronic
motor neuron diseases but rarely with peripheral neuropathy. Cutaneous sensory loss suggests peripheral
neuropathy. Laboratory data such as muscle enzymes,
electromyogram (EMG), or muscle biopsy can confirm
the diagnosis.
The source of myopathy can be a metabolic
derangement or one of the collagen-vascular
diseases or muscular dystrophies. Appropriate
metabolic tests should be performed based on the history and physical exam. In general, metabolic abnormalities result in an acute or subacute onset of muscle
weakness in which the weakness progresses over days
to weeks. Transient or intermittent muscle weakness is
usually due to a metabolic derangement and can be
secondary to hypokalemia caused by drug use or due to
216 Husc:uloskeletal Disorders
MuscleWeakness
familial periodic paralysis. The latter is an autosomal

dominant disorder in which serum potassium falls precipitously during attacks of muscle weakness.
Rhalxlomyolysis is the rapid destruction of muscle tissue. With muscle destruction, large
amounts of myoglobin and other cellular products are released into the bloodstream and excreted
by the kidneys. Approximately 50% of patients with
rhalxlomyolysis develop acute renal failure as a result
of the release of these proteins. Myoglobinuria can be
seen in approximately 50% of patients with dermatomyositis, polymyositis, and many of the other progressive
muscle diseases. Acute alcoholic myopathy is due to
muscle necrosis occurring after a heavy bout of drinking. Urine myoglobin and serum muscle enzymes are
markedly elevated. Chronic alcoholic myopathy is probably secondary to a progressive peripheral neuropathy
rather than being a primary myopathy.
II
defining the myopathy and in ruling out other myopathic or neuropathic disorders.
Although nonspecific, an elevated erythrocyte
sedimentation rate (ESR) may allow for identification of one of the collagen-vascular diseaseassociated myopathies. If muscle enzymes are not elevated, an elevation of the ESR in the face of clinical
weakness would justify the use of the EMG to identify
disease.
Polymyalgia rheumatica (PMR) presents as

shoulder or hip girdle pain in the elderly. Muscles appear weak clinically due to the poor effort by the patient secondary to pain. The diagnosis is
made when the EMG is normal but the ESR is markedlyelevated. PMR is associated with an increased incidence of temporal arteritis. A temporal artery biopsy
aids in the diagnosis.
Polymyositis (PM) and dermatomyositis (DM)

A variety of drugs can cause muscle weakness
(see No. 10), but more commonly drugs unare relatively common diseases that manifest
mask muscle weakness that was not clinically
clinically as proximal limb weakness and aching.
DM is accompanied by characteristic skin changes. The apparent. Even in the face of drug use, other causes of
clinical manifestations of polymyositis can occur in isola~ muscle weakness should be sought. However, if evaluation or can be associated with other collagen diseases tion of muscle weakness is negative, the drug should
such as rheumatoid arthritis, scleroderma, or systemic be discontinued and the patient observed clinically. If
lupus erythematosus. An underlying malignancy is weakness resolves, the muscle weakness can be assumed
thought to account for the clinical symptoms in approxi- to be drug-induced. If the weakness persists despite
mately 10% of patients with OM and PM. The muscle discontinuation of the drug, an EMG and a muscle
changes can precede the detection of malignancy by as biopsy should be performed.
much as 2 years. The diagnosis of idiopathic PM and
DM is based on the clinical picture, elevated muscle
Steroid myopathy is muscle weakness resulting
enzymes, electromyography (EM G), and muscle biopsy.
from the administration of systemic steroids.
No single criterion is diagnostic. Probably fewer than
A similar myopathy may accompany Cushing's
one fourth of all patients demonstrate the characteristic
syndrome, in which adrenal corticosteroids are elevated.
abnormalities in all four categories.
The proximal muscles of the limbs are primarily affected. The severity of muscle weakness is poorly correThe muscular dystrophies are a group of ge- lated with steroid dose, and the onset of the symptoms
is variable, occurring within weeks to months after the
netic diseases that cause progressive muscle
weakness and wasting. Most of these disorders initiation of corticosteroids.
begin in infancy or childhood, although a few manifest
as late as middle age. Serum muscle enzymes are markCongenital myopathies are due to a metabolic
edly elevated in some of the muscular dystrophies and
or structural abnormality of the muscle fiber.
are normal in others. The diagnosis is based upon the
Serum muscle enzyme levels are usually norclinical picture, including the mode of inheritance, the mal, the disease is slowly progressive over many years,
localization of involvement, the disease's progression,
and muscle biopsy is usually diagnostic. Muscle biopsy
and its associated features. Serum muscle enzyme ab- alone is diagnostic of the rare congenital myopathies
normalities, EMG abnormalities, and muscle biopsy are and of myopathy associated with infection, sarcoidosis,
not diagnostic but are used as adjunctive information in amyloidosis, and vasculitis.
1m
II
Neuro exam
abnormal
Gudlaln-Barresyndrome
P-yna
Myastheniagravis
Eatoo-Lambertsyndrome
AmyotrophICIataral sclerosis
Neurogenic
myopathy
Systemic
symptoms &
fever
Pf8senI
Infection
-i
Poliomyelitis
Rabie.
Coxsackievirus
Innuenza
Rubella
HIV (AIDS)
=-1 1
Viral
Bactenal
Epstein-BarrViruS(EBV)
Slaph_
StreptococcaJ
Salmonella
ParaSItIC
Clostridial
Mycobacfenum I8pras
Familial periodic paralysis

Diabetes meUltus
Hypoitlyperthyroidism
_Ia
Hypercalcemia
Hypemlal;1'l8S8lTlla
Hypophosphatemia
Hyperparathyroidism
Vitamin D deficiency
Progressive myopathy
Rsnal tubular acidosisHSeiZUres
Cushing's syndrome
Hyperthermia
Rl'\abdomyOtysis
Crush injury
McArdle's syndrome
Extntme exertion
FamiHalmyoglobinuria
Alcoholic myopathy
Polymyosm.
Dermatomyositis
Muscular dystrophy
SarcoidosJs
Rheumatoidarthritis
Polyarteritis nodosa
Dermatomyosltlslpolymyosltis
A~
Sarcoidosis
8 Potymyalgiarh9umatica (PMR)
Cecil Chapter'
Harrison Chapter'
296
23
Am_=-{
Metabolic
:~=
Endoganou.
depressive
psychosis
Adult ackl
maltase
deficiency
Camlline
deficiency
Muscle Weakness 217
LOW BACK PAIN
II
Low back pain is one of the most common

physical complaints and is a major cause of lost
work time. Most back pain is benign, and the
majority of patients recover within 3 months. Fewer than
5% of patients suffer from chronic back pain, of which
only a small number have an underlying serious disease.
In the initial evaluation of low back pain, a complete history and physical exam should identity
patients with potentially serious disease who require more extensive, immediate evaluation. The evaluation should include a complete neurologic exam. If the
neurologic exam uncovers muscle weakness, sensory
deficits, or loss of reAexes, further prompt evaluation is
indicated. In the appropriate clinical setting, the diagnosis of an abdominal aortic aneurysm should always be
considered during the initial evaluation, because the mortality associated with rupture is greater than 50%.
If neurologic findings, including bowel or bladder dysfunction, are present, or the physical
examination is abnormal. cr or MRI should be
utilized immediately.
II
Rapid onset of severe low back pain suggests

rupture or dissection of an abdominal aortic
aneurysm.
The diagnosis can be suspected
when physical examination demonstrates
a midepigastric pulsating mass. Retroperitoneal leakage of the aneurysm may result in radiation of pain to the posterior
thighs. Unlike acute musculoskeletal pain in which the
patient can usually find a position in which the pain is
relieved, the patient with a leaking or dissecting aortic
aneurysm experiences persistent pain despite position.
Most abdominal aortic aneurysms are secondary to arteriosclerosis and are therefore found most often in men
over 50 years old. More than 50% of these patients have
associated hypertension.
At
times, acute lumbosacral strain can be so

severe that physical examination is unable to
distinguish between true weakness and weakness due to pain. In these cases, if cr examination is
normal, supportive treatment can be undertaken
initially, with further evaluation it symptoms progress or
pain does not resolve (see No.6).
II
Most back pain has an acute onset, usually ac

companied by a history of new, different, or
vigorous physical activity. In this setting, if neurologic examination is normal and vascular rupture is
unlikely, the patient can be treated supportively, with
218 Musculoskeletal
Disorders
Low Back Pain
further, more extensive evaluation if the pain does not

subside within several weeks. Radiographic studies are
sometimes performed with the initial evaluation of back
pain, but the radiographic abnormalities
may not be
associated with the current episode of pain.
Plain radiographs are relatively inexpensive and
can be quite helpful in identifying a variety of
abnormalities, ranging from bone lesions to kidney stones. Many of the changes that are identified by
radiographs are suggestive but not diagnostic for a particular disorder, so that further study might be needed
to confirm a diagnosis. In addition, some findings on
radiography may be coincidental or contributory rather
than causative of the current episode of back pain.
Degenerative joint disease (DJD) is probably

the most common cause of chronic low back
pain in persons over 50 years old. DJ D is actually degenerative
disc disease in which the disc has
gradually collapsed with time. This alters the mechanical
balance betw"een the bony structures, including the in~
telVertebrai facet joints, resulting in pain. The patient
experiences a baseline chronic low back pain with episodic occurrences of acute pain. Radiographic examination reveals disc space narrowing and marginal osteophytes along the vertebral margins.
Various benign and malignant pelvic disorders

can be common causes of low back pain. These
disorders
include endometriosis,
uterine fibroids, menstrual cramps, and even pregnancy. In the
male, prostatic disorders, including chronic prostatitis,
can result in low back pain. Some pelvic disorders, such
as tumors, may be suspected on the basis of radiographs
and confinned by pelvic examination. cr or MRI may
help to delineate the size and extent of pelvic tumors.
1m
Based on physical findings and plain radioI graphs, further study may be undertaken if a
diagnosis cannot be made with certainty. cr is
a sensitive tool for the diagnosis of lumbar spine lesions
that result in nelVe root encroachment and irritation. A
radionuclide bone scan can be a sensitive detector of
early bone lesions when the lesions are not yet apparent
on conventional radiographs.
II
Spinal infections are difficult to diagnose. Infection may involve the disc space or the bony
stmctures of the spine. Radiographic studies
may not be helpful unless a frank abscess or osteomyelitis is present, and MRI or cr may be more sensitive in
detecting infection. Epidural abscess formation occurs
in the setting of a history of bacteremia with the subsequent insidious development of diffuse low back pain
occurring over days to weeks. Rapid progression of
pain with radicular symptoms and limb weakness is
an indication of the presence of an epidural abscess.
Tuberculous arthritis of the spine begins in the vertebral
body and ultimately leads to vertebral collapse. Acute
pyelonephritis may present as low back pain, although
commonly it is referred to the Rank.
II
Herniated discs are not well identified on plain

films but can be easily identified on cr or
MRI scans. MRI may identify degenerative disc
disease not visualized vith cr. Disc herniations are most
common at the lA-L5 or L5--S1 levels. Disc herniation
at the L5 level may cause the typical pain of sciatica,
with pain radiating from the back into the posterior
thigh, the anterolateral leg, and the dorsolateral foot.
Back pain secondary to disc disease characteristically is
exacerbated by coughing or sneezing.
III
Back pain that has an onset after continuous

walking is suggestive of arterial insufficiency
that can result from spinal stenosis or spinal
claudication.
The patient complains of an aching,
cramping pain in the lower back or buttocks that occurs
after walking. The pain can be relieved by sitting or
lying down but returns when activity is resumed. Physical examination is normal when the patient is at rest,
but if the patient is examined immediately after activity,
abnormalities such as weakness and reflex and sensory
abnormalities will be confirmed. The cr scan is invaluable in diagnosis if the claudication-like symptoms are
due to spinal stenosis.
III
Polymyalgia rheumatica (PMR) is a syndrome

that occurs in elderly patients, most frequently
as insidious shoulder pain and stiffness, associated with a markedly elevated ESR, often as high as
100 mmlhr. PMR may occur as hip girdle pain and low
back pain. The significance of diagnosis of PMR is its
association with temporal arteritis in 30% to 50% of
these patients. Temporal arteritis may lead to blindness
if left undiagnosed and untreated.
~
II
Complaints of back pain \'vith a paucity of abnormalities on physical exam, in the setting of
secondary gain, suggest malingering. Malingering should be a diagnosis of of exclusion, however .
because severe lesions can, at times, be accompanied
by a normal physical examination. Drug-dependent
patients may complain of ongoing back pain to obtain
additional prescriptions for narcotics.
Abdominal aortic aneurysm

Disc herniation/rupture
Vertebral compressloo fracture
Spinal tumors
Spinal abscess
Peptic ulcer
Pancreatitis
:::{
Muscles
.
Ugaments
Lumbosacral S1ra~n
Sacroiliac stram
Ae-evaluate it pain persists
Myofascial
(see below)
Osteomalacia
Osteoporosis
Metabolic bone disease
H
~
-{
Paget's disease
yperpara,"I' ..
,sm
,
low back~In
X-rays
abnormal
II
II No neurologic
deficits
Osteoarthritis
Ochronosis
Compression fracture
Ankylosing spoodyIitis
Sp0ndy1oiisthesis
Tumor
Degenerative joint disease
Kidney stone
Hemangioma
Osteosarcoma
Neural tumors
Metastatic disease
Muniple myeloma
Osleoid osteoma
Aneurysmal bone cyst
Prostatitis
Endometriosis
Pelvic tumor
Pelvic infection
Pregnancy
----E
Abscess
Cervicitis
Pelvic inflammatory disease
~"'toomY.Uti'
Tuberculosis
Funoa
'
Syphilis
Paraspinal abscess
Polymyalgla meumatica (PMA)

Familial Medite"anean fever (FMF)
Spif'llll tuberculosis (TB)
Cecil Chapter'
HalTison
Chapter'
493
Lumbosacral strain
Malingering
Chronic pain syndrome
Herpes zoster
Ae-evaluate if pain persists
16
II
Approximately
2% of patients with low back
pain cannot be diagnosed. Periodic reevaluation
reveals underlying disease in approximately one
third of these patients.
Bibliography
Borenstein D.: A practical guide to mechanical low back
pain. Intern M 18(9),37-44.
1997.
Finneson BE: Diagnosis and Management of Pain Syndromes. Philadelphia, WB Saunders, 1969.
Hickling P, Golding JR: An Outline of Rheumatology.

Bristol, UK, John Wright & Sons, 1984.
Katz WA: Rheumatic Diseases: Diagnosis and Management. Philadelphia, J8 Lippincott, 1977.
Kaye JJ: Arthritis: Roles of radiography and other imaging techniques
in evaluation.
Radiology 177:601608, 1990.
Lewis RC: Primary
Care Orthopedics.
New York,
Churchill Livingstone, 1988.
Martinelli TA, Wiesel SW: Low back pain: The algOrithmic approach. Compr Ther 17(6):22-27,
1991.
Moskowitz RW: Clinical Rheumatology: A Problem-Oriented Approach to Diagnosis and Management.
Philadelphia, Lea & Febiger, 1982.
Rothschild
BM: Rheumatology:
A Primary Care Approach. New York, Yorke Medical Books, 1982.
Sanchez HB, Quinn SF: MRI of inflammatory synovial
proc'Csses, Magn Reson Imaging 7:529-540, 1989.
Musculoskeletal Olsorden: Low Back Pain
219
Amiodarone (Continued)
thyroid function tests and, 190
Amphetamines, mental status and, 174
pruritus from, 203
Amphotericin B, acute tubular necrosis and, 76
diabetes insipidus and, 84
hypokalemia and, 87
magnesium and, 100
renal tubular acidosis and, 104
Ampicillin, pseudomembranous colitis from, 40
Amyl nitrate, methemoglobinemia from, 138
Amylase, abdominal processes and, 52, 54
ascites and, 70
Amyloidosis,
162
alkaline phosphatase and, 75

arthritis in, 212
Bence Jones proteins in, 162
cardiomegaly and, 36
dysphagia and, 49
ecchymoses from, 206
folate deficiency and, 135
gastrointestinal bleeding and. 44
hepatomegaly and, 69
hyperkalemia and, 91
hypoparathyroidism and. 92
hypotension and, 26
jaundice and, 64, 65
myopathy and, 216, 217
proteinuria and, 80, 81

splenomegaly and, 116
Amyotrophic lateral sclerosis (ALS), dysphagia and, 49
hypercarbia and, 22
Analgesics. See Aspirin; Neutropenia; Nonsteroidal antiinflammatory agents (NSAIDs).
Anaphylaxis, disseminated intravascular coagulation and, 110
hypotension and, 26, 27
Androgen(s), in hirsutism, 184
Androgen therapy, and polycythemia, 138
Androstenedione, in hirsutism, 184
Anemia, 118, 119. See also Folic acid deficiency; Vitamin B/2
dejidency.
aplastic, 122, 128, 129
cardiac murmur and, 34
Fallcolli's. See Fanami's syndrome.
hemolytic, 122, 124, 125
hyperbilirubinemia and, 64
immune, 126,127
lymphadenopathy and, 113
hypochromic, dysphagia and, 48
iron deficiency, 120, 121, 122. See also Thrombocytopenia.
alopecia and, 208
pruritus and, 202
macrocytic, 130, 131
222
Index
Anemia (Continued)
megaloblastic, recovery granulocytosis and, 144
microcytic, 120, 121
normocytic, 122, 123
pernicious, 132, 133
dementia and, 171
hypoparathyroidism and, 92
pyridoxine-responsive, 136
refractory, 136
splenomegaly and, 116, 117
thiamine-responsive, 136
Anesthetics, diabetes insipidus and, 84
hypercarbia from, 22, 23
hypotension from, 26
oliguria and, 76, 77
platelet dysfunction from, 108
pseudoneutrophilia and, 144
Aneurysm, diabetes insipidus and, 84
low back pain and, 218
vertigo and, 169
Angiitis. See also Thromboangiitis obliterans; Vasculitis.
allergic granulomatous, eosinophilia and, 152, 154
leukocytoclastic vasculitis and, 207
glomerulonephritis and, 76
Angina, hypertrophic cardiomyopathy and, 36
variant, 25
Angina pectoris, 24, 25
Angiodysplasia, and gastrointestinal bleeding, 44
Angioedema, 204
Angiotensin-converting enzyme (ACE) inhibitors, aplastic
anemia and, 129
cough from, 13
hyperkalemia from, 88, 90, 91
hypertension and, 32
oliguria and, 77
Anion gap, 99, 1M, 105
Anorexia nervosa, 8
amenorrhea and. 182
edema and, 30
hypercholesterolemia and, 195
hypokalemia and, 86, 87
Anorexiants, hyperprolactinemia from, 182
Antacids, constipation from, 38
diarrhea from, 40
hypophosphatemia from, 96
Anthracyclines, aplastic anemia and, 129
neutropenia from, 142
Anti-arrhythmiq. See also Neutropenia.
syncope and, 28
weight loss and, 8
Antibiotics. See also Dem.entia; Neutropenia.
clotting factor abnonnalities and, 110, III
diarrhea and, 40, 41
hyperkalemia from, 88
hypokalemia and, 87
urticaria from, 204
Antibiotics (Continued)
weight loss and, 8
Anticholinergic agents, dementia and, 170
perspiration and, 172
Anticonvulsants, dementia and, 170
leukopenia from, 142
mental status and, 174
vitamin 0 and, 92
Antidepressants, dementia and, 170
tricyclic, cardiomyopathy and, 36
hypercarbia and, 22, 23
hyperprolactinemia from, 182
hyponatremia and, 82
~")'Tlcopeand, 28
vertigo and, 169
Antihistamines, leukopenia from, 142
weight loss and, 8
Antihypertensives. See also Neutropenia.
dementia and, 170
edema and, 30
oliguria and, 77
syncope from, 28
vertigo and, 169
Antilymphocyte globulin (ALG), thrombocytopenia from, 160
Antimetabolites, aplastic anemia and, 128
megaloblastic anemia and, 136, 137
Antineop1astics, acute tubular necrosis and, 76
aplastic anemia and, 12B
dementia and, 170
Antithyroid agents, leukopenia from, 142
oJ-Autitrypsin deficiency, and hepatitis, 66
Aortic stenosis, cardiomegaly and, 37
hypotension and, 26
Aplasia, red blood cell, 122
Appendicitis, 58, 59, 60
abdominal pain and, 50, 52, 57
Arginine hydrochloride, and hyperkalemia, 88
Arteriosclerosis, aneurysm and, 218
renal artery stenosis and, 32
Arteriovenous fistulas, 34
erythrocytosis and, 139
Arteritis. See also Polyarteritis nodosa.
fever and, 7
Takayasu's, proteinuria and, 81
temporal, 166
polymyalgia rheumatica and. 166,218
weight loss and, 8
Arthralgia, 212, 213
Arthritis, 212, 213
edema and, 30
inRammatory, 214, 215
rheumatoid, 214. See also Felty's syndrome; Pleuritis, rheumatoid
Arthritis (Continued)
anemia from, 122, 127
anti-intrinsic factor antibodies and, 132
cyanosis and, 18
eosinophilia and, 152
mixed cryoglobulinemia and, 206
myelofibrosis and, 140
red blood cell aplasia and, 122
thrombocytopenia and, 160
weight loss and, 8
tuberculous, 218, 219
Ascites, 70, 71
Ashennan's syndrome, 180
Aspartate aminotransferase (AST), 72
cerebrovascular accidents and, 72
congestive heart failure and, 66
hepatitis and, 66, 67
hyperbilirubinemia and, 64, 65
myocardial infarction and, 24, 72, 73
Aspiration, and cough, 12, 13
Aspirin. See also Gluoose-6-phosphate dehydrogenase
<kfide=J.
acidosis from, 104
hepatitis from, 68
hypoglycemia and, 199
nephritis and, 76
ototoxicity of, 168
urticaria from, 204
Asthma, eosinophilia and, 152, 153
pneumothorax from, 14
syncope and, 28
Atrial septal defects (ASDs), cardiomegaly and, 37
ostium secundum, mid-diastolic munnurs and, 34, 35
Autoerythrocyte sensiti7..ationsyndrome, 206
Autoimmune disease. See also Lupus erythematosus.
hemoptysis from, 16
thrombocytopenia from, 160
Azathioprine, and anemia, 137
6-Azauridine, and anemia, 137
Bacteremia, fever and, 4
oliguria and, 77
Bake{s cyst, and edema, 30
Banti's syndrome, 116
Barbiturates, hypercarbia from, 22, 23
hypotension from, 26
sulfonylureas and, 198
Bartter's syndrome, 86, 106
Basedow's disease. See Graves' disease.
Beh~rs syndrome, arthritis and, 215
hemoptysis from, 16
Behr;et's syndrome (Continued)

odynophagia and, 49
Bence Jones proteins, 162
acute tubular necrosis and, 76
Benign positional vertigo (BPV), 168
Benzene, aplastic anemia from, 128
neutrophilia and, 144
Benzoates, urticaria from, 204
Berger's disease, and hematuria, 78
Berylliosis, splenomegaly and, 117
vitamin D and, 94
Betablockers. See {J-Adrenergic blockers.
Bicarbonate ion, 105, 106, 107
hyponatremia and, 82, B3
Biopsy, chronic diarrhea and, 42
chronic hepatitis and, 68
cough diagnosis and, 12
hepatomegaly and, 67, 69
scalp metastases and, 208
Birth control drugs, dural sinus thrombosis and, 166
hepatitis from, 68
hypertriglyceridemia from, 196
jaundice and, 65
pruritus and, 202, 203
telogen effluvium following, 208
Bisphosphonate, and hypocalcemia, 93
Bleeding, abnonnal, 108, 109, llO, 111. See also
Gastrointestinal (GI) tract, bleeding from.
Blood screening tests, and gastrointestinal bleeding, 46
Blood transfusion, hyperkalemia from, 88
hypocalcemia and, 93
thrombocytopenia and, 158, 160
urticaria and, 205
Blood volume, and hypotension, 26
Bone disease, alkaline phosphatase and, 74, 75
low back pain and, 218, 219
Bone maJ'TOW",
myelophthisic, 122, 146
transplantation of, veno+occlusive disease and, 68
Bowel infarction, and periumbilical pain, 58, 59
Bowel ischemia, 56
alkaline phosphatase and, 74, 75
gastrointestinal bleeding and, 47
lower quadrant abdominal pain and, 61
Brain stem, herniation of, 174
lesions of, 174
Bromocriptine, and pleural effusion, 20
Bronchiectasis, and syncope. 28
Bronchitis, cyanosis and, 19
hemoptysis and, 16, 17
Budd-Chiari syndrome, 68
Bulimia, 8
Bulimia nervosa, 10
Bum injury. See Thermal injury.
Calcinosis, tumor, hyperphosphatemia and, 98, 99
Calcitriol, 92, 93
Calcium, absorption of, 92, 94
magnesium absorption and, 100
Calcium channel blockers, and edema, 30
Candida, and odynophagia, 48
Captopril, and fever, 4
Captopril challenge test, and hypertension, 32
Carbamazine, and hyponatremia, 82
Carbenicillin, metabolic alkalosis and, 106
Carbenoxolone, alkalOsiSand, 106
hypokalemia and, 87
Carbon monoxide, chron~c exposure to, 172
ototoxicity of, 168
Carboxyhemoglobinemia, 138
Carcinoembryonic antigen (CEA), and ascites, 70
Carcinoma. See also Malignancy; Tumor(s).
ascites and, 71
bladder, 78
bronchogenic, cough from, 12
hemoptysis and, 16
colon, diarrhea and, 42
gastric, anti-intrinsic factor antibodies and, 132
hepatocellular, 64
immune hemolytic anemia and, 127
inappropriate secretion of antidiuretic honnone and, 82, B3
large bowel, constipation and, 38, 39
lung, erythrocytosis and, 139
macrogfobulinemia and, 162
neutrophilia and, 144, 146
parathyroid, 94
proteinuria from, 80
pruritus from, 202, 203
rectal, pelvic pain and, 62
renal cell, 78
thyro;d, 186, 188
multiple endocrine neoplasia type 2 and, 94
ureteral,78
Cardiac insufficiency, oliguria from, 76, 77
seizure and, 176, 177
Cardiac munnurs, 34, 35
Cardiac tamponade, edema and, 30, 31
oliguria and, 77
Cardiac testing, 24
Cardiac rroponin I (cTn I), and chest pain, 24
Cardiomegaly, 36, 37
Cardiomyopathy, congestive, 36, 37
hypertrophic, 36
seizure and, 176
Cardiopulmonary abnonnalities. See also Cardiac murmurs;
Congestive hearl failure (CHF); Cyanosis; Hypotension;
Ischemia; Shunt, intracardiac; Syncope.
Index 223
Cardiopulmonary abnormalities (Continued)

dyspnea and, 14, 15
vertigo and, 169
Carotid sinus massage, 28
Catatonia, 174
Catecholamine, serum, hypertension and, 32
Celiac disease, 8. 42
tertiary hyperparathyroidism and, 94
Central nervous system. See also Brain stem.
lesions of, diabetes insipidus and, 84, 85
dysphagia and, 49
hypercarbia and, 22
hypotension and, 26
inappropriate secretion of antidiuretic hormone and, 82,
83
Cephalosporins, and nephritis, 76
Cerebrovascular accidents (CVAsl. creatine kinase and, 72
diabetes insipidus and. 84
Cervicitis, and pelvic pain, 62
Chemical compounds. See also Lead poisoning; Mercury.
altered mental status and, 174
dementia and, 170
headache from, 166
induced cyanosis from, 18
Chemotherapy, emuvium and, 208
hyperphosphatemia and, 98
neutropenia From, 142, 143
Chest pain, 24-2.5, 25
Chiari syndrome, 68
Chloramphenicol, 104. See also Clucose-6-phosphate
dehydrogenase deficiency.
aplastic anemia from, 128
Chloroquine, glucose-6-phosphate dehydrogenase deficiency
and,l24
muscle weakness and, 216, 217
Chlorpromazine, hepatitis from, 68
jaundice and, 65
Chlorpropamide, eosinophilia from, 152
pruritus and, 203
Cholangitis, sclerosing, biliary obstruction and, 64, 65
Cholecystitis, and upper abdominal pain, 52, 53, 54
Cholestasis, 64
Cholestyramine, and weight loss, 8
Choriocarcinoma, and hemoptysis, 16
Chronic active hepatitis (CAH), 66, 68
Chronic fatigue syndrome, 2
Chronic myelogenous leukemia (CML), 144
Chronic obstructive pulmonary disease (COPD). See also
Obstructive airway disease.

hypercarbia and, 22
224 Index
Chronic obstructive pulmonary disease (COPD) (Continued)

syncope and, 28
Chronic persistent hepatitis (CPHl. 66
Churg-Strauss syndrome, eosinophilia and, 152, 154
Cigarettes, 12. See also Nicotine.
carcinoma and, 78
hematuria and, 78
Cimetidine, menta] status and, 174
nephritis and, 76
vasculitis from, 206
Cirrhosis, 68
alkalosis and, 107
ascites and, 70
hyponatremia from, 82
hyperpro]actinemia and, 184
hypoglycemia and, 200, 201
hypokalemia and, 86
macroglobulinemia and, 163
primary biliary, 64, 202
spur cell anemia and, 124
vitamin 0 and, 92, 93
Cisplatin, acute tubular necrosis and, 76
hypomagnesemia and, 100
ototoxicity of, 168
Clindamycin, pseudomembranous colitis from, 40
Clofibrate, hyponatremia and, 82
nephritis and, 76
Clonidine, and edema, 30
Clonidine suppression test, 32
Coagulation abnormalities, 108,109, 1I0, 111
Coarctation of aorta, cardiomegaly and, 37
cyanosis and, 18
Cobalt, and hypothyroidism, 190
Cocaine, hypertension and, 33
pruritus and, 203
syncope and, 28
Coccidioidomycosis, lymphadenopathy and, 112
vitamin 0 and, 94
Colchicine, diabetes insipidus and, 84
vitamin Bill deficiency and, 133
Colic, biliary, 50
Colitis, 42
pseudomembranous, 40
ulcerative, arthritis and, 214
Collagen-vascu]ar disease See also Sckrodemul.
anemia from, 122
Co]lagen-vascular disease (Continued)

constipation and, 39
dural sinus thromboSis and, 166
eosinophilia and, 152, 153
fever and, 4
weight loss and, 8
Colon, cathartic, 38
Colonoscopy, and gastrointestinal bleeding, 44, 45
Coma, 172
hyperosmolar, 104, 105
Computed tomography (CT), in urinary tract imaging, 78
Congestive heart failure (CHF). See also Cardiome{!,aly
alkalosis and, 107
ascites and, 70
cyanosis and, 19
hemoptysis and, 17
hypokalemia and, 86
hyponatremia and, 82, 83
oliguria and, 77
pleura] effusion and, 20, 21
weight loss fmm, 8, 9
Constipation, 38, 39
Contraceptives. See Birth control dnlgs
Coombs' test, 126
Corticosteroids. See also Steroid(s).
edema and, 30
granulocytosis and, 144
monocytosis and, 148
myopathy from, 216
Cortisol, for glucocorticoid deficiency, 82
Costochondritis, 24-25
Cough, 12, 13
syncope and, 28
Coxsackieviruses, and cardiomegaly, 36, 37
Creatine kinase (CK), 72, 73
chest pain and, 24
Crohn's disease, 60
arthritis and, 214
pelvic pain and, 63
weight loss from, 8
Cryoglobulinemia, cyanosis from, 18
mixed,206
Cushing's disease, 184. See also Purpura.
alkalosis and, 107
dementia and, 171
granulocytosis in, 144
hypematremia and, 84, 85
polycythemia and, 138
weight gain and, 10
Cushing's syndrome, hypercalcemia and, 94
Cushing's syndrome (Continued)

hyperlif.idemia and, 197
hypoka emia and, 87
Cyanide, and mental status, 174
Cyanosis, 18, 19
Cyclophosphamide. alopecia and, 208
Cyclosporine. hyperkalemia from, 90
oliguria and, 77
Cystic fibrosis, pneumothorax from. 14
Cystinosis, hypophosphatemia and. 96
Cytomegalovirus (CMV). hemolytic anemia from, 127
hepatitis and, 64
hepatomegaly from, 68
in mononucleosis, 150
Cytosine arabinoside, and anemia, 137
Cytotoxics. See also Neutropenia.
parathyroid hormone and, 92
weight loss and, 8
Dantrolene. hepatitis and. 68
pleural effusion and, 20
Dapsone, and glucose-6-phosphate dehydrogenase denciency,
124
De Quervain's thyroiditis, 188, 192
OeJ(enerative disc disease. 218
Dehydroepiandrosterone (OHEA), in hinutism, 184
Delirium, 172
Demeclocycline, and diabetes insipidus, 84
Dementia, 170, 171
Depression, dementia and, 170
fatigue and, 2
weight gain and. 10
Dennatiti$. exfoliative, (olate deficiency and. 135
Dennatomyositis. 216
Dextran, platelet dysfunction (rom. lOB
Di Guglielmo's syndrome. 136
thrombocytopenia and. 159
Diabetes insipidus. 84
Diabetes mellitus, acidosis and. 104
anti-intrinsic (actor antibodies and. 132
cardiomegaly and. 37
constipation and. 38
diarrhea and. 43
dysphagia and, 49
(olate deficiency and. 135
hepatomegaly and. 68
hyperkalemia and, 88. 90, 91
hyperlipidemia and, 195, 196, 197
hypoglycemia and. 198, 200
hypokalemia and, 86
hypotension and, 26
insulin receptor antibodies in. 200
proteinuria and, 81
pruritus and. 202
Diabetic ketoacidosis (DKA). 104

abdominal pain from. 56
hypennagnesemia and. 102
hyperphosphatemia and. 98. 99
hypokalemia and. 86
hypophosphatemia from, 96. 97
neutrophilia and. 144, 145
Diarrhea, 40. 41
acidO$is from. 104
chronic, 42. 4J
hypematremia and, 85
hypokalemia from. 86
hypomagnesemia and. 100, 101
of unknown origin, 42
sigmoidoscopy and. 40. 41. 42, 4J
Diazoxide. for hypokalemic periodic paralysis, 86
Digitalis, neutrophilia and. 144
pot<wium and, 88
toxicity of, 2
weight loss and, 8
Digoxin. and dementia. 170
Dipyridamole. platelet dysfunction from, lOB
Disopyramide, and hypoglycemia, 199
Di.ueminated intravascular coagulation (DIC), 110
hemolytic anemia and, 125
thrombocytopenia of. 160
Diuretics. See also Neutropenia.
alkal()jis and, 106
constipation and. 38
hypematremia and, 85
hypokalemia and, 86
hyponatremia from, 82. 8J
hypophO$phatcmia and, 97
oliguria from, 76
,>",cope from, 28
thiazide, hypercalcemia and, 94, 95
nephritis and, 76
sUlfon~ureas and, 198
throm
openia and, 158
urticaria rom, 204
triglycerides and, 196
weight loss and, 8
Diverticulitis, 50, 61, 62
hematuria and, 79
Diverticulum, Meckel's, 44, 57, 58
Zenker's, 48
Dopamine, and thyroid-stimulating honnone, 190
Doppler ultrasonography/ultrasonogram(s), 34
venous occlusion on, 30
Down's syndrome. leukemoid reaction in, 144
Doxorubicin, hypocaJcemia and. 93
myocarditis (rom, cardiomegaly and, 36, 37
Drug(s). See also specific agents.
alcohol ingestion with, 170
Drug(s) (Continued)
alopecia from, 208
altered mental status and. 174
aplastic anemia and, 128, 129
autoimmune hemolytic anemia and. 126
cardiomegaly and, 36, 37
constipation and. 38. 39
dementia from. 170
diarrhea and. 40, 41
chronic, 42, 4J
edema and. 30, 31
fatigue and, 2
fever of unknOW'llorigin and, 4
headache (rom, 166
hepatitis and. 68
hirsutism and, 184, 185
hyperbilirubinemia and, 64, 65
hypercaroia and, 22. 23
hyperkalemia and, 88, 89, 90, 91
hyperprolactinemia from, 182, 184
hypotension and, 26, 27
hypothyroidism and. 190, 191
lymphadenopathy and. 112
magnesium wasting and, 100
neutropenia from, 142, 143
oliguric renal failure and. 76
proteinuria and. 80
seizure and. 177
syncope from, 28. 29
syndrome o( inappropriate secretion of antidiuretic hormone and. 82
thrombocytopenia from, 156. 158. 160
triglycerid.es and. 196, 197
weight gain and, 10. 11
weight loss and, 8
Dubin-Johnson syndrome, 65
Dysfibrinogenemia, 110
Dysphagia, 48, 49
Dyspnea, 14. 15
hypertrophic cardiomyopathy and, 36
Dysproteinemia, 162, 163
Dystrophy, muscular, 216
Echocardiography, 36
Edema, 30. 31. See also Angioedema.
oliguria and, 77
Index225
Edema (Continued)
pulmonary. hypercarbia and, 22
Effiuviuln,208
Electrocardiogram (EKe), stress testing and, 24
syncope evaluation and, 28
upper abdominal pain and. 50
Electroenccphalogram (EEGl. epilepsy on, 178
Electrolyte disorders, 82-107. See also specific disorders.
dementia and, 171
Embolism, mesenteric, periulllbilical pain and, 58. 59
oliguria and, 77
pulmonary. alkalosis after. 106
chest pain and. 24, 25
cyanosis and, 18, 19
hemoptysis from, 16
hypercarbia and, 22
hypotension and, 27
pleural effusion and. 20
Emesis, alkalosis and, 106
hypokalemia and, 86. 87
with diarrhea, 40
Emetine. and cardiomyopathy, 36
Empyema, 20
dysphagia and, 49
Encephalitis. See also Alterell m~mtol status.
alkalosis and, 107
inappropriate secretion of antidiuretic hormone and, 83
Endocarditis. cardiomegaly and, 37
fever and, 4, 5, 7
polyarthritis in, 214
proteinuria and, 80
subacute bacterial, disseminated intravascular coagulation
and,110
purpura and, 108
weight loss and, 8
Endometriosis, pneumothorax from, 14
Endoscopic retrograde cholangiopancreatography (ERep), 52
Endoscopy, d~phagia evaluation with, 48, 49
gastrointestinal bleeding ev.lluation with, 44, 45
upper abdominal pain and, 52, 54, 55
Endotoxin, acute tubular n(,"Crosisand, 76
Enema(s), appendicitis and, 59
barium, ~ellesions
and, 38, 42, 44
diverticulitis and, 50, 62
hyperphosphatemia from, 98, 99
Enteritis, regional, 50, 61
arthritis and, 214
pelvic pain and, 63
weight loss from, B
Enteroclysis, 44
Eosinophilia, 152, 153, 154, 155
Epidural abscess, and low back pain, 218
Epilepsy, 178
226 Index
Epinephrine, pseudoneutrophilia and, 144

transitol}' thrombocytosis and, 156
Epstein-Barr virus (EBV). 2
hepatitis and, 64
in mononucleosis, 150
Ergotamine, and cyanosis, 18
Erythroblastosis fetalis, 126
Erythrocytosis, idiopathic familial, 139
Erythroderma, and cardiomegaly, 36
Erythroleukemia, 136
Erythromycin estolate, eosinophilia from, 152
hepatitis from, 68
jaundice and, 65
Esophageal stricture, and dysphagia, 48
Estrogen(s), amenorrhea and, 180
edema and, 30
in hyperlipidemia, 196
jaundice and, 65
synthetic, hyperprolactinemia from, 182
Ethambutol, and nephritis, 76
Ethanol. See Alcohol.
Ethylene glycol, acidosis from, 104
mental statw and, 174
Etidronate disodium, and hyperphosphatemia, 99
Evans' syndrome, 160
Fabry's disease, 36
proteinuria and, 80
Familial hyperlipidemias, 194,195, 196, 197
Familial Mediterranean fever, 6, 7
arthritis and, 215
back pain and, 219
Fanconi's syndrome, 128
hypophosphatemia and, 96, 97
tubular proteinuria and, 80
Fatigue, 2, 3
Felty's syndrome, 1l6, 142
Fenoprofen, and oliguric renal failure, 76
Ferritin, 120, 121
Fever, cardiac murmur and, 34
hematuria and, 78
Fever of unknown origin (FUO), 4, 5, 6, 7
Fibrin, in hemolytic anemia, 124
Fibrinogen, and reactive thrombocytosis, 156
Fistula, arteriovenous, cardiomegaly and, 36
murmurs and, 34
Fitz-Hugh-Curtis syndrome, 52
S-Fluorouracil, and anemia, 137
Folic acid deficiency, 130, 134, 135

mental status and. 174
Folinic acid, for drug-induced folate deficiency, 134
Foscamet, and acute tubular necrosis, 76
Furosemide, hypothyroidism and, 191
ototoxicity of. 168
Gaisbock's syndrome, 138
Gammopathy, monoclonal, 162, 163
Gardner-Diamond syndrome, 206
Gastrectomy, folate deficiency and, 135
vitamin Bll deficiency and, 132
Gastrointestinal (GO tract, bleeding from, 44, 45, 46, 47
iron deficiency anemia and. 120
occult blood screening tests and, 46
chest pain and, 25
Gaucher's disease, arthritis in. 212
myelophthisic bone marrow and, 123
Geophagia, B6
Gilmlia lamblia, 40
Gilbert's disease, 64, 65
Globus hystericus, 48
Glomerulonephritis, 76, 77, 78
hematuria and, 78
proteinuria from, 80, 81
Glucocorticoid deficiency, 82
Clucocorticoids, and thyroid-stimulating hormone, 190
Clucose, hypokalemic periodic paralysis from, B6
hypophosphatemia and, 96
lactic acid from. 104
Glucose-6-phosphate dehydrogenase deficiency, 124
Glycosides, cardiac, mental status and, 174
Glycosuria, and hypokalemia, B6
Goiter, 186, 188
toxic multinodular. 190,191
Gold compounds, aplastic anemia and, 129
eosinophilia from, 152
Gout, 212
Granulomatous disease. See also Berylliosis; De Queroains
thyroiditis; Enteritis, regional; Sarcoidosis; Wegener's
gra'luWnUltosis.
alkaline phosphatase and. 75
ascites and, 71
diabetes insipidus and, B4
hypernatremia and, B4
monocytosis in, 148
myelophthisic bone marrow and. 122, 146
pleural effusion and. 21
vertigo and, 169
Granulomatous disease (Continued)

vitamin 0 and, 94, 9.5
weight loss and, 8
Graves' disease, 188, 189
Guillain-Barre syndrome, 22
diabetes insipidus from, 84
inappropriate secretion of antidiuretic honnone and, 83
Haloperidol, and hyponatremia. 82
Halothane, hepatitis from. 68
jaundice and. 65
Hashimoto's thyroiditis, 188
anti-intrinsic factor antibodies in, 132
hyperparathyroidism and, 94
Headache, 166-167,167
Heart block. murmurs and, 34
Heart disease. See also Cardiomegaly
cyanotic, 18, 19
Heart failure, congestive, See Congestive heart failure (CHF).
hypotension and, 27
Hematemesis. 44
Hematochezia, 44
Hematuria, 78, 79
Hemochromatosis, and cardiomegaly. 36
Hemodialysis, and iron deficiency anemia. 120
Hemoglobin. variant, erythrocytosis and, 138
Hemoglobinuria, 78. 122
paroxysmal cold. 126
paroxysmal noctunml. See paroxysmlll nocturnal hemoglobinuria
(PNIl)
Ilemolysis. See Anemia. hemolytic.

Hemol)'tk-uremic s)'ndrome, 160
Hemophilia. 110
hemarthrosis and. 214
Hemoptysis. 16. 17
J lemorrhage, cerebral. See also Altered mental status.
hyponatremia and. 83
hypotension frolll. 26
seizure and. 176
postpartum, ischemic acute tubular necrosis and, 76
Jlenoch-Schonlein purpura, 108,206
proteinuria and, 81
Heparin. 110
alopecia and. 208
fever and, 4
hyperkalemia from. 88
hypothyroidism and, 191
thromboc')'topenia and. 160
Hepatic failure. See also Liver, disease of

alkalosis from, 106
disseminated intravascular coagulation and, 110
hypothermia and, 172
Hepatitis, 64-65
ar.1astic anemia and, 128
c Ironic, 66, 68
hepatocellular carcinoma and, 64
proteinuria and, BO
toxic, 68
upper abdominal pain and, 50, 52. 53
urticaria and. 204
viral, polyarthritis in, 212
Hepatomegaly, 66, 67, 68, 69
Hemia, inguinal, lower quadrant abdominal pain and, 60
Hemiation, brain stem, 174
Herpes simplex virus, in mononucleosis, 150
odynophagia and. 48
Herpes zoster virus. abdominal pain and, 52, 53, 60
back pain and, 219
chest pain and, 24
vertigo and, 168
Hirschspnmg's disease, 38
Hirsutism. 184-185,185
Histiocytosis. and hyperprolac:tinemia, 184
Histoplasmosis. and vitamin D, 94
Hodgkins disease, eosinophilia and, 152
leukemoid readion and, 144
pruritus and, 202
thromboc)10penia and, 160
Human chorionic gonadotropin (HeG). hyperthyroidism and,
190
trophoblastic lumors and, 180, 190

Human immunodeficiency virus (HIV) infection. 4. See also
Acquired
immu,wdeficiency syndrome (A1DS).
aplastic anemia lind, 129
ascites and. 70
diarrhea and. 43
proteinuria and, 80
Hungry bone syndrome, 93, 100
Hyduntoins. See also Methylplumylethylhydantoin,
fever and, 4
lymphadenopathy alld, 112
lIydrala;rjne, edema and, 30
fever and, 4
Hydrocephalus, nonnal-pressure, 170
Hydronephrosis,.erythropoietin from, 138
hyrerkalemia from, 90. 91
H)'droxyelhyl starch. platelet dysfunction from, 108
Hydroxyurea, and anemia, 137
Hyperaldosteronism. See Aldosteronism.
Hyperalimentation, ac:idosis from, 104
Ilyperbilirubinemia, 64-65, 65
H)'perc-.llcemia, 94-95. 95. See also HypenUltremia.
Hypercalcemia (Continued)
Hypercalciuria, hypomagnesemia from, 100
Hyperemia, 22, 23
correction of, alkalosis and, 107
Hypereatabolic states. See also Hyperkalemia.
hypematremia and, 84, 85
Hypercholesterolemia, 194, 195
Hypereosinophilic syndrome, 152
Hyperglycemia, seizure and, 176
sodium and, 82
I-Iyperinsulinemia, 198
Hyperkalemia, 88, 89, 90, 91
acidosis and, 88
diabetes and, 88, 90, 91
from alkalosis treatment, 88
from hydronephrosis, 90, 91
from hypokalemia treatment, 88
renal failure and, 90
Hyperlipidemia, 194. 195, 196,197
Hypermagnesemia, 102, 103
Hypematremia, 84, 85
Hypernephroma. and fever. 6
Hyperparathyroidism, 94
Hyperphosphatemia, 98, 99
hypocalcemia and, 93, 93
Hyperplasia, adrenal, hirsutism and, 184, 185
hypertension from, 32
multiple endocrine, 94
'r.lenic. 116
t Iyroid, 186. 187, 188, 189
Hypersplenism, 116. 140
Hypertension, 32, 33
cardiomegal)' and, 37
hypokalemia and, 86. 87
malignant, hemol)'!:ic anemia and, 125
oliguria and. 76. 77
seizure and, 176
portal, 116
ascites from, 70
proteinuria and, 81
pulmonary. 14
cyanosi! from, 18
H)'pCrthcrmia, 172
hyperphmphatemia and, 98, 99
pseudoneutrophilia and. 144
rhabdomyolysis and, 217
Hyperthyroidism, 188, 190, See also Vitamin Bu tkficiency.
cardiomegaly and, J6
hypercalcemia and, 94
hyperphosphatemia and. 98, 99
Hypertrichosis. 185
Hypervitaminosis A. 94. 95
Index 227
Hypoaldosteronism, 90, 91
acidosis and, 104
Hypocalcemia, 92-93, 93
seizure with. 176
Hypogarnmaglobulinemia, anti-intrinsic factor antibodies and,
132
Hypoglycemia, 198, 199, 200, 201
diabetes and, 198. 200
mesenchymal tumors and. 200
seizure and, 176
Hypoglycemic agents. See also Neutropenta.
hypoglycemia from, 198
weight loss and. 8
Hypokalemia, 86-87, 87. See also Hypematremia.
Hypomagnesemia, 100, 101
hypocalcemia and, 93. 93
Hyponatremia, 82, B3
seizure and, 176
Hypoparathyroidism, 92
hyperphosphatemia and, 98, 99
Hypophosphatemia, 96, 97
hypercarhia and, 22
Hypopituitarism, and hypoglycemia, 201
Hypotension, 26, 27
ischemic acute tubular necrosis from, 76
Hypothermia, 172
Hypothyroidism, 190, 191,192. See also Hypernatremia
hyperlipidemia and, 195, 196, 197
hyperprolactinemia and, 184
iron deficien<-)'anemia and, 122
macrocytic anemia and, 130
weight gain and, 10
Hypoxemia, and cardiomegaly, 36
Ibuprofen, edema and, 30
oliguric renal failure and, 76
Idiopathic hypertrophic subaortic stenosis (IHSS), 36
Idiopathic thrombocytopenic purpura (ITP), 160
Imerslund-Grltsbeck syndrome, 132
Imipramine, eosinophilia from, 152
Immunodeficiency disorders, eosinophilia and, 152
Immunoglobulin, fever and, 6
in hemolytic anemia, 126
Immunologically mediated diseases. See also Arthritis,
rheumatoid; Dysproteinemia; Henoch-SchlJn1ein purpura;
Lupus erythematosus; Urticaria.
hemoptysis from, 16
Indomethacin, edema and, 30
Infection. See also Hepatitis; Sepsis.
alopecia and, 208
aplastic anemia and, 128, 129
228 Index
Infection (Continued)
ascites and, 70, 71
chronic, anemia from, 122
chronic hepatitis and, 68
diarrhea from, 40. 41
chronic, 42, 43
fatigue and, 2, 3
fever and, 4, 5, 6, 7
fungal, dementia and, 170
gastrointestinal bleeding from, 44
headache from, 166
hematuria and, 79
hemolytic anemia from, 124, 125, 127
hemoptysis and, 16
inappropriate secretion of antidiuretic honnone and, 82, 83
joint pain and, 212
lymphadenopathy and, 112, 113
lymphocytosis from, 150
nephritis and, 76, 77
neutropenia from, 142, 143. See also Neutrophilia.
odynophagia and, 48, 49
proteinuria and, 80
purpura and, 108
splenomegaly from, 116, 117
thrombocytosis and, 156, 157
upper quadrant abdominal pain and, 52, 53
vasculitis and, 206
weight loss and, 8
Inflammatory bowel disease, abdominal pain and, 57, 61
anemia from, 122
arthritis and, 214,215
diarrhea and, 42
gastrointestinal bleeding and, 47
Inflammatory conditions. See also Arthritis.
anemia and, 122
macroglobulinemia and, 162, 163
monocytosis in, 148
thrombocytosis and, 156, 157
Influenza, cardiomegaly and, 36, 37
Insecticides, aplastic anemia and. 129
dementia and, 170
Insulin, hypokalemia from, 86
potassium and, 88
Insulinoma, 200
tests of, 198
Iodides, eosinophilia from, 152
Iodine, and thyroid honnones, 190

Ionizing radiation, aplastic anemia and, 128
neutropenia from, 142, 143
Irritable bowel syndrome, 38
diarrhea and, 42
lower quadrant abdominal pain and. 61
Ischemia. See also Acute tubular necrosis, ischemic; Bowel
ischemia.
brain stem, altered mental status and, 174
coronary, hypokalemia and, 87
myocaliol,24
hypomagnesemia and. 101

Isoniazid, acidosis from, 104
hepatitis from, 68
jaundice and, 65
sideroblastic anemia and, 120
Isotretinoin, and alopecia, 208
Jaundice, 64-65, 65
alkaline phosphatase and, 64, 65, 72
Jodbasedow phenomenon, 188
Ketoconazole, vasculitis from, 206
Kidney. See also Renal entries.
medullary sponge, hematuria and, 79
polycystic, 78
diabetes insipidus and, B4
erythropoietin from, 138
tubular proteinuria and, SO
Kostmann's disease, 142
Kyphoscoliosis, cardiomegaly and, 37
hypercarbia and, 22
Lactate dehydrogenase (LDH), ascites and, 70
iron deficiency anemia and, 120
myocardial infarction and, 24
Laxatives, hyperphosphatemia from, 98, 99
phenolphthalein type, 42
stimulant type, 3R
Lead poisoning. 56. See also Fanconi's syndronte; Proteinuria;
Vertigo.
anemia and, 120, 125
constipation and, 39
dementia and, 170,171
dysphagia and, 49
Leukemia. See also Chronic myelogenous leukemia (CML).

alkaline phosphatase and. 75
chronic lymphocytic, macroglobulinemia and. 163
eosinophilic. 154
folate deficiency and, 134, 135
hyperphosphatemia from, 98. 99
hypokalemia and, 86
immune hemolytic anemia and. 127
lymphadenopathy ",d, 112
myelofibrosis and. 140
myelophthisic bone marrow and, 122, 146
pancytopenia of. 140, 141
pruritus and. 202
spleno~y
and, 116
versus leukemoid reaction, 144
Leukemoid reaction(s), 144
Leukocytosis. 144
_ in {'Olycythemia vera diagnosis. 138-139
Levodopa. alopecia and, 208
hypokalemia and. 87
Liddle's syndrome, 106
hypokalemia and, B6
Lincomycin, pseudomembranous colitis from, 40
Lindane. and aplastic anemia, 129
Lipase, serum, abdominal processes and, 52
Lithium, alopecia and, 208
diabetes insipidus and. 84
for neutropenia, 144
hypercalcemia from, 94
hypoglycemia and. 199
renal tubular acidosis and. 104
thyroid enlargement from, 188
thyroid hormones and. 190
Liver. See also Hepo.t- entries.
disease of. alkaline phosphatase and, 64, 65, 72, 73, 74, 75
chronic, anemia of, 122, 131
coagulation and, 110
oliguria and, 76, 77
fat infiltration of, 68
USffier's myocarditis, cardiomegaly and, 36
lOffier's syndrome, eosinophilia of, 154
Lumbar puncture, in mental status examination, 174
Lung disease, interstitial, J 4
cough from, 12
hyperearbia and, 23
Lupus erythematosus, alopecia and, 208
systemic, anemia from, 122, 127
arthritis in, 213
clotting factor antibodies and, 108
cyanosis and, IS
dementia and, 170
Lupus erythematosus (Continued)

dural sinus thrombosis and, 166
fever and, 5, 7
hyperkalemia and. 91
hyperlipidemia and. 195, 197
lymphadenopathyand,113
pancytopenia and, 140
proteinuria and, 81
red hlood ceO aplasia ..d, 122
urtlcaria and.. 205
'Neight loss and, B
Lupus pleuritis, 21
Lupus pneumonitis, hemoptysis from, 16
Lyme disease, 214
J.rmphadenopathy,
112, 113
lymphocytosis ",d, 151
Lymphatic obstruction, and 'Nelght loss. 8
J.rmphedema. 30
J.rmphccytosb.
150, 151
Lymphoma, 112. See also Hodgkin's disease.
ascites and, 71
biliary obstruction and. 64, 6S
dysphag;a ",d. 49
fever and. 4, 5, 7
hepatomegaly and. 69
hypelfhosphatemia from, 98, 99
lymphedema from. 30
macroglobulinemia and. 162
proteinuria from, BO
pruritus and, 202, 203
Lysine hydrochloride, and hyperkalemia, sa
Macroglobulinemia, 162
Magnesium, hyperphosphatemia and, 99
hypokalemia and, B6
Magnesium hydroxide, hypophosphatemia from, 96
Magnetic resonance imaging. lymphatic obstruction on, 30
Malabsorption, and vitamin Bli deficiency, 132, 133
Malabsorption syndrome, 42, 43. See also electrolyte
disorders.
Malignancy. See also Carcinoma; Sarcoma.
anemia from, 122
Malignancy (Continued)
ascites and.. 70
cough from, 12
dysphagia and. 48, 49
fever and, 4, 6. 7
hemoptysis and, 16
hirsutism and. 185, 185
hypercalcemia and, 94, 9S
hyperparathyroidism and. 94
hyperphosphatemia and. 98, 99
jaundice and. 64, 6S
Iymphadenopathy",d,
112, 113
lymphedema from, 30
macroglobulinemia and. 162, 163
pelvic pain and, 62. 63
pleural effusion and.. 20, 21
Mannitol. hypematremia and.. 84, 85
magnesium reabsorption and. 100
Manometry, dysphagia on, 48
Marfan's syndrome, cardiomegaly and. 37
Marijuana, and syncope. 28
Mastocytosis, cutaneous, 204
Measles, canl;omegaly ",<I, 36, 37
nephritis from, 76
Meckel's diverticulum, 44, 57, 58
Megacolon. 3B
Meigs' syndrome. 20, 21, 70
Melanosis coli, 38
Melena. 44
Mt';ni~re's disease, 16B
Meningitis,l66
dementia and, 170
inappropriate secretion of antidiuretic honnone and. 8J
vertigo and. 169
Mental status, altered, 172. 173,174,175
Mephenytoin, and proteinuria, BO
6-Mercaptopurine. and anemia, 137
Mercury. See also Proteinuria; Vertigo.
dementia and. 170, 171
Metabolic disorders. See also Acidosis; Alkalosis; and specific
disorders.
altered mental state and. 173
dementia and. 171
myopathy and, 216,217
Methanol ingestion. 104
Methemoglobinemia, 13B
Index 229
Methemoglobinemia (Continued)
Methotrexate, alopecia and, 208
folate deficiency from, 134
Methyldopa. fever and, 4
hemolytic anemia from, 126
hepatitis from, 68
nephritis and, 76
Methylphenylethylhydantoin, and aplastic anemia, 129
Methyltestosterone, and jaundice, 65
Metbysergide, cyanosis and, 18
Metronidazole, for Giardia infection. 40
Micturition, and syncope, 28
Migraine headache, 166-167
versus seizure, 178. 179
vertigo and, 169
Milk-alkali syndrome, 38, 95
alkalosis and, 107
Mineralocorticoids, and alkalosis, 106
Minoxidil, and edema, 30
Mitotic inhibitors, alopecia and, 208
aplastic anemia and, 129
Mitral insufficiency, cardiomegaly and, 37
hypotension and, 26
Mitral regurgitation, 34
Mitral stenosis, and hemoptysis, 16. 17
Mitral valve prolapse, cardiomegaly and. 37
chest pain and, 24, 25
Monoamine oxidase (MAD) inhibitors, edema and, 30
Monocytosis, 148, 149
Mononucleosis, 150
nephritis from, 76
upper quadrant abdominal pain from, 52
urticaria and, 205
Mucinosis, follicular, 208
Multiple endocrine neoplasia (MEN), 94
insulinoma in, 200
Mumps, cardiomegaly and, 36, 37
odEPhagia and, 49
po
ritis in, 212
Musc e weakness, 216, 217
Mycetoma, and hemoptysis, 16
Mycoplasma
infection, hemolytic anemia from, 127
nephritis from, 76
Myelodr-'Plastic syndromes (MDSs), 136, 137
Myelofibrosis, 140
230 Index
Myelofibrosis (Continued)
Myeloma, multiple, 78, 162
proteinuria from, 80, 81
pruritus and, 203
purpura in, 206
Myocardial infarction, 24
aspartate aminotransferase and, 24, 72, 73
oliguria and, 77
Myocardial ischemia, 24
Myocarditis, and cardiomegaly, 36,37
Myoglobin, and acute tubular necrosis, 76
Myopathy, neurogenic, 216, 217
Myxedema, ascites and, 70
pernicious anemia and, 122
proteinuria and, 81
Myxomas, 6
Nafcillin, and nephritis, 76
Naproxen, edema and, 30
Narcotics. See Opiates.
Neomycin, and vitamin BIt deficiency, 133
Neoplasia, multiple endocrine, 94
insulinoma in, 200
Neoplastic diseases. See also Carcinoma; Hyperplasia;
Malignancy;
Sarcoma;
Tumor(s).
anemia from, 122

dyspnea and, 14
Nephritis. See also Glomerulonephritis.
hematuria and, 78
proteinuria and, 80
salt-losing. 82
Nephrotic syndrome, and secondary hyperlipidemia, 196, 197
Neuralgia, cranial, 166
temporomandibular joint, 168
Neuroma, acoustic, 168
Neuropathy, dysphagia and, 49
hypercarbia and, 22
hypotension and, 26
Neuroses, dyspnea and, 14
weight gain and, 10
Neutropenia, 142, 143
Neutropenia (Continued)
Neutrophilia, 144,145, 146, 147
Nicotine. See also Tobacco.
Niemann-Pick disease, myelophthisic bone marrow and, 123
Nitrates, methemoglobinemia from, 138
syncope from, 28
Nitrofurantoin. See also Gluoose-6-phosphate
ckhydrogenase
dejidency.

hepatitis and, 68
Nitroglycerin, methemoglobinemia from, 138
Nitroprusside, methemoglobinemia from, 138
Nonsteroidal anti-inAammatory agents (NSAIDs). See also
&pirin;
Neutropenia.
edema and, 30
nephritis and, 76
peptic ulcer and, 44
proteinuria and, 80
urticaria from, 204
weight loss and, 8
Notalgia paresthetica, 202
5' -Nucleotidase, 74, 75
Nutritional deficiency. See also Sprue; Staroation;
I",,,.
Weight
alopecia and, 208, 209

amenorrhea and, 182
edema and, 30
fatigue and, 2, 3
hyperearbia and, 22
hypomagnesemia and, 100, 101
Nutritional recovery syndrome, alld hypophosphatemia, 96
Obstructive airway disease, 12, 14. See also Chronic
obstrucHoe
pulmonan;
disease
(COPD).
hyperearbia and, 22
pneumothorax and, 14
spirometry and, 14
Occupational exposure, cough from, 12
Odynophagia, 48, 49
Oligomenorrhea, 180
Oliguria, 76, 77
Opiates, dementia and, 170
dependency on, back pain and, 218
hypercarbia from, 22, 23
Opiates (ConHnlled)
pruritus from, 203
urticaria from, 204
weight loss and, 8
Orotic aciduria, 136
Orthopnea, 14
Osler-Weber-Rendu disease, 108, 206
Osmoreceptor ablation, hypernatremia from, 84
Osmotic diuresis, and hypokalemia, 86
Osteomalacia, and hypercalcemia, 94, 95
Osteomyelitis, and anemia, 122
Ostium secundum atrial septal defects, mid-diastolic murmurs
and, 34, 35
Ovarian failure, 180, 181
Oximetry, and dyspnea, 14
Paget's disease, alkaline phosphatase and, 74, 75
hypercalcemia and, 94
Pain, low back, 218-219,219
Palsy, progressive supranuclear, 170
Pancreatic enzymes, and vitamin HII de6ciency, 132
Pancreatitis, 52, 54
ascites and, 70, 71
generalized abdominal pain and, 57
hypocalcemia and, 92, 93, 93
ischemic acute tubular necrosis and, 76
vitamin D and, 92
Pancytopenia, 129, 140, 141
Paracentesis, ascites on, 70, 71
Paralysis, familial periodic, hypokalemic, 86
Paraneoplastic syndrome, 144
Paraquat, and acute tubular necrosis, 76
Parathyroid hormone (PTH), 92, 93, 94, 95
phosphate and, 96
Paroxysmal cold hemoglobinuria (PCH), 126
Paroxysmal nocturnal hemoglobinuria (PNH), 124
Patent ductus arteriosus (PDA), cardiomegaly and, 37
cyanosis and, 18
mid-diastolic murmurs and, 34, 35
Paterson Kelly syndrome, 48
Patient immobilization, and hypercalcemia, 94, 95
Pelvic pain, 62, 63
Penicillamine, muscle weakness and, 216, 217
proteinuria and, 80
Penicillin, hemolytic anemia from, 126
hypokalemia and, 87
metabolic alkalosis and, 106
Pentamidine, acute tubular necrosis and, 76

Periarteritis nodosa. See Polyarteritis nodosa.
Pericarditis, and edema, 30, 31
Perihepatitis, gonococcal, abdominal pain and, 52
Peritonitis, and ascites, 70, 71
Periumbilical pain, 50
Perspiration, drug-impaired, 172
hypokalemia and, 86
pH, calcium and, 92
intracellular, alkalosis and, 96
of urine. 104
pleural effusion and, 20, 21
Phenacetin, methemoglobinemia from, 138
sulfhemoglobinemia and, 138
Phenformin, 104
Phenobarbital, and folate deficiency, 134
Phenothiazines, cardiomyopathy and, 36
syncope and, 28
Phenylbutazone. aplastic anemia and, 129
edema and, 30
Phenytoin, folate deficiency and, 134
jaundice and, 65
lymphocytosis and, 151
nephritis and, 76
Pheochromocytoma, 32, 33
hypercalcemia and, 94, 95
multiple endocrine neoplasia type 2 and, 94
seizure and, 178
Phonocardiogram, 34
Phosphatase, alkaline, 72, 73, 74, 75
in polycythemia vera diagnosis, 138-139
jaundice and, 64, 65, 72
Phosphate replacement therapy, and hyperphosphatemia,
Pick's disease, 170
Pickwickian syndrome, 22
Platelets, dysfunction of, 108
sequestration of, 160
Platypnea, 14
PlethYsmography, impedance, 30
Pleural effusion, 20. 21
Pleuritis. rheumatoid, 20
Plumbism. See Lead poisoning.

Plummer's disease, 190, 191
Plummer-Vinson syndrome, 48
Pneumonia, alkalosis and, 107
cyanosis and, 19
empyema and, 20
Pneumothor.u:, 14
alkalosis and, 107
Poliomyelitis, cardiomegaly and, .36, 37
dysphagia and, 49
erythroc..'ytosisand, 138
hypercarbia and, 22
Polyarteritis nodosa. See also Glomerulonephritis.
arthritis and, 215
fever and, 7
hemoptysis from, 16
weight loss and, 8
Polycystic kidney disease, 78
erythropoietin from, 138
tubular proteinuria and, 80
Polycystic ovary disease (PCO), 180, 184
Polycythemia, 138-139,139
Polycythemia vera (peV), 58
diagnosis of, 138-139
pruritus and, 202
Polydipsia, 84
psychogenic. 82
Polymyalgia rheumatica, 216, 218
temporal arteritis and, 166,218
weight loss and, 8
Polymyositis, 216
creatine kinase and, 73
dysphagia and, 49
myoglobinuria from, 216
weight loss and, 8
Polyserositis, familiaJ paroxysmaJ. See Familial Mediterranean
98
f"""
Porphyria, 56
congenitaJ erythropoietic, 125
hirsutism and, 185
hypotension and, 26
intermittent, hypercholesterolemia and, 195
seizure and, 178
Potassium. See also Hyperlcalemia; Hypokalemia.
acidosis and, 88
alkalosis and, 86, 106
Index 231
Prednisone, and thrombocytosis. 156

Pregnancy. See also Creatine kinase (CK); Vitamin
BII
deficiency.
alkaline phosphatase during, 74, 75
ascites and. 71
cholestasis and, 65
ectopic. lower quadrant abdominal pain and, 60
suprapubic abdominal pain and, 63
neonatal hemolytic disease and, 126, 127
oliguria and, 77
pruritus and, 202
thyroid function tests and. 190
Primaquine, and glucose-6-phosphate dehydrogenase
deficiency, 124
Prinzmetal's angina, 25
Probenecid, hyperbilirubinemia and. 64
proteinuria and, 80
Procainamide, and fever, 4
Procarbazine, eosinophilia from, 152
Proctitis, and pelvic pain, 62, 6J
Proctosigmoidoscopy, gastrointestinal bleeding on, 47
Progeria, 208
Progesterone, alkalosis and, 106
edema and, 30
in amenorrhea test, ISO
Progestogens, hyperprolactinemia from, 182
Prolactin, amenorrhea and, 180
blood level of, drugs and, 182, 184
hirsutism and, 184
Propranolol, alopecia and, 208
for hypokalemic periodic paralysis, 86
Propylthiouracil, and fever, 4
prostaglandin inhibitors, oliguric renal failure and, 76
Prostatitis, hematuria and, 79
lower abdominal pain and, 62
Proteinuria, 80, 81
Pruritus, 202, 203
Pseudogout, 212
Pseudohyperaldosteronism, 86, 87
Pseudohyperkalemia, 88, 89
Pseudoh)1lOpaf3.thyroidism, 92-93
Pseudolymphoma, 112
Psoriasis, and folate de6cieocy, 135
Psychiatric disorders, and altered mental status, 174
Pulmonary embolism. See also Edema, pulmonary.
alkalosis after, 106
chest pain and, 24, 25
232 Index
Pulmonary embolism (Continued)

hemoptysis from, 16
hypercarbia and, 22
hypotension and, 27
oliguria and, 77
Pulmonary hypertension, 14
cyanosis from, 18
Purpura, 108, 109, 206, 207
Henoch-Schonlein, 108, 206
proteinuria and, 81
senile, 206
thrombocytopenic, 160
Pyrazinamide, and microcytic anemia, 121
Pyridoxine-responsive anemia, 136
Pyrimethamine, folate de6ciency from, 135
Quinidine, fever and, 4
Quinine, fever and, 4
ototoxicity of. 168
Radiography/radiograph(s), 218. See also Ultrasonography/
IJltrasonogram(s).
gallstones on, 52, 54
upper abdominal pain and, SO, 52, 53, 57
Radiology, in neurologic examination, 170
Radionuc1ide imagingiimage(s), agents in, thyroid function
tests and, 190
cholecystitis and, 52
gallium, nephritis on, 76
gastrointestinal bleeding on, 44
in stress testing, 24
lymphatic obstruction on, 30
pheochromocytoma on, 32
renal artery stenosis on, 32
thyroid nodules on, 186
venous occlusion on, 30
Radiotherapy. See Ionizing radiation.
Ramsay Hunt syndrome, 168
Rauwol6as, and edema, 30
Raynaud's phenomenon, 18
Renal. See also Kidney.
Renal artery stenosis, hypertension and, 32, 33
metabolic alkalosis and, 106
oliguria and, 77
Renal failure, 82, 83
acidosis from, 104
anemia from, 122
Renal failure (Continued)

chronic, hyperparathyroidism and, 94
pruritus from, 202
hyperphosphatemia and, 98, 99
hypotension and, 26
oliguric, drugs and, 76, 77
Renal tubular acidosis (RTA), 86, 87, 104
Renin de6ciency, 90, 91
Reserpine, hyperprolactinemia from, 184
Resorcinol, and hypothyroidism, 190
Rhabdomyolysis, 216, 217
hypercalcemia after, 94
hypocalcemia and. 93
iSchemic acute tubular necrosis and, 76
Rickets, hypophosphatemia and, 96. 97
vitamin D and, 92, 93
Riedel's thyroiditis, 188
Rifampin, hepatitis from, 68
nephritis and, 76
Ristocetin, and thrombocytopenia, 160
Rotor's syndrome, 65
Rubella, mononucleosis from, ISO
viral arthritis in, 212
Salicylates, acidosis from, 104
ingestion of, 106
Sarcoidosis, alkaline phosphatase and. 75
arthritis and, 215
ascites and, 71
cough and, 13
dementia and, 170
fever and, 5
hemoptysis from, 16
hypercalcemia from, 94, 95
pancytopenia and, 140, 141
Sarcoidosis (Continued)
proteinuria and, 80, 81
Sarcoma. osteogenic, alkaline phosphatase and, 74, 75
hemoptysis and. 16
Schilling test, 132
Sclenxlerma. See also Collagen.vascular
disease.
arthritis and, 215
cardiomegaly and. 36
cyanosis and, 18
dysphagia and, 48
oliguria and, 76
vitamin 811 deficiency and. 132
weight loss and. 8
Sclerosis. amyotrophic lateral. dysphagia and, 49
hypercarbia and. 22
focal glomerular, hematuria and. 18
multiple. dementia from, 170
proteinuria and. 81
vertigo and, 168
Scoliosis, and hypercarbia, 22
Seizure, 176,177, 178. 179
Sepsis, 106
hypotension and. 26. 27
hypothermia and. 172
ischemic acute tubular necrosis and. 76
oliguria and, 77
Serum sickne55. 112. 204
arthritis and, 215

Sheehan's syndrome. amenorrhea and, 183
Shock. 26
Shunt, intracardiac, erythrocytosis and, 138
murmurs and, 34
Shy-Drager syndrome, 28
Sickle cell disease, 120
hematuria and, 78
proteinuria and, 80
upper quadrant abdominal pain and, 52
Sigmoidoscopy, 38, 62
gastrointestinal bleeding on, 47
Silver nitrate, methemoglobinemia from, 138
Sipple's syndrome. See Multiple endocnne neoplnsia (MEN).
SjOgren's syndrome, diabetes insipidus and, 84
Sjogren's syndrome (Continued)

proteinuria and, 80
urticaria and, 205
Sldn di.mlers, 202-211
SLE (systemic lupus erythematosus). See wpm
erythematosus, systemic.
Sodium, concentration of, metabolic alkalosis and, 106
fractional excretion of, 76, 77
Sodium nitrite, methemoglobinemia from, 138
Sodium polystyrene sulfonate, and weight loss, 8
Somatostatin, and thyroid-stimulating hormone, 190
Spherocytosis, 120
hereditary, 124
Spinal claudication, 218
SpirometJy, cough diagnosis and, 12
dyspnea and, 14
Spironolactone, for hypokalemic periodic paralysis, 86
Splenectomy, neutrophilia following. 144
thrombocytosis following. 156
Splenomegaly, 114, 115, U6, 117
from infection, 116, 117
in polycythemia vera diagnosis, 138
neutropenia and, 142, 143
thrombocythemia and, 156
upper abdominal pain and, 50, 52
Spondylitis, ankylosing. arthritis and, 215
weight loss and, 8
Spontaneous bacterial peritonitis (SBP), 70
Sprue, alopecia and, 209
iron deficiency anemia and, 121
nontropical,8
vitamin BIt deficiency and, 133
vitamin D and, 92
Starvation, acidosis from, 104
Stein-Leventhal syndrome, 180, 184
h~ycemia
and, 201
SteiOidls). See also Cortfco8teroids.
edema and, 30
hepatocellular carcinoma and, 64
myopathy from, 216
telogen effluvium following. 208
Streptococcal infection, nephritis from, 76
Stroke, hypertensive, seizure and, 176
Stroma ovarii, 190
Stupor, 172
Subclavian artery, anomalous, dysphapa and, 48
Subclavian steal syndrome, 28
Succinylcholine, hypercarbia from, 22, 23
Succinylcholine (Continued)
Sucralfate, and weight loss, 8
Sulfhemoglobinemia, 138
Sulfinpyrazone, platelet dysfunction from, 108
Sulfonamides. See also GllJCOSe-6-phosphate
dehydrogenase
defic/e=J.
cardiomyopathy and, 36
hepatitis and, 68
methemoglobinemia from, 138
nephritis and, 76
sulfhemoglobinemia and, 138
Sulfonylureas, diabetes insipidus and, 84
drug interactions of, 198
Syncope, 28, 29
convulsive, 178
hypertrophic cardiomyopathy and, 36
Syndrome of inappropriate secretion of antidiuretic hormone
(SIADH),82
Synovial 8uid, in joint examination, 212
Syphilis. oIopecla and. 208
arthriw in, 213
back pain and, 219
dementia and, 171
hypotension and, 26
immune hemolytic anemia from, 126, 127
nephritis from, 76
proteinuria and, 80
secondary, hepatomegaly from, 68
vertigo and, 169
Systemic lupus erythematosw (SLE). See Lupu$
enphematosus, systemic.
Tachycardia, paroxysmal, pseudoneutrophilia and, 144
paroxysmal atrial, hypematremia and, 84
Tamoxifen, and hypercalcemia, 95
Telanpectasia, hereditary hemonhagic, 108, 206
Temporomandibular joint pain-d.ysfunction syndrome, 168
Tenosynovitis, and edema, 30
Testosterone, edema and, 30
hematopoiesis and, 122
in hirsutism, 184, 185
Index 233
Tetracycline, nephritis and, 76

vitamin B12 deficienL)' and, 132
lbalassemia, 120, 121
hemolytic anemia from. 124
splenomegaly and. 117
Thermal injury, alkalosis and, 107
hypomagnesemia after, 101
hypophosphatemia after, 96
Thiamine-responsive anemia, 136
6-Thioguanine, and anemia, 137
Thioxanthenes, hyperprolactinemia from, 182
Thoracic outlet syndrome, and cyanosis, 18
Thromboangiitis obliterans, cyanosis from, 18
Thrombocytopenia. 158, 159, 160, 161
drugs in, 156, 158, 160
Thrombocytosis, 156, 157
hyperkalemia and, 88, 89
versus polycythemia vera, 138, 156
Thromlx>sis, brain stem, erythrocytosis and, 138
of dural sinus, 166
of hepatic vein, 68
Thrombotic thrombocytopenic purpura (TIP), 160
Thyroid disease. alopecia and, 208
amenorrhea and, 180
anti-intrtnsic factor antibodies and, 132
dementia and, 171
1byroid enlargement, 188, 189
Thyroid function tests (TITs), 188, 190, 191, 192
euthyroid sick syndrome in, 192
secondary hypothyroidism and, 192, 193
thyroxine-binding globulin in, 190
Thyroid nodules, 186, 187
Thyroiditis, 188, 192
Hashimoto's. See Hashimoto's thyroiditis.
Thyrotoxicosis, anti-intrinsic factor antibodies and, 132
cardiac murmur and, 34
hypokalemia and, 86
pruritus and, 202
Thyrotropin-releasing hormone (TRH), hyperprolactinemia
from, 180
in thyroid function tests, 190
TIc douloureux, 166
Tietze's syndrome, 24-25
Tobacco, 12. See also Nicotine.
carcinoma and, 78
chewing, alkalosis and, 106
hematuria and, 78
Tolmetin sodium, and oliguric renal failure, 76
Tomography, in urinary tract imaging. 78
Toxoplasmosis, ascites and, 71
fever of unknown origin and, 6
234 Index
Toxoplasmosis (Continued)
mononucleosis from, 150
nephritis from, 76
Tranquilizers, dementia and, 170
h)percarbia from. 22, 23
syncope and, 28
vertigo and, 169
Transaminitis, 72, 73. See also Alanine
(ALT);
Aspartate
aminotransferase
See Blood transfusion.
aminotransferase
(AST).
Transfusion.
Transient ischemic attack (TlA), and syncope. 28
Transplantation, bone marrow, and vena-occlusive disease, 68
renal, erythrocytosis following, 139
rejection of, renal tubular acidosis in, 104
Transposition of great arteries, and cyanosis, 18
Trauma, amenorrhea and, 180, 182
edema and, 30
Trepopnea, 14
Triamterene, and potassium, 90
folate deficiency from, 135
Tricuspid insufficiency, and hepatomegaly, 66
Tricyclic antidepressants. See Antidepressants,
tricyclic.
Triglycerides, ascites and, 70
drugs and, 196, 197
in lipid testing, 194
Triiodothyronine, and hypothyroidism, 191
Trimethoprim, folate deficiency from, 135
Tuberculosis, alkaline phosphatase and, 75
anemia and, 122, 127
aplastic, 128
arthritis and. 218, 219
ascites and, 70, 71
dementia and, 170
dysphagia and, 49
fever and, 4, 5, 7
hematuria and, 79
hemoptysis and, 16
inappropriate secretion of antidiuretic hormone and, 8J
lymphadenopathy and, 112, 113
vitamin D and, 94
Tumor(s). See also Adenoma; Granulomatous
disease;
Myxomas;
Neoplastic
diseases.
amenorrhea and. 180, 181

hematuria and, 78, 79
hirsutism and, 184, 185
Tumor(s) (Continued)
hypoglycemia from, 200,201
inappropriate secretion of antidiuretic hormone and, 82, 8J
islet cell, hypokalemia and, 87
multiple endocrine neoplasia and, 94
low back pain and. 218,219
ovarian, ascites and, 70
hyperthyroidism from, 190
polycythemia and, 138
trophoblastic, human chorionic gonadotropin and, 180, tOO
vertigo and, 168, 169
Tumor lysis syndrome, 98, 99
Ulcer, peptic, 44
periumbilical abdominal pain from, 59
upper alxlominal pain of, 50
Ultrasonography/ultrasonogmm(s), 34
gallstones on, 64
renal obstruction on, 76
venous occlusion all, 30
Uremia, dementia and, 171
granulocytosis and, 144
hyperlipidemia and. 197
hypothennia and, 172
proritus and, 202, 203
Ureterosigmoidostomy, and hypokalemia, 87
Urine. nephritic, 76
proteinuria measurement of, 80
Urticaria, 204, 205
Vancomycin, acute tubular necrosis and, 76
Varicella, cardiomegaly and, 36, 37
Vascular disease, and cardiac murmurs, 34
Vasculitis, 206. See also Angiitis.
ascites and, 71
dementia and, 170
fever and, 6, 7
hematuria and, 79
in Henoch-Schonlein purpura, 206
infection and, 206
renal, red blood cell casts and, 78
urticaria and, 204
vertigo and, 169
Vasodilatation, hypotension from, 26. See also Syncope.
Vasomotor instability, hypotension from, 26
Vasopressin, hypertension and, 33
Vena cava, obslmction of, hepatomegaly and, 68

Venogram, morbidity of, 30
Venous occlusion, 30, 31
hepatic, 68
ascites and, 71
Ventricular septal defects (VSDs). cardiomegaly and. 37
murmurs and, 34, 35
Vertigo. 168. 169
Vincristine, hyponatremia and, 82
thromboc)1:osis and, 156
Vitamin A. alopecia and, 208
hypercalcemia and, 94, 95
Vitamin BII' eosinophilic disorden and, 154
in polycythemia vera diagnosis. 138-139
Vitamin BI. deficiency, 130, 132, 133
rebound thrombocytosis and, 156
Vitamin D, 92, 93
Vitamin D (Continued)
granulomatous disorders and, 94, 95
intoxication with. 94
phosphate and, 96
Vitamin K, 110
abnormal coagulation and, 108
Vitiligo, anti-intrinsic factor antibodies and, 132
Vomiting, alkalosis and, 106
with diarrhea, 40
Von Willebrand's disease, 110
WaidenstrtSm's macroglobulinemia, 162
purpura in. 206
Warfarin. and alopecia. 208
Wegener's granulomatosis. 206. See also Granulomatous

disease.
eosinophilia and. 152
hemoptysis from, 16
Weight gain, 10. 11
Weight loss, 8, 9
Wilson's disease, arthritis in, 212
hepatitis and, 66
hypoparathyroidism and, 92
tubular proteinuria and. 80
Zenker's diverticulum, 48
Index 235
1
:

) VHS DVD VCD ebook (... .
.
CD
.
.
.
CD
)3D Conformal Radiation Therapy A multimedia introduction to methods and techniques (Springer
1.1
)2.1 Abdominal and pelvic Ultrasound with CT and MR correlation (R. Brooke Jeffrey, Jr., M.D.
Self teaching Self evaluation CT Scan MRI

. CD Case ) MRI (CT Scan Click Text Case
.
Case CD :
Case
Case
Case
Case
Case
Case
)ACR - Chest (Learning file) (American college of Radiology
2001
3.1
CD :
4- Airway Disease
8-Pediatric Chest
12- Immunocompromised Host
3- Vascular Disease
7- Chest Wall and Diaphragm
11- Pulmonary Infection
2- Cardiac Disease
6- Pleural Disease
10- Neoplasma and Tumors
1- chest Trauma
5- Mediastinal Masses
9- Normal Disease
13- Diffuse Disease
- :
2
ACR - Gastrointestinal (Learning file) (American college of Radiology) (Igor Laufer, M.D., James M. Messmer, M.D.)
(Learning file) (American college of Radiology)
5.1 ACR - Genitourinary
( ... CT Scan ) Case . Case CD
. . Finding Click Imaging
: Case
4.1
Case
Case
Case
Case
Case
Case
Case
Case
Case
1998
1998
Case
6.1
ACR - Head & Neck (Learning file) (American college of Radiology)
1998
7.1
ACR - Neuroradiology (Learning file) (American college of Radiology)
1998
ACR - Nuclear medicine (Learning file) (American college of Radiology) (Paul Shreve, M.D. and James Corbett, M.D.)
9.1 ACR - Pediatric (Learning file) (American college of Radiology) (Beverly P. Wood, M.D., David C. Kushner, M.D.)
: Teaching File CD
8.1
Case
Chest
Case
Case
Skeletal
Case
Case
Genitourimary
10.1 ACR - Skeletal (B.J Manaster, M.D., Ph.D.) (Learning file)

1. Tumolrs
2. Arthritis
3. Trauma
4. Metabolic Congeaital
11.1 ACR
- Ultrasound (Learning file) (American college of Radiology)
1998
12.1 Anatomy and MRI of the JOINTS (A Multiplanar Atlas) (William D. Middleton, Thomas L. Lawson)
(Department of Radiology Medical College of Wisconsin Milwaukee, Wisconsin)

The Tmporomandibular
The Shoulder
The Wrist
The Finger
The Vertebral Column
The Hip
The Knee
The Ankle
TM
Brainiac!
Medical Multimedia Systems Presents (Version 1.52) (An interactive digital atlas designed to assist in learning human neuroanatomy)
Breast
Implant
Imaging (SALEKAN E-BOOK) (MICHAEL S. MIDDLETON, PH,D., M.D, MICHAEL P.MCNAMARA JR., M.D.)
13.1
9.9
(Serial # 316.34427)
A History and Overview of Breast Augmentation and Implant Imaging

Basic Principles of Breast Implant Imaging
Classification of Breast Implants
Evaluation of Silicone Fluid Injecitons
1998
Clinical Presentation
Principles of Imaging Breast Implant Rupture and Soft-Tissue Silicone
Practical Consideration in the Evaluaion of Implant Integrity
Breast Cancer Imaging
14.1 Carotid Duplex Ultrasonography Extracranial and Intracranial
2000
2003
Methods of Imaging
Artifacts of MR and Ultrasound Imaging of Breast Implants and Soft-Tissue Silicone
Evaluation of Soft-Tissue Silicone from Ruptured Implants
Surgical and Other Considerations
(Michael Jaff DO, Serge Kownator MD, Alain Voorons Audlovlsuel)
) ( CD
: .

Setting

Revaseularization
. Post-Test Pre-Test CD
- :
)(Pamela T. Johnson, Alfred B. Kurtz
WITH CROSS-REFERENCES TO THE REQUISITES SERIES
15.1 CASE REVIEW Obstetric and Gynecologic Ultrasound
CD Case ) ( Gynecology Obstetric .
)16.1 CD Roentgen (Michael McDermott, M.D., Thorsten Krebs, M.D.) (Williams & Wilkins
2000
17.1 Cerebral and Spinal Computerized Tomography

)18.1 Cerebral MR Perfusion Imaging CD-ROM to complement the book (A. Gregory Sorensen, Peter Reimer) (Thieme
CD MRI .
19.1 CHEST X-RAY INTERPRETATION
2002
CD ) (CD CXR . CD Clinic - seminar - Library - .

animatory .
Library : :
( CXR .
:
: Sings, clue : CXR (,westermark Sing, Sign) :
: Anatomy World : 3D .
: : .
:CME Quiz : . .
:Seminar :
- Soft tissue - - - - .
. Search Localize describe .
: Search ) (
:Localize CXR .
CXR .
:Describe CXR
CXR :Differential diagnosis pattern .
:Clinic .
CXR CT/MRI .
Softtissue
: ...... Softtissue air .....
)(Mosby
20.1 Comprehensive Reviw of Radiography
CD ) (Self evaluation :

CD
.
:
- :
)21.1 Computed Body Tomography with MRI Correlation (Joseph K. T. Lee, Stuart S. Sagel, Robert J. Stanley, Jay P. Heiken) (3rd Edition) (LIPPINCOTT WILLIAMS & WILKINS
2000
)(Salekan E-Book
)(Matthias Hofer) (Thieme
22.1 CT Teaching Manual
)23.1 Diagnostic Imaging Expert (A CD-ROM Reference & Review) (Ralph Weissleder, Jack Witterberg, Mark J. Rieumont, Genevieve Bennett
Imaging . CD :
1- Chest
2- Breast
5- Gastrointestinal
6- Pediatric
3- Cardiac
4- Obstetric
7- Genitourinary
8- Nuclear Imaging
9- Musculoskeletal
10- Contrast agent
11- Neurologic
14- Vascular 13- Head and Neck

12- Imaging Physics
)24.1 DIAGNOSTIC ULTRASOUND A LOGICAL APPROACH (JOHN P. McGAHAN, BARRY B. GOLDBERG
:
- Diagnostic Ultrasound Selp-assessment - . CMP .
:
- - bioeffects - ) ( -
:- Cervix Small-for-date , large-for-data ....
- )
( - ) -( - - - - - - Penis - testes
- Post meno Pausal Pelvis - Female Pelvis - - - Chest - Brest - trans cranial - - Skeletal Pediactric Head - Softtissue
- ultrasound-Guided Percutaneous tissue Ablation - Three dimensional ultrasound - Ultrasoud Contrast agent -
CD RUSR 2335 .
)25.1 Diagnostic Ultrasound of Fetal Anomalies: Principles and Techniques (CD I,II
CD . CD
. CD Case Multiple Choice question Case . Case
CD :
Case
Case
Case
Case
Case
Head
Neural tube
Amniotic Fluid
Body wall
Umblical Cord

Chest
2005
)(Salekan E-Book
)(MANOOP S. BHUTANI, MD, JOHN C. DEUTSCH, MD
26.1 Digital Human Anatomy and Endoscopic Ultrasonography

)27.1 EBUS (Endo Bronchial Ultrasound
)(Gregory G. Ginsberg, Michael L. Kochman
2004
Endoscopiy
28.1 Endoscopy and Gastrointestinal Radiology
Colonoscopy
Upper endoscopy
Percutaneous Management of Biliary Obstruction
Clinical Application of Magnetic Resonance Imaging in the Abdomen
Contrast Radiology
Endoscopic Ultrasound
Computed Tomography and Ultrasound of the Abdomen and Gastrointestinal Tract
Endoscopic Retrograte Cholagiopancreatography
29.1 Essentials of Radiology
CD Case . Case CD :
Case
Case
Case
Case
- :
obstetrics

RUQ
AIDS
Breast
TB
RLQ

LLQ

30.1 Exam Preparation for Diagnostic Ultrasound Abdomen and OB/GYN (RogerC. Sanders, Jann D. Dolk, Nancy Smith Miner)
31.1 Fundamentals of Body CT
(Second Edition) (W. Richard Webb, M.D. , William E. Brant, M.D. , Clyde A. Helms, M.D.) (Salekan E-Book)
32.1 Image Data Bank RADIOGRAPHIC ANATOMY & POSITIONING (APPLETON & LANGE)
33.1 Imaging Atlas of Human Anatomy
1998
(version 2.0)
(Mosby)
. ( MRI CT Scan )
. ... negative CD
. note
1998
34.1 Imaging of Diffuse Lung Disease (David A. Lynch, MB, John D. Newell Jr, MD, FCCP, Jin Seong Lee, MD)
( .... MRI,CT-Xray) .( DLN) CD

. Acrobat Reader .
:

X-Ray,CT DLD
DLD
DLD

___
35.1 Imaging of Spinal Trauma in Children (Lawrence R. Kuhns, M.D.) (University of Michigan Medical Center)
Principles AND TECHNIQUES
Normal Spine Variants and Anatomy
Mechanisms and Patterns of Injury
Thoracic Spine Injuries
Epidemiology
Measurements
Occipitocervical Injuries
ATLAS OF SPINAL INJURIES IN CHILDREN

Cervcal Spine
Lumbar Spine
Thoracic Spine
Sacrococcygeal Spine
Lumbar
Special Views and Techniques

Experimental and Necropsy Data
Sacral Injuries
36.1 MAGNETIC RESONANCE IMAGING (Third Edition) (Dauld Stark, William Bradley)
. CD David Stark
1. Generation and Manipulation of Magnetic Resonance Images
2. Magnetic Resonance: Bioeffects and Safety
3. Three-Dimensional Magnetic Resonance Rendering Technique
4. Principles of Echo Planar Imaging: Implications for Musculoskeletal System
5. MR Imaging of Articular Cartilage and of Cartilage Degneration
6. The Hip
9. The Shoulder
12. The Temporomandibular Joint
10. The Elbow
11. The Wrist and hand
7. The Knee
8. The Ankle and Foot

13. Kinematic Magnetic Resonance Imaging 14. The Spine
15. Marrow Imaging 16. Bone and Soft-Tissue Tumors 17. Magnetic Resonance Imaging of Muscle Injuries
37.1
Magnetic Resonance Imaging computed Tomography of the Head and Spine (C. Barrie Grossman)
38.1 Magnetic Resonance Imaging in Orthopedics and Sport Medicine (David W. Stoller)
MRI -
MRI -
Echo-Planar -
MRI -
- :
: MRI
MRI -
(Hip) -
-
MRI -
6
-
- )(TMJ
- MRI
-
-
-
2000
-
-
Kinematic MRI -
)(Ralphl. Smathers, M.D.
CD :
- ) Needle (
39.1 Mammography Diagnosis and Intervention
- Aggressive
)(O. Ratib & D. Didier
2001
Aortic Coarcation
Miscellaneous
Aortic Arch Anomalies

Congenital venous anomalies
Aortic Arch Anomalies

Aequised venous diseases
Aortic Aneurysms
Pulmonary astesies diseases
4th Edition
2001
40.1 MR Angiography Thoracic Vessels

Methods & Techniques
Aortitis
)41.1 MR Imagin Expert (Geir Torhim, Peter A. Rinck
"This version is a special adaptation for "Magnetic Resonance in Medicine The Basic Textbook of the European Magnetic Redonance Forum
42.1 MRI der Extremitaten
)43.1 MRI of the BRAIN & SPINE (SCOT W. ATLAS) (LIPPINCOTT-ROVEN
CD MRI Imaging
MRI . . Sectional
) + + (MRI . Case Case :
Case
Case

Aging

)44.1 Normal Findings in CT and MRI (Torsten B Moeller, Emil Reif) (Thieme
2000
20.3 Obstetric Ultrasound Principles and Techniques
CD :
FL . BPD AC HC Gs CRL FL AC ) - (........ )(Cord Insertion Case Study ) BPP ( - CNS Body
- :
7
)(DAVID A. STRINGER, PAUL S. BABYN, MDCM
)(Second Edition
45.1 PEDIATRIC GASTROINTESTINAL IMAGING AND INTERVENTION
)46.1 Peripheral Musculoskeletal Ultrasound Interactive Atlas A CD-ROM (J. E. Cabay, B. Daenen) (R. F. Dondelinger
MusculoSkeletal
) (Quiz . CD :
- :General item :
-
- :Region item :
2- Elbow
1- Ankle
4- Hand
3- Foot
5- Hip
7- Shoulder
6- Knee
47.1 Principles of MRI
2002
8- Wrist
)(Jeery Papp) (Mosby

)(UNIVERSITY OF FLORIDA COLLEGE OF MEDICINE DEPARTMENT OF RADIOLOGY
48.1 Quality Management in the Imaging sciences
Interactive Tutorial on Normal Radiology
49.1 RADIOLOGIC ANATOMY
(Lower Extremity
CD ) ( Click )
Click( .
Icon .
) (Self evaluation . CD ) Imaging Plain Film MRI CTScan (...
Imaging .
( : hCD CD CD-ROM Autoplay menu my computer CD-ROM Open
* Setup radiologic Anatomy installation OK . CD
OK Start Program radilogic Anatomy .
* icon ) (ssetup.apm setup.cfg ssetup Setup. setup.exe .
)(International Medical Multimedia
50.1 Radiology Image Bank: Orthopedic Radiology
)51.1 Radiology on CD-ROM Diagnosis, Imaging, Intervention (Juan M. Taveras, MD, Joseph T. Ferrucci, MD
CD Tavers
) ( 2001 :
- Gastrointestinal
- Vascular
- Cardiac
Breast Imaging -
-
-
- Adbomen
- Skeletal
- Pulmonary
- Genitourinary
)52.1 REVIEW FOR THE Radiography Examination (A & LERT) (McGrow-Hill's
2002
)(Thieme
)53.1 Teaching Atlas of Mammography (Laszlo Tabar, Peter B. Dean

54.1 The Basics of MRI of NMR
)(Joseph P. Hornak, Ph.D.
55.1 The Encyclopaedia of Medical Imaging from NICER
2001
)56.1 THE MRI TEACHING FILE (Robert B. Lufkin, William G. Bradley, Jr., Michael Brant-Zawadzki
CD Case MRI Case .

Case CD :
Case
Case
Case
Case
MRA
- :
8
57.1 THE RADIOLOGIC CLINICS OF NORTH AMERICA High-Resolution CT of the Lung II (DAVID A. LYNCH, MD)
(NUMBER 1 VOLUME 40)
: HRCT The Radiologic clinics of North America CD

Air Way CT Scan HRCT ( quantitative) CT -
Peripheral Airways HRCT Drug-Induced HRCT -
CT Scan -
Non-TB TB CT Scan
HRCT CT Scan -
58.1 THE RADIOLOGIC CLINICS OF NORTH AMERICA Imaging of Musculoskeletal and Spinal Infections
PRINCIPLES AND TECHNIQUES
1. Epidemiology
3. Normal Spine Variants and Anatomy
2. Thoracic Spine Injuries
4. Experimental and Necropsy Data
ATLAS OF SPINE INJURIES IN CHILDREN
1. Cervcal Spine
2. Thoracic Spine
3. Lumbar Spine
5. Measurements
6. Special Views and Techniwques
1999
7. Sacral Injuries
8. Occipitocervical Injuries
9- Mechanisms and Patterns of Injury
4. Sacrococcygeal Spine
59.1 THE RADIOLOGIC CLINICS OF NORTH AMERICA Pediatric Musuloskeletal Pediatric Radiology
(SALEKAN E-BOOK)
(James S. Meyer, MD)
2001
: CD
y Ultrasound in Padiatric Musculoskeletal Disease: Teachinques and Applications y Nuclear Medicnine Topics in Pediatric Musculoskeletal Disease: Teachinques and Applications
y Imaging of Musculoskeletal Infections y Malignant and Benign Bone Tumors
y Magnetic Rsonance Imaging of Musculoskeletal Soft Tissue Mass y Imaging of Pediatric Hip Disorder
y Imaging of Pediatric Foot Disorder in Children y Imaging of Sports Injuries in Children and Adolescents y A Pragmatic Approach to the Radiologic Diagnosis of Pediatric Syndromes and Skeletal Dysplasias
y The Orthopedists Perspective: Bone Tumors, Scoliosis, and Trauma y Imaging of Crowth Distubance in Children y Imaging of Child Abuse
60.1 THE RADIOLOGIC CLINICS OF NORTH AMERICA Update on Nuclear Medicine

61.1
THE RADIOLOGIC CLINICS OF NORTH AMERICA Update on Ultrasonography (FAYE C. LAING, MD) (W.B. SAUNDERS COMPABY)
: The Radiologic Clinics Of North America CD

-
- ( intervention) -
- -
-
Breast - Gynecology Obstetric -
Gynecologic -
-
-
-
Ultrasound Atlas of Vascular Diseases (Carol A. Krebs, RT, RDMS, Vishan L. Giyanani, , Ronald L. Eisenberg) (APPLETON & LANGE Stamford, Connecticut) (SALEKAN E-Book)
63.1 Ultrasound Teaching Manual The basics of Performing and Interpreting Ultrasound Scans (Matthias Hofer) (With the collaboration of Tatjana Reihs) (Thieme)
64.1 Uterosalpingography in Gynecology Hysterospingography (Salekan E-Book)
65.1 VOXEL-MAN 3D-Navigator Brain and Skull (Regional, Functional, and Radiological Anatomy) (IMDM university Hospital Eppendorf, Humburg) (Springer)
62.1
: CD . CD Interactive
. horizontal Ventricol : :- : (
: -
( ) : -
. o
. Sagittal Coronal :
: (
( ) --
CT --
--
CT --
X-ray --
X-ray --
X-ray --
X-ray --
X-ray
Zoom

.

Intractive
. MB * CD :
- :
VOXEL-MAN 3D-Navigator Inner Organs (Regional, Systemic and Radiological Anatomy) (IMDM university Hospital Eppendorf, Hamburg)
67.1 Whole Body Computed Tomography (Second Edition) (Otto H. Wegener) (Blackwell Science)
66.1
: . CT Scan CT Scan CD
CT Scan

( )
CT Scan
CT Scan

CT
CD
1.2
2.2
A Case Approach to Open Structure Rhinoplasty (Calevln, Johnson)

Advanced Rhinoplasty Techniques Cosmetic Rhinoplasty (Rollin K. Daniel, M.D.)
Analysis,
Marking & Anesthesia, Closed/Open Approach, Septum Exposure, Exposure & Dorsal Reduction, Caudal Septum Resection, Ideal Profile Line, Open Approach, Tip Analysis, Septoplasty &
Septal Harvest, Grafts, Spreaser Grafts, Grural Strut, Tip Suture Technique, Closure, Nostril Sill Alar Wedge, Composite Graft, Lateral Osteotomy, Final Steps, Acknowledgments
3.2
Advanced Therapy of OTITIS MEDIA
2004
4.2
Aesthetic Facial Plastic Surgery
5.2
Aesthetic Rhinoplasty (second Edition) (Jacizh-SHEEN, Anitra SHEEN) (Volume 1, 2)
6.2
An Atlas of Head & Neck Surgery (John M. Lore, Jr., M.D, Jesus E. Medina) (CD I , II)
2005
7.2
8.2
Aphasia & Related Neurogenic Language Disorders (Third Edition) (Leonard L. LaPointe, Ph.D.)
Atlas D'ORL Realise avec la collaboration des (Dr Michel Boucherat, Dr Jean-Robert Blondeau)
-Anatomie de loreille normale - Images pathologiques
- Cas cliniques
-Anatomie naso-sinusienne normale
-Images pathologiques
- Cas cliniques
- Rappels des principes de la TDM et de lIRM
2005
9.2
Atlas of Head & Neck Surgery Otolaryngology (TEXTBOOK) (Byron J. Bailey, Karen H. Calhoun, Amy R. Coffey, J. Gail Neely)
A Multidisciplinary Approach( Romo & Millman)
1- Atlas :
: .
- Head & Neck Surgery :
: . ....
Salivary Gland Nose & maxilla Oral Clarity Ear
Neck & Larynx
Thyroid & Parathyroid
- Otologic procedures
Middle Ear and Ossicular Chain
Tran temporal Skull Base
- Plastic & Reconstructive Surgery :

Larygoplasty, Rhytidectomy, Rhinoplasty
- Pediatric and General Otolaryngology
Frontal Sinus
Mandibular Surgery, Local & Regional Flaps,
Excision of skin Lesions
Nasal Polypectomy
2- Bilbo Med Medline :.
Congenital Aural Base
Ton Sillectomy
3- Head & Neck Surgery:

- Textbook
- Drug Reference
- :
10
- Textbook :
Bailey .
:
1- Basic Science / General Medicine
) (
2- Head & Neck :
3- Otology
4- Facial Plastic Reconstructive Surgery
- Drug Reference :
) (.....
)10.2 Atlas of Rhinoplasty Open and Endonasal Approaches (Gilbert Aiach, M.D
)11.2 AUDIOLOGY The Fundamentals (Third Edition) (Fred H. Bess, Larry E. Humes
)12.2 Causes of FAILURE in STAPES SURGERY (VCD I
)(Howard P. House, TED N. Steffen

)PITFALLS in STAPES SURGERY (VCD II
)STAPEDECTOMY (Prefabricated Wire-Loop and Gelfoam Technique) (VCD III
)13.2 Chirurgia Endoscopica Dei Seni Paranasali (A Cura di E. Pasquini G. Farneti
3. Aspetti radiologici
1. Principi di anatomia endoscopica
2. Tecnica chirurgica
14.2 Clinical Otoscopy
CD
)An Introduction To Ear Diseases (Michael Hawke, Malcolm Keene, Peter w. Alberti
)15.2 Cobblation Assisted Tonsillectomy (CAT) __ Cobblation Assisted Procedures (VCD) (CD I , II
Coblation . VCD :
2- Lop off "CAT" technique
3- Coblation Assisted tonsilectomg
1- Subtotal Cololation Assisted tonsillectomy
CD Coblation ENT .
. recovery
. ENT :
1- Coblation channeling of the inferior turbinate
Channeling . : .
2- Coblation channeling of the Soft palate
Channeling . . .
3- Coblation channeling of the tonsil
bulk . . .
. .
.
)(EIJI YANAGISAWA, MD
2002
)4- Coblation Assisted Tonsillectomy(CAT
16.2 Color Atlas of Diagnostic Endoscopy in Otorhinolaryngolgy
)(Salekan E-book) (Richard A. Chole, MD, PhL, James W. Forsen
17.2 Color Atlas of Ear Disease
)18.2 Color Atlas of Otoscopy From Diagnosis to Surgery (Mario Snna
19.2 Cosmetic Blepharolasty & Facial Rejuvenation
)(Stephen L. Bosniak, M.D.,
2005
)(CD 1-6
)20.2 Cosmetic Surgery of the Asian Face (John A. McCurdy, Samuel M. Lan
2005
)(E-Book & Image Colleciton) (Volume 1-4
)22.2 Current Diagnosis & Treatment in OTOLARYNGOLOGY HEAD & NECK SURGERY (Anil K. Lalwani, MD
2005
)(Second Edition
)(Kari-Bernd Huettenbrink
)21.2 Cumming's Otolaryngology Head & Neck Surgery (Fourth Edition
23.2 Current Topics in Otolaryngology -Head & Neck Surgery Lasers in Otorhinolaryngology
- :
24.2 DALLAS RHINOPLASTY
11
Nasal Surgery by the Masters (Reducing Tip Projection and Nostrill Show Via the Open Approach) (CD I , II)
VCD: 1
1) Cadaveric Rhinoplasty Dissection Technique
2) Role of Component Dorsal Reduction: Spreader Grafts in the Deviated Nose
2002
VCD: 2
Reducing Tip Projection and Nostril Show Via the Open Approach
: VCD
1)
Exposure/Nasal incisions
A. Closed endonasal approach
- Intracartilaginous (IC)
incision
B. Cartilage delivery technique
- Infracartilaginous incision
- Intercartilaginous incision
C. Open Rhinoplasty approach
- Transcolumellar incision
2) Tip Alteration
3) Sptal reconstraction
4) Osteotmies
5) Adjuctive techniques/Closure
A. Columellar Stat placement
A. Septal reconstraction
A. Medial Osteotomy
A. Alare base resection
- Intercarural suture stabilization
- Inferior tarbinate resection
B. Lateral Osteotomy
- Correction of alalr flaring
B. Controlling dome angalation
(Submacosal)
C. External Osteotomy
- Diminishing nostril shape
and tip defining points
- Septal reconstruction
B. Closare
- Interdomal sutures
B. Modification of the dorsum
C. Splints
- Transdomal Satares
- Component dorsum
C. Correction of alar
reduction
pinching/notching
- Spreader graft placement
- lateral crural strut grafts
- Alar contour grafts
D. Tip grafts
- Infratip graft
- Onlay tip graft
Gunter VCD . Open Gunter nostril show , Projected tip VCD
. .
4) Transaction of lat Crura
3) Underminig tip Skin
2) Infracartilaginous and trans columellar incisions
1)Complete transfixion incision
8) Reduction of dorsal septum (DS) and upper lateral cartilage (ULC)
7) reduction of bony darsum (BD)
6) Preparing submucosal tunnels
5) Resection of feet of medial crura
12) Cephalic resection of lateral Crura (LC)
11) Spreader grafts
10) Medial asteomius
9) Harvesting Septal cartilages for grafting
16) Final adjustment of dorsal height
15) Lateral asteotomy Cinternal
14) Aligning the dorsum
13) Preparation for lateral crural grafts (LCSG)
19) Closure
18) Placement of lateral crural strut grafts
17) Columellar strt placemend
!! VCD .
25.2 Dallas Rhinoplasty (Nasal Surgery by the Masters) (Salekan E-Book) (Volume 1, 2)
26.2 Diseases of the Sinuses Diagnosis and Management
(Darid W. Kennedy, MD, FRCSI, William E. Bolger, MD, FACS, S. James Zinreich, MD)
. .
2001 text book CD
27.2 EENT Welch Allyn Institute of Interactive Learning
28.2 ENDONASAL SINUSECTOMY WITH CORRECTION OF THE NASAL CAVITY (Rikio Ashikawe, Takashi Ohmae, Toshio Ohnisshi, Yutaka Uchida)
The Endonasal sinusectomy with correction of the nasal cavity (Takahash's methodn) is carried out in seven steps.
29.2 Endoscopic Assisted Procedures used in Astatic Facial Plastic Surgery (VCD) (CD I , II)
. . VCD
. Endoscopic forehead rhytidectomy and brow elevation Grlecory S. Keller .( closure)
Extended Composite face Lift
Endoscopic midface Lift
Endoscopic forehead Lift
: Endoscopic assisted forehead and face lifting VCD
. ( ) .
.
30.2 Endoscopic Management of Cholesteatoma
- :
(Muaaz Tarabichi) (CD I , II)
2005
12
(SALEKAN-eBook)
. CD
( Atlas and textbook) . .
: CD .
31.2 Endoscopic Sinus Surgery
1- Consistent and Relible Anatomical Landmarks in Endoscopic Sinus Surgery
32.2 Endoscopic Sinus Surgery
2- Surgical Instrumentation
3- Setup and patient positioning
4- Basic Dissection
5- Advanced Dissection
Anatomy Three-Dimensional Reconstruction, & Surgical Technique (Peter-John Wormald)
2005
33.2 Endoscopic Sinus Surgery NEW HORIZONS (Nikhil J. Bhatt, M.D.)
34.2 Essentials of Septorhinoplasty philosophy-Approaches-Techniques
2004
35.2 EVIDENCE-BASED OTITIS MEDIA (Richard M. Rosenfeld, MD, MPH, Charles D. Bluestone, MD)
. . CD
: CD . .
1- Methodology
2- Clinical Management
3- Consequences and Sequelae
36.2 Facial Nerve Surgery (Jack L. Pulec, M.D.)
37.2 Facial Plastic & Reconstructive Surgery
Otologic Medical Group, Inc. Los Angeies
(Terence M. Davidson, MD) (VCD I , II)
38.2 Functional & Selective Neck Dissection (Javier Gavihin, Jesus Herranz, Lawrence W. Desanto)
2004
39.2 Functional Reconstructive Nasal Surgery (egbert H. Huizing)
40.2 Handbook of Clinical Audiology
(Fifth Edition) (Jack Katz, Ph.D.)
41.2 Head and Neck Surgery (Jatin P Shah, MD, MS (Surg), FACS) (Mosby)
42.2 HEAD, FACE, AND NECK TRAUMA COMPREHENSIVE MANAGEMENT (Michael G. Stewart, M.D., M.P.H.)
2005
43.2 Hearing ITS Physiology & Pthophysiology
(Aage R. Moller, ph.d)
44.2 Imaging of the Temporal Bone (Third Edition) (Joel D. Swartz, H. Ric Harnsberger)
45.2 Introduction to Ear Acupuncture (Martin Franke)
2001
. Thieme CD
. ...
1- Localization Assignment
2- Localization Determination
3- Treatment
4- Evaluation
46.2 La Rhinoplastica Ragionata (Valerio Micheli-Pellegrini, Roberto Polselli)
47.2 Local Flaps in Head and Neck Reconstruction (Lan T. Jackson, M,D.) (SALEKAN E-BOOK)
2002
48.2 Medical Speech-Lanaguage Pathology A Practitioner's Guide
(Alex F. Johnson, Barbara H. Jacobson)
49.2 Nasal Aesthetics and Anatomy: A Cadaver Study (Rollin K. Daniel, M.D.)
50.2 Oculoplastic Surgery (William P. Chen)
51.2 Office-Based Surgery in Otolaryngology (Andrew Blizer, Harold C. Pillsbury, Anthony F. Jahn)
52.2 OPEN RHINOPLASTY Cadaver Dissection Program (Dean M. Toriumi, MD.) (Vol I , II) (College of Medicine at Chicago)
- :
13
7- Management of Lower third of the nose
- Cephalic trimming of lateral Crura
- Satured in place Collamellar Strut
- Transdomal Sutur
- Sutured in place tip
8- Chin augmentation
- Preparation of the implant
- Incision and dissection
- placement of Implant
5- Management of Middle Nasal Vault

- Division of apper Lateral Cartilages from septum
- Application of Spreader grafts
3- Open Rhinoplasty approach

- Incisions
- Flap Elevation
1- Access to nasal Septum

- Hemitrans Fixatu incision
- Havvestiong Septal Cartilage
6- Major septal reconstruction

- Reconstraction of L-Shaped Septal Strat
4- Stractural grafts used in Secondary

- loteral Crural grafts
- Alar Batten grafts
2- Havvestiog of Conchal Cartilage

- Anterior approach for harvestiog Cartilage
- Flap elevention
- Cartilage excision
- Closure and dressing
2005
)53.2 Open Structure Rhinoplasty (A Case Oriented Approach) (CD I , II
)54.2 Open Tip Graft in Twin Patient (Rollin K. Daniel, M.D.
55.2 Ophthalmic & Facial Plastic Surgery
Analysis, Operative Planning, Twins Pre and Post, Anesthesia, Transfixion Incision, Septal Harvest, Open Approach, Exposure, Tip Anatomy, Tim Strips, Graft Preparation, Radix Graft, Crural Strut,
Domal Excision, Graft, Shaping, Graft, Insertion, Closure, Post Op Result, Credits
)(Frank A. Nasi., Geoffrey J. Gladstone, Brian G. Brazzo
2003
)(SIXTEENTH EDITION) (James B, Snow Jr, MD, John Jacob Ballenger, MD,
Head and Neck Surgery
Laryngology
Bronchoesphagology
Rhinology
Pediatric Otolaryngology
56.2 Otorhinolaryngology Head and Neck Surgery
Facial Plastic and Reconstructive Surgery
Otology and Neurotology
)57.2 Plastic Surgery (Fifth Edition) (Grabb and Smith's) (Salekan E-Book
.
. .
General Reconstruction : implants flap graft ....
: Moths .
: ) Reconstruction (....
: dermabrasion, peeling) : (...endoscopic plastic surgery .
: breast : ... .
: .
: : Reconstruction .....
: : Reconstruction of peni....
Fitzpatrick Goldman Alster . :
. rejuvenation .
Primary
Rhinoplasty
(Bahman
)Guyuron, MD, FACS, Cleveland, Ohio) (VCD
58.2
VCD Ohio Open .

Case ) ( )( .
VCD .
)(ROBERT L. SIMONS, MD., NORTH MIAMI BEACH, FLORIDA) (VCD) (CD I , II
GOLDMAN TECHNIQUE
59.2 RHINOPLASTY
VCD . tip ) (tip plasty .

Case Stand by . projected tip . .
)A Practical Guide to functional and asthetic surgery of the nose (G. J. Nolst
60.2 RHINOPLASTY
. . ) ( ) ( .
:
- :
14
. open ) ( . tip
: CD . text
. Post-op Pre-op : Basic Knowledge external rhinoplasty Open osseocartileginous Spreadergrafs modified zplasty-Nasalvalve surgery turbinate surgery : Operative techniques . Wedgeresection in alar base surgery
. Pverprojected nasel tip. Saddle nose Revision surgery rhinosurgery augmentation rhinoplasty : Capita selecta . Conchal Cartilage harvesting ( ... ) : Video gallery CD
61.2 Rhinoplasty The American Academy of Facial Plastic and Reconstructive Surgery (CD I, II) (E. Gaylon McCollough, M.D.) (the St. Louis Aging Face Symposium)
. Stand by Aging Face ( E. Gaglon McCollough M.D.)

. LLC delivery . rotation tip . tip plasty Closed
. Alar base resection
62.2 RHINOPLASTY DOUBLE DOME UNIT (CD I , II) (E. Gaylon McCollough MD, Birmingham, Albama)
. tip . E. Gaglon MC Collouch

. management Double Dome Unit
Rhinoplasty
The
Overly
Projected
Nasal
Tip
(Trent
W.
Smith,
M.D.F.A.C.S.)
63.2
tip . tip
. .
64.2 San Diego Classics in Soft Tissue & Cosmetic Surgery Rhinoplasty (Part 1-6) (Richard C. Webster, MD, Terence M. Davidson, Alan M. Nahum)
65.2 Secondary Rhinoplasty & Nasal Reconstruction
(Rod J. Rohrich, Jack H. SHEEN, Gary C. Burget, Dean E. Burget)
66.2 Smile Train Virtual Surgery Videos (Unilateral Cleft Bilateral Cleft Cleft Palate) (Court B.Cutting, Donato LaRossa) (Vol I, II, III)
67.2 SURGERY of the EAR
(Fifth Edition) (Glasscock-Shambaugh) (Michael E. Glasscock III, MD, FACS, Aina Julianna Gulya, MD)
2003
: CD . .( 2003) textbook . CD
1- Scientific Foundations
3- Clinical Evaluation
5- Fundametals of Otologic/Neurotologic Surgery
7- Surgery of the External Ear
2- Surgery of the Tympanomastoid Compartment
4- Surgery of the Inner Ear
6- Surgery of the IAC/CPA/Petrous Apex
8- Surgery of the Skull Base
68.2 Surgical Approaches in Otorhinolaryngology

69.2
(W.F. Thumfort, W. Platzer)
Teaching Atlas of Head & Neck Imaging (Rtbert Lufkin, Alexandra Borges)
70.2 The Audiogram Workbook
(Sharon T. Hepfner) (Thieme)
71.2
The MACS Lift Short-Scar Rhytidectomy (Textbook) (Patrick L. Tonnard, Alexis M. Verpaele) (CD I , II)
2004
72.2
The MEDPOR Lower Eyelid Spacer (James Patrinely, M.D.F.A.C.S., and Charles N.S. Soparkar, M.D., Ph.D.) (VCD)
. . VCD
3) Medpore biomaterial
- :
2) Addressing and management potential Complications

- managing winging are edge flare
- managing ridging
- managing under correction
- managing overcorrection
1) Introduction and Surgical technique

- Cartilage grafts
- Non-rigid spacer grafts (hard Patale/Sclera,dermis)
- Medpore Lower Lid Advantages
15
- managing implant exposure
- managing entropion
- managing entropion
- Implant exchange
73.2 The MEDPOR Nasal Shell Implant (Paul O'Keefe, M.B, B.S., (SYD), F.R.C.S., F.R.A.C.S.) (VCD)
74.2 THE VIDEO ATLAS OF COSMETIC BLEPHAROPLASTY (8 CDs)
75.2 VCD Journal of ENT APPROACH VESTIBULAR NEURECTOMY-TRANSTEMPORAL SUPRALABYRINTHINE APPROACH
(S.LBosniak)
S.LBosniak VCD
. . ...
MICROSURGERY OF THE SKULL BASE TRANSOTIC APPROACH ACOUSTIC NEUROMA (Prof. U. Fisch Zurich) (VCD#2)
76.2 VCD Journal of ENT INFRATEMPORAL FOSSA APPROACH TYPE C
(Prof. U. Fisch Zurich) (VCD#4)
77.2 VCD Journal of ENT INFRATFMPORAL FOSSA APPROACH GLOMUS TEMPORALE TUMOR (Prof. U. Fisch Zurich) (VCD#1)
78.2 VCD Journal of ENT MICROSURGERY OF THE SKULL BASE TRANSOTIC APPROACH ACOUSTIC NEUROMA-INFRATEMPORAL FOSSA APRROACH TYPE C (Prof. U. Fisch Zurich) (VCD#3)
79.2 VJGS Invited Presentation: Thyroidectomy (Jon A. van Heerden, ND)
CD
1.3
Abdominal Colposacropexy and Vaginal Sacropinus Suspension (Harold P. Drutz MD FRCS (C) (VCD)
2.3 Active Management of Labour
2004
(Kieran O'Driscoll, Declan Meagher) (SALEKAN E-BOOK)
3.3
Adapted form Physical Examination and Health Assessment, 2/e (Carolyn Jarvis, RN, C, MSN, FNP) (W.B. Saunders Company) (VCD)
4.3
Advanced Colposcopy: Understanding Vessel Patterns (Dorothy M. Babo, MD) (VCD)
: : VJOG CD
. - -
( ..... )
.
Advanced Therapy of BRAST DISEASE (S. Eva Singletry, MD, Geoffrey L. Robb, MD)
6.3 American Cancer Society Atlas of Clinical Oncology (Cancer of the Female Lowe Genital Tract) (Patricia J. Eifel, M.D. Charles Levenback, M.D.)
2000
5.3
(SALEKAN E-BOOK)
2001
Cervix .
.
Chemotherapy in Curative
Management
Surgery for Vulvar Cancer
Post-treatment Surveillance
Radiation Therapy for Vulvar Cancer
Palliative Care
Acute Effects of Radiation Therapy

Late Complications of Pelvic Radiation
Therapy
- :
Surgical Treatment of Invasive Cervical

Cancer
Radiation Therapy for Invasive Cervical
Cancer
Radical Management of Recurrent Cervical
Cancer
Management of Vaginal Cancer
Diagnostic Imaging
Epidemiology
Screening for Neoplasms
Pathology
Treatment of Squamous Intraepithelial

Lesions
Molecular Biology
Invasive Carcinoma of the Cervix
Anatomy and Natural

History
7.3
8.3
16
An Atlas of Erectile Dysfunction (Second Edition) (Roger S. Kirby, MD, FRCS) (The Encyclopedia of Visual Medicine Series)
Atlas of Clinical oncology Breast Cancer (American Cancer Society ) (David J Winchester, MD, David P Winchester, MD)
2004
2000
: CD
yGenetics, Natural History, and DNA-Based Genetic Counseling in Hereditary Brast Cancer
y Breast Cancer Risk and Management: Chemoprevention, Surgery, and Surveillance
y Screening and Diagnostic Imaging yImaging-Directed y Breast Biopsy yHistophathology of Malignant Breast Disease
yUnusual Breast Pathology y Prognostic and Predictive Markers in Breast Cancer
y Surgical Management of Ductal Carcinoma In Situ
yEvaluation and Surgical Management of Stage I and II Breast Cancer y Locally Advanced Breast Cancer y Breast Reconstruction
9.3
ATLAS OF ENDOSCOPIC TECHNIQUES IN GYNECOLOGY (First Edition) (Jeffrey M. Goldberg, MD, Tommaso Falcone, MD) (W.B. Saunders, Philadelphia)
2001
:
Instrumentation and Pelvic Anatomy
Surgery for Pelvic Support
Patient Preparation
Surgery for Endometriosis and Pelvic Pain
Tubal Surgery
New Procedures
Ovarian Surgery
Uterine Surgery
Complications
Hysteroscopic Surgery
10.3 Atlas of Gynecologic Surgery
(3rd edition) (H.A. Hirsch, M.D., O. Kser, M.D., F.A. Ikl, M.D.) (Thieme)
11.3 Atlas of Transvaginal Surgery (Second Edition) (W.B. Saunders, Philadelphia) (VCD)
- Prolene sling in the treatment of stress incontinence
- Transvaginal repair of enterocele and vault prolapse
- Excision of urethral diverticula
12.3 Before We Are Born

13.3 COLPOSCOPY
- Fibro-fatty labial flap (Martius Flat) for vaginal reconstruction

- Transvaginal repair of vesico-vaginal fistula using a peritoneal flap
- Transvaginal repair of posterior vaginal wall prolapse
(SALEKAN E-BOOK)
- Transvaginal hysterectomy for severe prolapse

- Transvaginal repair of grade IV cystocele
Essentials of Embryology & Birth Defects (Moore, Oersaud) (6th Edition)
an Interactive
CD-ROM
2001
(Thomas V. Sedlacek, MD, Charles J. Dunton, MD)
14.3 Core Curriculum in Primary Care Patient Evaluation for Non-Cardiac Surgery and Gynecology and Urology (Michael K. Rees, MD, MPH)
. CD . Harvard CD CCC
. .
: .
) ( -
Male impotence -
.(AUB) -
15.3 Core Curriculum in Primary Care Gynecology
(Michael, Isaac Schiff, Keith, Thomas, Annekathryn)
(James R. Scott) (9 Edition) (SALEKAN E-BOOK)

17.3 Diagnosis of Benign Breast Disease (Dorothy M. Barbo, MD) (VCD) Submitted Subject The Limits of Laparoscopy: Diapharbmatic Endometriosis (David B. Redwine, MD)
.( Video Journal ob/Gyn) VJOG CD
CD .
. . CD . . Solid Cyst nipple discharge Mastodynia
2003
18.3 Endoscopic Surgery for Gynecologists
16.3 Danforth's Obstetrics and Gynecology
(Suttond & diamond) (second Edition)
19.3 Handbook of disease of the breast (Second Edition)
(Michael Dixon, Richarc Sainsbury) (Salekan E-book)
20.3 Haines & Taylor OBSTETRICAL & GYNAECOLOGICAL PATHOLOGY
(Fifth Edition) (Harold Fox-Michael Wells) (CD I , II)
21.3 INTERACTIVE COLOR GUIDES Obstetrics Gynecology Neonatology (David James, Mary Pillai, Janice Rymer, Andrew N. J. Fish, Warren Hye)
1. Normal Infant
2. Congennital Abnormalities
3. Birth Trauma
4. Syndromes
5. Deformations
6. Infection
7. Iatrogenic Lesions
8. Surgical Problems
22.3 LAVM: Our First one Hundred Cases; What have We Learned?
9. Skin Disorders
10. Low-Birth-Weight Infants
(Dr G. F. Stohs, MD & Dr. L. P. Johonson, MD)
. CD .
23.3 Male Infertility
A Guide for the Glinician) (Anne M. Jequier)
- :
17
)(Mrs Baruna Basu, Dr. Suresh Chandra Basu
2005
24.3 Male Reproductive Dysfunction
)25.3 Menopause Biology & Pathobiology (Rogerio, Jennifer Kelsey, Robert Marcus
)Nine Month Miracle (A.D.A.M. Software, Inc.
3. A Child's View of Pregnancy
2. The Family Album
)(Thirteenth Edition) (Jonathan S. Berek, MD
1. Anatomy
26.3
27.3 Novak's Gynecology
28.3 Obstetric Ultrasound Principles and Techniques
FL . BPD AC HC Gs CRL ) - (........ - ) BPP (
CNS Body FL AC )(Cord Insertion - Case Study
29.3 Operative Obstetrics
)(Larry C. Gilstrap III) (2nd Edition) (SALEKAN E-BOOK

)30.3 Safety principles for surgical techniques in minimally invasive gynecologic surgery (Dr. Samir Sawalhe) (CD I , II
)(Equipment, preparation, positioning, approach alternatives, safe entry, nots on application
4. Approach alternatives
5. Electrical morcellation
3. Disinfection/preparation
2. Positioning
1. Instruments/equipment
)31.3 Single Puncture Laparoscopic Technique (Marco Pelosi, MD) (VCD
CD Single puncture . multiple puncture .
32.3 Submitted Subject: Transvaginal Sonographic Assessment of Pelvic Pathology: Preoperative Evaluation
)(Frances R. Batzer, MD
CD :
) ( :
Case . :
resection
Septate uterus
-
-
-
-
-
Hysteroscopic Resection :
Cyst :
Cyst :
: YA
LMP
ectopicpregnancy
Left Salpingectomy
) (:
)(R.Viscarello.MD
Limiting Physician Exposure to Hepatitis B and HIV : Ob / Gyns
CD HBV HIV .
) (:
(Gordon. D. Davis, MD. & R.W.Lobel,MD
Laparoscopic Retropubic Colposuspension For Stress urinary incontinence
CD Stress incontinence .
:
- :
18
:()
Bi-polar Desiccation of Vascular Tissue: Laparoscopic Hysterectomy
(Paul, D. Indman,MD)
. bi-polar desiccation
33.3 TEXT AND ATLAS OF Female in Fertility Surgery (ROBERT B. HUNT) (Third Edition) (Mosby) (SALEKAN E-BOOK)
BASIC SCIENCE
ENERGY SOURCES
RADIOLOGIC PROCEDURES
HYSTEROSCOPY
LAPAROSCOPY
LAPAROTOMY
ENDOMETRIOSIS
ADDITIONAL CONSIDERATIONS
34.3 Textbook of Assisted Reproductive Techniques Laboratory and Clinical Perspectives (David K Gardner, Ariel Weissman, Colin M Howles, Zeev Shoham)
35.3 The Boston IVF Handbook of Infertility
A Practical guide for practitioners who care for infertile couples (Steven R. Bayer, Michael M. Alper, Alan S. Penzias)
2004
36.3 The Infertility Manual (2nd Edition) (Kamini A Rao, Peter R Brinsden, A Henry Sathananthan)
2004
37.3 Triplet Pregnancies and their Consequences (Louis G. Keith, MD, Isaac Blickstein, MD) (SALEKAN E-BOOK)
2002
Epidemiology and biology
Antepartum considerations
Delivery/birth considerations
The Matria database
Short-term outcomes
Prenatal diagnosis
Long-term outcomes
Preventive measures
Miscellaneous
Future dicections
Sources of information on multiple births
38.3 TVT Tension-free Vaginal Tape
Stress Incontinence
Anatomy&Terminology
Tension-free Vaginal Tape
Indication&Patient Selection
TVT Procedure
Clinical Information
Sales Support
39.3 Urogynecology: Evaluation and Treatment of Urinary Incontinence (Bruce Rosenzweig, MD, Jeffrey S. Levy, MD, Donald R. Ostergard, MD)
. CD
CD
: Urogynechology
Consideration for the OB/GYN Generalist
Types of incontinernce y
won surgical & surgical Management
- Evaluation - Introduction Definigg Incontinence : :Introduction & Defining Incontince (
incontinence awareness y
Patient misconceptions y
affected women y
incontince y
:incontinency (
Cystoscopy y uroflowmetry y Postvoid residual y Cystometrogram y Pad test y y y Voiding diary y un , u/s y
Pessary test y Multi-Channel urodynamics y
: Stress urinary incontinence (

.( .... funetional electrieal Stimalation biofeedback, Beharioral modification))
. Complication . Procedure :
: Consideration for the OB/Gyn Generalist (
:
incontinrence management to private patients y
Non surgical therapy y
urogynechology as a subdiscipline y
.
Allied Staff y
equipment cost y
Set-up requirement y
Urodynamics y professional consideration y
eystometry y
2005
40.3 Ultrasound in Obstetrics & Gynecology (Eberhard Merz.M.D)

41.3 UTEROSALPINGOGRAPHY IN GYNECOLOGY (Hysterosalpingography) It's Application in Physiological And Pathological Conditions
(SALEKAN E-BOOK)
2003
: Utero Salpingography CD
Uterosalpingography
( ) -
. USG CD
- :
19
)42.3 Video Journal of Gynecology (Vaginal Hysterectomy Wedge morcellization Technique for the Large Uterus) (The Infertile Couple) (David Olive, MD, George W. Morley MD,
2005
43.3 William's OBSTETRICS
)(F. Gary Cunningham, Kenneth J. Leveno) (CD I , II
)(Twenty-second edition
)44.3 WOMEN'S HEALTH (MOSBY'S PRIMARY CARE
CD Procedure ) (Female Genitalia Female Genitiourinary Tract.

L L .
CD : CD CNG :
CD :
Breast examination - : Pojition quiz

: Colposcopy - cervix .
. Positioning Procedne
Quiz . .
- : D&C . Procedure
Position .... . . Quiz .
: Pelvic Examination - ) (utenes , carivx , vagina , valve Position .
exetrnalgenifalicn rectovaginal , bimanual .
Quiz .
: Pap Smear - . Position .... .
.
) Vaginal Secretion - ( : KOH slide
Quiz .
45.3 Your Pregnancy, Your Newborn The Complete Guide for Expectant and New Mothers
CD
)(Sixth Edition) (SALEKAN E-BOOK
)(Frances Fischbach
A Manual of Laboratory & Diagnostic Tests
1.4
CD :
Stool Studies
Nuclear Medicine Studies
Pulmonary Functio and Blood Gas Studies
Special Systems, Organ Functions, and Post Mortem Studies
2002
Urine Studies
Immunodiagnostic Studies
Ultrasound Studies
X-ray Studies
Blood Studies
Microbiologic Studies
Endoscopic Studies
Cerebrespinal Fluid Studies
Diagnostic Testing
Cbemistry Studies
Cytology, Histology, and Genetic Studies
Prenatal Diagnosis and Tests of Fetal Well-Being
)A Slide Atlas of ATHEROSCLEROSIS (Progression and Regression) (Herbert C. Stary
2.4
.
.
2002
th
)American Sodiety of Hematology (CD 1-5) (44 Annual Meeting

-Hematology Grants Workshop
3.4
CD-1: ALL -AML -ASH/ASCO Joint Symposium -Atypical Cellular Disorders

CD-2: CLL -CML -CNS Lymphoma -Cutaneous Lymphoma -E. Donnall Thomas Lecture
CD-3: Enhancing Physician/Patient Communication Regarding Hematologic Disorders -Ham-Wasserman Lecture
- :
20
-Hypercoagulability: Too Many Tests, Too Much Conflicting Data -Malaria and the Red Cell -Marrow Failure
CD-4: Multi[ple Myeloma -Myelodysplastic Syndromes Non-Myeloablative Transplantation -Platelets: Thrombotic Thrombocytopenic -Purpura Plenary Policy Frum
CD-5: Presidential Symposium -Red Cell Antigens as Functional Molecules and Obstacles to Transfusion -Sickle Cell Disease -Stem Cell Transplantation: Supportive Care and Long-Term
Complications -Stem Cells: Hype and Reality Update on Epidemiology and Therapeutics for Non-Hodgkins Lymphoma
4.4
An Electronic Companion to Microbiology for MajorsTM (Mark L. Wheelis)
Reviw , Test yourself
: CD
What Are Microorganisms?
Classification
Methods of Microbiology
Prokaryotic Cell Struture
Eukaryotic Cell Struture

Growth & Reproduction
Metabolism & Energy

Microbial Genetics
Gene Regulation
Viruses
Microbial Ecology
Defenses Againses Infection
Disease
5.4
Animal Cell Culture (Third Edition) (A Practical Approach) (John R. W. Masters)
6.4
Antibody Engineering (R. Kontermann S. Dubel)
7.4
Antibody Phage Display Methods and Protocols (Philippa M. O'Brien, Robert Aitken)
8.4
APPLIED ANIMAL REPRODUCTION
9.4
Atlas of HEMATOLOGY
(h. jOEbEARDEN, John W. Fuquay)
: CD
1. Examination of Blood Cells
2. Normal Hematopoiesis and Blood Cells
3.Dynamic Cell Morphology
4. Hematolopathology
5. Cluster of differentiation Archive
6. Self-Assessment
10.4
Atlas of Diagnostic Cytopathology (Barbara F. Atkinson, MD)
2004
11.4
Atlas of Medical Parasitology (Dr. K. Ghazvini)

2000
: . . .
2003
* Heart and Muscles Parasites

* Lung Parasites
* Eye Parasites
* Skin Parasites
* Case reports and updates in parasitology

* Blood, Bone Marrow, Spleen Parasites
* Central Nervous System (CNS) Parasites

* Liver and Biliary Tree Parasites
* Gnito-Urinary Parasites
* Intestinal Parasites (Helminths)
* Intestinal Parasites (Protozoa)
12.4
Atlas of Surgical Pathology (Johns Hopkins) (Jonathan I. Epstein, Neera P. Agarwal-Antal, David B. Danner, Kim M. Ruska)
13.4
Basic Cell Culture A Practical Approach (I. M. Davis)
14.4
Basic histology: TEXT & ATLAS IMAGE LIBRARY (Tenth Edition)
2000
2 - Jose CARNEIRO
1- Luiz Carlos JUNQUEIRA

15.4
(Luiz Carlos, Juhqueira, Jose CARNEIRO) (A Division of The McGraw-Hill Companies)
Biochemical Interactions An electronic companion to: FUNDAMENTALS OF BIOCHEMISTRY (Donald voet, Judith G. voet, charlotte W. Pratt) (Version 1.02)
: CD
NUCLEOTIDES AND NUCLEIC ACIDS
PROTEINS: PRIMARY STRUCTURE
PROTEIN FUNCTION
LIPIDS
BIOLOGICAL MEMBRANES
MAMMALIAN FUEL METABOLOSM: INTEGRATION AND REGULATION
GLUCOSE CATABOLISM
GLYCOGEN METABOLISM AND GLUCONEOGENESIS
DNA REPLICATION REPAIR, AND RECOMBINATION
PHOTOSYNTHESIS
LIPID METABOLISM
AMINO ACID METABOLISM
NUCLEOTIDE METABOLISM
NUCLEIC ACID STRUCTURE
CITRIC ACID CYCLE
TRANSLATION
REGULATION OF GENE EXPRESSION
ENZYME KINETICS, INHIBITION, AND REGULATION
INTROCUCTION TO METABOLISM
ELECTRON TRANSPORT AND OXIDATIVE PHOSPORYLATION
PROTEINS: THREE-DIMENSIONAL STRUCTURE
1999
TRANSCRIPTION AND RNA PROCESSING
16.4
Bioinformatics for Geneticists
- :
/Michael R. Barnes, Lan C. Gray)
21
17.4
18.4
BIOLOGY CONCEPTS & CONNECTIONS
(Second Edition) (Richard M. Liebaert) (CAMPBELL.MITCHELL.REECE)
1. Introduction: The Sclentific Sindy of Life
3. The Life of the Cell
2. The Evolution of Biological Diversity
4. Animals: Form & Function
BLOOD PRINCIPLES AND PRACTICE OF HEMATOLOGY

Part I: Fundamentals of Hmatology: Tools of the trade
Part V: Hemostasis
Part VI: Red Blood Cells
5. Cellular Repoduction & Genetics
7. Concepls of Evolution
6. Plants: Form & Function
8. Ecology
(SECOND EDITION) (ROBERT I. HANDIN SAMUEL E. LUX THOMAS P. STOSSEL)
Part II: The Hematopoietic System

Part VII: Systemic Disease
Part III: Stem Cell Disorders

Part VIII: Hematologic Therapies
Part IV: White Blood Cells

Part VIIII: Appendices
20.4
Bone Marrow Pathology (Barbara J. Bain David M. Clark)

th
BRS Cell Biology CELL BIOLOGY AND HISTOLOGY (4 edition) (Leslie P. Gartner, James L. Hiatt, Judy M. Strum) (LIPPINCOTT WILLIAMS & WILKINS)
21.4
Carter, Patchefsky
22.4
Cellular & Molecular Neurobiology (Second Edition)
19.4
Plasma Membrane
Connective Tissue
Circulatory System
The Urinary System
Epithelia and Glands
Nucleus
Cartilage and Bone
Lymphoid Tissue
Female Reproductive System
Blood and Hemopoiesis
Cytoplasm
Muscle
Endocrine System
Digestive System: Oral Cavity and Alimentary Tract
Digestive System: Glands
Extracellular Matrix
Nervous Tissue
Skin
Special Senses
Comprehensive Exam
Tumors & Tumor-Like Lesions of the Lung (Darryl Carter, Arthur S. Patchefsky, Clifton F. MOD Tain)
1- Lonotropic and Metabotropic Receptors in Synaptic Transmission and Sensory Transduction

2- Somato-Dendritic Processing and Plasticity of Postsynaptic Potentials
2003
2003
3- Neurons: Excitable and Secretory Cells that Establish Synapses

4- Activity and Developmen of Networks: The Hippocampus as an Example
23.4
Clinical Diagnosis & Management by Laboratory Methods (twentieth Edition) (john bernard henry)
2001
24.4
Clinical Hematology (A Victor Hoffbrand , John E Pettit) (Mosby)
Normal Hemopoiesis and
Blood Cells
Anaemias
Blood Transfusion
Leucocyte Abnormialities
Hemostasis and Bleeding Disorders
Bone Marrow Transplantation
Hematological Malignancies
Further Reading
Coagulation Disorders
Acknowledgements
Bone Marrow in
Non-hemopoietic Disease
Parasitic Infections Diagnosed in Blood
25.4
Clinical Immunology
26.4
Color atlas of Cancer Cytology (Third Edition) (Masayoshi Takahashi)
27.4
Color atlas of differential diagnosis in Exfoliative & Aspiration CYTOPATHOLOGY (Sudha R. Kini, M.D)
28.4
COMMON PROBLEMS IN CLINICAL LABORATORY MANAGEMENT (Judith A. O'brien, M.S. CLSup (NCA)) (Salekan E-Book)
COMPLYING WITH CLIA '88

MEETING TUBERCULOSIS CONTROL
REGULATIONS
WRITING MANUALS: THE STANDARD
OPERATING PROCEDURE MANUAL (SOPM)
OVERCOMING OSHA'S OBST ACLES THE

EXPOSURE CONTROL PLAN
PROVIDING AND USING PERSONAL
PROTECTIVE EQUIPMENT
PASSING PROFICEINCY TEST
OVERCOMING OSHA'S OBSTACLES THE

CHEMICAL HYGIENE PLAN
WRITING MANUALS: THE GENERAL
OPERATING PROCEDURE MANUAL ( GOPM)
FULFILING QUALITY CONTROL
GUIDELINES
ESTABLISHING A QUALITY ASSURANCE

PROGRAM
SURVIVING INSPECTIONS AND ATTAINING

ACCREDIANCE
PURSUING PERSONNEL PERSPECTIVES
ENCOURAGING EDUCATION
THE ACQUISTION AND MAINTENANCE OF

LABORATORY INSTRUMENTATION
MASTERING FINANCES: BILLING AND

CODING
TAMING TECHNOLOGY: LABORATORY INFORMATION SYSTEM (LIS)

RE-ENGINEERING FOR THE FUTURE: THE CORE LABORATORY,
AUTOMATION, OUTREACH NETWORKING, AND THE MILLENNIUM BUG
GENERATING LABORATORY NUMBERS: STATISTICS LINEARITY,
CALIBRATION, REFERENCE, AND CRITICAL VALUES: CALCULATIONS
MANAGING THE PHYSICIAN OFFICE LABORATORY (POL)
TAMING TECHNOLOGY: POINT OF CARE TESTING (POCT)
29.4
Comprehensive Cytopathology (Marluce Bibbo)
30.4
Concise Histology (A data of multiple choice question in microscopic) (Bloom & Fawcett's) (Second Edition)
31.4
Diagnostic and Laboratory Test Reference (Seventh Edition) (Mosby) (Salekan E-Book) (Kathleen Deska Pagana, PhD, RN, Timothy J. Pagana, MD, FACS)
2005
32.4
Dianostic Hematology
- :
(Second Edition)
22
This textbook, 'Diagnostic Hematology: A pattern approach', is accompanied by a CD-ROM with three knowledge-based systems applied to 237 case studies. The 3 knowledge-based systems are:
1. Professor Petrushka for peripheral blood analysis
2. Professor Fidelio for flow cytometry immunophenotyping
3. Professor Belmonte for bone marrow interpretation
33.4
Discover Biology
34.4
DNA Science A First Course (Second Edition) (David A. Micklos, Greg A. Freyer, witli David A. Crotty)
2000
35.4
36.4
Electronic Atlas of Parasitology (John T. Sullivan)
EMBRYO (CD Color Atlas for Developmental Biology) (Gary C. Schoenwolf)

Chapter 1: Frog Embryos
37.4
38.4
39.4
university of the Incarnate Word
Chapter 2: Chick Embryos
Chapter 3: Pig Embryos
Essential Cell Biology Volume 1: Cell Structure A Practical Approach
Chapter 4: Gametogenesis
(John Davey and Mike Lord)
Essential Cell Biology (with the voice of Julie Theriot designed and programmed by Christopher Thorpe)
Fields Virology (Forth Edition) (Volume 1) (Lippincott Williams & Wilkins)
2001
Section One: General Virology
Chapter 1-22
Section Two: Specific Virus Families Chapter 23-90
40.4
Functional HISTOLOGY WHEATER'S (FOURTH EDITION) (BARBARA YOUNG, JOHN W. HEATH) (ALAN STEVENS JAMES S. LOWE) (PHILIP J. DEAKIN)
41.4
Genetic Predisposition to Cancer (Second Edition) (R.A. Eeles. D.F. Easton)

Genetics From Genes to Genomes (Ann Reynolds, Ph.D.) (University of Washington)
3- Molecular Genetice
1- Transmission Genetics
5- Gen RegVlation (... )
2- Gentral Dogma
6- Poplations & Evolvtion (... )
4- Chromosomes FISH ( )
. Quick time ... DVA PCR ... : CD
.( In teractive) . .
. CD Q.t. ( Setup . exe ) CD CD
2004
2000
43.4
GnRH Analogs in Human Reproduction
2005
44.4
Gram Stain TUTOR
42.4
(Bruno Lunenfeld)
(ANINTERACTIVE TUTORIAL THAT TEACHES THE MICROSCOPIC EXAMINATION OF URINARY SEDIMENT)
(Brad Cookson, MD, PHD, Ajit Limaye, MD, Lydia Matheson, BA)
1. Introduction
2. Morphology
3. Specimen Sites
4. Case Studies 5. Exam
6. Image Atlas
45.4
Halperin & Goldstein Fluid, Electrolyte, & Acid-Base Physiology (A Problem-Based Approack) (Mitchell L. Hlperin, Marc B. goldstein)
46.4
Histology & Cell Bilogy (An Introduction to Pathology)
____
47.4
(Abraham L. Kierzenbaum, MD)
HISTOLOGY EXPLORER
Microscope 3D
The Cell
Epithelium
Connective Tissue Proper

Blood and Bone Marrow
The Sketetal Tissues
Nervous Tissue
The Circulatory System
The Lymphoid Organs
The Digestive System

The Respiratory System
The Urinary System
The Reproductive System

The Mammary Giands
The Eye
Glands
Muscular Tissue
The Skin
The Endocrine Glands

The Ear
48.4
HUMAN HISTOLOGY CD-ROM (Alan Stevens. James Lowe)
49.4
Human Mulecular Genetics 3 Tom Strachan & Anderw P. Read)
2004
50.4
Images of Disease An image database for the teaching of Pathology (Nick Hawkins, Mark Dziegielewski)
case CD
. CD
51.4
Immunology (Blackwell Science)
- :
2000
23
52.4
Interactive Color Atlas of Histology (Version 1.0) (Leslie P. Gartner James L. Hiatt) (LIPPINCOTT WILLIAMS & WILKINS)
53.4
Interactive Embryology The Human Embryo Program (Jay Lash Ph.D.)
54.4
55.4
2000
Introduction to Immunocytochemistry (3rd Edition) (J.M. Polak & S. Van Noorden)

Laboratory Medicine: URINALYSIS (Chemical and microscopic examination of urine Atlas of Microscopic Analysis Procedures for Urinalsis) (Pesce Kaplan Pubishers Inc.)
2000
Extensive atlas of microscopic analysis: over 50 microphotographs of

urine sediment, including cells, casts, and artifacts
Method write-up for 15 chemical urinalysis procedures
Complete Specimen collection section
Interpretation of urine findings in common renal and

lower urinary tract diseases
Tables reviewing results of chemical urinalyses
56.4
Maternal- Fetal Medicine (4th Edition) (Robert K. Creasey, Robert Resnik)
57.4
Media Supplement for Biochemistry (FOURH EDITION) (Roy Tasker Carl Rhodes)
2000
1. Reaction mechanisms
58.4
59.4
60.4
61.4
2. Metabolic Pathways
3. Membrane Processes
4. Protein Synthesis
5. Molecular Representations
Methods in Enzymology Guide to Yeast Genetics & Molecular & Cell Biology
Microbes in Motion III (Dr. Gloria Delisle and Dr. Lewis Tomalty Queen's University)

( ... DNA )

Miscellaneous
Microbial Genetics (Second Edition)
2004
(Stanley R. Maloy, John E. Cronan, Jr., David Freifelder)
2002
MICROBIOLOGY AND IMMUNOLOGY (KEN S. ROSENTHAL) (Mosby)

1.
TUTORIAL: I. Topics
II. Systems
III. Random
2. TEST
62.4
MICROBIOLOGY AND MICROBIAL INFECTIONS (Topley & Wilson's) (Albert Balows, Max sussman) (NINTH EDITION)
63.4
64.4
65.4
MODERN GENETIC ANALYSIS (Anthony J. F. Griffiths, William M. Gelbart, Jffrey H. Miller, Richard C. Lewontin)
Introduction
System Requirements
Getting Started
Reference
Freeman Genetics Web Site
MOLECULAR BIOLOGY in Reproducteve Medicine (B.C.J.M. Fauser, Rutherford)
MOLECULAR CELL BIOLOGY 4.0 (Paul Matusdaru, Amold Berk, S. lawence Zipufsky, David Baltimore, James Damell, Harey lodish)
2000
66.4
Molecular Cloning A Laboratory Manual (Joseph Sambrook, David W. Russell) (Third Edition) (Volume 1-3)
67.4
Molecular Genetics of Bacteria
68.4
69.4
Molecuralar Genetics of Bacteria (Jeremy W. Dale, Simon F. Park) (Fourth Edition)

NCCL INFOBASE Serving the World's Medical Science Community Through Voluntary Consensus
2004
2002
70.4
PATHOLOGIC BASIS OF DISESE Interactive Case Study Companion to ROBBIMS
Inflammation and Repair

Infectious Disease
Genitouinary, Breast, and Pregnancy Disorders
(Larry Snyder & Wendy Champness) (Second Edition)
Fluid and Hemodynamic Disorders

Cardiovascular Diseases
Endocrine Diseases
Genetic Disorders
Hematopatholory Disorders
Skeletal Disorders
(W. B. Saunders Company) (Sixth Edition)
Diseases of Immunity
Gastrointestinal Diseases
Neuropathology
Neoplasia
Diseases of Liver, Galbladder, and Pancreas
Systemic Pathology
Diseases of Kidney
71.4
PATHOLOGY (Alan Stevens. James Lowe)
72.4
Pathology of Skin Atlas of Clinical-Pathologcical Corration (Robert M. Hurwitz, Antoinette F. Hood)
73.4
Pathology of the Lungs (Bryan Corrin)
2000
74.4
Pathology of the Skin
- :
Atlas of Clinical-Pathological Correlation Robert M. Hurwitz, MD, Antoinette F. Hood, MD)

:
24
75.4
Peripheral Blood TUTOR
(ANINTERACTIVE TUTORIAL THAT TEACHES THE MICROSCOPIC EXAMINATION OF URINARY SEDIMENT)

Final Exam
Introduction
Cell Morphologies
Disease Associations
Atlas
Overview, Smear Preparation

Stain Procedure, Smear
Evaluation
Cell Structure, Read Blood

Cells, White Blood Cells,
Platelets, Artifacts, Quiz
Red Blood Cells, White

Blood Cells, Neoplastic
Disorder
Cell Morphology
Disease Association
76.4
Phage display A laboratory Manual (Carlos F. Barbas, Dennis R. Burton, Jamie K. Scott, Gergg)
77.4
Primers in Biology Protein Structure and Function (Gregory A Petsko Dagmar Ringe)
PRINCIPLES OF Molecular Virology (THIRD EDITION)
2000
78.4
Contents
Introduciton
Particles
Genomes
Replication
Expression
Infection
Pathogenesis
Novel Infectious Agents
Appendices
Glossary, Abbreviations and Pronounciations
Classification of Sub-Cellular Infections Agents
The History of Virology
79.4
Principles of VIROLOGY Molecular Bilogy, Pathogenesis, and Control (S.J. Flint, L.W. Enquist, R.M. Krug)
80.4
Protein Bioinformatics
81.4
82.4
83.4
PROTEINS (Structure & function) (John Wiley & sons, Ltd)

RAPID REVIEW HISTOLOGY AND CELL BIOLOGY (E. ROBERT BURNS, M. DONALD CAVE) (MOSBY)
Rheumatology & Orthopaedics (Coote, Haslam)
Samter's Immunologic Diseases (SIXTH EDITION) (K. Frank Austen, M.D, Michael M. Frank, M.D., John P. Atkinson, M.D., Harvey Cantor, M.D.)
84.4
(An Algorithmic Approach to Sequence & Struture Analysis)
( ) -
(Ingvar eldhammer, Inge Jonassen, William R. Taylor)
2002
. . CD
.
85.4
Saunders Manual of Clinical Laboratory Science
86.4
Short Protocols in Molecular Bilogy (A compendium of Methods from Current Protocols in Molecular Biology) (Fifth Edition) (Frederick M. Ausubel, Reger Brent)(Vol 1 & 2)
87.4
SHORT PROTOCOLS IN MOLECULAR BIOLOGY FIFTH Edition
88.4
Sternberg's Diagnostic Surgical Pathology (Fourth Edition) (CD I, II, III) (Stacey e. Mills, Darryl Carter, Joel K, Greenson)
89.4
Surgical Pathology
2002
2004
90.4
Surgical Pathology of Non-Neoplastic Lung Disease (Third Edition)
91.4
The American Society of Hematology (41 Annual Meeting and Exposition)
92.4
The Cell 1.0 A Molecular Approach (Many Animations, Movies, Photos, and drawn images) (Geoffrey M. Cooper)
(Rosai & Ackerman) (Ninth Edition) (Juan Rosai)
A Compendium of Methods from Current Protocols in Molecular Biology

(CD 1-4)
(Anna-Luise A. Katzenstein, M.D) (W.B. Saunders Company)
st
Cell Overview
Organelles & Energy Metabolism
Humman Genetic Diseases

The Cytoskeleto
Floww of Information
The Plasma Membrane
The Nucleus
The Extracellular Machine
The Cell Cycle

Cancer-A Family od Diseases
Protein Sorting and Transport

The Meiotic Divisions
93.4
THE HUMAN GENOME PROJECT
2003
94.4
The Metabolic and Molecular Bases of Inherited Disease
____
95.4
The Microbial Models of Molecular Biology from Genes to Genomes
- :
(Rowland H. Davis)
25
96.4
2000
UNDERSTAND! Biochemistry (3/e Version) (Lehninger Principles of Biochemistry)

1. THE BACKGROUND
2. THE MOLECULES OF LIFE
3. PROTEINS IN ACTION
4. BIOENERGETICS
5. BIOSYNTHESIS
6. NUCLEIC ACIDS AND THEIR EXPRESSION
7. CELLULAR ARCHITECTURE AND TRAFFIC

8. THE DIVIDING CELL
9. SOME IMPORTANT TECHNIQUES
97.4
UNDERSTAND! Biochemistry (VERSION 1.0)
98.4
UNDERSTAND! Biology: Biochemistry (Molecules, Cell & Genes)
: CD
Basic Chemistry
99.4
Macromolecular assembly and modification
Urinalysis TUTOR
Bioenegetics
Signal transduction
Enzymology
The flow of genetic information
(ANINTERACTIVE TUTORIAL THAT TEACHES THE MICROSCOPIC EXAMINATION OF URINARY SEDIMENT) (Caria M. Phillips, MLM, MT(ASCP),
Metabolism
Molecular biology techniques
Paul J. Henderson, MS, MT(ASCP), Claudia Bein, BS, MT(ASCP))
. interactive
( . ) . ( ) .
.( . . B A ) .
( ) .
( ) .
100.4
Using Antibodies (A Laboratory Manual)
101.4
BLADDER BIOPSY INTERPRETATIONS (Jonathan I. Epstein, M.D., Mahul B. Amin, M.D., Victor E. Reuter, M.D.) (SALEKAN E-BOOK)
Normal Blodder Anatomy and Variants of Normal
histology
Invasive Urothelial Carcinoma
Squamous Lesions
Miscellaneous Nontumors and Tumors
(Ed Harlo, David Lanp)
Flat Urothelial Lesions

Conventional Morphologic, Prognostic, and Predictive Factors and Reporting of
Bladder Cancer
Cystitis
Second ary Tumors of the Bladder
2004
Papillary Urothelial Neoplasms with Inverted Growth

Patterns
Glandular Lesions
Mesenchymal Tumors and Tumor-Like Lesions
102.4
Male Infertility A Guide for the Glinician) (Anne M. Jequier)
103.4
Menopause Biology & Pathobiology (Rogerio, Jennifer Kelsey, Robert Marcus)
104.4
The Infertility Manual (2nd Edition) (Kamini A Rao, Peter R Brinsden, A Henry Sathananthan)
2004
105.4
WHO Laboratory Manual for the examination of Human Semen and sperm-cervical mucus interaction (Fourth Edition)
106.4
WHO Manual for the standardized investigation & diagnosis of the infertile couple (Patrick J, Rowe, Frank H. Conhaire, Timothy B. Hargreave)
107.4
WHO Manul for the standardized investigation, diagnosis and management of the infertile male (Patrick J. Rowe, Frank H. Comhaire)
___
108.4
PATHOLOGIC BASIS OF DISEASE (Robbins & Cotran) (7th Edition)
109.4
Obstetrical & Gynaecological Pathology (Fifth Edition) (Haines & Tailor)
110.4
Volume I: Basic Technologies Bioinformatics from Genomes to Drugs (Methods & Principles in Medicinal Chemistry) (R. Mannhold H. Kubinyi)
2002
111.4
Volume II: Applications Bioinformatics from Genomes to Drugs (Methods & Principles in Medicinal Chemistry) (R. Mannhold H. Kubinyi)
2002
112.4
Ute Schepers RNA Interference in Practice (Principles, Basics, & methode for Gene Silencing in c. elegans, Drosophila and Mammals)
2005
113.4
A Laboratory Guide to the Mammalian Embryo
2004
114.4
Bioinformatics (Genes, Proteins & Computers) (Christine Orengo, Janet Thornton, David Jones)
___
115.4
Genomics Proteomics & Bioinformatics (A. Malcolm Campbell, Laurie J. Heyer)
___
116.4
Computer-Aided Drug Design (Methods & Applications) (Thomas J. Perun. C. L. Propst)
___
- :
2005
___
26
117.4
Principles of Biochemistry (Molecular, Genetics) (Volume Three)
___
118.4
Fundamentals of Enzymology (The Cell and Molecular Biology of Catalytic Proteins) (Nicholas c. Pricc & Lewis Stevens) (Third Edition)
___
119.4
Protein-Protein Interactions (Methods & Applications)
2004
120.4
Molecular Cell Biology (The immune system in health & disease) (6th Edition) (Charles A. Janeway, Paul Traversm, Mark Walport)
2005
121.4
Mind Maps in pathology (Michele Harrison, Peter Dervan)
___
122.4
Short Protocols in PROTEIN SCIENCE (A Compendium of Methods from Current protocols in protein science) (John E. Coligan, Ben M. Dunn)
___
123.4
Short Protocols in CELL BIOLOGY (A Compendiuim of Methods from Current Protocols in Cell Biology) (Juan S. Bonifacino, Mary Dasso)
___
124.4
Molecular Markers, Natural History & Evolution (John C. Avise)
___
125.4
Molecular Cloning (A Laboratory Manual) (Volume 2) (Joseph Sambrook, David W. Russell) (Third Edition)
___
126.4
Molecular Cloning (A Laboratory Manual) (Volume 3) (Joseph Sambrook, David W. Russell) (Third Edition)
___
127.4
Practical Breast Pathology (Tibor Tot, Peter B. Dean) (Thieme)
___
128.4
Bioconjugation Protocols (Strategies & Methods) (Christof M. Niemeyer)
129.4
DNA Topology (Andrew D. Bates, Anthony Maxwell)
130.4
Bioinformatics Computing (The Complete, Practical Guide to bioinformatics for life scientists) (Bryan Bergeron, M.D.)
131.4
Before We Are Born Essentials of Embryology & Birth Defects (Moore, Oersaud) (6th Edition)
132.4
Proteins and proteomics (A Laboratory Manual) (Richard J. Simpson)
133.4
Phage Display (A Practical Approach) (Tim Clackson, Henry B. Lowman)
134.4
Phylogenetic Trees Made Easy (A How-To Manual) (Second Edition)
135.4
Biopsy Pathology of the Breast (John P. Sloane) (Second Edition)
136.4
Genomics Proteomics & Vaccines (Gude Grandi, Chiron Vaccines., Siena. Ite)
137.4
Molecular Analysis & Genome Discovery (John Wiley & Sons, LTD)
138.4
MPP (Whitehead) (Mucosal Biopsy of the Gastrointestinal Tract) (Fifth Edition)
139.4
Color Atlas & Text of Pulmonary Pathology (Philip T. Cagle, Timothy C. Allen, Roberto Barrios)
2005
140.4
Experiments with Fission Yeast (A Laboratory Course Manual) (Caroline Alfa, Peter Fontes, Jeremy Hyams)
141.4
Introduction to PROTEIN SCIENCE
142.4
Nanomedicine
143.4
Virus Life in diagrams
144.4
The Genetics of the Growth Hormone Axis (Albert Beckers)
145.4
How the Human Genome Works
146.4
Mouse Phenotypes (A Handbook of Mutation Analysis)
147.4
Principles of Genome Analysis & Genomics (Sandy B. Primrose, Richard M. Twyman)
2004
___
(Architecture, Function, and Genomies) (Arthur M. Lesk)
Volume 11A: Biocompatibility (Robert A. Freitas Jr., Research Scientist, Zyvex Corporation)
- :
(Hans-W. Ackermann, Laurent Berthiaume, Michel Tremblay)
2004
(Virginia e. Papaioannou, Richard R. Behringer)
2006
27
148.4
Genomics Applications in Human Biology (Sandy B. Primrose & Richard M. Twyman)
149.4
Pharmaceutical Biotechnology (An Introduction for Pharmacists & Pharmaceutical Scientists) (2 Edition) (Daan J.A. Crommelin, Robert D. Sindelar)
150.4
Case Studies in Genes and Disease
151.4
Bone Tumors (Howard D. Dorfman, Bogdan Czerniak)
152.4
Viral Hepatitis (Third Edition)
153.4
Immuno Biology the immune system in health & disease
nd
2004
A Primer for Clinicians (Bryan Bergeron)
(Professor Howard Thomas, Professor Stanley Lemon, Professor Arie Zuckerman)

(6th Editiion) (Chales A. Janeway, Paul Travers, Mark Walport, Mark J. Shomchik)
2005
-
CD
2.4
A Slide Atlas of ATHEROSCLEROSIS Progression and Regression (Herbert C. Stary, MD)

2002
.
.
1.5
A visible improvement in angina treatment (VCD)

Post-EECP stress perfusion image, Markedly improved anterior, septal, and inferior wall perfusion.
2.5
Advanced Echocardiography: Quantitaive 2-D & Doppler Ultrasoun (Miguel A. Quinones, William A. Zoghbl)
3.5
4.5
5.5
6.5
Advanced Therapy in CARDIAC SURGERY (Kenneth L. Franco, Edward D. Verrier)

ACCSAP (Adult Clinical Cardiology Self-Assessment Program) (C. Richard Donti, MD, Richard P. Lewis, MD) (AMERICAN COLLEGE of CARDIOLOGY)
Acute Heart Failure (THE CLEVELAND CLINIC FOUNDATION) (W. Frank Peacock, MD) (The Emergency Department and the Economics of Care)
American Heart Associations fighting Heart Disease and Stroke Abstracts from Scientific Sessions (Augustus O. Grant, Raymond J. Gibbons)
-Basic Science
-Clinical Science
-Population Science
Atlas of Transesophageal Echocardiography (Navin C. Nanda, MD, Michael J. Domanski) (Williams & Wilkins)
2003
2000
2004
2002
7.5
1. Normal Anatomy
2. Prosthetic Valves and Rings
3. Mitral Valve
4. Ischemic Heart Disease
5. Aortic Valve and Aorta

6. Cardiomyopathy
8.5
All in One (Diabetes and the Heart) (MERCK)
9.5
BEYOND HEART SOUNDS The Interactive Cardic Exam (John Michael Criley, MD) (VOL 1)
Introduction to anscultation
Frontal Chest Anatomy
The Cardinal areas of anscultation
Using the stethoscope
10.5
BRAUNWALD'S HEART DISESE
Hemodynamics tutorial The cardiac cycle

Mitral and aortic valve flow
Hemodynamic changes in disease
Mitral Stenosis
Aortic stenosis
2004
Pulse Tutorial
Introduction
Carotid Pulses
Jugular Venous Pulses
A Textbook of Cardiovascular Medicine (7th Edition) (Douglas P. Zipes, Peter Libby) (Volume I , II)
11.5 Cardiac Catheterization, Angiography, and Intervention
7. Tricuspid and Pulmonary Valves

8. Congenital Heart Disease
(SIXTH EDITION) (LIPPINCOTT WILLIAMS & WILKINS)
2000
. Grossmam's Cadiac Cathetrization ....... edition CD

. Procerdue- related Findinig Case50
(.... output blood flow - ) - ( -Brachiel Cutdown Percutaneous approuch) Basic - -
(... Ejection Fraction Test )- ( - ) -
- :
28
) : Special Catheter Techniquse - - - deivce intrathoracic balloon Counter Pulsation - - (... )
- Stent- ( Profile - ) :
- (... :
CAD Basic ) Stent - - Rotabalator (.....2004
12.5 Cardiovascular Surgery
)(VCD) (CD I, II, III

"Excerpted from "Medical & Surgical Controversies in CV disease: The Aorta and Peripheral Vessels
Course Directors: Thoralf M. Sundt III, MD and Peter C. Spittell, MD
2005
2004
2003
2003
)(Richard E. Klabunde
)(Nadim Al-Mubarak, Gary S. Roubin, Sriram S. Layer, Jiri J. Vitek
)14.5 Carotid Artery Stenting (Current Practice and Techniques
)15.5 CathSAP Cardiac Catheterization and Interventional Cardiology Self-Assessment Program (Carl J. Pepine, MD, Steven E. Nissen, MD
A Satellite Symposium held during the ESC Heart Failure meeting

)(Steven N. Konstadt
16.5 Challenging established treatment patterns in chronic heart failure
)17.5 Clinical TRANSESOPHAGEAL ECHOCARDIOGRAPHY (A PROBLEM- ORIENTED APPROACH) (Second Edition
2001
18.5 Clinical Utility of Contrast Echocardiography
)Sonovue: An ideal contrast agent for Low MI myocardial Perfusion (Dr. Daniela Bokor, Bracco sa, Milano
"What's new in cardic echography (Dr. Luciano Agati, University "La Sapienza Roma
)Ischemic coronary artery disease (Dr. Harld Becher, John Radcliffe Hospital, Oxford
Congestive
)Heart Failure (NOVARTIS) (CD I , II
19.5
CD Ciba . Frank .H.Netter . CD Case report . Case report
. . . multiple choice test CHF.
. :
13.5 Cardiovascular Physiology Concepts
. CHF
. CHF
. management CHF.
)20.5 Coronary Heart Disease (J. Hurley Myers, Ph.D., Frank H. Netter, M.D.
- : -
-
- : - -
. .
: - - - - - - - - - )
) ( .
(
2004
)21.5 Current Diagnosis & Treatment in CARDIOLOGY (7th Edition) (Michael H. Crawford. MD
2005
)22.5 Drugs for the Heart (Sixth Edition
)(Salekan E-Book) (Lionel H. Opie, Bernard J. Gersh
)23.5 Dynamic Practical Electrodiography (Lippincott Williams & Wilkins
)24.5 ECG (Jay W. Mason, MD
25.5 ECG DIAGNOSIS MADE EASY ROMEO VEGHT
Internet explorer . ECG . .

:
( 1. Basic Priciples
....) Ischaemic (Coronary) heart disease 3. ECG
5. Conductin impairment
7. Rhythm disturbances
6. Pacemakers, ICDs and cardioversion Mixed ECG quizzes
4. Pericarditis, myocarditis and metabolic disorders
6. Chardiomyopathies and autoimmune disorders
2. Hypertrophy
- :
29
Next . Setup . Setup CD . my
26.5 ECG-SAP III (Jay W. Mason, MD, FACC)
-Using ECG-SAP III -Standard Tracings -Syndromes
27.5
computer CD :(
. Finish Next
-Computer Overreads
-Serial Tracings
Echo Lecture (VIDEO SERIES) (7CD) (Mayo)

1. TEE in the Operating Room (Bijoy K. Khandheria, MD)
-Stress Testing
-ECG of the Month
-Guidelines
-Utilities
: CD
Intraoperative echocardiography has become an essential component to the surgical approach to valvular disease. Dr. Bijoy Khandheria discusses the utility of intraoperative echocardiography and its
impact on the surgical management of cardiovascular disease.
2. TEE in Adult Congenital Heart Disease (James B. Seward, M.D.)

Dr. James Seward Presents Adult Congenital Heart Disease. A generation of Children Have Grown into adulthood and Present with postoperative congenital heart disease. Transesophageal
echocardiography is extremely helpful but may not always be necessary in the assessment of adult congenital heart disease. Learn from the expert regarding appropriate use of transesophageal
echocardiography and assessment of residua and sequela of adult congenital heart disease.
3. Understanding Operative Procedures for Patients with Univentricular Heart from Palliation to Fontan (James B. Seward, M.D.)
Dr. Seward gives a detailed overview of complex anomalies and their applicable corrections. Topics included are Blalock, Mustard, Glen and Fontan corrections. Graphic depictions of each corrective
procedure, possible complications and echocardiographic example are included.
4. Mitral Valve Regurgitation: Essential Measurements. Pitfalls and Limitations. (Fletcher A. Miller, Jr., MD)
Dr. Fletcher Miller discusses and presents the current approach to the quantitative evaluation of mitral valve regurgitation. This is an excellent review of current quantitative assessment of mitral valve
regurgitation including pitfalls and limitations.
5. Mitral Vale Regurgitation: Evidence-Based Practice (A. Jamil Tajik, MD)
A Classic presentation by Dr. A. Jamil Tajik on a change in clinical practice with regard to the quantitation of regurgitation and then a change in medical management with early surgery and repair of the mitral valve.
6. Evaluating the Patient with Prothetic Valve (Fletcher A. Miller, Jr., MD)
Dr. Fletcher Miller, an expert on the echocardiographic assessment of prosthetic valves, presents a detailed in-depth review of the quantitative echo Doppler approach to the prosthetic valve. It is
important to understand the hemodynamic pitfalls and limitations of the echocardiographic assessment of cardiac prosthetic valves.
7. Stress Echocardiography and Contrast (Patricia A. Pellikka, M.D.)
Stress Echocardiography and Contrast Using illustrative cases, Dr. Pellikka gives an expert presentation and discussion on the role of contrast in stress echocardiography. Pitfalls and limitations of contrast stress
echocardiography are also discussed. New Horizons in Stress Echocardiography Dr. Pellikka, an expert in Stress echocardiography, discusses Dobutamine stress echocardiography and its role in preoperative risk
stratification. Also discussed are new advances in stress echocardiography such as color kinesis and acoustic quantification, color Doppler imaging, and strain and strain rate imaging.
ECHOCARDIOGRAPHY 2-D/DOPPLER WITH COLOR FLOW IMAGING (UPDATE NO. 1) (TRANSESOPHAGEAL- ECHOCARDIOGRAPHY)
ECHOCARDIOGRAPHY 2-D/DOPPLER WITH COLOR FLOW IMAGING (VOLUME 1) (VCD) (ECHOCARDIOGRAPHY Normal 2-D And M-MODE EXAM))
ECHOCARDIOGRAPHY 2-D/DOPPLER WITH COLOR FLOW IMAGING (VOLUME 10) (VCD) (CARDIAC MASSES)
ECHOCARDIOGRAPHY 2-D/DOPPLER WITH COLOR FLOW IMAGING (VOLUME 11-A,B) (VCD CD I, ii) (ECHOCARDIOGRAPHIC ASSESSMENT OF PROSTHETIC HEART VALVES)
ECHOCARDIOGRAPHY 2-D/DOPPLER WITH COLOR FLOW IMAGING (VOLUME 12) (VCD) (INTERVENTIONAL ECHOCARDIOGRAPHY)
ECHOCARDIOGRAPHY 2-D/DOPPLER WITH COLOR FLOW IMAGING (VOLUME 2) (VCD) (DOPPLER AND COLOR FLOW IMAGING: PHYSICS, INSTRUMENTATIONS AND THE NORMAL EXAM)
ECHOCARDIOGRAPHY 2-D/DOPPLER WITH COLOR FLOW IMAGING (VOLUME 4) (VCD) (ECHOCARDIOGRAPHY IN AORTIC VAL VE DISEASE)
ECHOCARDIOGRAPHY 2-D/DOPPLER WITH COLOR FLOW IMAGING (VOLUME 5) (VCD) (ECHOCARDIOGRAPHY IN CORONARY HEART DISEASE)
ECHOCARDIOGRAPHY 2-D/DOPPLER WITH COLOR FLOW IMAGING (VOLUME 6) (VCD) (ECHOCARDIOGRAPHY IN CONGENITAL HEART DISEASE IN THE ADULT)
ECHOCARDIOGRAPHY 2-D/DOPPLER WITH COLOR FLOW IMAGING (VOLUME 7) (VCD) (ECHOCARDIOGRAPHY IN CARDIOMYOPATHIES: DILATED, RESTRICTIVE AND HYPERTROPHIC)
ECHOCARDIOGRAPHY 2-D/DOPPLER WITH COLOR FLOW IMAGING (VOLUME 8) (VCD) (ECHOCARDIOGRAPHY IN PERICARDIAL DISEASE)
ECHOCARDIOGRAPHY 2-D/DOPPLER WITH COLOR FLOW IMAGING (VOLUME 9) (VCD) (ECHOCARDIOGRAPHY IN TRICUSPID AND PULMONIC VALVE DISEASE AND DESEASES OF THE AORTA)
ECHOCARDIOGRAPHY 2-D/DOPPLER WITH COLOR FLOW IMAGING (VOLUME3) (VCD) (ECHOCARDIOGRAPHY IN MITRAL VALVE DISEASE)
EchoSAP
III (Echocardiography Self-Assessment Program)(Echocardiography Overview: Technique and Applications) (Volume 1)
41.5
(Jemes D. Thomas, MD, Ellen Mayer-Sabik, MD)
28.5
29.5
30.5
31.5
32.5
33.5
34.5
35.5
36.5
37.5
38.5
39.5
40.5
- :
2000
30
-Introduction and Overview
-Examinations
-Applications
-Self-Assessment Questions
-Evidence-Based Medicine
-Conclusions
42.5 EECP: Current Experience and Future Directions
43.5 Electronic Image Collection of Comprehensive Vascular and Endovascular Surgery (John W. Hallet, Joseph L. Mills, Jonothan J. Eamsbaw, Jim A Reekers)
2004
1. Background
3. claudication
2. Mesenteric Syndromes 4. Renovascular disease
5. Chronic Lower Extremity Ischemia

6. Aneurysmal Disease
7. Acute Limb Ischemia

8. Cerebrovascular Disease
9. Upper Extremity Problems

10. Venous Disease
44.5 ENDOVASCULAR TECHNIQUES (Abdominal Aortic Aneurysms) (Workshop) (l. Flessenkmper) (15th Endovascular Symposium Berlin)
45.5 ESC Congress
2004
46.5 EVOLVING ISSUES IN THE MANAGEMENT CHD

SECTION 1
(National Lipid Education Council
SECTION II
TM
2002
SECTION III
SECTION IV
SECTION V
Emerging Evidence-Based Data From Clinical Trials PAD Lipids and Risk
Inflammatory Markers: Anovel Approach Use of Genomics to discover new targets for therapy Case study: Diabetes
NON-HDL-Case Secondary Targert of Therapy
Lipid Management Though combination Therapy Case Study: Novel Risk Markers
Examining the nonlipid effects of statins
What is it's Role in clinical practice?
Case Study:Combination Therapy
Case Study: NON-HDL-C
47.5 Feigenbun's Echocardiography
Textbook & Video Library (Sixth Edition) (Harvey Feigenbaum, William F. Armstrong, Thomas Ryan)
2005
48.5 Grossman's Cardiac Catheterization, Angiography and intervention (Sixth Edition) (Donald S. Baim, William Grossman)
49.5 HEART DISEASE (FIFTH EDITION)
A Textbook of Cardiovascular Medicine (W.B. SAUNDERS COMPANY)
. ( e-book)
(Mendelsohn) Reviwe and Assessment Book -
(Hennekens) Clinical Trials in Cardiovascular Disease -
(chien) Molecular Basis of Heart Disase -
(Braunwald) Heart Disease -
)( Search CD .
( e-book) . CD Search .
. CCU club
50.5 HEART SOUNDS
51.5 HEART SOUNDS Basic Cardiac Auscultation Version 3.0 (Leonard Werner, M.D., Brian Pitts, David Gilsdorf)
2003
52.5 Heart Sounds Basic Cardiac Auscultation CD-ROM to Accompany (M.D., F.A/C.P., Brian Pitts, M.D., David Gilsdorf) (Lippincott Williams & Wilkins)
2003
53.5 Highlights
2004
ESC Congress
54.5 HURST'S THE HEART (R. Wayne Alexander, Robert C. Schlant, Valentin Fuster
. CD Hurst Text Edition
. ( ) CD . CD
55.5 Hypertension & Olmetec
56.5 Interactive Atlas of Transesophageal Color Doppler Echocardiography (Raffaele De Simone)
57.5 Interactive Atlas of Transesophageal Color Doppler Echocardiography
58.5 Interactive Echocardiography: A Clinical Atlas

59.5 Interactive Echocardiography: Interactive ECG
- :
(Raffaele De Simone)
(Th. Binder, M.D., G. Rehak,G. Porenta. M.D., Ph.D., M. Zengeneh, M.D., G. Maurer, M.D., H. Baumgartner, M.D.)
(J.H. Myers, A.F. Moukaddem, N. Tongsak)
University of Vienna, Austria
31
60.5 Interactive Electrocardiography on Cd-Rom (Curtis M. Rimmerman, Anil K. Jain)
61.5 Interventional Cardiology Clinical Resource (Disc 1 & 2) (Evidence . Analysis . Recommendations . Consensus Reports)
2003
62.5 Intra-Aortic Balloon Catheter Insertion and Removal Technique

1. INTRODUCTION
2. LAB SELECTION
3. LAB PREPARATION
4. LAB INSERTION
63.5 Manual of Cardiovascular Medicine (Second Edition)
(ARROW)
5. LAB CATHETER
PREPARATION
6. LAB CATHETER INSERTION
7. LAB REMOVAL : CD
2002
2004
(Brian P. Griffin, Eric J. Topol)
64.5 Mastering Auscultation An Audio Tour to Cardiac Diagnosis Clinical Findings Diagnosis Treatment Tutorial Text Reference (Dr. Anthony Don Michael's)
65.5 Mechanical Support for Cardiac & Respiratory Failure in Pediatric Patients
66.5 MVP Video Journal of Cardilogy
(Brain W. Duncan)
(Maria-Teresa Olivari, M.D., Antonio M. Gotto, M.D., D. Phill.)
. ( VCD ) MVP CD
: .
1-Determination of Rejection in the Cardiac transplant Recipient
Maria-Teresa Olivari :
. ) ( MRI
Antonio Gotto :
2- Triglycerides, HDL and coronary Heat Disease
. .
Carl E. Orringer :
3- Management of Cardiac Disease in Pregnancy
... MRI - (... )
. ...
67.5 MVP Video Journal of Cardiology (Anthony C. Pearson, M.D., Charles B. Higgins, M.D., William W. O'Neill, M.D.) (VCD)
: . . 40 MVP CD
1- The stately Art of MR in Cardiovascuvlar Disease
Charles P. Higgins :
. .... MRI MRI MRI
2. Arguing for Angioplasy in Acute Myocardial infction
William w. ONeill :
Lone PTCA
Anthony C. Pearson : :
3- Improved understanding of cardioembolic Stroke prorided by Transesophageal Echoecardiography
. Case TEE TEE TEE TEE
68.5 MVP VIDEO JOURNAL OF CARDIOTHORACIC SURGERY (VIDEO SEGMENT I & II) Thromboexclusion for Treatment of Descending Aortic Dissection (John A. Elefteriades, MD)
69.5 Nicorandil in Angina Pectoris from symptom Management to Cardioprotection (Professor Derek, Professor James M Downey, PD Dr. Med, Christian Schneider)
70.5 Perioperative Transesophageal Echocardiography
2003
1. Basics of Echocardiography
(Patricia M. Applegate, Richard L. Applegate, I)
2. Clinical TEE Examination
71.5 Perioperative Transesophageal Echocardiography
3. Clinical Uses of Perioperative TEE
4. Unknowns
5. Perioperative
(Patricia M. Applegate, M.D., Richard L. Applegate, II)
2003
72.5 PLUMER'S PRINCIPLES & PRACTICE OF INTERAVENOUS THERAPY (SEVEN EDITION) (Sharon M. Weinstein)
73.5 Practical Perioperative Transoesophageal Echocardiography Introduction, instructions and acknowledgements (David Sidebotham, John Faris, Alan Merry, Andrew Kerr)
2003
74.5 TEE An Intractive Exam Review on CD-ROM (CD I , II) (Lippincott Williams & Wilkins)
2002
- :
32
nd
)75.5 TEXTBOOK OF CARDIOVASCULAR MEDICINE (2 Edition) (ERIC J. TOPOL
CD Text . CD Text book of Cardiovascular Medicine

) . ) (... ECG,M.S
. :
- - ) :
( - ) : -(.
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-transesophageal CT, PET , MRI - .( intraoperative Pacing ) : ECG
Pacemaker ( - invasive : ) - Procedures Percutaneos

-
( -
Restenosis approach
- :Multimedia - ) ( .
: - CT/MRI - ECG intravascular - .
: CT/MRI Pacing .
Endof-Life Care
CD
Percutaneous Coronaryintervantion
( : TEXTBOOK OF CARDIOVASCULAR MEDICINE Cardiovascular Medicine CD Flash

Install TOPOL ) - ( . C:\Program files\CardioVascularMedicine
Install ) ( Install Install complete
Done . .Quick Time, Internet Explorer :
5.5 . 2000, NT, ME, 98, 95 200 MHZ 32 .
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Vascular CD internet explorer Address . internet explorer .
http://127.0.0.1:83/PCIndex.htm.
)The Echo Manual (Second Edition) (Jae K. Oh, MD, James B. Seward, MD, A. Jamil Tajik MD
76.5
2003
The Netter Presenter Cardiovascular and Renal Edition
77.5
)Images from the Netter Collection (NOVARTIS

)(John Michael Criley, M.D., Conrad Zalace, David Creley
Catalog of Lesions
yNormal
Timing of Murmurs
ySystolic Murmurs
78.5 The Physiological Orgins of HEART SOUNDS and MURMUS
Timing of Heart Sounds

yValve Closure Sounds and Splitting of Sounds
General Tutorials:
yInspection and Palpation
- :
33
yValvar Lesions
yPericardial Disease
yCongenital Heart Disease
yCardiomyopathies
yMyxoma
yDiastolic Murmurs
yContinuous Murmurs vs. To and Fro Murmurs
yFriction Rubs
yOpening Sounds
yThird Sounds
yFourth sounds
yEjection Sounds
yMid-Systolic Clicks
yIntriduction to Auscultation
yEffect of Maneuvers and Perturbations
yHemoduction to Cardiac Imaging Modalities
)79.5 Valvular Heart Disease (Third Edition) (Joseph S. Alpert, James E. Dalen, Shahbudin H. Rahimtoola
)80.5 Vascular Vision (A Liberating Approach to Vascular health Expert Opinions in Dyslipidaemia) (Professor Philip Barter, Dr. John Kastelein,
81.5 VJC Video Journal of Cardiology
)(LAWRENCE S. COHEN, M.D, JOHN ELEFTERIADES, M.D.) (VCD
1. From a new perspective: mitral valve prolapse aortic dissections and aneurysms
2. Surgical and medical management of ascending and descending aortic dissections liporoten (A): a cardiovascular risk factor
)82.5 VJC Video Journal of Cardiology (Christopher White, M.D, Michael E. Cain, M.D., Bruce D. Lindsay, M.D., Herbert Geschwind, M.D.) (VCD
CD VJC VCD 50 .
. :
:christoher white :
1-Cold lege : The Approach to Acvte and progressive Peripheral Vascular Disease
. .
: Michael E. Cain :
Urokinase
.... .
2- RADiofrgvency ablation : Ablation of AVNode reentry tachycardias
ECG AV ... .
:Herbert Geschwind :
3- Laser Angioplasty for coronary Atherosclerotic Disease
Pulser ) ( PTCA .... .

2005
A guide to acronyms for cardiovascular trials
83.5 What's What
CD
2001
)20 Common Problems Dermatology (Alan B. Fleischer, Steven R. Feldman
1.6
)American Cancer Society Atlas of Clinical Oncology Skin Cancer (Arthur J. Sober, MD, Frank G. Haluka, MD, phD) (Bc Decker Inc
2.6
.
. Skin cancer
text . . :
Basic Concept : .
: : ) ( ) BCE ( ) Scc ( ) ( ) ) Merckle cell Carcinoma (: ( : ) (: .
Management : : ) ( ) ( ) adjuvant therapy ( ) ( ) (
) ( . ]) [MF (.
: .
- :
34
)AQUAMIDE; Poly Acryl Amide Ged (an injectable gel for correction of soft Tissue Deficiencies
3.6
CD filler Cosmetic Surgery . Aquamide

.
2002
)Atlas of Clinical Dermatology (Third Edition) (Anthony du Vivier
4.6
2002
)ATLAS OF COSMETIC SURGERY (MICHAEL S. KAMINER, MD, JEFFREY S. DOVER, MD, FRCPC, KENNETH A. ARNDT, MD) (W.B. SAUNDERS COMPANY) (Salekan E-Book
Dr. Kenneth. Arndt . ) Dr. Leffell (Yale"' :
Cosmetic Dr. Arndt . Archives of Dermatology Cosmetic
" ) Botox
( . Botox
Archive 2001 AAD 2002 ( ) Harvard
Scar management
. Laser in Dermatology " "Kenneth, Arndt . :
5.6
PART III
COSMETIC SURGERY PROCEDURES AND TECHNIQUES
10 Topical Skin Care
11 Lasers in the Treatment of Vascular Lesions
12 Lasers in the Treatment of Pigmented Lesions
13 Laser Hair Removal
14 Liposuction
15 Hair Transplantation
16 Soft Tissue Augmentation
17 Botulinum A Exotoxin Injections for Photoaging and Hyperhidrosis,
18 Chemical Peels
19 Lasers in Skin Resurfacing
20 Blepharoplasty
21 Surgical Rhytidectomy: Face Lifts and the Endoscopic Forehead Lift
22 Leg Vein Management: Sclerotherapy, Ambulatory Phlebectomy, and Laser Surgery
23 Scar Management: Keloid, Hypertrophic, Atrophic, and Acne Scars
PART I
EVALUATION OF THE COSMETIC SURGERY PATIENT
1 The History of Cosmetic Surgery
2 The History of Cosmetic Dermatologic Surgery
3 Evaluation of the Aging Face,
4 Photoaging: Mechanisms, Consequences, and Prevention
5 Beauty and Society
6 Psychosocial Issues and Their Relevance to the Cosmetic Surgery Patient
PART II
ANESTHESIA
7 Regional Anesthesia for Aesthetic Surgery
8 Office-Based Sedation and Monitoring
9 Postoperative Pain and Nausea Management
)(CD I , II
)(SALEKAN E-BOOK
)Atlas of Dermatology (Jhon's Hopkins
6.6
Sort Jhon's Hopkins.

1999
2003
)Atlas of Dermatology (T.L.Diepgen, M. Simon, A. Bittorf, M. Fartasch, G. Schuler) (with the DOIA team G. Eysenbach, J. Bauer, A. Sager) (springer
) (www . (DOIA) Dermatology online Atlas
. 600 DPI Case report ... . Offline DOIA
online .
)Atlas of Differential Diagnosis in DERMATOLOGY (Klaus F. Helm, M.D., James G. Marks, Jr., M.D.
CD .
Problem-oriented . CD
.
. CD Acrobat reader . ) (animation CD . image gallery .CD
quiz . index incon .
)Botulinum Toxin Aesthetic Indications (Mauricio de Maio, Segio Talarico, Benjamin Ascher, Nam Ho Kim South
7.6
8.6
9.6
2004
)10.6 Clinical Dermatology ( A Color Guide To Diagnosis And Therapy) (Fourth Edition) (Thomas P. Habif
11.6 Color Atlas and synopsis of Clinical Dermatology
)(Fitzpatrick, M.D. Richard Allen Johnson, M.D. Dick Suurmond, M.D
Common and Serious Diseases Thomas B.
- :
35
)12.6 COLOR ATLAS OF CLINICAL DERMATOLOGY COMMON AND SERIOUS DISEASES (Salekan E-Book
)(Thomas B. Fitzpatrick, MD, Richard Allen Johnson, MD, Klaus Wolff, MD, Dick Suurmond, MD
2004
)13.6 Color Atlas of Cosmetic Oculofacial Surgery (William PD Chen, Jemshed A Khan, Clinton D McCord
14.6 Color Atlas of Dermatoscopy (2
), enlarged and completely revised edition) (Wilhelm stolz, Otto Braun-Falco
nd
2001
)15.6 Color Atlas of Dermatoxcopy 2nd, enlarged and completely revised edition (Wilhelm Stolz. Otto Braun-Falco) (Salekan E-Book
2004
)16.6 Comprehensive Facial Rejuvenation (A Practical & Systematic Guide to Surgical Managemet of the Aging Face) (Edwin F. Williams III, Samuel M, Lam
17.6 Consult a Physician Before Beginning any new Exercise Program Rejenuve FACIAL MAGIC
)(Gynthia Rowland
18.6 Correction of Wrinkles & Augmentation of lip and cheek with Restylane & Perlane
)19.6 Cosmetic Dermatology (Leslie Baumann, MD
2000
20.6 COSMETIC LASER SURGERY
)(Natural beauty for as long as you like

Skin filler % . recombinant . Restyalne , Restyane fine

perlane ) ( . : VCD
. . animation . . . . Reslane fine
. . Restylana . . Perlane ) ( fonciel contouring ) Lip enhan cemenl (cheek enhancmeat
oral Commisure . . . . followup . . .
)PERFECT THE TECHIQUES, REDUCE THE RISKS, AND ENJOY THE RESULTS WHEN PERFORMING COSMETIC LASER SURGERY (Richard E. Fitzpatrick Mitchel P. Goldman
21.6 COSMETIC LASER SURGERY For Face and Body
2001
)(ALAN R. SHALITA, M.D., DAVID A. NORRIS, M.D
BASIC AND CLINICAL DERMATOLOGY
An Interdisciplinory Approach
22.6 Cosmetic Surgery
.
. .
Procedure . Pre-op Post-op .
.
. - . - .
Peel Peel ) total body peel Chest . ( . .
) Er: YAG, Co2 tattoo ( hair removal . Resurfacing .
Dermabrasion . Skin filler ) Restiylans inerrall , Perlane (....
Gortex . BotulinumsToxin . Cyst . flap Graft .
tumescent . procedure . fac, Neck - lifling Brow Reyirvenation
. D. Cook The cook weekend Altrnative to face lift .
Alopecia Redechion . . .
.
23.6 Cosmetic Surgery for FACE and BODY
)24.6 Cutaneous Laser Surgery (Second edition) The Art and Science of Selective Photothermolysis (Goldman, Fitzpartick
Cutaneous Laser Surgery . Cutaneus Laser text
Cosmetic Laser Surgery .
Laser tissue interaction mini text book . Wuond healing
Post procedural wound healing . co2 Erbium:Yag resurfacing Er:yag chest
- :
36
carbon Dioxide ultrapulse Er:yag . Nonablative Laser incisional laser Surgery
. Tinas.Alster manual of cutaneous laser techniques Scar revision . hair
] removal [ mtense light source hair transplant . Co2 Er:yag ) hair transplant (
. Leg vein . .
2001
)25.6 Cutaneous Medicine Cutaneous Manifestations of Systemic Disease (THOMAS T. PROVOST, MD, JOHN A.FLYNN, MD) (Johns Hopkins Medical Institutions Baltimore, Maryland
. .
. .
. .
Dr. Richard Dobson (AAD) American etcademy of Dermatology : Sir Willamosler
. Procedure medical Dermatologist AIDS
.
)26.6 Dermatology: A Multi-Media Teaching File (Disc 1,2) (Gross & Microscopic Symposium) (Mosby
27.6 Diagnosis & Management Anevidence-Based Approach
2002
)(Robert T Brodell, Sandra Marchese Johnson

)28.6 EVIDENCE-BASED DERMATOLOGY (Howard I. Maibach, MD, Sagib J. Bashir, BSc (Hons), MB, ChB, Ann McKibbon, BSc, MLS
(Evidence- Based Heatlth Care) EBMC EBHC . . :

- - - - .
. ...
EBME . .
29.6 Facial Lifting by "APTOS" threads Clinic of Plastic and Aesthetic Surgery
)30.6 Hair Removal with Intense Pulsed Laser (IPL
2002
) - -( +
sharing ... .
. IPL . Skin type Spot size
Therapeatic window . CD Ellipse . IPL IPL IPL
. clip .
HAIR
TRANSPLANTATION
(The
Art
of
Micrografting
and
)Minigrafting
)(Salekan E-Book
31.6
TECHNIQUE
PLANING AND PATIENT INSTRUCTUIONS

SPECIAL APPLICATIONS
PATIENT EVALUATION
REOPERATIVE SURGERY
ANATOMY AND PHYSILOGY OF HAIR

COMBINED FACE LIFT AND HAIR TRANSPLAYTATION
1999
)32.6 HANDBOOK OF ORAL DISEASE DIAGNOSIS AND MANAGEMENT Cripian Scully (MARTIN DUNITZ
2005
)33.6 Laser & Lights (Volume 1 & 2) (CD I, II) (Rejuvenation, Resurfacing, Hair Removal, Treatment of Ethnic Skin
2000
34.6 Laser Hair Removal
.
.
. symptom, sign .
. management Diagnosis Clinical feature Aetiology Sexmainly affected Agemainly affected incidence Defintion .
)(David J. Goldman) (Martin Dunits
) (hair removal . .
hair removal . . :
5- Intense pulsed light
ND: YAG laser
4-
3- Diode laser
2- Normal mode alexandrite laser
1- Normal mode Ruby laser
- :
37
.
.
)35.6 MANUAL OF CHEMICAL PEELS Superficial and Medium Depth (Mark G. Rubin, MD
)36.6 MANAGEMENT OF FACIAL LINES AND WRINKLES (ANDREW BLITZER, WILLIAM J. BINDER, J. BRIAN BOYD ALASTAIR CARRUTHERS) (SALEKAN E-BOOK
2000
) (Line 8 Wrinkle exfoliants

Superfical peel Chemical Vitamins TCA Peel Dermabrasion implant Dermal Allograft GORTEX
Directexcision facelifting, endoscopic Browloft Skeletal frame .
Botulinium Toxin . Botulinumtoxin .
Computer imaging .
(Tinal
S.
Alster,
)M.D.
(SALEKAN
)E-BOOK
MANUAL
OF
CUTANEOUS
LASER
TECHNIQUES
(Second
)Edition
37.6
.
. ) (Patient selection .
. edition
erbium :YAG laser Resurfacing hair removal .
)38.6 Minor Surgery a text and atlas Fourth edition (John Stuart Brown
)Clifford M Lawrence Neil H Cox (Joseph L Jorizzo) (SALEKAN E-BOOK
)39.6 PHYSICAL SIGNS IN DERMATOLOGY (SECOND EDITION
.
.
) ( ... . approach .
test . pitfalls
.
. Dr. Joav Merick .
. ...
40.6 Practical MINOR SURGERY
2002
)(Third Edition) (Antoinette F. Hood, Thedore H. Kwan, Martin C. Mihm, Jr., Thomas D. Horn, Bruce R. Smoller
7. Bonus Quizzes
6. Panniculus
4. Reticular Dermis
5. Appendages
41.6 Primer of Dermatopathology
3. Basement Membrane Zone, Oaoillary Dermis, and Superficial Vascular Plexus
2004
)(Darrell S. Rigel, Robert A. Weiss
1. Introduction
2. Epidermis
42.6 Photoaging
)Radiosurgical Treatment of Superficial Skin Lesions (S. Randolph Waldman, M.D.
43.6
)Radiosurgical Vaporization of Dermatologic Lesions (Dr. Stephen Chiarello
44.6
)6. Basal Cell Carcinoma (Nasal Bridge
)5. Scar Revision (Nose
)4. Basel Cell Carcinoma (Nasal Tip
)3. Scar Revision (Back
11. Tonsillectomy
10. Rhinoplasty
9. Turbinate Shrinkage
8. Radiosurgery in ENT
12. Tympanoplasty
)(SALEKAN E-BOOK
2- Keratosis Removal
1- Rhinophyma
)7. Scar Revision (Lower Forehead
Reconstructive Facial Plastic Surgery
45.6
) - -( +
sharing ... .
.
IPL . Skin type Spot size Therapeatic window .
CD Ellipse . IPL IPL IPL .
clip .
:
- :
38
)46.6 REFINEMENT IN HAIR TRANSPLANTATION: Micro and minigraft Megasession (Alfonso Barrera, M.D.
2002
2005
) -( ) -( . .
- .
- .
- .
- Case .
.
- face lifting . Case
- .
- Scafp face lift .
.
(June
K.
Robinson,
C.
William
Hande,
Roberta
D.
Sengelmann,
Daniel
)M. Siegel) (CD I- VI
Surgery
of
the
Skin
Procedural
Dermatology
47.6
Clip 6
Rejuvenation of the neck
using liposuciton and othe
technuques
Nail surgery
Legucer management
Benign subcutaneous lesions:
cysts & lipomas
Clip 5
Laser & light treatment of acquired
& congenital vascualr lesions
Endovenous ablation techniques
with ambulatory phlebectomy for
varicose veins
Minimum incision face lift
Blepharoplasty & brow lift
Clip 4
Chemical peels
Cyhin Implants
Use of Botulinum Toxin Type
A in facial rejuvenation
Liposuction
Autologous fat transfer:
evolving concepts & techniques
Follicular unit hair
transplantation
& Microdermabrasion
dermabrasion
& Laser treatment of tattoos
pigmented lesions
Laser Skin resurfacing: ablative
and non-ablative
Clip 3
Axial pattern flaps

Skin grafting
Regional reconstruction: trunk, extremities,
hands, feet, face (perioral, periorbital, cheek,
)nose, forehead, ear, neck & scalp
Scal revision
Soft tissu augmentation
Clip 2
Layered closures, complex
closures with suspension sutures
& plication of SMAS
Repair of the split earlobe, ear
piercing & earlobe reduction
Random pattern cutaneous flaps
Clip 1
Skin Structure and Surgical anatomy
Anesthesia and analgesia
Dressings & Postoperative Care
Electrosurgery, electrocoagulation,
electrofulguration, electrosetion,
electrocautery
Cryosurgery
Skin Biopsy Techniques
Suturing technique & other closure
materials
Hemostasis
Ellipse, ellipse variations & dos-ear
repairs
48.6 Skin Resurfacing
)(William P. ColemanIII, Naomi Lawrence

Skin
Rejuvenation
)with skin filler (E.E.A. Derm
49.6
2003
)50.6 Techniques in Dematologic Surgery (Keyvan Nouri MD, Susana leal-Khouri MD
51.6 Textbook of Dermatology (Sixth Editions) (R.H. CHAMPION, J.L. BURTON, D.A.BURNS, S.M.BREATHNACH) (ROOK) (Software c Gention I.T. Consuliants Ltd.,) Version 1.2.0
Rook . % - .
CD Juvederm . CD . Juvederm30 Juvederm24

Juvederm18 .
. CD Slide Conference . Board certification.

2004
2000
2002
)52.6 Textbook of Dermatology (Rook's
)(Seven Edition) (Volume 1-4) (E-Book

)53.6 Textbook of Pediatric Dermatology (JOHN HARPER ARNOLD ORANJE NEIL PROSE) (VOLUME 1 , 2
Pediatric dermatology Subspeciality . encyclopedic text
(RooK) text book of general dermatology.
185 board cerificaition .
adolescent . Psoriasis .
. ... ftrsthand knowledge .
Sedation Surgery . Surgery tissue expansion
graft . Pediatric dermatology .
.
The
Aging
Face
A
Systematic
Approach
(Calvin
M.
Johnson,
Jr.,
Ramsey
)Alsarraf
)(CD I , II
54.6
-Closure
4. The Procerus and frontalis 5. Closure

7. Fat Removal
9. Closure
8. The Skin Pinch
-The Submental Region
-Resuspension
y The Coronal Browlift: 1. Introduction 2. The Incision

3. The Corrugator Muscles
y Blepharoplasty:
1. Uooer Lids
3. Marking and Incision 5. Skin and Muscle
2. Lower Lids
4. The Incision
6. Fant Removal
-The Deep Plane Facelift
-Marking and Incision
-Skin Elevation
-The Deep Plane
- :
39
55.6 Treatment of Skin Disease Comprehensive therapeutic Strategies (Mark G Lebwohl Warren R Heymann, John Berth-Jones, Ian Coulson) (SALEKAN E-BOOK) (MOSBY)
. . management ( + +
: ) (
(specific investigations) - ( ) management strategy -
-
A-E evidence-Based . ( ) -
.( Clinical trial) ( B) ( double blind study) ( A) ( B) ( A) .
.
.
56.6 USING BOTULINUM TOXINS COSMETICALLY
(Jean Carruthers, Alastair Carruthers)
2002
2003
Introduction
Horizontal Forehead Lines
Periorbitalarea Infraorbital Orbicularis Oculi
MID and Lower Face Perioal Rhytides
Brow Injections Brow Lift
Periorbitalarea Lateral Orbital Wrinkles
MID and Lower Face Perioral Rhytides
MID and Lower Face Nasalis
Cervical Injections Vertical Platysmal Bands
Acknowledgemetns
MID and Lower Face Mouthe Frown and Mentalis
Cervical Injections Horizontal Necklace Lines
CD
1.7
A New Generation in Cemented Hip Design (VCD) (Part I , II) (David S. Hungerford, Clayton R. Perry)
Segment I: Core Decomtpression
2.7
3.7
Segment II: Trauma Case Studies: Retrograde Femoral Nailing
2001
AO Image Collection AO Principles of fracture Management (T.P. Ruedi, W.M. Murphy)

AO International AO Teaching Series-LCP (Thomas P. Ruedi, Prof. Michael Wagner)
Foreword-Basics
Methods of osteosynthesis
AO Principles
Biomechanical Principles
Surgical techniques
4.7
LCP system
Description
Implants and instruments
Application
Indications
Operating techniques
LCP cases
Humerus
Forearm
Pelvis and acetabulum
Femur
Tibia
Periprosthetic
2002
Literature and studies
Related Literature
Study results
2001
AO Principles of Fracture Management (Thomas P. Ruedi, William M. Murphy) (CD I , II)

1- AO philosophy and Its basis
2- Decision making and planning
3- Reduction and fixation techniques
4- Specific fractures
5- General topics
6- Complications
5.7
Arthroscopic Surgery (Michael J. Strobel)
6.7
Artthrex Techniques Transfix ACL Reconstruction (Eugene M. Wolf, San Francisco.CA)
7.7
Atlas of ORTHOPAEDIC Surgery A multimedia Refefence (Kenneth J. Koval, Joseph D. Zuckerman) (Textbook & Videos)
2004
8.7
Atlas of Orthopaedics Surgery (Disk 1-6)
Disk 1: Condylar Plate Fixation in the Distal Femur, Malleolar Fracture Fixation, Malleolar Fracture Type B, Malleolar Fracture Type C, Tension Band Wiring on the Elbow
Femoral Neck Rfacture Large Cannulated System, Fracture of the Radius Shaft 3.5 LC-DCP, Screw Fixation and Plating
Disk 2: Techniques of Absolute Stability, Proximal Humerus Fracture, Reduction with Clamps, Posterior Wall Fracture, Posteror + Transverse Wall Fracture,
Undeamed Tibial Nail (UTN), Intraaticular Fracture of the Distal Humerus
Disk 3: Fracture of the Tibiaplateau, Tibia Fracture in Foarm LEG UTN, Reduction Techniq, The Undeamed Femoral Nail System, Dynamic Condylar Screw (DCS),
Dynamic Hip Screw (DHS), Pilon Tibial Fractures (Foamed Foot)
Disk 4: Application of Large Distractor, AO Asif External Fixator, PC-FIX Point Contact Fixator an Internal Biologicl, The Proximal Femoral Nail (PFN),
Bicondylar Fracture of Tibia Plateau, Minimal Invasive Plating of the Tibia
Disk 5: Direct and Indirect Reduction Techniques, Short Oblique Radius Fracture, Small External Fixator, Intraarticular Fracture Distal Radius, Distal Radius,
Open Reduction & Fractures of the Calcaneus, Postoperative Treatment, Internal Fixation of a Humeral Shaft Fracture
- :
40
Disk 6: High Cinematography of a Butterfly Fracture, Posterior, Pelvic Fixations Symphysis Pubis & Pubic Rami, Pelvic Fixations, Anterior Plate Fixation 53028,
The Pelvic C-Clamp, Liss Less Invasive Stabilization System, LCP Locking Compression Plate
Body in Motion (Susan K. Hillman)

-Anatomy -Content -Everything -Anatomy Text -Surface Anatomy Videos -Muscle Aciton Videos
10.7 Bone Tumors (Howard D. Dorfman, Bogdan Czerniak)
9.7
2003
11.7 CCC (Core Curriculum in Primary Care) Orthopedics/Sport Medicine Section

1- Introduction
2- Orthopedic Procedures: A Rheumatology's Perspective
12.7 Click'X VenttoFix SynCage
3- Xercise and Aging A Prescripton for life
4- Foot and Ankle Problems Part Two
(J. Webb, O. Schwarzenbach J. Thalgott) (VCD) (AO ASIF OFFICIAL TAPE)
13.7 Double Socket Technique ACL/PCL Reconstruction Using Bio-Interference Screw Fixation & Anterior Tibialis Allograft
(David Caborn)
14.7 FRACTURES IN ADULTS (ROCKWOOD AND GREEN'S)

1- General Principles
2- Upper Extremity
3- Spine
4- Lower Extremity
15.7 FRACTURES IN CHILDREN General Principlse Upper Extremity Spine Lower Extremity (ROCKWOOD AND WILKINS) (James H. Beaty, James R. Kasser)
16.7 FRACTURES OF THE PELVIS AND ACETABULUM (G.F. Zinghi, A. Briccoli, P.Bungaro)
(Salekan E-Book)
17.7 Gait Analysis an introduction (Third Edition) An interactive multi-media presentation produced using polygon software (Micheal W. Whittle)
18.7 Green's OperativeHand Surgery (Fifth Edition) (David P. Green, Robert N. Hotchkiss) (CD I , II)
2005
33.1 Imaging of Spinal Trauma in Children (Lawrence R. Kuhns, M.D.) (University of Michigan Medical Center)
Epidemiology
Measurements
Occipitocervical Injuries
Principles AND TECHNIQUES

Normal Spine Variants and Anatomy
Mechanisms and Patterns of Injury
Thoracic Spine Injuries
ATLAS OF SPINAL INJURIES IN CHILDREN

Cervcal Spine
Lumbar Spine
Thoracic Spine
Sacrococcygeal Spine
Lumbar
Special Views and Techniques

Experimental and Necropsy Data
Sacral Injuries
19.7 Semi-Tendinous & Gracilis ACL Reconstruction with Gio-Interference Screws
(Champ L. Baker, M.D)
Interactive
orthopaedics and Sport
Medicine
20.7 Techniques for Performing Hip Arthroscopy (Joseph McCarthy, Boston, Massachusetts)
21.7
___
1. Interactive Spine
2. Interactive Hand
3. Interactive hand therapy
4. Interactive Hip
5. Interactive Shoulder
6. Interactive Knee
7. Sports Injuries The Knee
8. Interactive Food and Ankle
9. Interactve Skeleton
10. Interactive HAND Therapy Edition (Version 1.1) (J C Colditz, D A McG Routher, J M Harris)
22.7 Internal Fixation of a Humeral Shaft Fracture with the UHN

-Technical Information
-Operation
-Postoperative Concept
-Poat-op X-ray control
- Poat-op treatment
35.1 Magnetic Resonance Imaging in Orthopedics and Sport Medicine (David W. Stoller)
- :
(P.M.Rommens, J. Blum)
: MRI
41
MRI -
Echo-Planar -
-
-
Kinematic MRI -
MRI -
MRI -
-
-
-
MRI -
(Hip) -
-
(TMJ) -
MRI -
-
MRI -
23.7 MASTER TECHNIQUES IN ORTHOPAEDIC SURGERY RECONSTRUCTIVE KNEE SURGERY Southern California Center for Sports Medicine Long Beach, California (DOUGLAS W. JACKSON, M.D.)
: CD . serch TEXT ebook CD

PART IV INTRAARTICULAR FRACTURES OF THE TIBIA AND PATELLA
Operating Room Environment
Arthroscopic Management of Intraarticular Tibial Fractures

Arthroscopically-Assisted Fixation of Patella Fractures
Open Reduction Internal Fixation of Intraarticular Fractures of the Tibia
PART I EXTENSOR MECHANISM PATELLOFEMORAL PROBLEMS
Arthroscopic Lateral Release of the Patella with Electrocautery Anteromedial Tibial Tubercle
Transfer Patellectomy
PART II MENISCUS SURGERY
PART V ARTICULAR CARTILAGE AND SYNOVIUM
Meniscus Repair: The Outside-In Technique

Meniscus Repair: The Inside-Out Technique
Meniscus Repair: The All-Inside Arthroscopic Technique
Arthroscopic Chondroplasty
Osteochondritis Dissecans
Arthroscopic Synovectomy
PART III LIGAMENT INJURIES AND INSTABILITY
Anterior Cruciate Ligament Reconstruction

Arthroscope-Assisted Posterior Cruciate Ligament Repair/Reconstruction
Posterolateral Corner Collateral Ligament Reconstruction
Surgical Technique for Knee Dislocations
High Tibial Osteotomy in Knees with Associated Chronic Ligament Deficiencies
24.7 MATHYS ORTHOPAEDICS
(VCD) (Video-Atelier Othmar Keel AG)

-CCA - Straight Shaft -CCE -Vault Pan -CCB -Socket -CBC Stem -RM Cup
25.7 MATHYS-ORTHOPAEDICS HIP PROSTHESES (VCD)
1. Cemented Stem-CCA
2. Cemented Cup-CCB
3. Cementless Steam-CBC
4. Cementless Cup-RM Cup
26.7 OPERATIVE ORTHOPAEDICS
(CAMPBELL'S) (Tenth Edition) (Volume 1-4) (E-Book) (S. Terry Canale, MD)
Operative
Arthroscopy
(Third
Edition)
(John B. McGinty) (Lippincot, Williams & Wilkins)
27.7
Shoulder:
Arthroscopic Cuff Repair: -Mssive U-Shaped Tear: Subscapulais, Infraspinatus and Biceps (Stephen S. Burkhar, MD San Antonio, Texas)
-Partial: Repair of Oartial Articular Sufrace Rotator Cuff Tear (Stephen S. Burkhar, MD San Antonio, Texas), San Antonio, Texas
Slap Lesions:
-Arthroscopic Repair of the Slap Lesion (Stephen S. Burkhar, MD San Antonio, Texas)
Operative
Arthroscopy
(Third
Edition) (John B. McGinty) (Lippincot, Williams & Wilkins)
28.7
Hip: Southern Sport Medicine & Orthopaedic Center
Operative Hip Arthroscopy: -Dense Soft Tissue Envelope -Constrained Ball and Socket Anatomy
29.7 Operative Arthroscopy (Third Edition) (John B. McGinty) (Lippincot, Williams & Wilkins)
Ankle: Ankle Arthroscopy (James Tasto M.D.)
- Ankle & Subtalar Arthroscopy
Operative
Arthroscopy (Third Edition) (John B. McGinty) (Lippincot, Williams & Wilkins)
30.7
2003
2003
2003
-Thick Capsule, Limited Compliance

2003
2003
Wrist: Wrist Arthroscopy (Robert Richards MD FRCSC)

-Portal Markings -Establishing the 3/4 Portal -Radiocarpal Arthroscopy
Carpal Tunnel Release
- :
42
(Third Edition) (John B. McGinty) (Lippincot, Williams & Wilkins)
31.7 Operative Arthroscopy
2003
Knee (CD-1): Arthroscopic meniscal repair: -suture repair -implantable fixation

Knee (CD-2): -ACL -Complex articular surface injuries -Fractures -Patellofemoral
32.7 Operative Arthroscopy (SECOND EDITION) (John B. McGinty)
1- Basic Principles
2- The Knee
33.7 Operative Orthopaedics
3- The Shoulder
4- The Elbow
5- The Wrist
6- The Foot and Ankle
7- The Temporomandibular Joint
8- The Spine
9- The Hip
1999
(Ninth Edition) (CAMPBELL'S) (S. TERRY CANALE)

. Serch TEXT CD
2003
34.7 OPERATIVE ORTHOPAEDICS (CAMPBELL'S)
: CD TEXT CD
Trochanteric osteotomy-hip revision
Reconstruction nailing femoral fracture
Anterior Cervical discectomy & fusion
Arthroscopic assisted ACL reconstruction

Chevron osteotomy hallux valgus
Screw fixation SCFE

Ligament balancing Knee arthroplasty
Intramedullary nailing forearm fracture

ORIF calconeal fracture
2002
35.7 ORTHOPAEDIC SURGERY (Third Edition) (CHAPMAN)

- Surgical Principles and Techniques
- Sport Medicine
- Skeletal Disorders
- Fractures, Dislocations, Nonunions and Malunions

- Neoplastic, Infectious
- The Spine
36.7 PEDIATRIC ORTHOPAEDICS (Lovell and Winter's)
- The Hand
- Neurologic and Other
- Pediatric Disorders
(Fifth edition) (Salekan E-Book)
KYPHOSIS
THE UPPER LIMB
SPONDYLOLYSIS AND SPONDYLOLISTHESIS
DEVELOPMENTAL HIP DYSPLASIA AND DISLOCATION
THE CERVICAL SPINE

LEG LENGTH DISCREPANCY
SPORTS MEDICINE IN CHILDREN AND ADOLESCENTS
LEGG-CALVE-PERTHES SYNDROME
THE FOOT
MANAGEMENT OF FRACTURES
37.7 PEDIATRIC Fractures & Dislocations
- The Foot
- Joint Reconstruction, Arthritis, and Arthroplasty
(Volume II)
2001
SLIPPED CAPITAL FEMORAL EPIPHYSIS

DEVELOPMENTAL COXA VARA, TRANSIENT SYNOVITIS,
AND IDIOPATHIC CHONDROLYSIS OF THE HIP
THE LOWER EXTREMITY
THE LIMB-DEFICIENT CHILD
THE ROLE OF THE ORTHOPAEDICS IN CHILD ABUSE
(Lutz von laer, Former Director of trauma division basel pediatric hospital)
2004
38.7 Photographic manual of Regional Orthopaedic and Neurological Tests
. . . CD
. Test .
. . Sensitivity/Relialility Scale
Podiatric
Medicine
and Surgery (Stephen Kriss, Alan Sherman, Harold W. Vogler, Trevor Prior)
39.7
40.7 Practical Otrhopaedic Medicene (Brain Corrigan, G.D,. Maitland)
41.7 Prosthetics & Orthotics Lower Limb & spinal
45.1 Radiology imaging Bank:
1. Section
42.7
2. History
Orthopeadic
3. Findings
4. Diagnosis
5. Images
6. Classification
7. Imagenumber
(DR. L. Lafosse Annecy)
SPINE (VCD 1-A) (J. o' Dowd, P. Moulin, E. Morscher P. Moutin, J. Webb, M. Aebi)
Pedicie Identification (Conultant: J. O'Dowd)
- :
Range of Motion-AO Neutral-O Method
43.7 Shoulder Arthroscopy

44.7
(Ron Seymour)
Cervical Spine Locking Plate: Corporectomy C6 (P. Moulin)
Cervical Spine Locking Plate
Posterior Plating Technique
43
CS-Titanium Locking Plate (E. Morscher P.Moutin)
Vertebrectomy C6 (J. Webb, M. Aebi)

Posterior Cervical Plate Fixation ( C2-T1) ( j.wEBB, M.Aebi)
Cervical Spine Locking Plate (P. Moulin)
C6 to T1 (J. Webb, M.Aebi)
45.7 SPINE (VCD 1-B) (M. Aebi, J. Webb, Ghr. Ulrich, J. Nothwang, B. Jeanneret, M. Aebi J. Webb, J. Webb, M. Aebi P. Bryne)
AnteriorFixation of the Dens with Cannulated Screws ( M. Aebi, J. Webb Ghr. Ulrich, J. Nothwang)
Cervix: Fixation C3-C7 in Presenceb of a Laminectomy ( B. Jeanneret)
U.S.S: Lumbar Degenrrative Scotiosis Side-Opening Pedicte Screws (M.Aebi J.Webb)
U.S.S: Lumbosacral Stabilisation: Back-Opening Pedicte Screws (M. Aebi J. Webb)

USS: Lumbosacral Fusion Sacral Implants (J. Webb M.Aebi P.Bryne)
46.7 SPINE (VCD 1-C) (J. Webb, M. Aebi, G.Wisner, J. Webb M. Aebi, J. Webb M. Aebi, J. O'Dowd)
USS: Lumbosacral Stabilisation Side Opening Pedicle Screws
(J.Webb, M.Aebi, G. Winsner)
Universal Spine System Thoraco - Lumbar

Fractures (J. Webb M. Aebi)
Universal Spine
System:
Right Thoracic Scoliosis: Side Opening hooks & Screws

(J.Webb, M.Aebi, J.O'Dowd)
47.7 SPINE (VCD 1-D) (J. Webb, O. Schwarzenbach, J. Thalgott & J. Webb, J. Webb)
Click'X (J.Webb)
48.7 SPINE implants
The Snterior Rod System (J.Thalgott & J.Webb)
Contact Fusion Cage (J.Webb)
(CD I , II)
. CD : CD I
. Diapasone-hook CD : CD II
1999
49.7 Surgery of the Foot and Ankle (Michael J. Coughlin, Roger A. Mann)
Volume One:
1. General Considerations
2. The forefoot
Volume Two:
1. Miscellaneous Disorders
2. Sports Medicine
50.7 Surgery of the Knee
3. Postural Disorders
3. Pediatrics
4. Neurologic Disorders
5. Arthritic Conditions
4. Trauma
2001
(Third Edition) (John N. Insall, W. Norman Scott)
1- VIDEO
2- PHOTOS
3- ILLUSTRATIONS
- Anatomy
-Anatomical Aberrations
4- 3D KNEE
-Biomechanics
-Imaging
5-IMAGING
-Surgical Approaches
51.7 The Adult Hip On CD
52.7 The Shoulder (2nd Edition) (Rockwood and Matsen)
1- Disorders of the Acromiocavicular Joint
2- Disorders of the Sternoclavicular Joint
53.7 The Unreamed Femoral Nail System
( R Texhammar,
AO/ASIF VCD (CD 1-10)
P Holzach)
AO/ASIF Instrumentation Care and Maintenance
VCD 1-B
4- Glenohumeral Arthritis and Its Management
(N. Sudkamp P. Duwelius)
54.7 Video Collection Labor for Experimental Orthopaedics Surgery
VCD 1-A
3- Glenohumeral Instability
PreOperative Preparation of the Patient
Approaches to the Femur, Pelvis Knee and Elbow
(P Matter M.D., S.M. Perren, B Noesberger)
Approach to the Proximal Femur and Elbow
After-Care Following Lower Leg Surgery
Dynamic Compression Unit
Approaches to the Upper Limb
Reduction Techniques
DCP 4.5 Compression Tibial Shaft
VCD 1-C (B Noesberger, J.Stadler, P. Holzach, Th. Ruedi)

DCP 4.5 Butterss Tibial Plateau
- :
LC-DCP 4.5 for the Distal Tbia
DCP 3.5 Radius Shaft 3.5 LC-DCP
DCP 4.5 Neutralization Plate of a Spiral Fracture
Fracture of the Radius Shaft 3.5 LC-DCP with Shaft screws
44
VCD 2-A (S.M. Perren, K.M. Pfeiffer M.D.)
. Correctional Osteotomy (dist. Radius)
. Basic Lag Screw Techniques . Internal Fixation of a Closed Butterfly Fracture of Right Tibia (Operation Video)
VCD 2-B (Th. Ruedi, J. Mast M.D., P.E Ochsner)

Fracture of the Lateral Tibiaplateau
Pilon Fracture
Indirect Reduction and Plate Fixation of a Pilon Fracture

Malleolar fracture Type A
Malleolar Fracture Type B

Malleolar Fracture Type C
VCD 2-C (T.Ruedi, P.Holzach, Th. Ruedi M. Schuler, P. Hozach, P Regazzoni, Th. Ruedi M.D.)
Proximal Humerus Fracture
Distal Humerus Fracture Type C 1.3
VCD 3-A
Tension Band Wiring of the Elbow

Dynamic Hip Screw
Intaarticular Type C Fracture of the Distal Humerus

Dynamic Condylar Screw (DCS) Proximal Femur
Condylar Plate Fixation in the Distal Femur
(R. Ganz R.P. Jakob P.Koch, Th Ruedi M.D., P.Regazzoni)
Condylar Plate Proximal Femur
Large Cannulated Screw System
AO/ASIF External Fixator
VCD 3-B
Small External Fixator
Distractor Handling
Consultant Seija Pearson
VCD 3-C
Using the Small Air Drill

Compact Air Drive Basic Operating Procedure & Working with attachments
Intramedullary Nailing with the AO/ASIF Universal Femoral Nail
(R. Frigg, D. Hontzsch, Th. Ruedi)
The Interlocking of the Universal Femoral Intramedullary Nail

Opening Procedure of the Tibial Cavity for Intramedullary Nailing
The Universal Tibial Nail
VCD4
AO Universal Femoral Nail With Distractor
Intramedullary Nailing of the Tibia

Intramedullary Nailing of the Tibia with a Pseudarthrosis
Mid-Shaft Tibial Fracture Locked Universal Nail
(R. Frigg, Ch. Krettek)
UTN Unreamed Tibial Nail
Distal Aiming Device for UTN
CD
3.8
4.8
5.8
6.8
7.8
8.8
9.8
10.8
11.8
BASIC AND CLINICAL SCIENCE COURSE
2.8
AMERICAN ACADEMY OF OPHTHALMOLOGY
1.8
Section 1:
Update on General Medicine
2004-2005
Section 2:
Fundamentals and Principles of Ophthalmology
2004-2005
Section 3:
Optics, Refraction, and Contact Lenses
2004-2005
Section 4:
Ophthalmic Pathology and Intraocular Tumors
2004-2005
Section 5:
Neuro-Ophthalmolog
2004-2005
Section 6:
Pediatric Ophthalmology and Strabismus
2004-2005
Section 7:
Orbit, Eyelids, and Lacrimal System
2004-2005
Section 8:
External Disease and Cornea
2004-2005
Section 9:
Intraocular Inflammation and Uveitis
2004-2005
Section 10:
Glaucoma
2004-2005
Section 11:
Lens and Cataract
2004-2005
- :
45
2004-2005
Retina and Vitreous
Section 12:
12.8
2004-2005
International Ophthalmology
Section 13:
13.8
2004-2005
Refractive Surgery
Section 14:
14.8
2004-2005
Master INDEX
INDEX
15.8
)(T.A. Casey, K.W. Sharif
16.8 A Color Atlas of CORNEAL DYSTROPHIES & DEGENERATIONS
)17.8 A Color Atlas of UVEITIS (J. Michelson) (Second Edition
)18.8 A Practical Guide to Minimal Surgery for Retinal Detachment (Ingrid Kreissig
2001
)19.8 Atlas of Clinical Oncology Tumors of the Eye and Ocular Adnexa (American Cancer Society) (Devron H. Char, MD
CD :
4- ORBITAL TUMORS
3- RETINAL AND OPTIC NERVEHEAD TUMORS
2- UVEAL AND INTRAOCULAR TUMORS
1- LID AND CONJUNCTIVAL TUMORS
)20.8 ATLAS OF OPHTALMOLOGY (RICHARD K. PARRISG II) (CD I , II) (Mosby
)21.8 ATLAS OF OPHTHALOMOLGY (SUE FORDRONALD MARSH) (Mosby
2003

text CD .
Search Case .
Practice Case .
)22.8 Basic and Clinical Science Course Retina and Vitreous (Section 12) (American Academy of Ophthalmology) (SALEKAN E-BOOK
23.8 Basic Ophthalmology
Physiology of the Eye
)24.8 OPHTHALMOLOGY (Myron Yanoff.Jay S. Duker) (Mosby

CD . 25.8
CD
)Cataract Surgery & Intraocular Lenses (Second Edition) (Jerry G. Ford, Carol L. Karp
Clinical update course on Retina
26.8
27.8
CD CD (Lifelong education for the ophthalmologist) LEO ) (AAO Lecture

. CD endophthalmitis macular hole BRVO DR AMD ... .
)28.8 Clinical Update Course on Neuro-ophthalmology (Peter J. Savino, MD, Steven E. Feldon. MD, Barrett Katz, MD, Thmas L. Slamovits, MD
CD Lecture . CD
LTP Perimetry CPC .
2004
)29.8 Clinical Orthptics (Second Edition) (SALEKAN E-BOOK
___
)(Scott M. Steidl, Mary Elizabeth Hartnett
2004
30.8 Clinical Pathways in Bitreoretinal Disease
)31.8 Clinical Practice in Small Incision Cataract Surgery (Phaco Manual) (VCD I , II
)(SALEKAN E-BOOK
32.8 Complications in Phacoemulsification
phacosurgen , H. Gimbel H. Fine Phaco .

management .
:
- :
46
33.8 CONTACT LENS COMPLICATIONS Efron Grading Morphs For the clinical assessment of contact lens complications (NATHAN EFRON, PHILIP MORGAN)
1999
34.8
papillary
epithelial microcystes epithelial polymegethism Grading CD

. ... conjunctivitis
Cosmetic Blepharolasty & Facial Rejuvenation (Stephen L. Bosniak, M.D.,)

Dodick
Laser Photolysis (Ultra Small Incision Cataract Surgery) (Jack M. Dodik)
35.8
Journal of Cataract & Refractive Surgery Surgical Cases Provided by Photolysis System Manufacturer
36.8 Diabetes And The Eye (Hamish MA Towler, Julian A Patterson, Susan Lightman) Department of Clinical Ophthalmology Institute of Ophthalmology University College London
2000
. text Fluorescein angiography . diabetic retinopathy CD

. Seff-test CD
37.8 Diagnosing & Treating Computer-Related Vision Problems
__
(Sheedy, Shaw-McMinn)
2000
38.8 DICTIONARY OF VISUAL SCIENCE AND RELATED CLINICAL TERMS (Henry W. Hofstetter, John R. Griffin, Morris S. Berman, Ronald W. Everson)
39.8 Diseas of the Orbit A multimedia Approach (second Edition)
2004
40.8 Duanes Ophthalmology (Foundations of clinical Ophthalmology) (LIPPINCOTT-RAVEN)

41.8 Endoscopic Dacryocystorhinostomy (DCR) Advantages and Indications
42.8 EENT
(David I. Silbert, MD FAAP)
(CD I , II)
Welch Allyn Institute of Interactive Learning
43.8 European Society of Cataract & Refractive Surgeons
ROME
2005
9th ESCRS Winter Refractive Surgery Meeting
44.8 Endoscopic Laser Assisted Lacrimal Surgery (Russel S. Gonnering, MD) (VCD)
. VCD . endoscopic laser

Enucleation
Techniques With MEDPOR Orbital Implant MCP Placement in a Vascularized MEDPOR Implant (VCD) (Charles N. S. Soparker, Peter A. D.)
45.8
Natural Movement For Artificial Eyes With MEDPOR Biomaterial Orbit Implants ans the MEDPOR MPC Motility Coupling Post (VCD) (POREX)
46.8 Orbital Floor reconstruction using MEDPOR surgical implants

MEDPOR
enucleation
CD
MEDPOR
VCD
47.8 MEDPOR Surgical implant CD Motility MCP implant drilling
.
48.8 Essentials of Ophthalmic Lens Finishing
(Clifford W. Brooks)
16.2 Facial Plastic & Reconstructive Surgery
(Terence M. Davidson, MD) (VCD I , II)

FUNDAMENTALS
OF
CORMEAL
TOPOGRAPHY
49.8
artefact . CD
. OSCE CD .
50.8 Glaucoma Basic and Clinical Science Course (Section 10)
2003
(Salekan E-Book)
2000
51.8 Hereditary Retinal Dystrophies (Ulrich Kellner, Markus Ladewing, Christoph Heinrich)
52.8
Highlights of the XVIIth Congress of the ESCRS VIENNA'99

1. Intrastromal Corneal Rings
- :
2. Multifocal IOLs
3. Cataract Technidues
(EUROPEAN SOCIETY OF CATARACT & REFRACTIVE SURGEONS)
4. LASIK: Muopia & Mixed Astigmatism
5. Phakic IOLs
47
53.8 Illustrated Tutorials Clinical Ophthalmology
(Jack J Kansski, Anne Bolton)
54.8 Implantation of AcryFlex Foldable Lens (Surgery Performed by Dr. Jagdeep M Kakadla) (VCD)
55.8 IMPLANTE MEDPOR MANDIBULAR (VCD), (AJL OPHTHALMIC, S.A.)
Highlights of the ASCRS 1995 Annual Meeting
57.8
58.8
59.8
60.8
61.8
62.8
63.8
64.8
Cataract & Refractive Sugery
56.8
Cataract & refractive Surgury Lecture CD

... Robert J. Cionni Roger F. Steinert ouglas D. Koch I.Howard Fine

CD . PRK LASIK Phacoemulsification
LASIK Phaco
.

65.8 IMPROVING SUCCESS IN FILTRATION SURGERY American Academy of Ophthalmology (BRADFORD J. SHINGLETON)
CD . Filstratioh Surgery CD
. Viscocanalostomy Deep Sclerectomy
2000
th
66.8 Incomitant Deviatons (4 edition) a supplement chapter 17 of Pickwell's Binocular Vision Anomalies
... Brown's Duane's rectus

67.8 Intraocular Inflammation and Uveitis
(Section 9)
oblique Comitant CD
. Case
2003
(SALEKAN E-BOOK)
2005
68.8 Lasek, PRK, & Excimer Laser Stromal Surface Ablation (Dimitri T. Azar, Massimo Camellin, Rochard W. Yee)
69.8 LEO Clinical Update Course on Retina (H. Michael Lambert, Charles. Arr, J. Paul Diechert, Mark W. Johnson, James S. Tiedeman)
70.8 LEO Clinical Update Course on Cataract (Stephen S. Lane, MD, Alan S. Candall, MD, Douglas D. Koch, MD, Roger F. Steinert, MD)
71.8 LEO Clinical Update Course on Pediatric Ophthalmology and Strabismus THE AMERICAN ACADEMY OF OPHTHALMOLOGY (American Academy of Ophthalmology)
Lecture ( AAO) ( Lifelong education for the ophthalmologist)LEO CD CD

. ROP CD . M.X.Repka K.W.Wright
72.8 Loeil Prental Endoscopie du Vitre Phaco Chop (VIDEO Media) (Roussat B. Choukroun J, Boscher C, Lebuisson DA, Amar R, Escalas P)
: CD
- Reconnaissance des structures oculaires
- Lors des echographies prenatales
- Possibilites et limites actuelles
Roussat B, Choukroun J (Paris)
- :
- Anatomie endoscopique normale et Pathologique de la base du vitre anterieur

Boscher C, Lebuisson DA, Amar R (paris)
2000
2003
- Le Phaco Chop: Pour que les noyaux durs deviennet un plaisir

Escalas P (Nantes)
48
73.8 Management of Strabismus & Amblyopia A Practical Guide
74.8 Manual of Eye Emergencies Diagnosis & Management
(Second Editon) (John A. Pratt-Johnson, Geraldine Tillson)
2004
(Lennox A. Webb, Jack J. Kanski)
75.8 Manual of Oculoplastic Surgery (Third Edition) (Mark R. Levine)
76.8 MOVIMIENTQ NATURAL PARA EL OJO ARTIFICIAL (VCD), (AJL OPHTHALMIC, S.A.)
77.8 MVP VIDEO JOURNAL OF OPHTHALMOLOGY
78.8 New England Eye Center Imaging in Glaucoma
. OCT SLO . Optic nerve CD

79.8 New England Eye Center Photorefractive Keratectomy (PRK) Course (Helen K. WU, MD, Roger F. Steinert, MD, Michael B. Raizman, MD)
PRK Roger F. Steinert Lecture PRK New England CD

. Patient sclection
80.8 Ocular Pathology (FIFTH EDITION) (MYRON YANOFF, MD AND BEN S. FINE, MD) (Mosby) (SALEKAN E-BOOK)
2002
Basic Principles of Pathology

Congenital Anomalies
Cornea and Sclera
Neural (Sensory) Retina
Orbit
Ocular Melanotic Tumors
Surgical and Nonsurgical Trauma

Nongranulomatous Inflammation: Uveltis, Endophthalmitis, Panophthalmitis, and Sequelae Granulomatous Inflammation.
Uvea
Vitreous
Diabetes Mellitus
Retinoblastoma and Pseudoglioma
Skin and Lacrimal Drainage System

Conjunctive
Lens
Optid Nerve
Glaucoma
81.8 Ocular Syndromes and Systemic Disease (Frederick Hampton Roy) (SALEKAN E-BOOK)
82.8 Ocular Therapeutics Handbook A Clinical Manual (Bruce E. Onofrey, Leonid Skorin.Jr., Nicky R. Holdeman) (SALEKAN E-BOOK)
2004
83.8 Ophthalmic & Facial Plastic Surgery
(Frank A. Nasi., Geoffrey J. Gladstone, Brian G. Brazzo)

84.8 Ophthalmic Lenses & Dispensing (Mo JALIE)
. Refraction Optic CD
85.8 Ophthalmic Surgery: principles and Techniques (BLACKWELL SCIENCE) (SALEKAN E-BOOK)
86.8 Ophthalmology A multimedia tutorial for Primary care physicians and medical students (Robert Johnston FRCOpth, Jonathan Boulton MA MRCP FRCOpth)
87.8 Optometric Practice Management (Irving Bennett) (Second Edition)

88.8 Orbital Floor Reconstruction Using Medpor Surgical Implant
(Joseph M. Serletti, MD, Paul Manson, MD) (VCD)
89.8 PHACO TODAY
(The Latest Development in Phacomulsification and Small Incision Cataract Surgery) (HOWARD FINE, MD)
. phacoemulsfication Incisions Anesthesin I. Howard Fine Lecture CD
.
90.8 Phacoemulsification
Step by Step (Video & Textbook)
(Ric Caesar, Larry Benjamin)
91.8 Phakic Intraocular Lenses (Principles & Practice) (David R. Hardten. MD. FACS, Richard L. Lindstrom, Elizabeth A. David, MD, FACS) (SALEKAN E-BOOK)
2004
92.8 PhcoChop (Mastering Techniques, Optimizing Technology, and Avoiding Complications) (Text & Video clip) (David F. Chang) (CD I, II, III)
2004
- :
49
93.8 Phacoemyulsification Cataract Surgery (Multimedia Oculosurgical Module) (Robert M. Schertzer, David X. Pang, MSE, Luanna R. Bartholomew, PhD) (Mosby)
"Scleral tunnel"
CD . Mosby ( Multimedia Oulosurgical Module) MOM CD CD
. text phacoemulsification
94.8 Physiology of the Eye
Anatomy of the Eye 3-D Tour of the Eye Development of Vision Physics of Light & Color Illusions & Your Vision
95.8 Practical Viewing of the Optic Disc (KATHLEEN B. DIGRE, M.D., JAMES J. CORBETT, M.D.
Common Eye Conditions

2003
Getting Ready-Preparing to View the Opic Disc
What Should I Look for in the Normal Fundus?
Is the Disc Swollen?
Is the Disc Pale?
Amaurosis Fugax and Not So Fugax-Vaxcular Disorders of the Eye
White Spots-What Are They?
Hemorrhage
Pigment
What is That in the Retina?
Macula
Practical Viewing in Children
What to Look for in the Aging
Viewing the Disc in Pregnancy
Practical Viewing of the Optic Disc and Retina in the Emergency Department
96.8 PROVISION INTERACTIVE: Clinical Case Studies (AAO) (Thomas A. Weingeist, MD., ph, D)
97.8 RECONSTRUCCIN DE BASE ORBITAL CON IMPLANTE MEDPOR (VCD), (AJL OPHTHALMIC, S.A.)
98.8 Review of Ophthalmology (Friedman, Kaiser, Trattler)

99.8 Refractive Surgery First interactive Symposium (Marguerite B. McDonald, MD)
2005
(American Academy of Ophthalmology)
Roger F. Steinert Jack T. Holladay : Lecture Manus C. Kraff ASCRS CD CD

.PRK LASIK phacoemulsification . ...
100.8 Refractive Surgery in the new millennium.

101.8 Evolution in LASIK
102.8
LASIK: Customized Ablations and Quality of Vision

Patient Selection LASIK ( AAO) ( Ophthalmology Interactive) CD CD

103.8 RETINA (Stephen J. Ryan, M.D., Thomas E. Ogden, M.D.,)
2000
104.8 Retina and Optic Nerve Imaging (Thomas A. Ciulla, Carl D. Regillo, Alon Harris)
2003
105.8 RETINA LIBRARY
106.8 Retina & Vitneous
Hereditary retinal dystrophies

CD . Case . CD
.
107.8 Refractive Surgery: A Guide to Assessment and Management (Shehzad A Naroo)
108.8 Stereoscopic Atlas of Macular Diseases: diagnosis and treatment (Fourth Edition) (J. Donald M. Gass, M.D.) (Mosby)
109.8 Subjective Refraction: Cross Cylider Technique
110.8 SURGICAL TECHNIQUES WITH MEDPORIMPLANTS AND THE MCP (VCD), (AJL OPHTHALMIC, S.A.)
111.8 ADVANCED CONCEPTS IN CATARACT SURGERY The American Society of Cataract and Refractive Surgery (ASCRS)
112.8
- :
50
)113.8 Clinical Update Course on Glaucoma (Mark B. Sherwood, MD, James D. Brandt, MD, Neil T. Choplin, MD, Joel S. Schuman, MD
)Techniques in CLEAR CORNEAL CATARACT SURGERY OPHTHALMOLOGY Interactive
"Clear cornea" Phacoemulsification Prep & drape intracameral capsulorrhexis Clear cornea setting hydrodissection
2004
Foldable IOL CD Lecture .

)114.8 Technique of Cosmetic Eyelid Surgery (A Case Study Approach) (Joseph A. Mauriello, Jr., M.D.
)115.8 TEXBOOK OF OPHTHALMOLOGY (KENNETH W.WRIGHT
)REVIEW QUESTIONS IN OPHTHALMOLOGY (KENNETHC. CHERN.KENNETH W. WRIGHT
) (CD Print . CD
CD text
text .
.
)116.8 THE FAILING GLAUCOMA FILTER: EARLY IDENTIFICATION & TREATMENT (Bradford J. Shingleton, MD
CD Failing Filtration Surgery Lecture . CD Choroidal tap
.
bleb revision
)(MICHAEL K. SMOLEK, PH. D.
117.8 The Multimedia Atlas of Videokeratography Basics of Map Interpretation
)118.8 The Retina ATLAS ( Yannuzzi,Green) (Mosby
2004
)office & eoffice & emergency rom diagnosis & treatment of eye disease (Derek &. Kunimoto, Kunal D. Kanitkar
119.8 The Wills Eye Manual
)120.8 THE VIDEO ATLAS OF COSMETIC BLEPHAROPLASTY (8 CDs
)121.8 Vitreoretinal Course Bascom Palmer Eye Institute's (William E. Smiddy, Philip Rosenfeld, Patrick E. Rubsamen, Janet L.
)(S.LBosniak
VCD S.LBosniak
... . .
CD CD (Ophthalmology interactive) OI ) (AAO Lecture W.E.Smiddy H.W.Flynn
. CD Macular hole Giant retinal tearDislocated IOLs AMD , ROP Endophthalmitis : ... .
)122.8 VJO Ophthalmology (I, I , III ,) (VCD) (Charles, H. Cozean, James S. Lewis, Richard J. Mackool
)123.8 Wavefront Analysis Aberrometers & Corneal Topography (Benjamin F. Boyd, M.D.,FACS) (SALEKAN E-BOOK
CD

2004
2003
)5 Minute Neurology Consult (SALEKAN E-BOOK) (D. Joanne Lynn

CD . 5-Minute .
. Follow up Medications Management Diagnosis Basics Miscellaneous CD . .
-Neurologic Symptoms and Signs
-Neurologic Diagnostic Tests
-Neurologic Diseases and Disorders
-Short Topics
)55th Annual Meeting March 29-Aprill 5, American Academy of Neurology (HAWAII
2.9
Abnormal Psychology LIVE and interactive tutorial
3.9
1.9
Full text Presentation 2003 .

2000
)(Barlow/Durand's, Durand/Barlow's, Trull/Pharcs
CD - : :
- :
- :
2004
51
)Advanced Therapy of HEADACHE CONQUERING HEADACHE (SECOND REVIED EDITION) An Illustrated Guide to Understanding The Treatment and Control of Headache (Alan M. Rapoport, Fred D. Sheftell
( PDF ) Advanced Therapy of headache (1999 ) Alan rappaport ) Fred sheftell ( Yale ( Newyork . 48
management .
( PDF Conquering headache 1998 2nd edition -
- - - . ( PDF Seminars in Headache mamagement James W.Lance 1996- 1998 . : -
Post traumatic - - .
American Academy of Neurology 2004 Syllabi
4.9
5.9
CD .
Presentation . Java Autorun Search .
:
Stroke
Demyelinating dyorden
Botutinum Toxin Injection

Movement disorders
Bedside Neurology
Clinical EEG
Balance and gaif disorder

Clinical EMG
Seizure and antiepilep drugs

Child Neurology
2005
)Aphasia & Related Neurogenic Language Disorders (Third Edition) (Leonard L. LaPointe, Ph.D.
6.9
2000
)Atlas of Functional Neuroanatomy (Dr. Walter J. Hendelman
7.9
Boehringer Ingelheim Satellite Symposium Interanational Stroke Conference
8.9
)(Phoenix, Arizona
2003
)(An interactive digital atlas designed to assist in learning human neuroanatomy
2004
2002
)(Version 1.52
Medical Multimedia Systems Presents
)(A Primer for Clinicians) (Bryan Bergeron

CD 2. The Movement Disorder Society's Guide to Botulinum Toxin Injections
2005
TM
!Brainiac
9.9
10.9 Case Studies in Genes & Disease
11.9 CD 1. BOTOX Injection Tracking Tool
12.9 Cerebral Palsy Resource Guide for Speech-1-anguage Pathologists
)13.9 Clinical Electromyography Nerve Conduction Studies (Third Edition
)14.9 Clinical Neurology (G David Perkin Fred H Hochberg Douglas C Miller
15.9 Comprehensive Handbook of PSYCHOTHERAPY
)(Florence W. Kaslow, Jeffrey J. Magnavita) (Volume 1-4

: CD I : CD II - ) : CD III (CBT ) (humanistic )(existential
: CD IV
)16.9 Comprehensive Textbook of PSYCHIATRY (Seventh Edition CD-ROM) (Benjamin J. Sadock, MD Virginia A. Sadock, MD) ( LIPPINCOTT WILLIAMS & WILKINS
. . MRI
CD .
. .
- - - - - - - ((Delirium Dementin, -
- - Mood - - Dissociative - - - - Tic -
- Adoption - ) ( ... . .
)17.9 Computational Neuroscience Realistic Modeling for Experimentalists (Erik De Schutter

Introduction to Equation Solving and Parameter Fitting Modeling Networks of Signalling Pathways Modeling Local and Global Calcium Signals Using Reaction-Diffusion Equations Monte Carlo
Methods for Simulating Realistic Synaptic Microphysiology Using Mcell Which Formalism to Use for Modeling voltage-Dependent Conductances? Accuate Reconstruction of Neunal Morphology
Modeling Dendritic Geometry and the Development of Nerve Connections Passive Cable Modeling-A practical Introduction Modeling Simple and Complex Active Neurons Realistic Modeling of Small
- :
52
Neuronal Circuits Modeling of Interactions Between Neural Networks and Musculoskeletal System
18.9 CONTEMPORARY NEUROSURGERY A BIWEEKLY PUBLICATION FOR CLINICAL NEUROSURGICAL CONTINUING MEDICAL EDUCATION (Ali F. Krisht, MD)
19.9 Core Curriculum in Primary Care Psychiatry and Pain Management Section
(Micheal K. Rees, MD, MPH, Robert Birnbaum, MD, PHD, James A.D. Otis)
CCC CD
: ." Current best Standard of therapy"
: Harvard Medical School Robert Birnbaum : Psychopharmacology for primay Care Medicine -
Anxiety disorder- Panic disorder- Social phobia- Specific phobia- Obcessive & Compulsire disorder- PTSD- Generalized Anxiety disorder- Depression-Dysthymia
. ( - - - )- - Boston James A.D. otis : Pain Management -

. CD . . print
20.9 Corel Medical Series Epilepsy (Alan Guberman MD, FRCP (C)) (Professor of Neurology University of Ottawa
Quiz - : . Allan Guberman

. problem based interactive review . Print - Search .
Definitions
Topic index
Epilepsy Notes
Patient & Family information
Epilepsy Case Study
Video
Reference list
Epilepsy Facts
What is Epilepsy
Learning Objectives
2002
21.9 CRANIAL NERVES in health and disease (Second Edition)
. 2002 PDF CD
Problem-oriented . CD animation .
. . ENT
22.9 Critical Decisions in Headache Management
(Giammarco. Edmeads. Dodick)
(SALEKAN E-BOOK)
2002
23.9 CURRENT MANAGEMENT IN CHILD NEUROLOGY (SECOND EDITION) (Bernrd L. Maria, MD, MBA)
Section 1: Clinical Practice Trends
Section 2: The Office Visit
Section 3: The Hospitalized Child
24.9 DICTIONARY OF MULTIPLE SCLEROSIS (Lance D Blumgardt) (Martin Dunitz)

25.9 DISORDERS OF COGNITIVE FUNCTION
(VCD-I)
Severe Amnesic Syndrome: Anterograde and Retrograde Amnesia

Left Spatial Neglect
Broca's Aphasia

Wernicke's Aphasia
Negative Signs of Executive Dysfunction
Basic Mental Status Examination
28.9
Perseverative Verbal Behavior in Amnesia

Eye Movements in Severe Left Spatial Neglect
Lewy Bodies
Semantic Memory Loss

Anosognosia for Hemiparesis
Impaired Verbatim Repetition
Fluctuativng Sensorium in Dementia With

Paraphasias
2002
(VCD-II) (AMERICAN ACADEMY OF NEUROLOGY) (CONTINUUM)
Dysexecutive Syndrome
Prosopognosia and Visual Agnosia
2002
(AMERICAN ACADEMY OF NEUROLOGY) (CONTINUUM)
Disinhibited Behavior
Simultanagnosia
Grasp Response and Imitation Behavior

Optic Ataxia
Positive Signs of Executive Dysfunction

Ocular Apraxia
Progressive Apraxia
2002
(VCD-III) (AMERICAN ACADEMY OF NEUROLOGY) (CONTINUUM)
Token Test for Auditory Comprehension
Confrontation Naming
Finger Constructions
Luria 3-Step Test
Line Cancellation
Gestural Praxis
Electromyography & Neuromuscular Disorders Clinical Electrophysiologic Correlations (David C. Preston, Barbara E. Shapiro)
29.9 EMG Training (Kenneth Ricker, M.D.)
. EMG . TOENNIES
- :
53
. CD Search EMG glossary . Case .
30.9 ENS Teaching Course
. ENS CD
. Title
Dizziness and vesthg

Neurogenetics for Clinicians
Neuroimaging
ICU in Neurology
31.9 EPILEPSY
Clinical Neurophysiology
NeuroSurgery for Neurologist
Neurology of Systemic disease
Movement discords
The Comprehensive CD-ROM
Clinical Neuropathology
Epilepsy
Parkinson's diseane
Neuroplathies
Sleep Disorder
Multiple Sclerosis
Ultrasound in Neurology
Current Treatments Neurology
(Jerome Engel, Jr., M.D., Ph.D., Timothy A. Pedley, M.D.)
Stroke
Muscle disorders
Dementia
1999
Lippincott Williams & Wilkins
. CD imaging . Full text . Epilepsy: A comprehensive textBook CD

. Weblink- Seasch
32.9
Essentials of Clinical Neurophysiology (Karl E. Misulis MD. PhD, Thomas C. Head MD)
33.9
Foundations of NEUROBIOLOGY
34.9
2002
. Self evaluattion CD
. -
- Expansion Module - . -
. Neurobiology CD . play list CD
Foundations of Behavioural Neuroscience
-Neural Communication - Central Nervous system
-Research methods
-Visual System
- Control of movements
Quiz . . glossary , Search .
.
35.9 FUNDAMENTALS OF HUMAN NEURAL STRUCTURE (S. Mark Williams) (Sylvius
36.9 General depression and its pharmacological treatment (Professor Brain Leonard)
TM
2.0)
(VCD)
37.9 Guidelines (American Academy of Neurology) (SALEKAN E-BOOK)

. Offline Salekan E-Book Search Guidline CD
- Brain Injury & Brain Death - Child Neurology
38.9
- Dementia
- Epilepsy
- Headache - Movement Disorders - Multiple Sclerosis
Human Brain Cancer: Diagnostic Decisions (Lauren A. Langford, MD, Dr. med,)
- Neuroimaging
- Neuromuscular
- Stroke and Vascular Neurology
-Technology Assessment
American Medical Association
39.9 ICU Syllabus

PDF ICU Patient Care ICU CD
: . Search
Anemia and blood Transfusion
Hyperghycemia and Ihsulia
Non invasive Ventilation
ARDS
Hypothermia for cardiac arrest
Nutritions
40.9 Interactive Guide to Human Neuroanatomy

Atlas: -Surface Anatomy of Brain
Exam:I -Surface Anatomy of the Brain
2. Vessels and Meninges
Fever Wokup
Liver disease
Pulmonary Embolism
Hemodynamics
Mechanical Vetitation
Renal failure
RARS
Sedation
Sepsis
3. Brain Slices
-The Spinal Cord -The Anatomy Nervous System

-Comprehensive Exam
Weaning
From Mechanical Vetitation
2002
(Mark F. Bear, Barry W. Connors, Michael A. Paradiso)
-Cross-Sectional Anatomy of Brain

-Cross-Sectional Anatomy of the Brain
41.9 InterBRAIN (Martin C. hirsh) (Springer)

1. Gross Anatomy
Ethics
Impaired cognition
Pneumonia
2004
-The Cranial Nerves -The Blood Supply to the Brain
4. Microscopical Sections
5. Functional Systems
42.9 International Symposium ON 10 Years Betaferon
2003
: . MS CD
- :
54
MS
2003
Geomics and Proteomics

BENEFIT BEYOND
MS
MS
Stem Cell Transplant Aggressive MS
Primary Progressive MS
)43.9 Kaplan & Sadock's STUDY SUIDE & SEIF-EXAMINATION REVIEW IN PSYCHIATRY (Seventh Edition) (Benjamin James Sadock
Synopsis ) ( Synopsis .
.
44.9 MANAGE STRESS
CD
2002
)45.9 MANAGING STRESS (Audio CD
CD .
2005
)46.9 Manual of Nerver Conduction Study & Surface Anatomy for Needle Electromyography (Hang J. Lee, Joel A. Delisa) (Fourth Edition
2004
)47.9 Manual of Neurologic Therapeutics (seventh edition
)(Martin A. Samuels, Brigham & Women's Hospital, Harvard Medical School
)(SALEKAN E-BOOK
)(Second Edition
)48.9 Manual of Pain Management (Carol A. Warfield, Hilary J. Fausett
CD . . .
CD . Procedure . HIV
.
-Pain Management
-Common Painful Syndromes
2005
-Understanding pain
-Pain by Anatomic Location
)49.9 Merritt's Neurology (Eleven Edition) (Lewis P. Rowland
)(CD I, II , III , IV
)50.9 Microneurosurgery (M. G. Yasargil) Cassette 1 Aneurysms (VCD) (Thieme AV
2001
)51.9 Migraine Current Approaches To Treatment (Dr. Andrew Dowson
)52.9 Motor Speech Disorders (Joseph R. Duffy, PHD
2002
)53.9 Movement Disorders Society Official Journal of The Movement Disorder Society Published by John Wiley & Sons, Ins VCD (I, II
2002
)54.9 Needle Electromyography (Daniel Dumitru, M.D., PhD.

CD Needle EMG Daniel Dumitru . EMG Video Library . .
EMG Pitfull . Glossary , Search .
1999
)55.9 NEUROANATOMY-3D-Stereoscopic Atlas of the Human Brain (Martin C. Hirsch, Thomas Kramer) (Springer
Gross .
. .
56.9 Neurofunctional Systems 3D
)57.9 Neurological surgery (julian R. Youmans , MD Editor-in-Chief) (Fourth Edition) (Y.O.U.M.A.N.S
2001
)58.9 Neurology (Baker's clinical on CD-ROM
2002
59.9 New Analgesic Options: Overcoming Obstacles to Pain Relief

-References
-Trauma
-Post Op Pain
-OA Pain
-Back Pain -Fibromyalgia
-Pharmacist Answer Sheet
- MD, NP, PA, RN Answer Sheet
25.7 Photographic manual of Regional Orthopaedic and Neurological Tests
CD . . .
:
- :
1998
55
. Test .
Sensitivity/Relialility Scale . .
)60.9 Principles of Neurology (6th Edition) (Raymond D. Adams, M.A., M.D.
61.9 PROFESS
CD International Stroke Conference
Lecture . :
- - . CVA MI - . - II - .
2001
)62.9 Recognizing Extrapyramidal Symptoms (VCD

- and Tardive- Dyskinesia
CD:
2001
- Parkinsonism
- Akathisia
- Clinical Examples of Acute Dystonia
63.9 Rune Aaslid TCD Simulator Version 2.1

TCD Rune Aaslid CD . CD . - -
. : - - - CBF - -
HITS - . CD TCD .
.
)31.7 SPINE implants (CD I , II
: CD I : CD II . Diapasone-hook .
64.9 Stroke
Overview of Stroke: 1. Stroke in Perspective 2. Pathogenesis & Pathophysiology 3. Evaluation & Diagnosis 4. Interventions 5. Thrombolytic Therapy Studies
IV Tissue Plasminogen Activator(t-PA) Studies: 1. Recent Multicenter, IV Streptokinase (SK) Studies
Ultra Rapid Response: 1. Increasing Public/Professional Awareness 2. Modifying Care Patterns 3. Stroke Care Systems 4. Assessing Critical Resources
Case Studies
1999
)65.9 TEXTBOOK of CLINICAL NEUROLOGY (Christopher G. Goetz, MD, Eric J. Pappert, MD) (W.B. Saunders Company
2005
)66.9 Textbook of CRITICAL CARE (Salekan E-book
SECTION I RESUSCITATION AND MEDICAL EMERGENCIES

SECTION II TRAUMA
SECTION III IMAGING
SECTION IV CELL INJURY AND CELL DEATH
SECTION V INFECTIONS DISEASE
SECTION VI ENDOCTINOLOGY, METABOLISM, NUTRITION, PHARMACOLOGY
SECTION VII CARDIOVASCULAR
SECTION VIII PULMONARY
TM
)Atlas of Brain Anatomy An interactive tool for students, teachers, and researchers (Wieslaw L. Nowinski, A. Thirunavuukarasuu, R. Nick Bryan
67.9 The Cerefy
68.9 The Clinical Atlas of Parkinson's Disease
MRI .
Grid . interactive . Glossory
. CD - - - .
)(D.J. Nicholl & A. Williams
)69.9 The Clinical Diagnosis of Alzheimer's Disease (An Interactive Guide for Family Physician
Alzheimer disease group RiverView . Flowchart
. :
Case Studies
)(Marion Hall David Robinson
70.9 THE HUMAN BRAIN
)71.9 THE HUMAN NERVOUS SYSTEM (Springer
- :
56
72.9 The Massachusetts General Hospital Handbook of Pain Management (Second Edition)
(Jane Ballantyne, Scott M. Fishman, Salahadin Abdi) (SALEKAN-E-book)
I. General Considerations
II. Diagnosis of Pain
III. Therapeutic Options: Pharmacologic Approaches
IV. Therapeutic Options: Nonpharmacologic Approaches
V. Acute Pain VI. Chronic Pain
VII. Pain Due to Cancer
VIII. Special Situations
- Apendices
- Subject Index
2002
73.9 The Movement Disorder Society's Guide to Botulinum Toxin Injections
. . . : CD
. - - - - .
. Search : CD
. CD . CD PDF .
74.9 The Washington Manual Survival Guide Series Neurology Survival Guide
(Dave A. Rengachary, Tammy L. Lin, Daniel M. Goodenberger)
2001
75.9 Thinking a head (Critical question in ms therapy)
Video CD Collection
The John Hopkins

Neuroradiology Review
76.9
VCD 1.1: Neuroradiology Practice Techniques

VCD 1.2: MR Spectroscopy Techniques
VCD 1.3: Oral Cavity
VCD 2.1: I- Oral Carity
VCD 2.2: I- Extramucosal Spaces (Suprahyoid)
VCD 3.1: I- Head and Neck Case Review
VCD 3.2: I- Stroke Imaging (CT, CTA, CTP)
VCD 5.1: I- Spinal Interventions
VCD 5.2: I-Temporal Bone External and Middle Ear
VCD 6.1: I-Orbit
VCD 6.2: Spaces of the Neck (Infrahyoid)
VCD 6.3: Head and Neck Case Review
VCD 7.1: I- Cancer of the Nesopharynx
VCD 7.2: I- Brain (Molecular Imaging
VCD 8.3: I- Demyelinating Disorders
VCD 8.4: I- Carotid Imaging (part 1)
VCD 9.1: I- Pediatric Brain Tumors
VCD 9.2: Carotid Imaging (part2)
VCD 9.3: Brain Case Review
VCD 10.1: Anatomy and DJD Spine
VCD 10.2: Extradural (Non-DJD) Spine Sinus CT
VCD 11.1: I- Intradural Extramedullary Spine
VCD 11.2: I- Intradural Intramedullary Spine
VCD 12.1: I- Spine Case Review
VCD 12.2: New Techniques (Diffusion Tensor Imaging)
VCD 12.3: Functional Imaging
VCD 13.1: Functional Imaging
VCD 13.2: MR Spectroscopic Imaging
VCD 13.3: An overview of 3.0 Tesla Imaging
2004
2002
II- Imaging the Larynx
II- Extraaxial Adult Tumors
II- Vascular Disease
II- AVMS
II- Brain Case Review
II- Irbit
II- Temporal Bone Inner Ear
III- Head and Neck Case Review
II- Brain Case Review

II- Congenital Imaging (part 1)
II- Congenital Imaging (part 2)
II- Pediatric Brain Tumors
II- Hemorrhage/Head Trauma
II- Spine Trauma

II- Spine Infection and Inflammation
77.9 Understanding and Diagnosing Restless Legs Syndrome
. PDF . RLS Foundation CD

. CD
- :
57
-
2004

___

)78.9 101 DEFENSES (How the Mind Shields Ltself) (Taylor & Francis Books

)79.9 A Clinical Guide to PEDIATRIC SLEEP (Diagnosis & Management of Sleep Problems) (Jodi A. Mindell, Judith A. Owens

2004

)80.9 Case Files Psychiatry (Toy, Klamen

...
...
2005
)(Paul R. Carney, Richard B. Berry, James D. Geyer

81.9 Clinical Sleep Disorders
2005
)82.9 Clinical Geriatric Psychopharmacology (Fourth Edition) (Cari Salzman
2002
)83.9 Comprehensive Handbook of Psychotropics (Florence W. Kaslow, Jeffrey J. Magnavita) (Volume 1-4
2005
)84.9 Comprehensive Textbook of Psychiatry (Kaplan & Sadock) (Eighth Edition) (Volume I , II
2004
)85.9 Concise textbook of CLINICAL PSYCHIATRY (KAPLAN & SADOCK
)(Benjamin James Sadock, Virginia Alcott Sadock
___
)86.9 DSM-IV-TR GuideBook the essential companion to the diagnostic & statistical manual of mental disorders (Fourth Edition) (Michael B. First, Allen Frances
) . (DSM-IV-TR DSM-IV-TR
.

___
)87.9 Handbook of SLEEP MEDICINE (John M. Shneerson

...
)Principles & Practice (Antony Ryle & Lan B Kerr
___
-
2004
) (CAT CAT
88.9 Introducing Cognitive Analytic Therapy
CAT
)89.9 Neurological and Neurosurgical Intensive Care (Allan H. Ropper, Daryl R. Gress, Michael N. Diringer) (Fourth Edition
___
)90.9 Pocket Guide to the ICD-10 Classification of Mental & Behavioural Disorders (Compilation and editorial arrangements by JE Cooper
ICD WHO )(DCR-10
___
)91.9 Practical Guides in Psychiatry Consultation Liaison Psychiatry (Michael Blumenfield, Maria L.A. Tiamson
- . - ) (C-L Psychonephrology, Psychocardiology
...
2005
)92.9 Psychiatry: 1200 Questions To Help Youpass the Boatds (Salekan E-Book
)(A Practitioner's Guide) (Naney MeWilliams
2004

93.9 Psychoanalytic Psychotherapy
___
94.9 Quick Reference to the Diagnostic Criteria from DSM-IV-TR Published by the American Psychiatric Association Washington, DC
) -(APA )(DSM-IV-TR
___
)95.9 Social Skills Training for Schizophrenia A Step-by-Step Guide (Alan S. Bellack, Kim T. Mueser, Susan Gingerich, Julie Agresta
. .
...
2003
)96.9 Study Guide & Self-Examination Review in Psychiatry (Kkaplan & Sadock) (Seven Edition
comprehensive Synopsis Synopsis
- :
58
97.9 SUBSTANCE ABUSE (A Comprehensive Texbook) (Fourth Edition) (Joyce H. Lowinson, Pedro Ruiz, Robert B. Millman, John G. Langrod) (CD I , II)
. ( ... )
2005
98.9 The American Psychiatric Publishing Textbook of Consultstion Liaison Psychiatry (Second Edition) (Michael G. Wise, James R. Rundell)
- . . (C-L) -
.( ... )
___
99.9 The many Faces of Mental Disorders (Adult Case Histories According to ICD-10)
. ICD-10
.
___
CD

2003
1.10 (AGA Postgraduate Course) A Day and Night in the Life of a Gastroenterologist
Esophagus and Stomach Liver Pancreas and Biliary Tract

2.10 3DClinic (Version 1.0) Seeing is Understanding
Nutrition
GI Malignancy
Small Bowel and Colon
Clinical Challenge Sessions

___
Desktop ( 2D Clinic) Icon . Restart .( SN: BI-B25600000-131) CD QTS Autorun

-Cardiovascular - . . .
3D . Disorder Healthy Gastrointestinal -Musculoskeletal -Respiratory -Nervous -Urinary -Sensory -Endocrine -Lymphatic -Skin
.
. .
3.10 Adult Airway Management Principles & Techniques American Association (afael A. Ortega, M.D., Harold Arkoff, M.D.)
4.10 Advanced Therapy of INFLAMMATORY BOWEL DISEASE (Theodore M. Bayless, MD, Stephen B. Hanauer, MD)
5.10 AGA Postgraduate Course CONTROVERSIES And CLINICAL CHALLENGES in Pancreatic Diseases
2001
(An Intensive Two-Day Course Covering A Diversity of Topics Related to the Pancreas)
6.10
-Expanded Content
-Includes Results of the Q&A
-Section Challenge Sessions
Atlas of GASTROINTESTINAL in Health and Disease (Marvin M. Schuster, Michael D. Crowell, Kenneth L. Koch)
Part 1: Physiologic Basis of Gastrointestinal Motility

Part 2: Motility Test for the Gastrointestinal Tract
Atlas
of
GASTROINTESTINAL
MOTILITY
in
Health
and
Disease
(Second Edition)
7.10
2002
(Marvin M. Schuster, MD, FACP, FAPA, FACG, Michael D. Crowell, PhD, FACG, Kenneth L. Koch, MD)
Part I: Physiologic Basic of Gastrointestinal Motility
Part II: Motility Tests for The Gastrointestinal Tract

American Cancer Sosiety (Raphael E. Pollock, MD, Phd)
9.10 Atlas of Clinical Oncology Cancer of the Lower Gastrointestinal Tract (Christopher G. Willett, MD)
nd
10.10 Atlas of Clinical Rheumatology (2 Edition) (David J. Nashel, Chief, Rheumatology Section Va Medical Center, Washington, Professor of Medicine Georgetown University)
2002
2001
11.10 Atlas of INTERNAL MEDICINE (Eugene Braunwald)
12.10 CANCER Principles & Practice of Oncology
8.10 Atlas of Clinical Oncology Soft Tissue Sarcomas
1. Clinical Atlas of Rheumatic Diseases

2. Radiograph Intrerpretation Instructional Module
- :
3. Physical Examination
4. Procures
5. Physical Findings Instructional Module Radiography

6. Aspiration/Injection Instructional Module
(6th Edition) (Vincent T. DeVita, Jr., Samuel Hellman, Steven A. Rosenberg)
59
13.10 Case Studies in GASTROENTEROLOGY (Second Edition) (Ingram Roberts, MD)
14.10 CD-ATLAS OF DIAGNOSTIC ONCOLOGY
15.10 Clinical Endocarinology
(G. Michael Besser MD, DSc, FRCP, Michael O. Thorner MB BS, DSc, FRCP)
Adrenals
Gonads
Growth
Hormone Assay
Imaging Techniques
Pancreas
Ectopic Humoral Syndromes Gastrointestinal Tract Lipids and Lipoproteins Thyroid & Parathyroide Pituitary and Hypothalamus
16.10 Clinical Immunology PRINCIPLES AND PRACTICE (Second Edition) (Robert R Rich, Thomas A Fleisher, William T Shearer, Brain L Kotzin, Harry W Schroeder)
: . Rich Clinical Immunology
-
- - -
-
-
-
( Slide vision ) drag & drop . Search .

. Slide vision Autorun . .
17.10 CLINICAL ONCOLOGY (Raymond E. Lenhard, J. MD, Robert T. Osteen, MD, Ted Gansler, MD)
2001
18.10 Clinician's Guide to Laboratory Medicine (Saml, P. Desai, MD)
2004
19.10 Colonoscopy New Technology & Technique (CB Williams, JD Waye, Y Sakai)
20.10 Color Atlas & Text of Pulmonary Pathology
2005
(Philip T. Cagle, MD)
2000
21.10 Comprehensive Clinical Endocrinology G. Michael Besser MD, DSc, FRCP, Michael O. Thorner
Hypothalamus and Pituitary, Thyroid, Adrenal, Control of Blood glucose and its disturbance, gonad and growth, General conditions-basic, General conditionsclinical, Imaging, Patient Perspectives on endocrine Diseases
22.10 COMPREHENSIVE MANAGEMENT OF Chronic Obstructive Pulmonary Disease (Jean Bourbeau, MD, MSc, FRCPC, Diane Nault, RN, MSc, Elizabet Borycki)
2002
23.10 Core Curriculum in Primary Care Metabolic Diseases Section
. Harvard CD CCC
. . CD
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24.10 Critical Diagnostic Thinking in Respiratory Care A Case-Based Approach
(James K. Storier, Eric D. badow, david L. longworth)
25.10 Differential Diagnosis (Seventh Edition) (LC Gupta Abhitabh Gupta Abhishek Gupta) (Salekan E-Book)
-Common Signs and Symptoms -Causes
-Differentiating Tables -Essentials of Diagnosis
-Staging of Diseases
-Syndromes
-Synonyms
-Investigations
2005
26.10 Digestive Diseases
Self-Education Program
27.10 Diseases of the Liver
(8th Edition) (Lippincott Williams & Wilkins)
General Considerations
Autoimmune Liver Disease
The Liver in Pregnancy and Childhood
28.10 ESAP
(A Core Curriculum and Self-Assessment in Gastroenterology and Hepatology)
The Consequences of Liver Disease

Alcohol and Drug-Luduced Disease
Infections and Granulomatous Disorders
(Endocrinology Self-Assessment Program)
The Cholestasis Disorders

Genetic and Metabolic Disease
Transplantation
Viral Hepatitis
Vascular Disease and Trauma
Benign and Malignant Tumors
Immunology of Liver
(Clark T. Sawin, MD, Kathryn A. Martin, MD) (The Endocrine Society)
29.10 Evidence-Based Asthma Management PATHOPHYSIOLOGY/DIAGNOSIS/MANAGEMENT (7 edition)

. Evidence-Based in medicin
. .
TH
- :
2003
2001
60
: .
1. Natural History and Epidemiology
2. Diagnosis
3. Role of Childhood Infection
4. Management of Persistent Asthma in Childhood
5. Use of Theophylline and Anticholinergic Therapy
6. Leukotriene Modifiers
7. Acute Life-Threatening Asthma
8. Role of Asthma Education
30.10 EVIDENCE-BASED DIABETES CARE
9. Genetics of Asthma
10. Role of the Outdoor Environment
11. Diagnosis and Management of Occupational Asthma
12. Mechanisms of Action of 2-Agonists and Short-Acting 2 Therapy
13. Environmental Control and Immunotherapy
14. Alternative Anti-inflammatory Therapies
15. Management of Asthma in the Intensive Care Unit
16. Asthma Unresponsive to Usual Therapy
17. Cellular and Pathologic Characteristics

18. Role of Indoor Aeroallergens
19. Principles of Asthma Management in Adults
20. Role of Long-Acting 2-Adrenergic Agents
21. Role of Inhaled Corticosteroids
22. Exercise-Induced Bronchoconstriction
23. Severe Acute Asthma in Children
24. Measures of Outcome
2001
(Hertzel C. Gerstein, MD, R. Brain Haynes, MD,)
1- EVIDENCE
2- DEFINITION AND IMPORTANCE OF DIABETES MELLITUS
4- PREVENTION AND SCREENING FOR DIABETES MELLITUS
3- ETIOLOGIC CLASSIFICATION OF DIABETES

5- LONG-TERM CONSEQUENCES OF DIABETES
6- DELIVERY OF CARE
2001
31.10 EVIDENCE-BASED Diagnosis: A Handbook of Clinical Prediction Rules (Mark Ebell, MD, MS) (Springer-Verlag)
-Cardiovascular Diseases -Endocrinology -Gastroenterology -Gynecology and Obstetrics -Hematology/Oncology

-Musculoskeletal -Neurology -Pulmonary Diseas -Renal Disease -Surgery and Trauma
32.10 First Principles of Gastroenterology
-Infectious Disease
The basis of disease & an approach to management (5th edition) (A.B.R. Thomson, E.A. Shaffer)
2000
33.10 Gastric Cancer Diagnosis and Treatment (An interactive Training Program) (J.R. Siewert, D.Kelsen, K. Maruyama) (Springer)
34.10 Gastroenterology
Endoscopy (2nd Edition)
2002
th
35.10 Gastrointestinal and Liver Disease Pathophysiology/Diagnosis/Management (7 edition) (Sleisenger & Fordtran's)
Esophagus
Pancreas
Liver
Biliary tract
Nutrition in gastroenterology
Approach to patients with symptoms and signs
Topics involving multiple organs

Small and Large Intestine
Biology of the Gastrointestinal Tract and Liver

Vasculature and Supporting Structures
Stomach and duodenum

Psychosocial
36.10 HARRISON'S 15 McGraw-Hill presents
37.10 Linear ECHO ENDOSCOPY Tome I anatomy (Dr. Marc Giovannini)

38.10 Management of Patients with
-Equipment
-Environment
-Echo-anatomy
Viral Hepatitis from the state of the Artto Real Life (Patrick Marcellin)
39.10 Menopausal Osteoporosis (Neill Musselwhlte, M.D., Herman Rose, M.D.)
-
-
Impact of osteobrosis -
40.10 MKSAP 12 (American College of Physiciance-American Sosiety Internal Medicine)
: CD
-
-
-
-Gastroenterology and Hepatology - Endocrinology and Metabolism -Infectious Disease Medicine - Rheumatology
-Neurology
- Dermatology - Nephrology -Hospital-Based Medicine and Critical Care
- Oncology
- Hematology
- Cardiovascular Medicine
2001
- Pulmonary Medicine
- Ambulatory Medicine
41.10 Oxford Textbook of Medicine (OTM) (Weatherall, Ledingham, Weatherall)
. CD .
: . .
. . . .
. . CD
. CD .
- :
61
. CD ) ( .
42.10 Parenting Guide
43.10 Pre-Colonoscopy Education Program (Dr. Michael Shaw, Dr. Oliver cass Dr. James Reynolds Patricia Tomshine, Rn)
- Reason for Colonoscopy
- The Colon and The Colonoscope
- Preparations - Day of the Procedure
- About the Procedure -After the Procedur - Minor Complicaions
- Major Complications
th
44.10 Reproductive Endocrinology Physilogy, Pathology & clinical management) (4 edition) (Yen, Jaffe, Barbieri)
45.10 Rheumatology (John H. Klippel.Paul A Dieppe)
-Rheumatic Diseases
-Regional Pain Problems
-Signs and Symptoms

-Connective Tissue Disorders
46.10 TEXTBOOK OF Gastroenterology (Third Edition)
-Rheumatoid Arthritis and Spondylopathy

-Disorders of Bone, Cartilage
-Infection and Arthritis

-Management of Rheumatic Disease
ATLAS OF Gastroenterology (Second Edition) (David H. Alpers, MD, Loren Laine, MD)
2001
47.10 Textbook of Rheumatology (Kelley's) (W.B. Saunders Company)

Section I BIOLOGY OF THE NORMAL JOINT
Section III EVALUATION OF THE PATIENT
Section V DIAGNOSTIC TESTS AND PROCEDURES
Section VII CLINICAL PHARMACOLOGY
Section IX SPONDYLOARTHROPATHIES
Section XI VASCULITIC SYNDROMES
Section XIII STRUCTURE, FUNCTION, AND DISEASE OF MUSCLE
Section XV CRYSTAL-ASSOCIATED SYNOVITIS
Section XVII ARTHRITIS RELATED TO INFECTION
Section XIX DISORDERS OF BONE AND STRUCTURAL PROTEIN
Section XXI RECONSTRUCTIVE SURGERY FOR RHEUMATIC DISEASE
Section II IMMUNE AND INFLAMMATORY RESPONSES

Section IV MUSCULOSKELETAL PAIN AND EVALUATION
Section VI SPECIAL ISSUES
Section VIII RHEUMATOID ARTHRITIS
Section X SYSTEMIC LUPUS ERYTHEMATOSUS AND RELATED SYNDROMES
Section XII SCLERODERMA AND MIXED CONNECTIVE TISSUE DISEASES
Section XIV RHEUMATIC DISEASES OF CHILDHOOD
Section XVI OSTEOARTHRITIS, POLYCHONDRITIS, AND HERITABLE DISORDERS
Section XVIII ARTHRITIS ACCOMPANYING SYSTEMIC DISORDERS
Section XX TUMORS INVOLVING JOINTS
48.10 Textbook of TRAVEL MEDICINE and HEALTH (Herbert L. Dupont, M.D., Robert Steffen, M.D.) (B.C.DECKER INC)
. . Steffen Dupont .
. CD . . . .
57.9 The Massachusetts General Hospital Handbook of Pain Management (Second Edition) (Jane Ballantyne, Scott M. Fishman, Salahadin Abdi) (SALEKAN-E-book)
: CD
I. General Considerations
II. Diagnosis of Pain
III. Therapeutic Options: Pharmacologic Approaches
IV. Therapeutic Options: Nonpharmacologic Approaches
V. Acute Pain VI. Chronic Pain
VII. Pain Due to Cancer
VIII. Special Situations
- Apendices
- Subject Index
49.10 UEGW Gastroenterology Week 10th United European (Geneva, Switzerland)
2003
50.10 UEGW IBS: Management not myth

1. IBS: the clinician's view
2. IBS: care, cost and consequences
: CD
3. Diagnosis: identigy, Probe, eliminate
51.10 Upper GI Endoscopy An Interactive Aducasional Program
4. Tegaserod: a world of experience
5. Chairman's summary
Video Segments of Common Pathologics of the Upper Gl tract (Iencludes Educational text)
52.10 UpToDate CLINICAL REFERENCE LIBRARY 13.3 (CD I , II) (Burton D. Rose, MD, Joseph M. Rush, MD)
2005
: CD
Adult Primary Care Allwrgy and Immonology Cardiology

Critical Care
Drug Information Enodcrinoology Family Medicine Rheumatology
Women's Health
Gastroenterology
Gynecology
Hematology Infections Disease
Nephrology
Oncology
Pediatrics
Pulmonology
53.10 YEAR BOOK of RHEUMATOLOGY, ARTHRITI, AND MUSCULOSKELETAL DISEASE

Health Sciences, Epidemiology, Economics, & Arthritis Care
- :
TM
(Richrd S. Panush, MD) (SALEKAN E-BOOK)
2003
Systemic Lupus Erythematosus and Related Disorders
62
Rheumatoid Arthritis
Vasculitis and Systemic Rheumatic Diseases and Other Related Disorders
Systemic Selerosis and Related Disorders
Osteoarthritis, Crystal-Related Arthropathies, Osteoporosis, Infectious Arthritides, and Spondyloarthropathies
Regional Pain Syndromes, Non-Articular Musculoskeletal Disorders, and Fibromyalgia
Miscellaneous Topics
54.10 Critical Care Clinics Infections in Critical Care I & II (W.B. Saunders)
55.10 Differential Diagnosis of Infectious Diseases
56.10 Infectious Disease Pathology
(David Schlossberg, Jonas A. Shulman)
(Clinical Cases) (Gail l. Woods, Vicki, Schnadig, David H. Walker)
57.10 Infectious Disease Secrets (Second Edition) Questions & Answers Reveal the Sectet to the Diagnosis & Management of Infectionus Diseases (Robert H. Gates)
58.10 INFECTIOUS DISEASES
(W Edmund Farrar, Martin J Wood, John A Innes, Hugh Tubbs)
The Head and Neck

The Urinary Tract
Vira, Fungal and Ectoparasitic Infections
Lower Respiratory Tract

The Genital Tract
The Eye
The Nervous System

Bones and Joints
Systemic Infections
The Gastrointestinal Tract

The Cardiovascular System
HIV Infection and Aids
The liver and Biliary Tract

Bacterial Infections
Acknowledgements
59.10 Infectious Diseases Handbook Diagnostic Medicine Series (Carlos M. Isada, Bernard L. Kasten, Morton P. Goldman) (5th Edition)
60.10 Manual of Clinical Problems in Infectious Disease (Nelson M. Gantz, Richard B. Brown)
61.10 Principles & Practice of Infectious Diseases
2000
A Harcourt Health Sciences Company
: CD . . CD
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62.10 The Washington Manual INFECTIOUS DISEASES Subspecialty consult
(Richard Stalin)
CD
1.11 A Major Contributor to Neonatal Infant Morbidity and Mortality (SURVANTA) (Part I , II) (Alan J. Gold, MD, J. Harry Gunkel, Arvin M. Overbach)
2.11 Atlas of Pediatric Gastrointestinal Disease
3.11 AVERY'S DISEASES OF THE NEWBORN (EIGHTH EDITION) (H. William Taeusch, M.D., Roberta A. Ballard, M.D., Christine A. Gleason, M.D.) (CD I, II)
4.11 Basic Mechanisms of Pediatric Respiratory Disease (Second Edition) (Gabriel G. Haddad,MD, Steven H. Abman, MD)
Genetic and Developmental Biology of the Respiratory System
Developmental Physiology of the Respiratory System
2002
Structure-Function Relations of the Respiratory System During Development

Inflammation and Pulmonary Defense Mechanisms
5.11 Care of the Newborn: A Handbook for Primary Care (David E. Hertz, MD)
6.11 Care of the Sick Neonate (A Ouick Reference for Health Care Providers)
7.11 Child Development, 9/e (John W. Santrock)
- :
2005
(Paulette S. Haws, MSN, RNC)
2005
2004
2001
8.11
18.9
63
Clinical Use of Pediatric Diagnostic Tests (Enid Gilbert-Barness, M.D, Lewis A. Barness, M.D., Philip M. Farrell, M.D.)
CURRENT MANAGEMENT IN CHILD NEUROLOGY (SECOND EDITION) (Bernrd L. Maria, MD, MBA)
Section 1: Clinical Practice Trends

Section 2: The Office Visit
Section 3: The Hospitalized Child
9.11 EVIDENCE-BASED PEDIATRICS (William Feldmam, MD, FRCPC) (B.C. Decker Inc.)
10.11 HANDBOOK A Manual for Pediatric House Officers (Jason Robertson, MD, Nicole Shilkofski, MD)
11.11 Nelson TEXTBOOK OF PEDIATRICS (17th Edition) (CD I, II, II)
12.11 Neonatal and Pediatric Pharmacology Therapeutic Principles in Practice (Third Edition) (Sumner J. Yaffe, MD, Jacob V. Aranda, MD)
13.11
14.11
15.11
16.11
17.11
Nutrition in Pediatrics (W. Allan Walker, John B. Watkins, Christopher Duggan)

Oski's Essential Pediatrics (Michael Crocetti, M.D., Michael A. Barone, M.D.,) (Second Edition)
PEDIATRIC GASTROINTESTINAL DISEASE Pathophysiology . Diagnosis . Management (Third Edition)
TEXTBOOK OF NEONATAL RESUSCITATION (4TH EDITION MULTIMEDIA CD-ROM)
THE HARRIET LANE HANDBOOK (Seventeenth Edition) (Jason Robertson, MD Nicole Shilkofski, MD) A Manual for Pediatric House Officers
2003
2002
2000
2005
2004
2005
2004
2005
:
CD
1.12 1. Review for USMLE NMS (Step 1)

2. Review for USMLE NMS (Step 2)
3. Review for USMLE NMS (Step 3)
2.12 A.D.A.M. PracticePractical Review Anatomy Create New Test Open Existing Test
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3.12
Atlas of Clinical Medicine
4.12
Infection
Cardiovascular Renal
Joints and Bones Respiratory
Endocrine, Metabolic and Nutritional
CECIL TEXTBOOK of MEDICINE (21st Edition)
(Version 2.0) (Forbes. Jackson)
Gastrointestinal
Liver and Pancreas
Blood
Nerve and Muscle
2001
Part I MEDICINE AS A LEARNED AND HUMANE PROFESSION

Part II SOCIAL AND ETHICAL ISSUES IN MEDICINE
Part III AGING AND GERIATRIC MEDICINE
Part IV PREVENTIVE HEALTH CARE
Part V PRINCIPLES OF EVALUATION AND MANAGEMENT
Part VI PRINCIPLES OF HUMAN GENETICS
Part VII CARDIOVASCULAR DISEASES
Part VIII RESPIRATORY DISEASES
Part IX CRITICAL CARE MEDICINE
Part X RENAL AND GENITOURINARY DISEASES Part XI GASTROINTESTINAL DISEASES
Part XII DISEASES OF THE LIVER, GALLBLADDER, AND
BILE DUCTS
Part XIII HEMATOLOGIC DISEASES
Part XIV ONCOLOGY
Part XV METABOLIC DISEASES
Part XVI NUTRITIONAL DISEASES
Part XVII ENDOCRINE DISEASES
Part XVIII WOMEN'S HEALTH
- :
64
Part XX DISEASES OF THE IMMUNE SYSTEM
Part XXII INFECTIOUS DISEASES
Part XXIV DISEASES OF PROTOZOA AND METAZOA
Part XXVI EYE, EAR, NOSE, AND THROAT DISEASES
Part XXVIII LABORATORY REFERENCE INTERVALS AND VALUES
2003
XIX DISEASES OF BONE AND BONE MINERAL METABOLISM

XXI MUSCULOSKELETAL AND CONNECTIVE TISSUE DISEASES
XXIII HIV AND THE ACQUIRED IMMUNODEFICIENCY SYNDROME
XXV NEUROLOGY
XXVII SKIN DISEASES
Part
Part
Part
Part
Part
BEST MEDICAL COLLECTION
5.12
CD . :
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Clinical Examination
Nervous system
Male genitalia
Heart & cardiovascular system
Respiratory system
Skin, nails & hair
Infants & children
Bones, joints & muscle
Abdomen
Femal breast & genittalia
Ear, nose & throah
CMDT CURREAT Medical Diagnosis & Treatment
Endoscopic Assessment of Esophagitis According to the Los Angeles Classification System
y Viewing Area 1 :Slide Viewer 2: Slide Gallery 3:Video Gallery
3: Complicatins
2: Los Angeles Classification
2: On Endoscopic Assessment of Esophagitis
2002
1: Mucosal Break
y Definitions
1: International Working Group
y Quiz
GRIFFITH'S 5-MINUTE CLINICAL CONSULT
6.12
7.12
8.12
9.12
CD ` ENT .... .
. . CD ) ( .
. :
1- BASICS
Description
Genetics
Prevalence
Age
Signs and symptoms
Causes
Risk factors
2- DIAGNOSIS
Differential
Laboratory
Pathological findings
Special tests
Imaging
3- TREATMENT
Genral measures
Surgical measures
Activity
Diet
Patient education
4- MEDICATION
Drugs of choice
Contraindications
Precautions
Interactions
Alternate drugs
5- FOLLOW-UP
Monitoring
Prevention
Complications
Prognosis
6- MISCELLANEOUS
Associated conditions
Age-related factors
Pregnancy
Synonyms
ICD-9-CM
See also
Other notes
Abbreviations
References
- :
65
)10.12 HEALTH ASSESSMENT (Gaylene Bouska Altman, RN, Ph.D., Karrin Johnson, RN, Robert W. Wallach, MD
2002
.
: : .
: : ) ( . .
: : Case . ) ( .
.
: C .
.
2000
((Marcus Law & Brain Rotengberg
Review Nots and Lecture Series
11.12 MCCQE
Section Menu:
Anesthesia, Cardiology, Color Atlas, Community Med, Dermatololgy, Diagnostic Imaging, Emergency, Endocrinology, Family Medicinne, Gastroenterology,
General Surgery, Geriatrics, Gynecology, Hematology, Infectious Disease, Nephrology, Neurology, Neurosurgery, Obstetrics, Ophthalmology, Orthopedics, Otolaryngology,
Pediatrics, Plastic Surgery, Psychiatry, Respirology, Rheumatology, Urology
)12.12 Medical Dictionary (Dorland's) (by W. B. Saunders
2000
)13.12 MEDICAL Encyclopedia For Health Consumers (With Atlas

TM
)(The Best Internal Medicine Board Review
14.12 MedStudy
2000
4. The Most Talked About
3. The Most Effective
2. The Most Powerful
1. The Most Board Specific
2002
)15.12 Natural Medicine Instructions for Patients (Lara U. Pizzorno, Joseph E. Pizzorno, Jr, Michael T. Murray
2002
16.12 Patient Teaching Aids

. .
Print . . Search
. Tapic .
)(Third Edition
2002
)17.12 Practical General Practice (Guidelines for effective clinical management) (Alex Khot, Andrew Polmear
)18.12 RAPID REVIEW FOR USMLE STEP 1 (Mosby
y Anatomy y Behavioral Science y Biochemistry y Histology/Cell Biology y Microbiology/Immunology y Neuroscience y Pathology y Pharmocology y Physiology y Randomize All
Sciences:
2003
19.12 SPSS 12.0 for Windows
2002
)20.12 Textbook of Physical Diagnosis HISTORY AND EXAMINATION (Fourth Edition) (Mark H. Swartz, M.D.) (W.B. SAUNDERS COMPANY
21.12 The Basics for Interns
:
-
-
-
-
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2003
) airway Management Apnea hypoxia . . . (

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)22.12 The MERCK MANUAL of Medical Information (Second Edition) (Mark H. Beers, MD) (CD I , II) (Salekan E-Book
- :
66
23.12 Understanding Lung Sounds (Audio CD)
24.12 UNDERSTANDING PATHOPHYSIOLOGY (Second Edition) (Sue E. Huether, Kathryn L. McCance)
25.12 Virtual Medical Office CHALLENGE (to accompany Bonewit-West Clinical Procedures for Medical Assistants, 5 Edition)
th
(W.B. Saunders Company)
Triage Critical . CaseStudy

: CD .
- Case Study
- Clinical Skills
- Challenge Status
-Help
26.12 Contemporary Nutrition Food Wise (Food Wise, Weight Manager)
2002
27.12 Food Works (College Edition)
___
28.12 INTRODUCTION TO NUTRIOTION AND METABOLISM (Third Edition) (DAVID A Bender)

29.12 Multimedia Workout
2002
(Jeffrey S. Smith, Joseph D. Cook)
30.12 NUTRIENTS IN FOOD (Elizabet S. Hands)
2002
31.12 THE FOOD LOVER'S ENCYCLOPEDIA Culinary Techniques Recipes Nutrition Foods
CD
1.13
A Primer on Quality in the Analytical Laboratory (John Kenkel)
2.13
American DRUG INDEX (FACTS AND COMPARISONS)
3.13
Appleton and Lange's Quick Review PHARMACY
4.13
Basic Concepts in Biochemistry A Student's Survival Guid (Hiram F. Gilbert, Ph.D.) (Second Edition)
5.13
Bioethics for Scientists (Professor John Bryant D. Linda Baggott La Velle, Revd Dr John Searle)
6.13
British Pharmacopoeia (version 6.0)

Vol 1: -Notices -Preface -British Pharmacopoeia Commision -Introduction -General Notices -Monographs: Meidicinal and Pharmaceutical Substances
Vol 2: -Notices -General Notices -Monographs -Infrared Reference Spectra -Appendices -Supplementary Chapters
British Pharmacopoeia (Veterinary): -Preface -British Pharmacopoeia Commission -Introduction -General Notices -Monographs -Infrared Reference Spectra -Appendics
7.13
Characterization of Nanophase Materials (Zhong Lin Wang) (Salekan E-Book)
8.13
Chem Office (Renate Buergin Schaller)
9.13
Chemometrics Data Analysis for the Laboratory and Chemical Plant Richard G. Brereton (University of Bristol, UK)
-Parmaceutics/Pharmokinetics
-Pharmacology
2001
(Twelfth Edition) (Joyce A. Generali, Christine A. Berger)
-Microbiology and Public Health
-Chemistry and Biochemistry
___
-Physiology/Pathology
-Clinical Pharmacy
___
2003
___
10.13 Cleanroom Design (Second Edition) (Second Edition)

th
11.13 CLINICAL DRUG THERAPY Rationnales for Nursing Practice (7 Edition)
-Dosage Calc Challenge!
- :
-Animations
-NCLEX Questions
2002
(ANNE COLLINS ABRAMS) (Lippincott Williams & Wilkins)
-Monographs of 100 Most Commonly Prescribed Drug
-Preventing Medication Errors Video
___
-Patient Teaching Sheets
67
12.13 Common Fragrance and Flavor Materials (Kurt Bauer, Dorothea Garbe, Horst Surburg)
13.13
___
DERIVATIZATION REACTIONS FOR HPLC (Georgelunn, Louise C. Hellwic)
2000
14.13 Dosages and Solutions CD Conpanion (Virginia Daugherty, RN, MSN, Diana Romans, RN, BSN) (Harcourt Health Sciences)
-Mathematics Review
-Introducing Drug Measures
-How to Read a Drug Label
-Calculatin Dosages
DRU
ERUPTION
REFERENCE
MANUAL
(The
Parthenon
Publishing
Group)
(Jerome
Z. Litt, MD)
15.13
Search by:
- Drug Name
-Reactions
-Interactions
-Categories
-Company
-Multiple Search
-Comprehensive Posttest
2004
-Printing
-Common
-Reaciton
___
16.13 DRUG CONSULT (Mosby)

17.13
Drug Identifier
Find Products by: -Drug name
2003
-Imprint
-NDC code
-Manufacturer name
18.13 Drug-Membrane Interactions Analysis, Drug Distribution, Modeling (Joachim K. Seydel, Michael Wiese)
2002
19.13 Encyclopedic Dictionary of Named Processes in Chemical Technology (Ed. Alan E. Comyns)
20.13
European Pharmacopoeia (4th Edition)
___
21.13
FIRE AND EXPLOSION HAZARDS HANDBOOK OF INDUSTRIAL CHEMICALS (Tatyana A. Davletshina Nicholas P. Cheremisinoff, Ph.D.)
22.13 Fluid Flow for Chemical Engineers
(Second edition) (Professor F. A. Holland Dr R. Bragg)
23.13 From Genome To Therapy: Integrating New Technologies with Drug Development
24.13
___
GoodMan and Gilmans's CD-ROM
25.13 Handbook of Solvents
(George Wypych)
26.13
HERBAL MEDICINE Expanded Commission E Monographs (INTEGRATIVMEDICINE)
___
27.13
Herbal Remedy FINDER
___
28.13
HPLC and CE METHODS for Pharmaceutical Analysis
(Version 2.0)
(George Lunn) (John Wiley and ons)
2000
___
Patient Education Guide to Oncology Drugs Name Search Categories Comparisons

(Gail M. Wilkes, RNC, MS, AOCN, Terri B. Ades, RN, MS, AOCN)
30.13 PDQ PHARMACOLOGY (GORDON E. JOHNSON, PHD)
PDR Electronic Library PHYSICIANS DESK REFERENCE (Thomson Medical Economics).
29.13
2002
2004
CD ( PDR, PDQ) .
. ...
2004
31.13 PDR for Herbal Medicines (Third Edition) (David Heber, MD. Phd, Facp, FACN)
32.13
PHARMACOLOGY (Thomas L. Pazderink, Laszlo Kerecsen, Mrugshkumar K. Shah) (Mosby)
33.13 PHYSICANAS' CANCER CHEMOTHERAPHY DRUG MANUAL

- Principles of Cancer Chemotheraphy
- Common Chemotherapy Regimens in Clinical Practice
The Aqueous Cleaning Handbook A Guide to Critical-cleaning Procedures, Techniques, and Validation)
- :
2004
(Jones & Bartlett)
- Physician's Cancer Chemotherapy Drug Manual 2004

- Guidelines for Chemotherapy and Dosing Modifications
- Antimetic Agents for the Treatment of Chemotherapy-Induced Nausea and Vomiting
34.13 The Analysis of Controlled Substances (Michael D. Cole) (Wiley)

35.13
2003
2003
2002
:
36.13
37.13
38.13
39.13
40.13
68
The Constituents of Medicinal Plant (2nd Edition) (An introduction to the chemistry and therapeutics of herbal medicine)
The Herbalist (David L. Hoffman)
THE MERCK INDEX on CD-ROM (Version 12:3)
USP 27-NF 22 Through Supplement Two (U.S. PHARMACOPEIA) (The standard of Quality) (The United States Phamocopeial Convention, Inc)
Workplace Safety Volume 4 of the Savety at Work Series (John Ridley, John Channing)
2004
___
2000
2004
CD
1.14
BUILDING A MEDICAL VOCABULARY (FIFTH EDITION) (FEGGY C. LEONARD) (W.B. Saunders Company)
2001
2.14
ELECTRONIC MEDICAL DICTIONARY (STEDMAN'S) (LIPPINCOTT WILLIAMS & WILKINS)
2001
3.14
English Family (Merriam-Webster)
4.14
Entertainment Collection
5.14
How to Prepare for TOEFL
6.14
Mad About English Spelling (Interactive Learning)
7.14 Medical Information on the Internet (A Guide for Health Professionals) (Second Edition)
Why use the Internet?
Internetive Learning
The future
Appendix D: Configuring TCP/IP
Getting Wired
E-mail, discussion lists and newsgroups
Appendix A: Finding more information information
Appendix E: Glossary
(Robert Kiley)
Finding what you want

The quality issue
Appendix B: Netscape Navigator and Internet
The top ten medical resources

Consumer health information
Appendix C: Optimising your computer
8.14
Preparation For the TOEFL (Dictionary Crossword Puzzle Matching Game)
9.14
Preparing for the GRE Writing Assessment
What does the GRE General Test measure? The GRE General Test is designed to measuregeneral knowledge and reasoning skills in three areas that are important for a academic
Analytical Ability
achievement: Verbal Ability Quantitative Ability
10.14 Speak Fluent Series
11.14 Studying a Study Texting a Test (Fourth Edition) (Richard K. Riegelman)
Accreditation Statement
Designation Statement
Instructions to Users
Target Audience
Lippincott Williams & Wilkins

Test-CME Needs Assessment
Continuing Medical Education

Glossary
CME User assessment

Learning Objectives
Faculty Credentials/Disclosure
12.14 The AMERICAN HERITAGE TALKING DICTIONARY (Daniel Finkel)
13.14 TriplePlayPlus! ENGLISH (Syracuse Languag Systems)
14.14 Users' Guides To The Medical Literature (A manual for Evidence-Based Clinical Practice) (Gordon Guyatt, MD, Drummond Rennie, MD, Robert Hayward, MD)
15.14 Learn To Speak English Dictionary & Grammer
16.14 THE LANGUAGE OF MEDICINE (6
TH
1. Word Ports
(Chapters 1-4)
- :
(CD1-4)
EDITION) (W.B. Saunders Company)
2.Body Systems
(Chapter 5-18)
2002
3. Specialties
2000
(Chapter 19-22)
69
-
CD
1.15 1. Reflux Disease and Nissen Fundoplication (Philip E. Donahue, MD) (VCD)
2. Supraceliac Aortic-Celiac Axix-Superior Mesenteric Artery Bypass (Gregorio A. Sicard, Charles B. Anderson)
2.15 Advanced Therapy in THORACIC SURGERY (Kenneth L. Franco, MD, Joe B. Putnam Jr., MD)
3.15 Aesthetic Department
ARTECOLL: Injectable micro-Implant, for long lasting levelling of facial wrinkles and folds
4.15
American Collage of Surgeons ACS Surgery Principles & Practice (CDI , II)
5.15
6.15
7.15
Aspects of Electrosurgery (Dr. Anthony C. Easty, PhD PEng CCE) Department Medical Engineering
Atlas of RENAL TRANSPLANTATION (Prof. Legndre, Martin, Helenon, Lebranchu, Halloran, Nochy)
Basic Surgical Skills (David A. Sherris. M.D., Eugene B. Kern, M.D.) (Mayo Clinic)
8.15
Cholecystectomy by Laparoscopy (Department of Surgery Hospitalor Saint-Avold France) (VCD)
9.15
Clinical Surgery (Second Edition) (Michael M. Henry, Jeremy N. Thompson)
12.3
Core Curriculum in Primary Care Gynecology (Michael, Isaac Schiff, Keith, Thomas, Annekathryn)
2005
(Salekan E-Book)
(Michael, Isaac Schiff, Keith, Thomas, Annekathryn)
11.15 Core Curriculum in Primary Care Patient Evaluation for Non-Cardiac Surgery and Gynecology and Urology (Michael K. Rees, MD, MPH)
. Harvard CD CCC
. . CD
: . .
Male impotence
.(AUB)
) ( -
. text
12.15 LAPAROTOMY (Royal Society of Medicine in association with Royal College of Surgeons of England) (VCD)
13.15 Lipostructure (Sydncy Coleman, M.D.) (byron) (VCD)
14.15 Lower Body Lift (Abdominoplasty) (Lockwood, M. d., Kansas Gity) (VCD) (CD I , II)
15.15 MALAR AUGMINTATION (CLINICAL MIRASIERRA MADRID)
(Ulrich T. Hinderer Dr. Juan L. Del Rio) (VCD)
16.15 Mammary augmention by High-Cohesive Silicon Gel Implant
(Igar Nicchajev, Goran Jurell)
17.15 Mastery of Endoscopic & Laparoscopic Surgery (Second Edition)

18.15 Nail Surgery
A text & Atlas (Edward A. Krull, Elvin G. Zook, Robert Earan, Eckart Haneke)
19.15 NMS Surgery Tutor
(Dereck Mooney, T. Mack Brown, Cristian Jansenson, Denise Riedlinger)
20.15 Open Repair of Abdominal Wall Hernias Using Prosthetic materials (Arthur I. Gilbert, M.D.)
- :
2005
2000
70
-Small Bowel Obstrution Immediately Following Laparoscopic Herniorraphy (Karl A. Zucher, MD)
-VJGS Case Study: Laparoscopic Loop Ilestomy for Temporary Fecal Diversion (Steven D. Wexner, Petachia Reissman)
-VJGS Consultants Corner: Managed Care Update, Pt, III (Michael A. Wood)
21.15 Plug Repair for Inguinal Hernias
1- First Case: Inguinal Hernia type "Direct"
2- Second Case: Injuinal Hernia type "Indirect"
25.6 Practical MINOR SURGERY

22.15 Principles of Surgery (Eight Edition) (Schwartz's)
Part1: Basic Considerations
2005
(E-Book) (CD I , II)
Part II: Specific Considerations
23.15 SCHWARTZ'S PRINCIPLES OF SURGERY (8th Edition) (F. Charles Brunicardi, Dana K. Andersen, Timothy R. Billiar) (Salekan e-book) (CD I, II)
24.15 Single Puncture Laparoscopic Technique (Marco Pelosi, MD) (VCD)
25.15 Submitted Subject: Transvaginal Sonographic Assessment of Pelvic Pathology: Preoperative Evaluation
26.15 SURGERY (John D Corson, Robin CN Willimson)
-Surgical Principles and Critical Care
-Trauma
(Frances R. Batzer, MD)
(Launching Slide Vision) (Mosby)
-Gastrointestinal surgery
-Vascular Surgery
-Brast and Endoceine Surgery
-Transplantation Surgery
27.15 Surgery of the Liver & Biliary Tract 3e: Selected Operative Procedures (L.H. BLUMGART, Y. FONG)
-Allied Surgical Specialties
(W.B. Saunders)
-Hepatic Procedures
-Biliary Procedures
-Special Procedures
The
Distal
Splenorenal
Shunt:
Effective
or
Obsolete?
(VIDEO JOURNAL OF GENERAL SURGERY) (Layton Fredrick Rikkers, M.D.) (VCD)
28.15
- Options for Treating Portal Hypertension
-HIPS Advantages
2005
-Ideal Candidates for Distal Splenorenal Shunt

-HIPS Disadvantages
2000
-Components of Distal Splenorenal Shunt Procedure

-Distal Splenorenal Shunt Patency
29.15 The Ileana Pull-through Operative Prpcedure of Ulcerative Colitis: Eliminating the Permanent Ileostomy (Eric W. Fonkalseud, M.D.) (VCD)
30.15 The Massachusetts General Hospital Handbook of Pain Management (Second Edition)
- General Considerations
- Acute Pain
- Diagnosis of Pain
- Chronic Pain
- Therapeutic Options: Pharmacologic Approaches

- Pain Due to Cancer
(Jane Ballantyne, Scott M. Fishman, Salahadin Abdi) (SALEKAN-E-book)
- Therapeutic Options: Nonpharmacologic Approaches

- Special Situations
- Apendices
- Subject Index
31.15 TISSUE ADHESIVES In Wound Care (James V. Quinn, M.D., FACEP)
32.15 Tolaryngology Surgery for Fronatal Sinus Disease
33.15
Video Journal General Surgery
(Professor & Chairman, Bobby R. Alford, M.D.) (VCD)
(VCD)
1. Reflux Disease and Nissen Fundoplication (Philip E. Donahue, MD)

2. Supraceliac Aortic-Celiac Axis-Superior Mesenteric Artery Bypass
34.15 Video Journal General Surgery

1.
2.
3.
4.
(Gregorio, Leonardo, Brent, Charles)
(VCD)
Open Repair of Abdominal Wall Hernias Using Prosthetic materials (Arthur I. Gilbert, M.D.)
Small Bowel Obstrution Immediately Following Lapatoscopic Herniorraphy (Karl A. Zucker, MD)
Laparoscopic Loop Ileostomy For Temporary Fecal Diversion (Steven D. Wxner, MD, Petachia Reissman, MD)
Consultants Corner: Managed Care Update, Pt, III (Michael A. Wood)

35.15 Aesthetic Plastic Surgery
36.15 Atlas of Liposuction (Tolbert s. Wilkinson, MD)
- :
(Thomas D. Rees)
(Salekan E-Book)
2005
:
71
37.15 Breast-Augmentation with NovagoldTM
The PVP-Hydrogel Filled Implant
2004
39.15
40.15
41.15
42.15
43.15
44.15
45.15
46.15
47.15
48.15
49.15
COMPREHENSIVE FACIAL REJUVENATION

(A practical and systematic guide to surgical
management of the aging face)
38.15 Case Presentations In Plastic Surgery (Christopher Stone, Consultant Plastic Surgeon)
VCD 1: Rhinophyma (9:52) - Alloderm Lip Augmentation (14:04) - Collagen Injection Sequence
VCD 2: Full-Face Jessners/35% Trichloroacetic Acid Pell (31:21)
VCD 3: Combined Resurfacing Technique for Aone Scarring (10:18)

Botox Reconstitution and Injection Sequence (20:53) - Carbon Dioxide Laser Resurfacing (8:10)
2000
VCD 4: Postoperative Care of the Chemical Peel Patient (31:21)

VCD 5: Transconjunctival Lower-Lid Blepharoplasty (9:05)
Skin-Muscle Flap Lower-Lid Blepharoplasty with Midface Extension (16:20)
VCD 6: Follicular Transfer Hair Transplantation Session (30:20)
VCD 7: Upper-Lid Blepharoplasty (11:25) - Chin Augmentation with Gore-Tex Alloplast (13:21)
VCD 8: Minimal Incision Brow and Midface Lift (31:02)
VCD 9: Primary Facelift (37:17)
VCD 10: Secondary Facelift with Gore-Tex Sling (30:21)
VCD 11: Scalp Reduction Sessions (31:47)
50.15 Facial Rejuvenation Greams, Toxins, Lasers & Surgery (Thomas C Spoor MD, Ronald L Moy MD)
51.15 FACIAL SURGERY Plastic and Reconstructive
52.15 Fundamental Techniques of Plastic Surgery and their Surgical Applications
(10th Edition) (Alan D McGrergo, Ian A. McGregor)
2000
53.15 Plastic and Reconstructive Breast Surgery (Second Edition) (Volume 1 , 2)
54.15 Plastic Surgery (Indications, Operations & Outcomes) (Volume five)
(Bahman Gayuran, MD FACS)
55.15 Structural Fat Grafting (Sydney R. Caleman) (E-book & Film)
2004
56.15 Techniques of Cosmetic Eyelid Surgery
2004
A Case Study Approach (Joseph A. Mauriello, Jr)
57.15 Tissue Glues in Cosmetic Surgery (RENATO SALTZ, M.D., DEAN M. TORIUMI, M.D.)
2004
(Salekan E-Book)
58.15 Transaxillary Augmentation
CD
1.16
2.16
Burkect's Oral Medicine Diagnosis and Treatment
- Manage - Mange th
Caratera's Clinical PERIODONTOLOGY 9 Edition
PDL ... PPL - - Textbook -
- :
72
)COLOR ATLAS OF Dental Medicine Aesthetic Dentistry (Josef Schnidsedes
3.16
Color Atlas of Endodontics
4.16
Contemporary Orthodontics PROFFIT

- - TMJ ..
5.16
Craniofacial Development
6.16
Critical Decisious in Periodoutology
7.16
Dental Assisting
- - - Position - ) Instroment( - - Dessing Dental Implant System
- - - -
8.16
)Dental Implant System Fixed Implant Restorations (ITI Dental Implant System) (VCD
10.16
Endodontics
11.16
)Endodontics 5th Edition (John I. Ingle, DDS, MSD, Leif K. Bakland, DDS
12.16
)ESSENTIAL OF ORAL MEDICINE (Silverman, Roy Eversole, Truelove

Case
)ESTHETIC DENTISTRY 2th Edition (Dennet W. Aschheim, Barry G. Dale
- : - - - - ) - (PFM - ) ( -
13.16
)Esthetic Implant Dentistry (Daniel Buser, Hans Peter Hirt) (VCD
15.16
)ESTHETIC IMPLANT DENTISTRY (Daniel A. Bases, Urs.E.Belses
16.16
- - - - - ) ( (PFM) -
- - Acsess - Textbook - -
)(William T. Johnson DDS.MS

... )(Retreatment - -
- ...
- - -
)(Walte R.B.HALL
-
- Shaping - Cleaning ...
- ITI
- TPS
9.16
14.16
- .
)Esthetic in Dentistry (Vol 1- Vol 2
17.16
)ESTHETICS IN DENTISTRY (Second Edition
18.16
Glossary of Orthodontic Terms
19.16
)Guide to Physical Examination (Mosby
20.16
Implant Medpor Mandibular A method to Restore Skeletal Support to the Lower Face
21.16
ITI Dental Implant
22.16
- -
PRINCIPLES COMMUNICATIONS TREATMENT METHODS
)(John Daskalogiannakis
Case .
)(Oscar M. Ramirez M.D., F.A.C.S.) (POREX) (VCD
)(CD I , II , III
- :
73
)ITI TE Solution ITI TE Implant (DENTAL IMPLANT SYSTEM) (Daniel Buser) (Disk 1-3
2004
- -
-
- - - Packable
Post -
Crown -
Journal of Esthetic & Restorative Dentistry

- - -
)LINGUAL ORTHODONTICS (Rafi Romano) (TO EXPLORE THE CD-ROM

)Local Anesthesia in Dentistry (VCD
- -
26.16
)Local Anesthesia in Dentistry (Dr. Markus D. W. Lipp Wolfgang Kelm) (VCD
27.16
My Orthodontics
28.16
)Oral & Management Surgery Trauma (Raymond J. Fonseca, Robert, Barry H. Hendler
29.16
Oral Disease Diagnosis & Treatment
30.16
- -
- Case -
Oral Pathology 4th edition
31.16
)Orthodontics Current Principles and Techniques (Third Edition
32.16
Orthodontics & Paediatric Dentistry
33.16
Orthodontics Priociples & Techniques 3th Edition
34.16
)Pathways of the PMP (8th Edition
35.16
- TMJ
)(Thomas M. Graber, Robert L. Vanaradall, Jr.

- Mixed dentition-
- TMJ Part III: Related Clinical Topics
Part II: The Science of Endodoutics
)(James J. Sciubba, DMD, PhD, Joseph A. Regezi, DDS, MS , Roy S. Rogers III, MD
Part I: The Art of Endodoutics
36.16 PDQ ORAL DISEASE Diagnosis and Treatment
)PERIODONTAL MEDICINE (L.F. Rose, R.J.Genco, B.L. Mealey, D.W. Cohen
37.16
Periodontal Surgery
38.16
Periodontal Surgery Clinical Atlas
39.16
Removal Orthodontics Apliances
40.16
)Saunders Dental Assisting (Multimedia Resource) (Second Edition) (Doni L. Bird , Debbie S. Robinson
41.16
)Strauman Dental Implant System (VCD
42.16
2000
- - - -
2003
24.16
25.16
- -
23.16
Case I II III .
- - )The Center of Education, Teaching and Research for Oral Implant Reconstruction (Prof. Dr. Hns L. Grafelmann) (CD I , II
- Vertical Load
-Pitt-Easy BIO OSS
-Phase TPS Cylinder Implant
43.16
)The Entegra Dental Implant System Entegra Surgical Videos (Robert Schroering
44.16
- :
74
45.16
The IMZ Implant System (VCD) (Dr. Karl-Ludwing Ackermann, Dr. Axel Kirsch)
46.16
Toothcolored Restoratives
(CD I , II)
47.16
Case - TOOTH-COLORED RESTORATIVES Ninth Edition (Principles and Techniques) (Harry F. Albers, DDS)
48.16
Treatment Planning in Dentistry
49.16
Treatment Planning in Dentistry (Stephen Stefanac, D.D.S., M.S.Sam Nesbit, D.D.S., M.S.)
50.16
UCD Implant
2002
Case -
... - - -
CD
1.17 ANATOMY & PHYSIOLOGY (5 Edition)

th
(Gary A. Thibodeau, Kevin T. Patton)

2.17 BODY WORKS 6.0 A 3D Journey Through The Human Anatomy
3.17 Interactive Physilogy MUSCULAR SYSTEM (A. D. A. M. Benjamin/Cummings) (Marvin J. Branstrom, Ph.D.)
-Anatomy Review: Skeletal Muscle Tissue
-The Neuromuscular Junction
-Sliding Filament Theory
-Muscle Metabolism
-Contraction of Motor Units
-Contraction of Whole Musle
4.17 InterActive PHYSIOLOGY Cardiovascular System
5.17
The Heart
Blood Vessels
Anatomy Review: The Heart Intrinsic Conduction System

Cardiac Action Potential
Cardiac Cycle
Cardiac Output
Anatomy Review: Blood

Vessel Structure and Function
Measuring Blood Pressure
Factors that Affect Blood Pressure
Interactive PHYSIOLOGY for Windows Urinary System
Blood Pressure Regulation

Autoregulation and Capillary Dynamics
Version 1.0
(
( .
: ( . :(
. CD . .
. ( Quiz)
Interactive Physiology RESPIRATORY SYSTEM (A. D. A. M. Benjamin/Cummings) (Andrea K. Salmi)

-Anatomy Reviw: Respiratory Structures
-Pulmonary Ventilation
-Gas Exchange
-Gas Transport
7.17 MedWorks Anatomy & Physilogy
6.17
Anatomy Y Physiology:
Overview
The Endocrine System
The Sensory Organs
-Control of Respiration
Cells and Tissues
The Integumentary System
Body Chemistry
The Skeletal System
The Muscula System
Cardiovascular System: The

Blood
Somatic and Autonomic
Systems
Cardiovascular System, The

Heart
The Peripheral Nervous
Systems
Lymphatic and Immune

System
The Respiratory System The Digestive System
Inheritance
The central Nervous

System
The Nervous System

Organization
The Urinary System
The Reproductive
System
. Medwork Setup.exe
8.17
Panorama of Anatomy & Physiology Structure & Function of the Body
- :
(Eleven Edition)
(Gary A. Thibodeau, Kevin T. Patton)
9.17 Range of Motion-AO Neutral-0 Method

10.17 The Interactive Skeleton Tutorial
1. Head
2. Spine
75
Measurement and Documentation
(Thime)
(Dr. peter Abrahams of cambridger University, UK.)
3. Ribs
4. Upper Limb
5. Lower Limb
11.17 World of SPORT examined

12.17 Interactive Guide to Human Neuroanatomy
Atlas: -Surface Anatomy of Brain
Exam:I -Surface Anatomy of the Brain
2002
(Mark F. Bear, Barry W. Connors, Michael A. Paradiso)
-Cross-Sectional Anatomy of Brain

-Cross-Sectional Anatomy of the Brain
-The Spinal Cord -The Anatomy Nervous System

-Comprehensive Exam
-The Cranial Nerves -The Blood Supply to the Brain
2002
13.17 Sobotta (Atlas of Human Anatomy) (Urban & Schwarzenbery)

1. General Anatomy
2. Head and neck
3. Upper Limb
4. Brain and Spine Cord
Past ( Setup ) C:\Urban Sobotta 1.5Crack
5. Eye
6. Ear
7. Thoracic and Abdominal Wall
8. Thoracic Oegans
9. Lower Limb
Crack . Setup English :(

. .
14.17 Student Companion CD-ROM for Principles of Anatomy & Physiology (Tenth Edition) (John Willey & Sons, INC.)
15.17
Gray's Anatomy The Anatomical Basis of Clinical Practice (Thirty-Ninth Edition) (Susan Standring) (CD I , II) (Salekan E-Book)
2003
2005
:
CD
1.18
2.18
3.18
4.18
5.18
6.18
The Oncology Nursing Society presents THE ADVANCED PRACTICE ONCOLOGY NURSING REVIEW
Textbook of MEDICAL SURGUCAL NURSING (Ninth Edition) (Katherine H. Dimmock) Student Self Study Disk to Accompany BRUNNER & SUDDARTH'S
Focus on Nursing Pharmacology (Lippincott Williams & Wilkins)
Wongs ESSENTIALS OF Pediatric Nursing (Mosby) A Harcoun Health Sciences Company
Maternal, Neonatal and Women's Health Nursing
By Delmar, a division of Thomson Learning
Nursing Care of Infants and Children (Seven Edition)
2000
2001
2002
2003
: CD
- Childre, Their Families, and the Nurse
- Family-Centered Care of the Newborn
- Family-Centered Care of the Infant
- Family-Centered Care of the Young Child - Family-Centered Care of the School-Age Child
- Assessment of the Child and Family
- Family-Centered Care of the Adolescent
- Family-Centered Care of the Child with Special Needs
- The Child who is Hospitalized
- The Child with Problems Related to Transfer of Oxygen and Nutrients
- The Child with Disturbance of Fluid and Electrolytes
- The Child with Problems Related to Production & Circulation of Blood
7.18
8.18
- The Child with Disturbance of Regulatory Mechanisms
- The Child With a Problem that Interfers with Physical Mobility
McMinn's Interactive Clinical Anatomy

INRERACTIVE ATLAS OF CLINICAL ANATOMY (Illustrations by Frank H. Netter, M.D.)
CD
1.19 A Manual of ACUPUNCTURE (Peter Deadman & Mazin Al-Khafaji with Kevin baker)
2.19 BACK STABILITY
Christopher M. Norris, MSc, MCSP, Director, Norris Associates, Manchester, UK)

3.19 Chiropractic Pediatrics A Clinical Handbook (Neil J. Davies, Jennifer R. Jamison)
- :
(Salekan E-Book)
76
(Raymond T. Broome)
Chronic Pain Management for Physical Therapists (Second Edition) (Harriet Wittink, Theresa Hoskins Michel)
Clinical Tests for the Musculoskeletal System (Klaus Buckup, KlinikumDortmund Orthopaedic Hospital Dortmund Germany) (Salekan E-Book)
Daniels and Worthingham's MUSCLE TESTING Techniques of Manual Examination
DIET & FITNESS
DIGITAL SHIATSU
4.19 Chiropractic Peripheral Joint Technique

5.19
6.19
7.19
8.19
9.19
2004
:
-
(therapies) -
(total body) -
(self- shiatsu) -
. . -
. -
(... : ) . -
Namikoshi -
. -
. Autorun
. program Lifestyle softuare Group Setup.exe :(
. install.exe . Desktop Jurassic Park Entertainment CD

10.19 EXERCISE THERAPY PREVENTION AND TREATMENT OF DISEASE
2005
___
( John Gormley and Juliette Hussey)

(
11.19 Fibromyalgia Syndrome Bodywork Management Strategies
. Leon Chitow CD
.
Assessment Methodes
- Manual Thermal Diagnosis
- Skin on Fascia Adherence
- Hyperalgesic Skin Zones reduced Skin elasticity
- Drag palpation for increased hydrosis
- Neuro muscular Technique Evaluation (NMT)
rd
12.19 Fundamentale of Sensation ad Perception (3 Edition) (M.W. Levine)
: CD
Introduction and instructions

Afterimages
Depth from motion of random dots
Traveling waves on the basilar
membrane
Gnglion Cells responding to light
Threshold experiment or Signal Detection

Brain anatomy, Blink Suppression, or Cortical
Cell responses
Optical IIIusions and Constancies
Motion demonstrations
Retinal Cells responding to light

Demonstratuins of Fourier
components
Color mixing or Opponent cells
Pitch and Loudness of tones
Speech sounds of Mystery phrase
Muscle spindle feedback
Mechanics of the middle and inner ear
Taste-influenced by vision
Motions from form of Impossible figures

13.19 Health & Fitness (DataSel Software, Inc)
1. Getting Started 2. The Exercise Demonstration Screen 3. Strength 4. Stretch
Specializations of the Vertebrate eye

Cortical columns or Equiluminant demos
5. Equipment
6. Muscles
14.19 Hysical Agents in Rehabiliation from Research to practice (Michelle H. Cameron)

15.19 Interactive Atlas of Human Anatomy
- :
7. Workouts
8. Setup
9. Technical Support
77
16.19 Introduction to Massage Therapy (Mary Beth Braum, Steplianic Simonsoon) (Salekan E-Book)
17.19 Kinesiology of the Musculoskeletal Foundations for Physical Rehabilitation
(Donald A. Neumann.PT.PHD)
18.19 Maintaining Body Balance Flexibility and Stability A Practical Guide to the Prevention and Treatment of Musculoskeletal Pain and Dysfunction (Leon Chaitow ND DO, Douglas C. Lewis ND)
19.19 MANIPULATION OF THE SPINE, THORAX AND PELVIS An Osteopatic Perspective (Peter Gibbons, Philip Tehan)
2005
: . manipulation CD
- Cervical and cervicothoracie spine
: HVLA thrust techniques-spine and thorax
-Thoracic spine and rib cage
-Lumbar and thora Columbar spine
: HVLA thrust techniques-pelvis

. Autorun CD . manipulafion
20.19 Massage Therapy Review
(interactive Edition) (Mosby)
21.19 Medical Acupuncture (A Western scientific approach) (Jacqueline Filshie)

22.19 Men's Health GET RID OF THAT GUT
STAGE 1: BEGINNERS LEVEL
STAGE 2: INTERMEDIATE LEVEL
23.19 Modern Neuromuscular Techniques

24.19 MUSCLE ENERGY TECHNIQUES
STAGE 3: ADVANCED LEVEL

2003
(Leon Chaitow)
2001
ADVANCED SOFT TISSUE TECHNIQUES (Second Edition)
. Muscle Energy Techniques CD

Post . MET
: . Reciprocal inhibtion isometric Relaxation

30.19 Palpation Skill in Assessment and Tr eatment Fibromyalgia Syndrome (Leon Chaitow)
2005
2003
31.19 Physical Education and the Study of Sport (Bob Davis, Ros Bull, Jan Roscoe, Dennis Roscoe) (Mosby)
25.19 Muscles (Testing and Function with Posture and Pain)

26.19 Myofascial Release Techniques
(John F. Barnes, PT) (VCD I , II)
27.19 Occupational Therapy for Physical Dysfunction (Fifth Edition) (Catherine A. Trombly, Mary Vining Radomski)
28.19 Orthopaedics for Nurses (John Ebnezar) (Salekan E-Book)
29.19 Orthopedic Massage Theory and Technique (Whitney Lowe Leon Chaitow)
1- Physical Education and the Study of Sport
2- Synoptic Questions Harcourt Health Sciences
3- The Project Personal Performance Profile
rd
32.19 Physical Rehabilitatioon of the Injured Athlete 3

33.19 Physiotherapy in Obstetrics & Gynaecology
34.19 Positional Release Techniques
Edition (James R. Andrews, Gary I., Harrison, Kevin) (Salekan E-Book)

(Second Edition) (Jill Mantle, Jeanette Haslamk Sue Barton) (Second Edition)
ADVANCED SOFT TISSUE TECHNIQUES (Leon Chaitow) (Harcourt) (Second Edition)
2004
. Positional Release CD
Positional Release
. .
Spontaneous Positional relese variations
The evolution of dysfunction
Unloading and Proprioceptive taping
Modified strain/counterstrain technique
Learning SCS
SCS for muscle pain (plus INTT and self-treatment)
Goodheart and Morrison's Positional release variations and lift techniques
SCS (and SCS variations) in hospital settings
The Mulligan concept: NAGs, SNAGs, MWMs, etc.
- :
78
Functional technique
Facilitated Positional release (FPR)
Cranial and TMJ Positional release methods
35.19 Power Touch
36.19 Principles & Pracice of Sport Management (Second Edition) (Lisa Pike Masteralexis, Carol A. Barr, BS, Mary A. Hums)
37.19 Principles of Manual Therapy (A Manual Therapy Approach to Musculoskeletal Dyslimction) (Salekan E-Book)
2005
2005
38.19 Rehabilitation for the Postsurgical orthopedic patient
39.19 Running Biomechanics & Exercise Physiology Applied in Practice (Frans Bosch & Ronald Klomp)
40.19 Surface and Living Anatomy
2002
(Gordon Joslin SOtJ)
. . CD
41.19 The Back Pain Revolution
(Gordon Waddell)
42.19 The Complete Acupuncture
43.19 The Principles of Harmonic Techniques
(Eyal Lederman) (VCD)

. Eyal Lederman )(
: CD .
1- The Principles of Harmonic Technique
2- The Principles of Harmonic Technique Using Thoracic Mass Oscillations
44.19 Therapeutic Exercise (Foundations and Techniques)

45.19
3- The Principles of Harmonic Technique Using Pelvic Mass Oscillations

4- The Principles of harmonic Technique Using Appendicular Oscillations
(4th Edition) (Carolyn Kisner, MS, PT, Lynn Allen Colby, MS, PT)
2004
Therapeutic Exercise for Lumbopelvic Stabilization A motor Control Approach for the Treatment and Prevention of low back pain
(Second Edition) (Carolyn Richardson, Paul W. Hodges, Julie Hides) (Salekan E-Book)
2003
46.19 Tidy's Physiotherapy (Stuart B.Porter) (13th edition)

47.19 YOGA for YOU (Anatomy)
CD
11.20 A manual of Acupuncture

1.20
(Peter Deadman& Mazin Al-Khafaji, With Kevin Baker)
Advanced Pediatric Life Support: The Critical First Hour CPR and ACLS Review (David G. Nichols, MD)
: - CD
1: Initial Evaluation, 2: Airway Management, 3: Epiglottitis and Gidup, 4: Respiratory Failure, 5: Advanced Pediatric CPR, 6: Resuscitative Drugs
2.20
3.20
American College of Surgons ACS Surgery Principles & Pracitce (CD I , II)
ANESTHESIA (Ronald D. Miller, MD) (Fifth Edition)
(E-Book)
Anesthesiology (The Journal of the American Society of Anesthesiologists, Inc) Abstracts of Scientific Papers
5.20 Anesthesiology (The Journal of the American Society of Anesthesiologists, Inc) Abstracts of Scientific Papers
6.20 Anesthesiologist's manual of Surgical Procedures
. )( Preob
4.20
7.20
Atlas of Interventional Pain Managemetn (Steven D. Waldman)
- :
2004
2000
2002
2000
2004
79
8.20
Bonica's Management of Pain (John D. Loser, M.D.) (3th Edition)
9.20
CHINA ZHENJIUOLOGY
(VCD) (VCD 1 30)
. ... ( ... )
10.20 Clinical Procedures in EMERGENCY MEDICINE (4th Edition) (James R. Roberts, MD, Jerris R. Hedges, MD, MS) (E-Book) (CD I, II)
11.20 Critical Care Handbook of the Massachusetts general hospital (3th edition) (William E. Hurford)
2004
12.20 Critical Care Secrets
(Third Edition) (Pollye, parsons, jeantne p. wiener-kronish)
13.20 Decision Making in ANESTHESIOLOGY An Algorithmic Approach (Lois L. Bready, Rhonda

14.20 Emergency Medical Training (MedEMT) Victory Technology, Inc. Presents (DISC ONE, TWO)
M. Mullins)
MedEMT Overview
Emergency Medical Services (EMS)
The Well-Being of the EMT-Basic
Anatomy and Physiology-Part 1
Anatomy and Physology-Part 2
Medical Terminology
Vital Signs and SAMPLE History
Lifting and Moving Patients
Airway Management
Patient Assessment
Medical and Behaval Care I
Medical and Behavioral Care II
Obstetric and Gynecological Care
Trauma
Infants and Children
Operations
Appendix A: Video/Animation List
Appendix B: Victory Products
15.20 EMERGENCY MEDICINE A COMPREHENSIVE STUDY GUIDE (Rosen's ) (Volume 1-3) (Sixth Edition) (Judith E. Tintinall, MD, MS)
16.20 EMT-Basic Slide Set Slide Program Guide (John A. Stouffer, EMT-P, Richard S. Bennett, RN, EMT-P, BSN) (Mosby)
17.20 Fluid, Electrolyte & Acid Base Physiology
(A Problem Based Approach)

.
2003
18.20 Intensive Care Medicine (Irwin & Rippe) (Vol A,B)
12.20 Interactive Regional Anesthesia
13.20 Medical Acupuncture
A western scientific approach (Jacqueline Filshie, Adrian White)
2005
14.20 Miller's Anesthesia (Vol I & II) (Salekan E-book)

SECTION I: INTRODUCTION
SECTION II: SCIENTIFIC PRINCIPLES
SECTION III: ANESTHESIA
VOLUME 2
SECTION IV: SUB SPECIAL TV
SECTION V: CRITICAL CARE MEDICINE
SECTION VI: ANCILLARY
RESPONSIBILITIES AND PROBLEMS
COMPANION VIDEO CD-ROM
Video 1 Patient Positioning in Anesthesia
Video 2 Code Blue Simulation
48.9
2002
New Analgesic Options: Overcoming Obstacles to Pain Relief

- MD, NP, PA, RN Answer Sheet
-Pharmacist Answer Sheet
-Back Pain
-Fibromyalgia
-OA Pain
-Post Op Pain
-Trauma
-References
15.20 NEW YORK SCHOOL OF REGIONAL ANESTHESIA PERIPHERAL NERVE BLOCKS PRINCIPLES AND PRACTICE
2004
-TRAINING IN PERIPHERAL NERVE BLOCKS - ESSENTIAL REGIONAL ANESTHESIA ANATOMY -EQUIPMENT AND PATIENT MONITORING IN REGIONAL ANESTHESIA
-PERIPHERAL NERVE STIMULATORS AND NERVE STIMULATION
-CLINICAL PHARMACOLOGY OF LOCAL ANESTHETICS
-NEUROLOGIC COMPLICATIONS OF PERIPHERAL NERVE BLOCKS
-KEYS TO SUCCESS WITH PERIPHERAL NERVE BLOCKS -CERVICAL PLEXUS BLOCK
-INTERSCALENE BRACHIAL PLEXUS BLOCK
-INFRACLAVICULAR BRACHIAL PLEXUS BLOCK
-AXILLARY BRACHIAL PLEXUS BLOCK
-INTRAVENOUS REGIONAL BLOCK OF THE UPPER EXTREMITY
-CUTANEOUS NERVE BLOCKS OF THE UPPER EXTREMITY -THORACIC PARAVERTEBRAL BLOCK
-THORACOLUMBAR PARAVERTEBRAL BLOCK
-LUMBAR PLEXUS BLOCK
- SCIATIC BLOCK: POSTERIOR APPROACH 234
-SCIATIC BLOCK: ANTERIOR APPROACH 252
-FEMORAL NERVE BLOCK
-POPLITEAL BLOCK: INTERTENDINOUS APPROACH
-POPLITEAL BLOCK: LATERAL APPROACH
- :
80
-DIGITAL BLOCK
2004
2005
-CUTANEOUS NERVE BLOCKS OF THE LOWER EXTERMITY
- WRIST BLOCK
)19.20 PERIPHERAL NERVE BLOCKS Principles & Practice (Admir Hadzic, Jerry D. Vloka
)20.20 Peripheral Regional Anaesthesia Tutorial in the Ulm Rehabilitation hospital (Prof. Dr. Med. H. Mehrkens
)(VCD) (CD I , II
1. Anatomical Fundamentals
2. Peripheral Neve Stimulation
3. Regional Anaesthesia
4. Upper, Lower Extremity
5. Peripheral Neve Blocks 6. Peripheral Neve Blocks
)16.20 Textbook of CRITICAL CARE (Salekan E-book
SECTION I RESUSCITATION AND MEDICAL EMERGENCIES
SECTION II TRAUMA
SECTION III IMAGING
SECTION IV CELL INJURY AND CELL DEATH
SECTION V INFECTIONS DISEASE
SECTION VI ENDOCTINOLOGY, METABOLISM, NUTRITION, PHARMACOLOGY
SECTION VII CARDIOVASCULAR
SECTION VIII PULMONARY
)21.20 The American Academy of Pediatric (David G. Nichols, MD Associate Professor of Anesthesiology and Clinical Care Medicine
-Endotracheal Intubaion
-Chest Compressions
-ANKLE BLOCK
)(Version 2.0) (Paul G. Barash, MD

)(Salekan E-Book
-Intitial Steps in Resuscitation -Ventilating the Infant

)17.20 The ICU Book (Second Edition) (Paul L. Marino
22.20 The Lipponcott-Raven Interactive Anesthesia Library on CD-ROM

23.20 The Massachusetts General Hospital Handbook of Pain Management
CD Mass.Gen . Edition Poacet guide

. CD .
. :

CD

2002
)(Jay Y. Gillenwater, john T. Grayhack, Stuart S. Howards, Michael E. Mitchell
1.21 Adult and Pediatric Urology
Adult Urology
Adult Urology Continued
Pediatric Urology
Video Library
Advanced
Therapy
of
Prostate
Disease
(Martin
I.
Resnick,
MD,
Ian
M.
)Thompson, MD
2.21
2000
Acrobat reader . .
.
- . - . - . -
- . -- . -- staging - : .
Stage - -- .Radical Perianal Prostatectomy - . Brachy therapy -- (TNM) Staging
-- PSA - ... genitourinary -
-- erction -- - -- . BPH - .
- Voding :BPH - BPH -- / - BPH 5 --
BPH ) needle Ablation TUIP TUFP open( -- . : .
___
)(Male Reproductive Health and Dysfunction) (2nd Edition
3.21 ANDROLOGY
- :
81
2005
)(ESE Hafez and SD Hafez
4.21 Atlas of Clinical Andrology
5.21 AUA Vide Digest The American Urogical association (AUA) Impotence and Infertility
CD ) (AUA video digest . Impotence Infertilitey.

:Impotence( (Diagnosis8 treatment option) .
( :Penile Venous Ligation .
:Rectal Probe Electroejaculation :Infertiliry ejaculation
ejaculation .
2004
)(SALEKAN E-BOOK
6.21 BLADDER BIOPSY INTERPRETATIONS
)(Jonathan I. Epstein, M.D., Mahul B. Amin, M.D., Victor E. Reuter, M.D.
:
Papillary Urothelial Neoplasms with Inverted Growth
Patterns
Flat Urothelial Lesions

Conventional Morphologic, Prognostic, and Predictive Factors and Reporting of
Bladder Cancer
Cystitis
Second ary Tumors of the Bladder
Glandular Lesions
Mesenchymal Tumors and Tumor-Like Lesions
Normal Blodder Anatomy and Variants of Normal

histology
Invasive Urothelial Carcinoma
Squamous Lesions
Miscellaneous Nontumors and Tumors
)Bristol Urological Institute (Computer Aided Learning Program

CD CD .
CD :
-
impotence -
- -
7.21
- - . - .
. Score .
CAMPBELL'S UROLOGY
2003
& Voiding Function
Dysfunction
Infections and Inflammations of the

Genitourinary Tract
Physiology, Pathology, and Management of Upper

Urinary Tract Diseases
Oncology
Pediatric Urology
Sexual Function and Dysfunction
Urologic Examination and Diagnostic

Techniques
Reproductive Function and
Dysfunction
Radiology Atlas
Pathology Atlas
Urologic Surgery
Urinary Lithiasis and Endourology

Additional Media
2004
8.21
Anatomy
Benign Prostatic
Hyperplasia
Carcinoma of the
Prostate
Study Guide
)Case Studies in Genes & Disease A Primer for Clinicians (Bryan Bergeron
9.21
)10.21 Core Curriculum in Primary Care Patient Evaluation for Non-Cardiac Surgery and Gynecology and Urology (Michael K. Rees, MD, MPH
CCC CD Harvard .
CD . .
. . :
- ) (
- Male impotence
- ).(AUB
)(Michael, Isaac Schiff, Keith, Thomas, Annekathryn

)(John A. Libertino MD, FACS
12.21 Cystectomy and Construction an Ileocecal Neobladder for Urethral Voiding
- :
82
13.21 Erectile Dysfunciton
Current Investigation and Management (lan Eardley, Drishna Sethia)
14.21 Glenn's Urologic Surgery
(Sixth Edition)
15.21 Hot Topics in UROLOGY
(Roger S Kirby, Michael P O'Leary) (SALEKAN E-BOOK)
2004
(Sam D. Graham, James F. Glenn,) (Salekan E-Book)
Premature ejaculation Michael P O'Leary

Angiogenesis as a diagnostic and therapeutic tool in urological
malignancy
Robotic surgery and nanotechnology
2004
New developments for the treatment of erectile dysfunction: Present and Future
Erectile dysfunction and cardiovascular disease
Chemoprevention of prostate cancer
Apoptosis in the prostate
Marginally worse? Positive resection limits after radical prostatectomy
Adjuvant therapy for prostate cancer
Bisphosphonates: a potential new treatment strategy in prostate cancer I mmunotherapy for prostate
What,s hot and whats not - the medical management of BPH
Three-dimensional imaging of the upper urinary tract
Future prospects for .. nephron conservation in renalcel I carcinoma
Urethral stricture surgery: the state of the art
Reducing medical errors in urology
Management of female sexual dysfunction
Laparoscopic radical prostatectomy
Antisense therapy in oncology: current
The overactive bladder
Organ preserving therapies for penile carcinomas
2004
16.21 HOW the Human Genome Works (Edwin H. McConkey.Ph.D)
(Salkan E-Book)
17.21 Male and Famale Sexual Dysfunction (Allen D. Seftel)
.
.
18.21 Male Hypogonadism
2004
.
2004
(Feiedpich Jockeahovel)
19.21 Mind Maps in pathology
___
(Michele Harrison, Peter Dervan)
20.21 Pelvic Floor Exercises for Erectile Dysfunction (Grace Dorey phD MSCP)
2004
21.21 Smith's
(Sixteenth edition) (Emil A. Tanagho, Jack W. Mcaninch) (Salekan E-Book)
2004
(Spring & Summer)
2003
General Urology
22.21 The Journal of UROLOGY

CD I:
CD II:
- Clinical Urology
- Clinical Urology
-Pediatric Urology
-Pediatric Urology
(CD I, II)
-Investigative Urology
-Investigative Urology
(Official Journal of the American Urological Association)
-Urological Survey
-Urological Survey
-CME Participant Assessment Test and Course Evaluation
23.21 Urogynecology: Evaluation and Treatment of Urinary Incontinence (Bruce Rosenzweig, MD, Jeffrey S. Levy, MD, Donald R. Ostergard, MD)
. CD
CD
: Urogynechology
Consideration for the OB/GYN Generalist
Patient misconceptions y
won surgical & surgical Management
affected women y
incontince y
Evaluation -
Introduction Definigg Incontinence
:Introduction & Defining Incontince (
Types of incontinernce y
incontinence awareness y
:incontinency (
Cystoscopy y uroflowmetry y Postvoid residual y Cystometrogram y Pad test y
y y Voiding diary y
Pessary test y
un , u/s y
Multi-Channel urodynamics y
: Stress urinary incontinence (

.( .... funetional electrieal Stimalation biofeedback, Beharioral modification))
. Complication . Procedure :
- :
83
: Consideration for the OB/Gyn Generalist (

:
urogynechology as a subdiscipline y
Non surgical therapy y
professional consideration y
___
incontinrence management to private patients y
Urodynamics y
)(Patrick J, Rowe, Frank H. Conhaire, Timothy B. Hargreave
equipment cost ySet-up requirement y
eystometry y
Allied Staff y
24.21 WHO Manual for the standardized investigation & diagnosis of the infertile couple
25.21 WHO Manul for the standardized investigation, diagnosis and management of the infertile male
)(Patrick J. Rowe, Frank H. Comhaire
)(Prof. Legndre, Martin, Helenon, Lebranchu, Halloran, Nochy
-immunosupperssive
-immunology
-imaging
26.21 Atlas of RENAL TRANSPLANTATION
-clinical section
-surgery
-Histopathology
)27.21 Core Curriculum in Primary Care Nephrology (Michael K. Rees, MD, MPH
CCC CD Harvard .
CD .
. .
. CD .
4-Clinical Application of Renal Physiology
3- Treatment of Mypertension-Special Case
1- How to erahcate Renal mass/Tumor
2- Drugs vs Diet in Modifying Renal failure
)28.21 PRIMER ON KIDNEY DISEASES (Second Edition) (NATINAL KINDEY FOUNDATION SCIENTIFIC ADVISORY BOARD
. .
- : U/A .
- : .
Glomerular Diseuse - : MGN FSGN MPGN MCD IGA .
- : CHF PSGN SLE HIV .....
- : approach .
- : NSAID
- : Sickle cell Cystic Alport
- : .
- .
- : CRF CRF .
- : Renovascular .
)Seven Edition (Barry M. Brenner) (E-Book
)(Volume 1-2
29.21 The Kidney
. . . :
- .... .... .
- : AVP CHF
.... .
:
( : : .... .
( : ) (renovascular ... .
( : .... .
:
CD

2002
)(Jay Y. Gillenwater, john T. Grayhack, Stuart S. Howards, Michael E. Mitchell
Adult and Pediatric Urology
1.22
- :
84
Adult Urology
Adult Urology Continued
Video Library
Pediatric Urology
2.22 American Cancer Society Atlas of Clinical Oncology (Cancer of the Female Lowe Genital Tract) (Patricia J. Eifel, M.D. Charles Levenback, M.D.) (SALEKAN E-BOOK)
2001
Cervix .
.
Chemotherapy in Curative
Management
Surgery for Vulvar Cancer
Post-treatment Surveillance
Radiation Therapy for Vulvar Cancer
Palliative Care
Acute Effects of Radiation Therapy

Late Complications of Pelvic Radiation
Therapy
3.22
Surgical Treatment of Invasive Cervical

Cancer
Radiation Therapy for Invasive Cervical
Cancer
Radical Management of Recurrent Cervical
Cancer
Management of Vaginal Cancer
Diagnostic Imaging
Epidemiology
Screening for Neoplasms
Pathology
Treatment of Squamous Intraepithelial

Lesions
Molecular Biology
Invasive Carcinoma of the Cervix
Anatomy and Natural

History
2001
American Cancer Society Atlas of Clinical Oncology Skin Cancer (Arthur J. Sober, MD, Frank G. Haluka, MD, phD) (Bc Decker Inc)
.
. text Skin cancer .
: .
. Basic Concept :
.( : ( ): )Merckle cell Carcinoma (: ( ) ( ) )Scc ( )BCE ( ): :
) ( )( )adjuvant therapy ( )( ) ( ): Management :
.( [ )MF] .(
. :
Atlas of Clinical oncology Breast Cancer (American Cancer Society ) (David J Winchester, MD, David P Winchester, MD)
4.22
yGenetics, Natural History, and DNA-Based Genetic Counseling in Hereditary Brast Cancer
2000
y Breast Cancer Risk and Management: Chemoprevention, Surgery, and Surveillance
y Screening and Diagnostic Imaging yImaging-Directed y Breast Biopsy yHistophathology of Malignant Breast Disease
yUnusual Breast Pathology y Prognostic and Predictive Markers in Breast
Cancer
y Surgical Management of Ductal Carcinoma In Situ
yEvaluation and Surgical Management of Stage I and II Breast Cancer y Locally Advanced Breast Cancer y Breast Reconstruction
5.22 Atlas of Clinical Oncology Cancer of the Lower Gastrointestinal Tract (Christopher G. Willett, MD)
6.22 Atlas of DIAGNOSTIC ONCOLOGY
7.22
CANCER Principles & Practice of Oncology (7th Edition) (Vincent T. Devita, Jr., Samuel Hellman, Steven A. Rosenberg)
8.22
Color atlas of Cancer Cytology (Third Edition) (Masayoshi Takahashi)

Gastric Cancer Diagnosis and Treatment (An interactive Training Program) (J.R. Siewert, D.Kelsen, K. Maruyama) (Springer)
Handbook of Cancer Combination Chemotherapy
Holland.frei CANCER 6 MEDICINE (volume 2) (Danald W. Kufe, MD, Raphael E. Pollock, Md, PHD)
Human Brain Cancer: Diagnostic Decisions (Lauren A. Langford, MD, Dr. med,) American Medical Association
PHYSICANAS' CANCER CHEMOTHERAPHY DRUG MANUAL (Jones & Bartlett)
9.22
10.22
11.22
12.22
13.22
- Principles of Cancer Chemotheraphy

- Common Chemotherapy Regimens in Clinical Practice
14.22 Thyroid Cancer 4
2001
2000
2003
2004
- Physician's Cancer Chemotherapy Drug Manual 2004

- Guidelines for Chemotherapy and Dosing Modifications
- Antimetic Agents for the Treatment of Chemotherapy-Induced Nausea and Vomiting
& Asso Schilddruse (Werner Langsteger, Paul Sungler, Peter Lind, Bruno Niederle)
2004
)(
RADIOLOGY
- :
85
1.
Pediatric Radiology (The Requestions) (Hans Blickman)
200,000
2.
Differential Diagnosis in Conventioanl Gastrointestinal Readiology (Francis A. Burgener, Marti Konnano)
240,000
3.
Dynamic Radiology of the Abdomen: Normal and Pathologic Anatomy (Morton A. Meyers, 5 Edition Springer Verla)
500,000
4.
Primary Care Radiology (Mettker, Guibert EAU. VO.SS', URBINA)
250,000
5.
Textbook of Uroradiology (N. Reed Dunnick, MD, Carl M. Sandler, Md, Jeffrey H. Newhouse, MD, Estephen Amis', JR., MD)
400,000
6.
Head and Neck Radiology a Teaching File (Anthony a Mancusd, Hiroya Ojiri, Ronald G. Quisling)(Lippincottt Williams & Wilkins)
400,000
7.
Essentials of Skeletal Radiology (Terry R. Yochum; Lindsay J. Rowe)
700,000
8.
Textbook of Radiology & Imaging (David Stutton) (2003)

()
1,400,000
9.
Radiology Reviw Manual (Fourth Edition) (Wolfgang Dahnert) (2003)
400,000
10. Forensic Radiology (B. G. Brogdon MD)
300,000
11. The Core Curriculum Neuroradiology (Mauricio Castillo) (Lippincott Williams & Wilkins)
400,000
12. Diagnostic Neuroradiology (Anne G. Osborn) (Mosby)
500,000
13. Bone and Joint Disorders (Conventional Radiologic Differentioal Diagnosis) (Francis A. Burgener Marti Kormano)
300,000
14. Atlas of Radiologic Measurement (Theodore E. Keats, Christopher Sistrom) (Mosby)

630 14
400,000
15. Radiobiology for the Radiologist (Fifthe Edition)
400,000
16. Anatomy Positioning & Procedures Workbook (Steven G. Hayes)
470,000
17. Atlas of Normal Roentgen Variants That May Simulate disease (Seven Edition) (Theodere E. Keats & Mark W. Anderson) (Mosby)
700,000
18. ( : )
50,000
19. ( )
180,000
20. ( : )
50,000
21. Radiographic Anatomy Positioning and Procedures Workbook (Second Edition) (volume I , II) (Steven G. Hayes, Sr.)
380,000
22. Gastrointestinal Radiology A Pattern Approach (4th Edition)
600,000
th
: .
- Hip - - - - - - - - - -
- :
(Ronald L. Eisenberg)
(Lippincott Williams & Wilkins) (2003)
86
. 80 10 1200
Pattern Approach .
250,000
)23. Imaging Atlas of Human Anatomy (Third Edition) (Jamie Weir, Peter H. Abrahams) (2003
600,000
)24. Pediatric Sonography (Third Edition) (Thieme) (Francis A. Burgener, Steven P. Meyers) (2004
500,000
)25. Musculoskeletal Imaging Companion (Thomas H. Berquist) (2002
550,000
600,000
500,000
)28. The Neurologic Examination (Dejong's) (William W. Campbell) (2005
800,000
)29. Abrams' Angiography Interventional Radiology (Stanley Baum, Michael J. Pentecost) (2006
350,000
)30. The Practice of Ultrasound A Step-by-Step Guide to Abdominal Scanning (Berthold Block) (Thieme
1,400,000
350,000
)32. Ultrasonography in Urology A Practical Approach to Clinical Problems (Edward I. Bluth-Peter H.
70,000
33. Seminars in Ultrasound CT and MR
1,400,000
)34. Diagnostic Ultrasound (Rumack, Wilson, Charboneau) (2005

1991 . 6
.
.
. %25 .
450 . .
highlight . . .
. ) (interrcntional.
Intraoperative ) (small part . .
. .
.
800,000
)35. Diagnostic Ultrasound (John P. McBany Gorgon, B. Gorgon, MD) (2005
500,000
)36. Ultrasound A Practical Approach to Clinical Problems (Edward Bluth, Peter H. Arger Carol B. Benson, Philip W. Rails, Marilyan) (Thieme
800,000
)37. Breast Ultrasound (A. Thomas Stavros, MD, FACR) (2004
500,000
)38. Musculosceletal Ultrasound (Thomas R. Nelson, Donal B. downey, Dolores H. Pretorius, A aron Fenster
)(2004
)(2004
)26. Surgical Neuroangiography 2.1 (A. Berenstein, P. Lasjaunias, K.G. TER Brugge) (Springer) (Second Edition
)27. Surgical Neuroangiography 2.2 (A. Berenstein, P. Lasjaunias, K.G. TER Brugge) (Springer) (Second Edition
)(Mitchell P. fink, Edward Abraham, Jean-Louis Vincent, Patrick M. Kochanek) (2005
)31. Textbook of CRITICAL CARE (FIFTH EDITION
SONOGRAPHY
- :
87
39. The Core Curriculum Ultrasound (William E. Brant) (Lippincott Williams & Wilkins)
400,000
800,000
450,000
250,000
500,000
44. Body CT A Practical Approach
240,000
45. High Resolution CT of the Lung (W. Richard Webb)
280,000
46. High Resolution CT of the Chest Comprehensive Atlas (Second Edition) (Eric J. ster, Stephen J. Swensen)(Lippincott Williams&Wilkins)
320,000
47. Pediatric Body CT (Marilyn J. Siegel)
320,000
48. CT Teaching Manual (Marthias Hofer) (Thieme) (2000)
250,000
49. CT Teaching Manual (A Systematic Approach to CT Reading) (Second Edition) (Thieme) (2005)
550,000
50. Spiral CT (Eliot K Fishman & R. Brocke Jeffrey)
400,000
51. Helical (Spiral) computed Tomography (A Practical Approach to Clinical Protocols) (Paul M. Silverman)
250,000
52. Norma findings in CT and MRI (Torsten B. Moeller, EmilReif) (Thieme)
300,000
53. CT and MR Imaging of the Whole Body (John R. Haaga, MD) (2003)
1,000,000
54. Multidetector CT (Principles, Techniques, & Clinical Applications) (Elliot K. Fissman, R. Brooke Jeffrey, JR.)
550,000
55. Spiral and Multislice Computed Tomography of the Body (Aart J. Van der Molen Cornelia M. Schaefer-Prokop) (Thieme) (2003)
800,000
MRI
56. MRI of the Musculoskeletal System (2006) (Thomas H. Berquist)
600,000
57. MRI of the Musculoskeletal System MRI Teaching file Series (Karence K Cahn, Mini Pathria)
240,000
58. MRI of the Head and Neck MRI Teaching file Series (Jrffrey S. Ross)
240,000
59. MRI of the Spine MRI Teaching file Series (Jeffrey S. Ross)
240,000
60. MRI of the Brain I & II MRI Teaching file Series (Michel Brant, Zawadzki and)
480,000
61. MRI the basics fray h. Hashemi and William g. bradley, Jr.) (Williams & Wilkins)
35,000
62. MRI Principles (Donald G. Mitcell, MD)
190,000
63. Clinical Pelvic Imaging CT, Ultrasound, and MRI (Arnold C. Friedman, MD)
300,000
40. Ultrasound in Obstetrics and Gynecology (Eberhard Merz) (Thieme) (Vol.1: Obstetrics
2005
41. Color Atlas of Ultrasound Anatomy (B. Block) (Thieme) (2004)

CT
42. Fundamentals of Body CT (Second Edition) (Webb & Brant & Helms)
43. Fundamentals of Body CT (Third Edition) (W. Richard Webb, William E. Brant, Nancy M. Major)
- :
(2006)
88
700,000
)64. MRI and CT of the Cardiovascular System (Second Edition) (Charles B. Higgins, Albert de Ross) (2006
105,000
)65. Magnetic Resonance in Medicine The Basic Textbook of the European Magnetic Resonance Forum (Peter A. Rinck
450,000
)66. Magnetic Resonance in diagnosis of C.N.S. disorders (vaso antunavic, gradimir dragutinovic, zvonimir lec) (Thieme
450,000
)67. Section and MRI anatomy of the human body (slobodan marinkovic, milan milisavljevic, dieter sehellinger, vaso antunovic) (Thieme
450,000
)68. PRACTICAL GUIDE TO ABDOMINAL & PELVIC MRI (JOHN R. LEYENDECHER, JEFFERY J. BROWN
600,000
)69. Vascular diagnosis with Ultrasound Clinical References With Case Studies (Hennerici, Neuerburg-Heusler)(Thieme
850,000
)70. Introduction to Vascular Ultrasonography (Fourth Edition) (Zwiebel) (James Saunders
550,000
)71. Teaching Manual of Color Duplex Sonography A Wokbook in color duplex ultrasound and echocardiographer (Matthias Hofer) (Thieme) (2005
400,000
)72. Vascular Ultrasound of the Neck an Interpretive atlas (Antonio Alayon)(Lippincott Williams & Wilkins
600,000
)73. Duplex Scanning in Vascular Disorders (Third Edition) (D. Eugene Strandness, Jr.
500,000
)74. Doppler Ultrasound in Gynecology and Obstetrics (Christof Sohn, Hans-Joachim Voigt, Klaus Vetter) (2004
500,000
Doppler
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. . ) (AVF
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. ) Native ( . Penis
90,000
600,000
250,000
250,000
500,000
Imaging
)75. Skeletal Imaging Atlas of the Spine and Extremities (John A. M. Donald Resnick, MD
76. Imaging for Surgeons
)77. Imaging of the Newborn, Infant and Young Child (Fourth Edition) (Leonard E. Swischuk) (2004
)78. Thoracic Imaging A Practical Approach (Richard H. slone Fernando R. Gutier
)79. Gastrointestinal Imaging, Case Review (Peter J. Feczko, Obert d. Halperi
)80. Imaging in Hepatobiliary and Pancreatic Disease A Practical Clinical Approach (Dirk Van Leeuwen, Jacques Reeders, Joe Ariyama
- :
89
81. Aids Imaging A Practical Clinical Approach (J WA J. Reeders, J. R. Mathieson)
420,000
4 00,000
93. Clinical Imaging
94. Diagnostic Imaging Brain (Osborn) (2004)
1,100 ,000
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1,000 ,000
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83. Breast Imaging (Second Edition) (David B. Kopans)
84. The Core curriculum Breast Imaging (Gilda Cardenosa)
85. Neuroimaging I & II (William It. On'ison, jr)
86. Fundamentals of Neuroimaging (William w. Woodruff.M.D.)
87. Atlas of Musculoskeletal Imaging (Thomas Lee Pope, Jr. Stephen Loehr)(Thieme)
88. Atlas of Head and Neck Imaging (The Extracranial Head and Neck) (Suresh K. Mukherji, Vincent chong)
89. Magnetic Resonance Imaging of Orthopeadic Trauma (Stephen J. Eustace)(Lippincott Williams & Wilkins)
90. Pediatric Gastrointestinal Imaging and Intervention (David A. Stringer-Paul S. Babyn MDCM)
91. Modern Head and Neck Imaging Medical Radiology, Diolopy, Nostic Imaging (S. K. Mukhetji, J. A. castelijins)(Springer)
92. Variants and Pitfalls in Body Imaging (Ali Shirkhoda)(Lippincot Williams & Wilkin's)
350,000
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Disorders, Acquired
PART II (Anatomy-based Diagnoses): Ventricles and Cysterns-Sella and Pitutary-CPA-IAC-Skull, Scalp and
Meninges
:
Terminology-Imaging Findings-Differentioal Diagnosis-Pathology Clinical Issues-Selected references-Imaging
Gallery-Key Facts

. Key Facts .
-" Diagnostic Imaging Brain Osborn 2004"
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95. Diagnostic Imaging Orthopaedics
(Stoller.Tirman Bredella) (2004)
96. Diagnostic Imaging Head and Neck (Harnsberger) (2004)
- :
90
1,000,000
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99. Cranial Neuroimaging and Clinical Neuroanatomy Atlas of MR Imaging and Computed Tomography (Hans-Joachim Kretschmann)
. . 2004 Cranial Neuroimaging and Clinical Neuroanatomy
. .
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MRI .
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1,350 ,000
100. DIAGNOSTIC MUSCULOSKELETAL IMAGING (THEODORE T. MILLER, MARK E. SCHWEITZER) (2005)
450,000
101. Orthopedic IMAGING (A Pracitcal Approach) (ADAM GREENSPAN) (Michael W. Chapman) (2004)
700,000
102. Aids to RADIOLOCIAL DIFFERENTIAL DIAGNOSIS (Forth Edition) (Stephen Chapman and Richard Nakielny) (2003)
250,000
103. Teaching Atlas of Brain Imaging (Nancy J. Fischbein, William P. Dillon, A. James Barkovich)
500,000
104. Diagnostic Musculoskeletal Imaging (Theodore T. Miller. Mark E. Schweitzer)

105. Head and Neck Imaging (Peter M. Som, Hugh D. Curtin) (4th Edition)
106. Adams and Victor's Principles of Neurology (Allan H. Ropper, Robert H. Brown)
600,000
1,300,000
107. The Radiologic Clinics of North America Imaging of Obstructive Pulmonary Disease (W. Richard Webb.M.D.)
150,000
108. The Radiologic Clinics of North America Neonatal Imaging (Janet L. ST. Rife, M.D.)
115,000
109. The Radiologic Clinics of North America Lung Cancer (Claudia I. Henschke. Phil, M.D.)
140,000
110. The Radiologic Clinics of North America Interventional Procedures in Musculoskeletal Radio I Interventional Techniques (Jamshid Tehranzadeh, MD)
100,000
111. The Radiologic Clinics of North America Interventional Procedures in Musculoskeletal Radio II Advanced Arthrography (Jamshid Tehranzadeh)
200,000
112. The Radiologic Clinics of North America Advances in Emergency Radiology I & II (Robert A. Novell)
120,000
113. The Radiologic Clinics of North America Cardiac Radiology (Lawrence M. Boxt. MD)
150,000
114. The Radiologic Clinics of North America Interventional Chest Radiology (Jeffrey S. Klein, M.D.)
150,000
97. Diagnostic Imaging Spine
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98. Diagnostic Imaging Abdomen
(Federle, Jeffrey.Desser.Anne.Eraso) (2004)
(Eghth Edition) (2005)
500,000
The Radiologic Clinics of North America
ROCKWOOD & GREEN'S 1. FRACTURES IN CHILDREN 2. FRACTURES IN ADULT (Sixth Edition) (James h. Beaty, James R.Kasser) (2006)1,800,000 :
Imaging of the newborn, infant, and young child

- :
(LEONARD E. SWISCHUK, M. D.) (FIFTH EDITION)
(2004)
600,000 :
)(Fifth revised edition
91
Borderlands of Normal and Early Pathological Finding in Skeletal Radiography

)(Thieme
600,000 :
)(Juergen Freyschmidt, Joachim Brossmann, Juergen Wiens, Andreas Sternberg
)(2003
)(Forth Edition
(Ronald L. Eisenberg, Amelda County
Clinical Imaging
)(an atlas of differential diagnosis) (Lippincott Williums & Wilkins
(multiple Pulmonary nodules

)
. ) Imaging Plain film
MRI CTScan (... . :
- Chest
- Gastrointestinal
- Breast
- Genitourinary
.
.
) ] 2272 :[ (
)CT and MR Imaging of the Whole Body (Mosby) (2003
Cleveland )(Charles F. Lanzieri, MD, FACR
Cleveland )(John R. Haaga, MD , FACR
Thoracic , Head Case Western Reserve Cleveland )(Robert C. Gilkeson, MD
1000,000 :
MRI ,CT Scan Imaging

MRI, CT Scan . . :
MRI, CT Scan
-
-
CT Scan
MRI
-
) :(MRI
- MRI, CT Scan
Magnetic Resonance Spectroscopy -
-
-
-
-
MRI, CT Scan -
CT Scan -
- )(
MRI -
- :
92
:
-
-
-
MRI, CT Scan -
-
- )(Hip
-
-
-
- :
-
-
-
-
-
-
- ) (
CT Scan -
MRI -
1307
)(Seventh Edition
-
MRI, CT Scan - :
-
-
-
-
-
-
-
-
-
)(Mosby Inc.) (2001

700,000 :
Atlas of Normal Roentgen Variants that may Simulate Disease

) , Mark W. Anderson M.d.
(Theodore E. Keats M.D.
Over diagnosis .
. . :

-
500,000 :
)(Springer) (2003
478
) Leuven
Magnetic Resonance Angiography
, Guy Marchal, PhD, M.D. (Ingolf P. Arlart, Phd, M.D.
) (MRA MRA
. :
- :
-
)(MRA
- ) (NMR
- K
Resolution
- Acquistion
- Acquistion
- ) (Guide
Resolution - Resolution MRA
Implant - :
MRA
- :
93
Looking for the number key to the diagrams? Just fold out this page
A didactically brilliant and unprecedented approach to understanding CT imaging
MRI and CT Scan of Head and Spine

(Williams & Wilkins)
(Matthias Hofer, MD)
500,000 :
(C. Barrie Grossman, M.D. Indiana )
( 810 :
: MRI CT Scan
:
-
-
-
MRI CT Scan -
MRI CT Scan -
-
-
-
CT Scan -
MRI -
:
(Sella) -
:
-
-
-
-
-
-
BASIC AND CLINICAL SCIENCE COURSE
AMERICAN ACADEMY OF OPHTHALMOLOGY

Section 1:
1
Update on General Medicine
Section 2:
2
Fundamentals and Principles of Ophthalmology
Section 3:
3
Optics, Refraction, and Contact Lenses
Section 4:
4
Ophthalmic Pathology and Intraocular Tumors
Section 5:
5
Neuro-Ophthalmolog
Section 6:
6
Pediatric Ophthalmology and Strabismus
Section 7:
7
Orbit, Eyelids, and Lacrimal System
Section 8:
8
External Disease and Cornea
Section 9:
9
Intraocular Inflammation and Uveitis
Section 10: Glaucoma
10
Section 11: Lens and Cataract
11
Section 12: Retina and Vitreous
12
Section 13: International Ophthalmology
13
Section 14: Refractive Surgery
INDEX
Master INDEX
14 WAVEFRONT ANALYSIS, ABERROMETERS and CORNEAL TOPOGRAPHY
15 OPHTHALMOLOGY MONOGRAPHS Cataract Surgery and Intraocular Lenses
16 COSMETIC OCULOPLASTIC SURGERY Eyelid, Forehead, and Facial Techniques
17 Glaucoma THE REQUISITES IN OPHTHALMOLOGY
18 LASIK Principles and Techniques
19 THE GLAUCOMAS
20 THE WILLS EYE MANUAL Office and emergency Room Deagnosis and Treatment of Eye Disease
21 Complications in Phacoemulsification (Avoidance, Recognition, and Management)
- :
( )
2004-2005
260,000
600,000
600,000
750,000
700,000
750,000
600,000
750,000
530,000
500,000
520,000
600,000
600,000
500,000
240,000
1100,000
200,000
300,000
200,000
250,000
180,000
220,000
400,000
2004-2005
2004-2005
2004-2005
2004-2005
2004-2005
2004-2005
2004-2005
2004-2005
2004-2005
2004-2005
2004-2005
2004-2005
2004-2005
2004-2005
2003
2001
1999
2000
1998
2000
1999
2002
94
- :

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COMMON

Edwin J. Jacobson, M.D.

Assisllwt Clinical Professor of Medicine

Clinical Professor of Medicine

A Harcourt Health ScienCes Company

W.B. SAUNDERS COMPANY

The Curtis Center

Ubrery of Congreaa Cataloglng-ln-Publlcatlon

Includes bibliographicaJ references and index.

COMMON MEDICAL DIAGNOSES: An Algorithmic Approach

Copyright C 2000, 1994, 1990 by w'B. Saunders Company.

Doctors lIealey and Jacobson have approached the

The purpose of this text has been to provide the

Jaime Moriguchi, Gayle Randall, and Martin Pops for

SIGNS AND SYMPTOMS.

SIGNS AND SYMPTOMS

Right Upper Quadrant and Left Upper Quadrant

SIGNS AND SYMPTOMS

Acid-Base and Electrolyte

SIGNS AND SYMPTOMS

SIGNS AND SYMPTOMS.

SIGNS AND SYMPTOMS

SIGNS AND SYMPTOMS.

SIGNS AND SYMPTOMS.

Common Medical Diagnoses

SIGNS AND SYMPTOMS

or her life. The causes of the fatigue usually are stress,

The. medical history and physical examination

2 Generalized Disorders Fatigue

worse in the evenings and is partially relieved by sleep.

Depression is probably the most common cause

Chroni.c viral infections are controversial causes

Chronic fatigue syndrome is the name given to

Chronic fatigue syndrome

The body's temperature

Culture of blood, bodily secretions, the throat,

Fever of Unknown Origin

Endocarditis should always be suspected in the

Lymj)homas arc the malignancies

Fever is a common fonn of aJlergic reaction to

of the lung, pancreas,

stomach is frequently associated with fever.

Cardiac myxomas are rare primary tumors of

Fever Of Unknown Origin

Non lupus vasculitis is a common cause of

Among the solid localized

As many as 10% of FUOs may go undiagnosed

Fever Of Unknown Origin

Involuntary weight loss is one of the most omi-

Weight loss may be caused by a deficiency of

Celiac disease (nontropical

8 GeneraJlzed Disorders Weight Loss

Several resins are used in the treatment of hyperlipidemia

Several drugs can cause weight loss as a result

Chronic infection is a common cause of weight

Weight loss and anorexia may be prominent

As much as 15% to 20% of total body weight

Social stresses, including poverty and physical

The causes of weight gain may include physical.

psychological, and socioeconomic factors. Six

Excessive caloric intake is the most common

reluctant to discuss their dietary habits or may

Several classes of drugs are associated with