Eugene C. Toy, MD
The John S. Dunn, Senior Academic Chair and Program Director
The Methodist Hospital Ob/Gyn Residency Program
Houston, Texas
Vice Chair of Academic Affairs
Department of Obstetrics and Gynecology
The Methodist Hospital
Houston, Texas
Associate Clinical Professor and Clerkship Director
Department of Obstetrics and Gynecology
University of Texas Medical School at Houston
Houston, Texas
Associate Clinical Professor
Weill Cornell College of Medicine
John T. Patlan, Jr., MD
Assistant Professor of Medicine
Department of General Internal Medicine
MD Anderson Cancer Center
Houston, Texas
New York Chicago San Francisco Lisbon London Madrid Mexico City
Milan New Delhi San Juan Seoul Singapore Sydney Toronto
THIRD EDITION
CASE FILES
®
Internal Medicine
Copyright © 2009 by The McGraw-Hill Companies, Inc. All rights reserved. Except as permitted under the United States Copyright
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ISBN: 978-0-07-161365-1
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or cause whatsoever whether such claim or cause arises in contract, tort or otherwise.
To our coach Victor, and our father–son teammates Bob & Jackson, Steve &
Weston, Ron & Wesley, and Dan & Joel. At the inspirational JH Ranch
Father–Son Retreat, all of us, including my loving son Andy, arrived as strangers,
but in 6 days, we left as lifelong friends.
— ECT
To my parents who instilled an early love of learning and of the written word,
and who continue to serve as role models for life.
To my beautiful wife Elsa and children Sarah and Sean, for their patience and
understanding, as precious family time was devoted to the completion of “the book.”
To all my teachers, particularly Drs. Carlos Pestaña, Robert Nolan,
Herbert Fred, and Cheves Smythe, who make the complex understandable,
and who have dedicated their lives to the education of physicians,
and served as role models of healers.
To the medical students and residents at the University of Texas–Houston Medical
School whose enthusiasm, curiosity, and pursuit of excellent and compassionate
care provide a constant source of stimulation, joy, and pride.
To all readers of this book everywhere in the hopes that it might help them to grow
in wisdom and understanding, and to provide better care for their patients who
look to them for comfort and relief of suffering.
And to the Creator of all things, Who is the source of all knowledge and healing
power, may this book serve as an instrument of His will.
— JTP
DEDICATION
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vii
CONTRIBUTOR
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The curriculum that evolved into the ideas for this series was inspired by
Philbert Yau and Chuck Rosipal, two talented and forthright students, who
have since graduated from medical school. It has been a tremendous joy to
work with my excellent coauthors, especially Dr. John Patlan, who exemplifies
the qualities of the ideal physician—caring, empathetic, and avid teacher, and
who is intellectually unparalleled. I am greatly indebted to my editor,
Catherine Johnson, whose exuberance, experience, and vision helped to shape
this series. I appreciate McGraw-Hill’s believing in the concept of teaching
through clinical cases. I am also grateful to Catherine Saggese for her excellent
production expertise, and Cindy Yoo for her wonderful editing. I cherish the
ever-organized and precise Gita Raman, senior project manager, whose friend-
ship and talent I greatly value; she keeps me focused, and nurtures each of my
books from manuscript to print. It has been a privilege and honor to work with
one of the brightest medical students I have encountered, Molly Dudley who
was the principal student reviewer of this book. She enthusiastically provided
feedback and helped to emphasize the right material. I appreciate Dorothy
Mersinger and Jo McMains for their sage advice and support. At Methodist,
I appreciate Drs. Judy Paukert, Dirk Sostman, Marc Boom and Alan Kaplan
who have welcomed our residents; John N. Lyle VII, a brilliant administrator
and Barbara Hagemeister, who holds the department together. Without my
dear colleagues, Drs. Weilie Tjoa, Juan Franco, Waverly Peakes, Nicolas
Stephanou, and Vincente Zapata, this book could not have been written. Most
of all, I appreciate my ever-loving wife Terri, and our four wonderful children,
Andy, Michael, Allison, and Christina, for their patience and understanding.
Eugene C. Toy
ACKNOWLEDGMENTS
ix

How to Approach
Clinical Problems
SECTION
I
➤ Part 1. Approach to the Patient
➤ Part 2. Approach to Clinical Problem Solving
➤ Part 3. Approach to Reading
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Clinical Pearl
➤ The history is the single most important tool in obtaining a diagnosis. All
physical findings and laboratory and imaging studies are first obtained
and then interpreted in the light of the pertinent history.
Part 1. Approach to the Patient
The transition from the textbook or journal article to the clinical situation is one
of the most challenging tasks in medicine. Retention of information is difficult;
organization of the facts and recall of a myriad of data in precise application to
the patient is crucial. The purpose of this text is to facilitate in this process. The
first step is gathering information, also known as establishing the database. This
includes taking the history (asking questions), performing the physical examina-
tion, and obtaining selective laboratory and/or imaging tests. Of these, the his-
torical examination is the most important and useful. Sensitivity and respect
should always be exercised during the interview of patients.
HISTORY
1. Basic information: Age, gender, and ethnicity must be recorded because
some conditions are more common at certain ages; for instance, pain on
defecation and rectal bleeding in a 20-year-old may indicate inflammatory
bowel disease, whereas the same symptoms in a 60-year-old would more
likely suggest colon cancer.

exclude potentially serious diagnoses.
4. Past history
a. Any illnesses such as hypertension, hepatitis, diabetes mellitus, cancer,
heart disease, pulmonary disease, and thyroid disease should be elicited.
If an existing or prior diagnosis is not obvious, it is useful to ask exactly
how it was diagnosed; that is, what investigations were performed.
Duration, severity, and therapies should be included.
b. Any hospitalizations and emergency room visits should be listed with the
reason(s) for admission, the intervention, and the location of the hospital.
c. Transfusions with any blood products should be listed, including any
adverse reactions.
d. Surgeries: The year and type of surgery should be elucidated and any
complications documented. The type of incision and any untoward
effects of the anesthesia or the surgery should be noted.
5. Allergies: Reactions to medications should be recorded, including severity
and temporal relationship to the medication. An adverse effect (such as
nausea) should be differentiated from a true allergic reaction.
6. Medications: Current and previous medications should be listed, including
dosage, route, frequency, and duration of use. Prescription, over-the-counter,
and herbal medications are all relevant. Patients often forget their complete
medication list; thus, asking each patient to bring in all their medications—
both prescribed and nonprescribed—allows for a complete inventory.
7. Family history: Many conditions are inherited, or are predisposed in family
members. The age and health of siblings, parents, grandparents, and oth-
ers can provide diagnostic clues. For instance, an individual with first-
degree family members with early onset coronary heart disease is at risk for
cardiovascular disease.
8. Social history: This is one of the most important parts of the history in that
the patient’s functional status at home, social and economic circumstances,
and goals and aspirations for the future are often the critical determinant in

be taken in lying and standing positions to look for orthostatic hypoten-
sion. It is quite useful to take the vital signs oneself, rather than relying
upon numbers gathered by ancillary personnel using automated equip-
ment, because important decisions regarding patient care are often made
using the vital signs as an important determining factor.
3. Head and neck examination: Facial or periorbital edema and pupillary
responses should be noted. Funduscopic examination provides a way to visu-
alize the effects of diseases such as diabetes on the microvasculature;
papilledema can signify increased intracranial pressure. Estimation of jugular
venous pressure is very useful to estimate volume status. The thyroid should
be palpated for a goiter or nodule, and carotid arteries auscultated for bruits.
Cervical (common) and supraclavicular (pathologic) nodes should be palpated.
4. Breast examination: Inspect for symmetry, skin or nipple retraction with
the patient’s hands on her hips (to accentuate the pectoral muscles), and
also with arms raised. With the patient sitting and supine, the breasts should
then be palpated systematically to assess for masses. The nipple should be
assessed for discharge and the axillary and supraclavicular regions should be
examined for adenopathy.
HOW TO APPROACH CLINICAL PROBLEMS 5
5. Cardiac examination: The point of maximal impulse (PMI) should be
ascertained for size and location, and the heart auscultated at the apex of
the heart as well as at the base. Heart sounds, murmurs, and clicks should
be characterized. Murmurs should be classified according to intensity,
duration, timing in the cardiac cycle, and changes with various maneu-
vers. Systolic murmurs are very common and often physiologic; diastolic
murmurs are uncommon and usually pathologic.
6. Pulmonary examination: The lung fields should be examined systemati-
cally and thoroughly. Wheezes, rales, rhonchi, and bronchial breath
sounds should be recorded. Percussion of the lung fields may be helpful in
identifying the hyperresonance of tension pneumothorax, or the dullness

cyanosis may be helpful. Clubbing of the nails might indicate pulmonary
diseases such as lung cancer or chronic cyanotic heart disease.
12. Neurological examination: Patients who present with neurological com-
plaints usually require a thorough assessment, including the mental status,
cranial nerves, motor strength, sensation, and reflexes.
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13. The skin should be carefully examined for evidence of pigmented lesions
(melanoma), cyanosis, or rashes that may indicate systemic disease (malar
rash of systemic lupus erythematosus).
LABORATORY AND IMAGING ASSESSMENT
1. Laboratory
a. CBC (complete blood count) to assess for anemia and thrombocytopenia.
b. Chemistry panel is most commonly used to evaluate renal and liver function.
c. Lipid panel is particularly relevant in cardiovascular diseases.
d. Urinalysis is often referred to as a “liquid renal biopsy,” because the
presence of cells, casts, protein, or bacteria provides clues about under-
lying glomerular or tubular diseases.
e. Gram stain and culture of urine, sputum, and cerebrospinal fluid, as well
as blood cultures, are frequently useful to isolate the cause of infection.
2. Imaging procedures
a. Chest radiography is extremely useful in assessing cardiac size and con-
tour, chamber enlargement, pulmonary vasculature and infiltrates, and
the presence of pleural effusions.
b. Ultrasonographic examination is useful for identifying fluid-solid inter-
faces, and for characterizing masses as cystic, solid, or complex. It is also
very helpful in evaluating the biliary tree, kidney size, and evidence of
Clinical Pearl
➤ Ultrasonography is helpful in evaluating the biliary tree,looking for ureteral

be added to increase the sensitivity and specificity of the test.
Individuals who cannot run on the treadmill (such as those with severe
arthritis), may be given medications such as adenosine or dobutamine
to “stress” the heart.
INTERPRETATION OF TEST RESULTS: USING PRETEST
PROBABILITY AND LIKELIHOOD RATIO
Because no test is 100% accurate, it is essential when ordering them to have
some knowledge of the test’s characteristics, as well as how to apply the test
results to an individual patient’s clinical situation. Let us use the example of
a patient with chest pain. The first diagnostic concern of most patients and
physicians regarding chest pain is angina pectoris, that is, the pain of
myocardial ischemia caused by coronary insufficiency. Distinguishing angina
pectoris from other causes of chest pain relies upon two important factors:
the clinical history, and an understanding of how to use objective testing. In
making the diagnosis of angina pectoris, the clinician must establish whether
the pain satisfies the three criteria for typical anginal pain: (1) retrosternal
in location, (2) precipitated by exertion, and (3) relieved within minutes by
rest or nitroglycerin. Then, the clinician considers other factors, such as
patient age and other risk factors, to determine a pretest probability for
angina pectoris.
After a pretest probability is estimated by applying some combination of sta-
tistical data, epidemiology of the disease, and clinical experience, the next deci-
sion is whether and how to use an objective test. A test should only be ordered
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if the results would change the posttest probability high enough or low enough
in either direction that it will affect the decision-making process. For example,
a 21-year-old woman with chest pain that is not exertional and not relieved by
rest or nitroglycerin has a very low pretest probability of coronary artery disease,

➤ Posttest Probability = Pretest Probability × Likelihood Ratio
➤ Likelihood Ratio = Sensitivity/(1 − Specificity)
HOW TO APPROACH CLINICAL PROBLEMS 9
Part 2. Approach to Clinical Problem Solving
There are typically four distinct steps to the systematic solving of clinical
problems:
1. Making the diagnosis
2. Assessing the severity of the disease (stage)
3. Rendering a treatment based on the stage of the disease
4. Following the patient’s response to the treatment
Figure I–1. Nomogram illustrating the relationship between pretest probability,
posttest probability, and likelihood ratio.
Reproduced with permission from Braunwald
E,Fauci AS,Kasper KL,et al.
Harrison’s Principles of Internal Medicine.
16th ed. New York,
NY: McGraw-Hill; 2005:10.
%
%
99
1
2
5
10
20
30
40
50
60
70

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MAKING THE DIAGNOSIS
There are two ways to make a diagnosis. Experienced clinicians often make a
diagnosis very quickly using pattern recognition, that is, the features of the
patient’s illness match a scenario the physician has seen before. If it does not
fit a readily recognized pattern, then one has to undertake several steps in
diagnostic reasoning:
1. The first step is to gather information with a differential diagnosis in mind.
The clinician should start considering diagnostic possibilities with initial
contact with the patient which are continually refined as information is
gathered. Historical questions and physical examination tests and findings
are all pursued tailored to the potential diagnoses one is considering. This is
the principle that “you find what you are looking for.” When one is trying to
perform a thorough head-to-toe examination, for instance, without looking
for anything in particular, one is much more likely to miss findings.
2. The next step is to try to move from subjective complaints or nonspecific
symptoms to focus on objective abnormalities in an effort to conceptualize
the patient’s objective problem with the greatest specificity one can
achieve. For example, a patient may come to the physician complaining of
pedal edema, a relatively common and nonspecific finding. Laboratory
testing may reveal that the patient has renal failure, a more specific cause
of the many causes of edema. Examination of the urine may then reveal red
blood cell casts, indicating glomerulonephritis, which is even more specific
as the cause of the renal failure. The patient’s problem, then, described
with the greatest degree of specificity, is glomerulonephritis. The clini-
cian’s task at this point is to consider the differential diagnosis of glomeru-
lonephritis rather than that of pedal edema.
3. The last step is to look for discriminating features of the patient’s illness.

would not be a good candidate for chemotherapy might be best left alone with-
out any diagnostic testing. Decisions like this are difficult, require solid med-
ical knowledge, as well as a thorough understanding of one’s patient and the
patient’s background and inclinations, and constitute the art of medicine.
ASSESSING THE SEVERITY OF THE DISEASE
After ascertaining the diagnosis, the next step is to characterize the severity
of the disease process; in other words, it is describing “how bad” a disease is.
There is usually prognostic or treatment significance based on the stage.With
malignancy, this is done formally by cancer staging. Most cancers are catego-
rized from stage I (localized) to stage IV (widely metastatic). Some diseases,
such as congestive heart failure, may be designated as mild, moderate, or
severe based on the patient’s functional status, that is, their ability to exercise
before becoming dyspneic. With some infections, such as syphilis, the staging
depends on the duration and extent of the infection, and follows along the
natural history of the infection (ie, primary syphilis, secondary, latent period,
and tertiary/neurosyphilis).
Clinical Pearl
➤ There are three steps in diagnostic reasoning:
1. Gathering information with a differential diagnosis in mind
2. Identifying the objective abnormalities with the greatest specificity
3. Looking for discriminating features to narrow the differential diagnosis
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TREATING BASED ON STAGE
Many illnesses are stratified according to severity because prognosis and treat-
ment often vary based on the severity. If neither the prognosis nor the treat-
ment was affected by the stage of the disease process, there would not be a
reason to subcategorize as mild or severe. As an example, a man with mild
chronic obstructive pulmonary disease (COPD) may be treated with inhaled

dent must be prepared to know what to do if the measured marker does not
respond according to what is expected. Is the next step to retreat, or to repeat
the metastatic workup, or to follow up with another more specific test?