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FIRSTAID

Q&AFOR THE
USMLE
STEP 1
Third Edition
SENIOR EDITORS
Tao Le, MD, MHS James A. Feinstein, MD
Associate Clinical Professor Clinical Instructor, Section of General Pediatrics
Chief, Section of Allergy and Clinical Immunology The Children's Hospital Colorado
Department of Medicine Research Fellow
University of Louisville Primary Care Research Program
University of Colorado School of Medicine

EDITORS
Mark W. Ball, MD Kimberly Kallianos
Resident Harvard Medical School
The James Buchanan Brady Urological Institute Class of 2012
The Johns Hopkins Hospital
Cesar Raudel Padilla
Annie Dude, MD University of Rochester School of Medicine
Resident Class of 2012
Department of Obstetrics and Gynecology
Duke University Medical Center Lauren Rothkopf, MD
Masters in Public Health candidate
Rebecca L. Hoffman, MD Temple University College of Health Professions and
Resident Social Work
Department of General Surgery
Hospital of the University of Pennsylvania James Yeh, MD
Resident
Mark Robert Jensen Department of Medicine
University of Rochester School of Medicine Cambridge Hospital, Cambridge Health Alliance
Class of 2012

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P O W E R E D BY usmte

FIRST AID
STEP 1 EXPRESS

FIRST AID

RESPIRATORY
PHYSIOLOGY
TAO LE, MD, MHS The official FIRST AID course
Assistant Clinical Professor of Medicine and Pediatrics
Chief, Section of Allergy and Immunology
Department of Medicine
by the FIRST AID authors
University of Louisville

50+ hours of high-yield online


lectures based on FIRST AID
600+ new color images & multimedia
expand key FIRST AID concepts
Exclusive FIRST AID color PDF
workbook reinforces your test prep
Watch as many times as you want
100% pass guarantee!
See website for Terms and Conditions.

www.usmlerx.com
D e d i c at i o n

To the contributors to this and future editions, who took time to share their
knowledge, insight, and humor for the benefit of students, residents, and
clinicians.

and

To our families, friends, and loved ones, who supported us in the task of
assembling this guide.
This page intentionally left blank
Contents

Authors vii

Preface ix

Acknowledgments xi

How to Contribute xiii

S EC T I O N I G e n e r al P r i n c i p le s 1

Chapter 1 Behavioral Science 3

Chapter 2 Biochemistry 17

Chapter 3 Embryology 53

Chapter 4 Microbiology 71

Chapter 5 Immunology 101

Chapter 6 Pathology 123

Chapter 7 Pharmacology 141

S EC T I O N I I O r g a n Syst e m s 15 9

Chapter 8 Cardiovascular 161

Chapter 9 Endocrine 197

Chapter 10 Gastrointestinal 233

Chapter 11 Hematology-Oncology 271

Chapter 12 Musculoskeletal 307

Chapter 13 Neurology 339

Chapter 14 Psychiatry 363

Chapter 15 Renal 379

Chapter 16 Reproductive 415

Chapter 17 Respiratory 451

v
S EC T I O N I I I F u ll-Le ng t h E x am i nat i o n s 487

Test Block 1 489

Test Block 2 527

Test Block 3 563

Test Block 4 599

Test Block 5 633

Test Block 6 669

Test Block 7 705

Appendix: Common Laboratory Values 741

Index 743

About the Authors 767

vi
AUTHORS

Kirsten Austad Katherine Latimer


Fellow Johns Hopkins University School of Medicine
Edmond J. Safra Center for Ethics Class of 2012
Harvard University
Joseph Liao
Eike Blohm Boston University School of Medicine
Johns Hopkins University School of Medicine Class of 2012
Class of 2012
Jerry Loo
Benjamin Caplan, MD University of Southern California Keck School of Medicine
Resident Class of 2012
Department of Family Medicine
Boston University Aya Michaels, MD
Resident
Po-Hao Chen Department of Radiology
Harvard Medical School Brigham and Womens Hospital
Class of 2012
Somala Muhammed, MD
Lauren de Leon, MD Resident
Intern Department of General Surgery
Department of Internal Medicine
Baylor College of Medicine
The Alpert Medical School of Brown University
Behrouz Namdari, MD
Philip Eye Resident
Boston University School of Medicine
Department of Psychiatry
Class of 2012
Duke University Medical Center
Jim Griffin, MD
Resident
Tashera Perry, MD
Resident
Department of Surgery and Surgical Oncology
Department of Obstetrics and Gynecology
Johns Hopkins Hospital
The University of Illinois at Chicago School of Medicine
John Hegde
Harvard Medical School Christopher Roxbury
Class of 2012 Johns Hopkins University School of Medicine
Class of 2012
Emily Heikamp
Johns Hopkins University School of Medicine Neepa Shah
Class of 2014 Boston University
Class of 2012
Thomas Robert Hickey, MD
Resident Bethany Strong
Department of Anesthesiology Harvard Medical School
Brigham and Womens Hospital Class of 2012

Henry R. Kramer, MD Seenu Susarla, MD, DMD, MPH


Resident Resident
Department of Medicine Department of Oral & Maxillofacial Surgery
Massachusetts General Hospital Massachusetts General Hospital

Thomas Lardaro Jeffrey Tosoian


Johns Hopkins University School of Medicine Johns Hopkins University School of Medicine
Class of 2012 Class of 2012

vii
Jackson Vane, MD Marc E. Walker
Resident Harvard Medical School
Department of Pediatrics Class of 2012
University of California, Irvine School of Medicine

Daniel J. Verdini, MD
Resident
Department of Internal Medicine
University of Nevada School of Medicine at Reno

viiiviii
Preface

With the third edition of First Aid Q&A for the USMLE Step 1, we continue
our commitment to providing students with the most useful and up-
to-date preparation guides for the USMLE Step 1. This new edition represents
an outstanding effort by a talented group of authors and includes the following:

Almost 1000 high-yield USMLE-style questions based on the top-rated


USMLERx Qmax Step 1 Test Bank (www.usmlerx.com)
Concise yet complete explanations to correct and incorrect answers
Questions organized by general principles and organ systems
Seven full-length test blocks simulate the actual exam experience
High-yield images, diagrams, and tables complement the questions and
answers
Organized as a perfect complement to First Aid for the USMLE Step 1

We invite you to share your thoughts and ideas to help us improve First Aid
Q&A for the USMLE Step 1. See How to Contribute, p. xiii.

Louisville Tao Le
Denver James A. Feinstein

ixix
ix
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Acknowledgments

This has been a collaborative project from the start. We gratefully acknowl-
edge the thoughtful comments and advice of the medical students, interna-
tional medical graduates, and faculty who have supported the authors in the
continuing development of First Aid Q&A for the USMLE Step 1.

For support and encouragement throughout the project, we are grateful to


Thao Pham, Louise Petersen, Selina Franklin, Jonathan Kirsch, and Vikas
Bhushan. Thanks to our publisher, McGraw-Hill, for the valuable assistance
of their staff. For enthusiasm, support, and commitment to this challenging
project, thanks to our editor, Catherine Johnson. For outstanding editorial
work, we thank Mary Dispenza and Emma D. Underdown. A special thanks
to Rainbow Graphics for remarkable production work.

Louisville Tao Le
Denver James A. Feinstein

xi
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How to Contribute

This edition of First Aid Q&A for the USMLE Step 1 incorporates hundreds of contributions and
changes suggested by faculty and student reviewers. We invite you to participate in this process. We also
offer paid internships in medical education and publishing ranging from three months to one year (see
next page for details). Please send us your suggestions for:

Corrections or enhancements to existing questions and explanations


New high-yield questions
Low-yield questions to remove

For each entry incorporated into the next edition, you will receive a $10 gift certificate, as well as per-
sonal acknowledgment in the next edition. Diagrams, tables, partial entries, updates, corrections, and
study hints are also appreciated, and significant contributions will be compensated at the discretion of
the authors.

The preferred way to submit entries, suggestions, or corrections is via our blog:
www.firstaidteam.com

Alternatively, you can email us at: firstaidteam@yahoo.com. All entries become property of the authors
and are subject to editing and reviewing. Please verify all data and spellings carefully. In the event that
similar or duplicate entries are received, only the first entry received will be used. Include a reference to
a standard textbook to facilitate verification of the fact. Please follow the style, punctuation, and format of
this edition if possible.

I N TER N SHI P O P P ORTU N ITIES

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publishing to motivated medical students and physicians. Internships may range from three months (e.g.,
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editing experience, familiarity with Microsoft Word, and Internet access are desired. For more informa-
tion, e-mail a rsum or a short description of your experience along with a cover letter to firstaidteam@
yahoo.com.

xiii
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Section I

General Principles

Behavioral Science

Biochemistry

Embryology

Microbiology

Immunology

Pathology

Pharmacology

1
This page intentionally left blank
Chapter 1

Behavioral Science

3
High-Yield Principles
4 Section I: General Principles Questions

Q u e st i o n s

1. Researchers investigating the development comes nervous before a test, he feels as if he


of the idiopathic inflammatory myopathies cannot move his legs. He admits that he has
(IIMs) such as polymyositis read that vitamin even fallen to the floor because of leg weak-
D may act as an immunomodulator that re- ness while laughing. Which of the following is
duces the development and severity of autoim- the best choice for treating this patient?
mune diseases. Given that many Americans
(A) Chloral hydrate
are vitamin D deficient, the researchers design
(B) Hydroxyzine
an observational study to assess the impact of
(C) Modafinil
vitamin D supplementation on IIM symptom
(D) Prochlorperazine maleate
severity. Subjects are surveyed at time 0 and af-
(E) Zolpidem
Behavioral Science

ter two years, and the results are listed in the


chart. Which equation represents the chance 3. A 52-year-old woman is being treated by a
of symptom improvement in subjects who took male psychiatrist for depression stemming
vitamin D supplements relative to subjects from her recent divorce. Recently, the patient
who did not take vitamin D supplements? has been coming to her appointments dressed
up and wearing expensive perfumes. She has
also started to flirt with the doctor. The pa-
Vitamin D Vitamin D
supplement supplement tients demeanor and appearance had initially
taken not taken reminded the psychiatrist of his aunt. He is
Symptoms improved 50 60 uncomfortable with the patients new behav-
ior patterns and tells her so. She becomes very
Symptoms not
300 400 angry and storms out of the office, canceling
improved
all remaining appointments on her way out.
Reproduced, with permission, from USMLERx.com.
Which of the following behaviors is an exam-
ple of negative transference?
(A) The doctor seeing the patient as his aunt
(A) (50 / 300) / (60 / 400) (B) The doctor telling the patient he is un-
(B) (50 / 350) / (60 / 460) comfortable
(C) (50 / 460) / (60 / 300) (C) The patient being angry with the doctor
(D) (60 / 400) / (50 / 300) (D) The patient dressing up for appointments
(E) (60 / 460) / (50 / 350) (E) The patient flirting with the doctor
2. A 16-year-old boy is brought to the pediatri- 4. A 28-year-old woman presents to her primary
cian by his mother because of excessive day- care physician because of depressed mood.
time sleepiness. She states that over the past She states that she has been depressed for as
six months she has received numerous phone long as she can remember and feels bad about
calls from the boys school informing her herself almost all of the time. She states that
that her son sleeps throughout all of his after- her only happy moments were during her hon-
noon classes and is often difficult to arouse at eymoon two years ago, and during a ski trip in
the end of class. The patient reports that oc- college when she felt on top of the world.
casionally when he wakes up in the morning She confides that for a couple weeks last
he cannot move for extended periods. He says month she felt life was no longer worth living.
that sometimes when he laughs at jokes or be- At that time, she was having extreme difficulty
High-Yield Principles
Chapter 1: Behavioral Science Questions 5

sleeping, a complete loss of energy, and a lack 7. The figure below is a common representation
of appetite. A review of the patients history used in studying the characteristics of a tests
shows that during the past two years she has results. Using the letters in the figure, which
seen a physician for complaints of stomach up- of the following accurately describes the preva-
set, fatigue, headaches, and an unintentional lence of the disease?
3.6-kg (8-lb) weight gain. Physical examina-
tion and results of laboratory tests are within
normal limits. Which of the following is an ad- Disease
verse effect the patient may experience during +
the course of the treatment of this illness?
(A) Agranulocytosis + W X
(B) Anorgasmia

Test

Behavioral Science
(C) Arrhythmia
(D) Polyuria
(E) Stevens-Johnson syndrome Y Z

5. A 6-year-old girl is brought to the pediatrician


by her mother because of fecal incontinence. Reproduced, with permission, from USMLERx.com.
The mother says this behavior usually occurs
at school. According to Freud, which stage of
psychosexual development has this child failed (A) (W+X) / (W+X+Y+Z)
to progress through? (B) (W+Y) / (W+X+Y+Z)
(A) Anal stage (C) W / (W+X+Y+Z)
(B) Genital stage (D) W / (X+Y+Z)
(C) Latency stage (E) W / (X+Z)
(D) Oral stage
8. A 75-year-old man is recovering in the hospi-
(E) Phallic stage
tal from a left-sided below-the-knee amputa-
6. A 20-year-old man became very agitated at a tion. Three days after the surgery, the patient
party, and as a result was brought to the emer- suddenly develops chest pain and shortness of
gency department. In the waiting room he is breath that last for 20 minutes. His pain medi-
belligerent and uncooperative. A physical ex- cation is increased, which improves the pain
amination reveals fever, tachycardia, horizon- but not the shortness of breath. X-ray of the
tal nystagmus, hyperacusis, and pupils that are chest is negative for a pulmonary embolus, so
3 mm in diameter bilaterally. Which of the the medical team decides to monitor him ex-
following substances is most likely causing the pectantly. The next day, a similar episode of
behavioral changes and physical findings ex- shortness of breath and chest pain occurs. The
hibited by this patient? patient then sustains cardiac arrest and dies.
Autopsy reveals multiple pulmonary emboli.
(A) Alcohol The family threatens to sue for malpractice for
(B) Amphetamines mismanaged postoperative care. Which of the
(C) Cocaine following is necessary to prove malpractice?
(D) Lysergic acid diethylamide
(E) Nicotine (A) A patient directly suffers harm
(F) Phencyclidine (B) A physicians presence at the time of injury
(C) Intent to harm
(D) Proof beyond reasonable doubt
(E) Use of standard procedures
High-Yield Principles
6 Section I: General Principles Questions

9. A 2-month-old boy is brought to the emer- (A) 8%


gency department with respiratory insuffi- (B) 20%
ciency and failure to thrive. The pregnancy (C) 80%
and perinatal course were uneventful. Gener- (D) 85%
alized hypotonia, tongue fasciculations, and (E) 93%
flaccid paralysis are noted on physical exami-
nation. His hospital stay is complicated by the 11. A 66-year-old man presents to his primary care
development of tracheobronchomalacia and physician with a complaint of erectile dysfunc-
respiratory insufficiency that necessitates me- tion. His past history is significant for hyper-
chanical ventilation. Despite these efforts, tension, type 2 diabetes mellitus, peripheral
the patient dies of respiratory complications. vascular disease, and coronary artery disease
Muscle biopsy shows denervation and panfas- status postmyocardial infarction. His current
cicular atrophy. A genetics consult yields the medications are propranolol, captopril, aspirin,
Behavioral Science

pedigree shown in the image. Which of the lovastatin, metformin, fluoxetine, and sublin-
following diseases is most consistent with this gual nitroglycerin. On further questioning, he
patients presentation and the pedigree shown admits to wanting a prescription for sildenafil.
in the image? Which of his medications is unsafe to take
with sildenafil?
(A) Aspirin
(B) Captopril
(C) Fluoxetine
(D) Lovastatin
(E) Metformin
(F) Nitroglycerin
(G) Propranolol

12. A 17-year-old girl presents to her primary care


Reproduced, with permission, from USMLERx.com. physician with a complaint of missed menses.
A urine pregnancy test confirms that she is
pregnant. She returns to the office two weeks
(A) Becker muscular dystrophy later asking for recommendations on obtaining
(B) Duchenne muscular dystrophy an abortion. She explains that she works, lives
(C) Kugelberg-Welander disease with her husband, and is not ready for a child.
(D) Spinal muscular atrophy, type II She decides that she does not want to notify
(E) Werdnig-Hoffmann disease anyone, and says she has chosen not to talk
with her parents for many months. Her doctor
10. A new screening test for the development of understands that he must abide by her wishes
mitral regurgitation in the setting of rheumatic because she is emancipated. Which of the fol-
fever is created. A study of 1000 patients with a lowing makes this patient emancipated?
history of Streptococcus pyogenes infection and
(A) Age 17 years is considered an adult
a diagnosis of rheumatic fever is performed
(B) Full-time work
using this test, which has 90% sensitivity and
(C) High school diploma
85% specificity. The prevalence of mitral re-
(D) Living separately from her parents
gurgitation in this population is estimated to
(E) Marriage
be 40%. What is the positive predictive value
of this test?
High-Yield Principles
Chapter 1: Behavioral Science Questions 7

13. A group of scientists decides to conduct a study (D) Projection of the areola and papilla (with
addressing the long-term effects of maternal separate contours), and adult-type pubic
alcohol consumption on their infants after hair limited to the genital area
conception. Two hundred women, including (E) Small breast buds with elevation of breast
those who suffer from alcoholism and those papilla, and sparse, straight, downy hair on
who do not, are recruited into the study when the labial base
they present for their first primary care visit. A
medical history is taken on alcohol use, prena- 15. A 10-year-old Hispanic boy is admitted for
tal care, nutritional status, and smoking behav- bone marrow transplantation as treatment
iors; these are measured monthly during the for acute myelogenous leukemia. The doctor
pregnancy. The researchers follow the wom- wants to enroll the patient in a clinical trial
ens pregnancies until term, after which they for a new pain medication, but both the par-
devote their attention to the health and behav- ents speak only Spanish. The consent form

Behavioral Science
iors of the offspring. Which of the following is in English, and the physician has a limited
is the most appropriate statistic the research- knowledge of Spanish. What is the physicians
ers will be able to calculate as a result of their best option for obtaining consent from this pa-
study? tient?
(A) Attributable risk of offspring abnormalities (A) Explain the study to the whole family in
in mothers who smoke Spanish, to the best of the physicians abil-
(B) Odds ratio of offspring abnormalities in ity
mothers who consume alcohol during (B) Have a Spanish-speaking employee of the
pregnancy hospital translate for the patient
(C) Prevalence of alcohol consumption during (C) Have the parents sign the English form af-
pregnancy ter discussing the study via an interpreter
(D) Proportion of all offspring abnormalities (D) Obtain a translated consent form and dis-
that are due to alcohol consumption dur- cuss the study via an interpreter
ing pregnancy (E) The boy speaks English, so the parents
(E) Relative risk of offspring abnormalities in consent will not be required
mothers who consume alcohol during
pregnancy 16. A 70-year-old man comes into his doctors of-
fice for a routine check-up. His past medi-
14. An 11-year-old girl is brought to the pediatri- cal history is significant for a heart attack,
cian with complaints of back pain. On physical for which he takes a daily baby aspirin and a
examination, a right thoracic scoliotic curve is b-blocker. He practices safe habits and always
noted. The pediatrician mentions to the parent wears his seat belt while driving. His health
that the development of adolescent idiopathic has been great for the past few years, al-
scoliosis is due to the girl being at peak height though he is concerned about his wife because
growth velocity. Peak height velocity is associ- she recently suffered a mild stroke. He denies
ated with a certain Tanner stage; what other any visual loss or motor or sensory weakness.
physical attributes would one expect to occur The patients physical examination is unre-
in this girl at the same time? markable. Which of the following is the lead-
ing cause of death among people age 65 years
(A) Elevation of the breast papilla only, and no
or older?
pubic hair
(B) Enlargement of the breast and areola with (A) Heart disease
a single contour, and darker, coarse, curled (B) Malignancy
pubic hair (C) Motor vehicle crashes
(C) Mature breast, and adult quantity and pat- (D) Stroke
tern of pubic hair that extends to the (E) Suicide
thighs
High-Yield Principles
8 Section I: General Principles Questions

17. A 54-year-old man with a history of poorly con- (A) The incidence rate of diabetes among
trolled hypertension complains of new-onset mothers with LGA babies is four times that
headaches. His mother passed away at an early of non-LGA mothers
age due to a stroke, and his father died of a (B) The incidence rate of LGA among women
myocardial infarction. When asked why he with diabetes is four times that of women
does not take better care of his blood pressure, without diabetes
he states that he is so busy with work and with (C) The incidence rate of LGA among women
the church that, by the end of the day, he often without diabetes is four times that of
forgets to take his pills. He states that he feels women with diabetes
fine, anyway. What ego defense mechanism is (D) The odds of diabetes among mothers with
this patient using? LGA babies is four times that of non-LGA
mothers
(A) Denial
(E) The odds of LGA among women with dia-
Behavioral Science

(B) Displacement
betes is four times that of women without
(C) Projection
diabetes
(D) Rationalization
(E) Repression
20. A 45-year-old man presents to a psychiatrist at
his wifes prompting. He is an English profes-
18. A 3-year-old girl presents for her regular check-
sor at the University of Virginia and regularly
up. Her mother reports that she is fully toilet
wins accolades for his well-organized and ar-
trained, and that she can dress and undress
ticulate lectures. In the past three months, he
with minor assistance. She speaks in full sen-
has become convinced that his wife is having
tences, can name four colors, and can copy a
an affair with a co-worker, despite her protests
simple circle drawing. What other milestone
to the contrary. His wife recently discovered
would this child most likely have reached
that he hired a private investigator to track her
since her last visit one year ago?
whereabouts. He is very defensive when the
(A) Engages in cooperative play counselor questions his suspicions about his
(B) Has imaginary friend(s) wife. Mental status examination reveals a well-
(C) Hops on one foot dressed, middle-aged man without hallucina-
(D) Reads tions or other mood disturbances. His speech
(E) Rides a tricycle is normal and displays an appropriate affec-
(F) Stacks five blocks tive range. Which of the following is the most
likely diagnosis?
19. A retrospective cohort study is examining birth
complications in women with diabetes. The (A) Antisocial personality disorder
study determines that babies are more likely to (B) Avoidant personality disorder
be born large for gestational age (LGA) if the (C) Delusional disorder
mother has diabetes. The relative risk for the (D) Schizoid personality disorder
study is calculated to be 4. Which of the fol- (E) Schizophrenia
lowing accurately describes this relative risk? (F) Schizophreniform disorder
High-Yield Principles
Chapter 1: Behavioral Science Answers 9

An s w e r s

1. The correct answer is B. This prospective, ob- 2. The correct answer is C. This patient exhib-
servational study is a cohort study. Therefore, its some of the classic symptoms of narcolepsy,
the likely unit of measure is the relative risk, including daytime sleepiness, cataplexy, and
which is the risk of a health outcome with a sleep paralysis. Cataplexy is defined as brief
given exposure versus the risk of a health out- episodes of bilateral weakness brought on by
come without the exposure. In this case, the strong emotions such as laughing or fear, with-
relative risk of a health outcome is really the out alteration in consciousness. Sleep paralysis
relative chance of improvement of symptoms. is an episode of partial or total paralysis that
To calculate the relative risk, first calculate occurs at the beginning or end of a sleep cycle.
the chance of improvement with vitamin D Patients are often aware that they are awake,

Behavioral Science
supplementation by dividing the number of but may suffer from frightening hallucina-
subjects receiving supplementation whose tions known as hypnagogic when they occur
symptoms improved (50) by the total number at sleep onset, and hypnopompic when they
of subjects taking vitamin D; this is 50/350. occur on awakening. Modafinil is an amphet-
Then calculate the chance of improvement amine derivative used to treat attention deficit/
without vitamin D supplementation by divid- hyperactivity disorder and narcolepsy. Patients
ing the number of subjects not receiving sup- suffering from cataplexy and sleep paralysis
plementation whose symptoms improved by may also benefit from the initiation of tricyclic
the total number of subjects not taking vitamin antidepressants or selective serotonin reuptake
D; this is 60 / 460. The ratio of these values is inhibitors.
the relative risk: (50 / 350) / (60 / 460).
Answer A is incorrect. Chloral hydrate is a
Answer A is incorrect. This value does not ap- nonbenzodiazepine hypnotic that is used for
propriately calculate the relative risk with vita- sedation and insomnia. This patient does not
min D supplementation. The value is equiva- need help sleeping.
lent to the odds ratio, which is the measure
Answer B is incorrect. Hydroxyzine is a non-
typically used to analyze a retrospective, case-
selective antihistamine that is used in the treat-
control study.
ment of anxiety, pruritus, nausea/vomiting, se-
Answer C is incorrect. This value does not ap- dation, and insomnia.
propriately calculate the relative risk with vita-
Answer D is incorrect. Prochlorperazine
min D supplementation. It does not represent
maleate is a typical antipsychotic used in the
any commonly used measure of analysis.
treatment of nausea, vomiting, anxiety, and
Answer D is incorrect. This value does not ap- psychosis.
propriately calculate the relative risk with vita-
Answer E is incorrect. Zolpidem is a nonben-
min D supplementation. Instead, the value is
zodiazepine hypnotic that is used in the treat-
essentially equivalent to the inverse of a calcu-
ment of insomnia.
lation for odds ratio, which is not a measure
used in data analysis. 3. The correct answer is C. Transference occurs
Answer E is incorrect. This value does not ap- when a patient projects feelings from his or her
propriately calculate the relative risk of vitamin personal life onto a doctor; countertransfer-
D supplementation. The value instead calcu- ence takes place when the doctor projects feel-
lates the chance of improvement without vita- ings onto the patient. These feelings can be
min D supplementation relative to the chance either positive or negative. The patients anger
of improvement with vitamin D supplementa- at the doctor when her sexual advances are re-
tion. This is the inverse of what the question buffed is an example of negative transference.
asked.
High-Yield Principles
10 Section I: General Principles Answers

Answer A is incorrect. The doctor being re- est (anhedonia), Guilt, Energy loss, Concen-
minded of his aunt by this patient is an exam- tration changes, Appetite changes, Psychomo-
ple of countertransference. tor abnormalities, and Suicidal thoughts (SIG
E CAPS). One of the symptoms has to be de-
Answer B is incorrect. The doctor telling the
pressed mood or anhedonia. Major depressive
patient that he is uncomfortable is not an ex-
disorder is diagnosed after a major depressive
ample of countertransference or transference.
episode without a history of mania, hypoma-
Answer D is incorrect. The patient dressing nia, or mixed episodes (when criteria for both
up for appointments is positive transference. manic and major depressive episode are simul-
Answer E is incorrect. The patient flirting taneously present for at least one week), and
with the doctor is positive transference. In its is further specified by modifiers such as recur-
most extreme form, positive transference can rent, chronic, or postpartum onset.
Behavioral Science

take the form of sexual desire. Answer C is incorrect. Arrhythmias are a


well-known adverse effect of the tricyclic anti-
4. The correct answer is D. This patient has a depressants. This class of medications, which
history of at least one major depressive episode includes imipramine, clomipramine, and
and at least one hypomanic episode without amitriptyline, work to block the reuptake of
the presence of mixed or manic episodes, a his- norepinephrine and serotonin. They are com-
tory consistent with bipolar II disorder. Treat- monly used medications in the treatment of
ment for this disorder is a mood stabilizer, major depression, obsessive compulsive disor-
most commonly lithium. A common adverse der, and fibromyalgia. However, the patient in
effect of this therapy is nephrogenic diabetes this case has a clinical history most consistent
insipidus, in which the principal cells of the with bipolar II disorder, and thus a mood sta-
renal collecting duct are unable to respond to bilizer such as lithium should be used rather
ADH secreted by the posterior pituitary. As a than an antidepressant, which could lead to
result, the patient will be unable to concen- further manic episodes in this patient.
trate urine and will thus experience frequent
urination. Answer E is incorrect. Stevens-Johnson syn-
drome is a well-known adverse effect of carba-
Answer A is incorrect. Agranulocytosis is a tox- mazepine, an anti-epileptic drug that is some-
icity associated with clozapine, an atypical an- times used to treat bipolar disorder. Although
tipsychotic. This medication is generally used this patient has a medical history consistent
in treatment of schizophrenia, but may be with bipolar II disorder, first-line treatment is
used in cases of mania that are unresponsive to generally with a different mood stabilizer such
first-line drugs such as lithium. Although the as lithium, as this medication has been proven
patient did have a history of a hypomanic epi- effective, is cheaper, and has a relatively less
sode, there is no indication for clozapine as a severe adverse-effect profile.
first-line treatment for bipolar II disorder.
Answer B is incorrect. Anorgasmia is a com- 5. The correct answer is A. The proper stage se-
mon adverse effect of selective serotonin quence of Freuds psychosexual theory is oral,
reuptake inhibitors. This class of medication, anal, phallic, latency, and genital. Freuds the-
which includes fluoxetine, paroxetine, sertra- ories of psychosexual development associate
line, and citalopram, is commonly used in the pleasure with certain bodily functions. Freud
treatment of major depression. Although this believed that between the ages of 18 months
patient has a history of feeling depressed, she and 3 years, children are preoccupied with
also has a history notable for a hypomanic epi- anal functions. Encopresis is fecal inconti-
sode. A major depressive episode is diagnosed nence and can range from mild to severe.
if the patient has 5/9 symptoms for at least two Answer B is incorrect. Freuds genital stage
weeks, including Sleep changes, loss of Inter- encompasses adolescents to adults and is char-
High-Yield Principles
Chapter 1: Behavioral Science Answers 11

acterized by the desire to achieve sexual grati- Answer C is incorrect. Patients presenting
fication. with acute cocaine intoxication will show
symptoms of euphoria, psychomotor agitation,
Answer C is incorrect. Freuds latency stage
impaired judgment, tachycardia, pupillary di-
encompasses the ages of 6-12 years and is char-
lation, hypertension, hallucinations, paranoid
acterized by a suppression of sexual desire.
ideations, angina, and sudden cardiac death.
Answer D is incorrect. Freuds oral stage en- On withdrawal, they will show a post-use
compasses birth to the age of 18 months. crash that includes severe depression, hyper-
Freud believed that children of this age gain somnolence, fatigue, malaise, and severe psy-
satisfaction from oral functions. chological craving.
Answer E is incorrect. Freuds phallic stage Answer D is incorrect. Patients presenting
encompasses the ages of 3-5 years and is most with acute lysergic acid diethylamide intoxica-
commonly known as the oedipal phase. Freud

Behavioral Science
tion will display marked anxiety or depression,
believed that at this stage children begin to de- delusions, visual hallucinations, flashbacks,
velop sexual fantasies. and pupillary dilation.

6. The correct answer is F. This patient has Answer E is incorrect. Patients presenting
taken phencyclidine, or PCP. Patients with with acute nicotine intoxication will show
PCP intoxication show signs of belligerence, symptoms of restlessness, insomnia, anxiety,
impulsiveness, fever, psychomotor agitation, and arrhythmias. On withdrawal, they will
vertical and horizontal nystagmus, tachycardia, have symptoms of irritability, headache, anxi-
ataxia, homicidality, psychosis, and delirium. ety, weight gain, craving, and tachycardia.
On withdrawal, patients may demonstrate a
7. The correct answer is B. The prevalence is
recurrence of intoxication when the PCP,
the number of individuals with a disease in a
which was trapped in an ionized form in the
given population at a given time. Prevalence is
acidic gastric lumen, is reabsorbed in the alka-
estimated by test results but is not a measure of
line duodenum. PCP users will have normal
a tests validity. In the chart shown, the preva-
or small pupils. Death can result from a variety
lence can also be determined by calculating
of causes, including respiratory depression and
the number of true-positive plus false-negative
violent behavior.
results divided by the total number of patients.
Answer A is incorrect. Patients presenting with
Answer A is incorrect. This term represents
acute alcohol intoxication will show symptoms
the incidence of positive test results.
of disinhibition, emotional lability, slurred
speech, ataxia, coma, and blackouts. On with- Answer C is incorrect. This represents true-
drawal, they will demonstrate a tremor, tachy- positive results divided by the total number of
cardia, hypertension, malaise, nausea, seizures, patients. This would be the percent of true-
delirium tremens, tremulousness, agitation, positive results of all tested, but it is not used
and hallucinations. very often.
Answer B is incorrect. Patients presenting Answer D is incorrect. This represents true-
with amphetamine intoxication will display positive results divided by the total number of
psychomotor agitation, impaired judgment, patients tested less those with true-positive re-
pupillary dilation, hypertension, tachycardia, sults, and would not be a meaningful calcula-
euphoria, prolonged wakefulness and atten- tion.
tion, cardiac arrhythmias, delusions, hallucina-
Answer E is incorrect. This represents the
tions, and fever. On withdrawal, they will show
number of true-positive results over the to-
a post-use crash that includes depression,
tal number of patients without disease. This
lethargy, headache, stomach cramps, hunger,
would not be a meaningful calculation.
and hypersomnolence.
High-Yield Principles
12 Section I: General Principles Answers

8. The correct answer is A. Malpractice suits fascicles (panfascicular atrophy). Unlike SMA
require that the patient prove dereliction, types II and III, this patients disease developed
damage, and direct harm by a physician with at an early age, so early milestones were not
whom there was an established relationship. achieved. This is not the case in the less severe
Direct harm is a concept that the injury is forms of SMA.
causally related to the actions of the physician.
Answer A is incorrect. BMD involves the
This is also known as proximal cause, and in
same genetic locus that is affected in DMD,
many cases is the most difficult aspect to prove,
but its occurrence is less common. It follows a
as a temporal relationship does not necessarily
more indolent course, with onset often occur-
imply a causal relationship.
ring in late childhood.
Answer B is incorrect. It is not necessary for
Answer B is incorrect. Duchenne muscular
the doctor to have been present at the time of
dystrophy (DMD) and Becker muscular dystro-
Behavioral Science

injury, but there must be an established rela-


phy (BMD) are both characterized by defects
tionship between the physician and patient.
in the 427-kDa protein dystrophin, encoded on
Answer C is incorrect. Intent is not a factor the Xp21 region. DMD is the most common
in malpractice proceedings. These proceed- form of muscular dystrophy, with an incidence
ings are civil lawsuits, not criminal. As such, of about one in 3500 live births. Onset typi-
when intent or gross misconduct is proven, cally occurs after infancy and before the age
additional punitive damages may be assessed of five. The clinical course is characterized by
against the physician. progressive muscle weakness and wasting that
lead to wheelchair dependence by 10-12 years
Answer D is incorrect. As malpractice suits
of age. Early motor milestones are met in pa-
are civil rather than criminal proceedings, the
tients with BMD and DMD.
plaintiff is required only to prove more likely
than not that the actions of the defendant led Answer C is incorrect. Type III spinal muscu-
to damages. lar atrophy, or Kugelberg-Welander disease, is
characterized by the onset of proximal muscle
Answer E is incorrect. Proof of malpractice re-
weakness after the age of 2 years, the ability
quires dereliction, or deviation from standard
to walk independently until the disease pro-
procedure, that leads to the injury in question.
gresses, and survival into adulthood.
9. The correct answer is E. Spinal muscular Answer D is incorrect. Type II spinal mus-
atrophy (SMA) is one of the most common cular atrophy is characterized by the onset of
autosomal-recessive diseases, affecting ap- proximal muscle weakness before 18 months
proximately one in 10,000 live births. It has a of age, the ability to sit but not to walk un-
carrier frequency of approximately one in 50 aided, and survival beyond 4 years of age.
and is characterized by symmetric proximal
muscle weakness due to the degeneration of 10. The correct answer is C. Positive predictive
the anterior horn cells of the spinal cord. SMA value (PPV) is the probability that a positive
is classically divided into three subtypes based test result is truly positive. It can be calculated
on age of onset and clinical severity. Type I by taking the number of true-positive results
SMA (Werdnig-Hoffmann disease), the most and dividing it by the total positive results.
severe, is characterized by the onset of signifi- Since the prevalence is 40%, the number of
cant muscle weakness and hypotonia in the positive patients will be 0.4 1000 = 400 and
first few months of life, and the inability to the number of negative patients will be 1000 -
sit or walk. Manifestations may even occur in 400 = 600. The number of true-positives can
utero with reduced fetal movement. Fatal res be found by multiplying the sensitivity by this
piratory failure usually occurs before the age total, giving us 0.9 400 = 360. The number
of 2 years. Muscle biopsy demonstrates large of false-positives can be found by multiplying
numbers of atrophic fibers that involve entire the specificity by the total negative patients
High-Yield Principles
Chapter 1: Behavioral Science Answers 13

and subtracting that product from the total tension-related adverse effects. However, the
negatives, or 600 - (0.85 600) = 90. Then, captopril is probably contributing to his erec-
360 / (360 + 90) = 0.8, or 80%. Remember: tile dysfunction.
PPV and negative predictive value change
Answer C is incorrect. Fluoxetine and silden
with prevalence in a population, so the esti-
afil have no known dangerous interactions.
mated prevalence must be taken into account
However, the fluoxetine is probably contribut-
when calculating the number of true-positives
ing to his erectile dysfunction.
and true-negatives.
Answer D is incorrect. Lovastatin and silden
Answer A is incorrect. Dividing the number of
afil have no known dangerous interactions.
false-negative results by the total negative re-
sults would give an answer of 8%. Answer E is incorrect. Metformin and silden
afil have no known dangerous interactions.
Answer B is incorrect. Dividing the number

Behavioral Science
of false-positive (rather than true-positive) find- Answer G is incorrect. Propranolol and
ings by the total positive results would give an sildenafil have no known dangerous interac-
answer of 20%. tions, though the combination may increase
the risk of hypotension related adverse effects.
Answer D is incorrect. Switching the values
However, the propranolol may be contributing
for sensitivity and specificity would give an an-
to his erectile dysfunction.
swer of 85%.
Answer E is incorrect. The negative predictive 12. The correct answer is E. Emancipation is a
value is 93%. legal definition through which minors become
independent of their parents and are free to
11. The correct answer is F. As is common for make medical decisions for themselves. A mi-
many older patients, this man is taking several nor, which is a legal condition defined by age,
prescription medications. Though a couple of can generally acquire emancipation through
his prescriptions should be used with caution court order or marriage. These situations usu-
with sildenafil (captopril and propranolol), the ally suggest that the minor will be financially
only one that might significantly interact with independent of his or her parents. This patient
sildenafil is sublingual nitroglycerin. Nitroglyc- is married and is therefore emancipated.
erin is used for prompt relief of an ongoing at-
Answer A is incorrect. While this patient has
tack of angina precipitated by exercise or emo-
many adult responsibilities, 18 years is the le-
tional stress. Nitrates relax vascular smooth
gal age of consent and adulthood.
muscle by their intracellular conversion to
nitrite ions and then to nitric oxide, which in Answer B is incorrect. Full-time work suggests
turn activates cGMP and increases the cells that the patient is financially independent, but
cGMP level. Elevated cGMP ultimately taken alone it is not proof of emancipation.
causes vascular smooth muscle relaxation. Answer C is incorrect. A high school diploma
This is the same mechanism sildenafil uses to does not provide emancipation. Even though a
cause smooth muscle relaxation and increased minor becomes the primary decision maker af-
blood flow into the corpus cavernosum at a ter high school graduation, he or she is not nec-
certain level of sexual stimulation. Using these essarily financially independent of the parents.
drugs together can lead to severe hypotension
and cardiovascular collapse. Answer D is incorrect. A teenager may state
he or she has separated from the parents, but
Answer A is incorrect. Aspirin and sildenafil unless the courts have approved a legal separa-
have no known dangerous interactions. tion, merely saying she is separated from her
Answer B is incorrect. Captopril and sildenafil parents is not enough; legally the parents are
have no known dangerous interactions, though still financially responsible for the child until
the combination may increase the risk of hypo- he or she turns 18.
High-Yield Principles
14 Section I: General Principles Answers

13. The correct answer is E. The study described the prevalence of the risk factor in the popula-
here is a cohort study, because it includes a tion, which would not be known in this study.
group with and a group without a given risk
factor (fetal exposure to alcohol) and then 14. The correct answer is B. Tanner stage 3 is the
looks at whether the risk factor changes the stage when most girls experience peak height
chances of offspring getting the disease (abnor- velocity. Peak height velocity occurs approxi-
malities). The study is prospective, because the mately one year after the initiation of breast de-
group members are looked at before the dis- velopment. Also, pubic hair becomes dark and
ease (abnormality) develops in the offspring. curly during this stage.
Relative risk can be calculated from the results Answer A is incorrect. This description corre-
of a cohort study by comparing the rate of dis- sponds to Tanner stage 1.
ease in the group with the risk factor to the rate
of disease in the group without the risk factor. Answer C is incorrect. This description corre-
Behavioral Science

sponds to Tanner stage 5.


Answer A is incorrect. Attributable risk can be
calculated from the results of a cohort study Answer D is incorrect. This description corre-
and describes the proportion of disease that is sponds to Tanner stage 4.
due to the risk factor under study. Although Answer E is incorrect. This description corre-
smoking behavior of the women is being re- sponds to Tanner stage 2.
corded, the study is not designed to look at
the impact of this risk factor on fetal abnor- 15. The correct answer is D. Obtaining informed
mality; the rate of smoking in the two groups consent from the patient means that the pa-
of women is unknown, and thus we do not tient understands the risks, benefits, and al-
know whether there are sufficient numbers ternatives to the study, and that the doctor re-
of women in the exposed and unexposed lays to the patient pertinent matters about the
groups when it comes to tobacco. plan of care. For the non-English-speaking
Answer B is incorrect. An odds ratio is similar patient, the consent is translated into the ap-
to relative risk, but it is calculated from the re- propriate language and discussed with him/her
sults of a case-control study, not from a cohort through an interpreter. This allows the patient
study. Because birth abnormality is a relatively (or in this case, his parents) freedom to read
rare outcome, the odds ratio from a case-control and process the consent and to discuss it later.
study would likely closely approximate the ac- Whereas this option may not be possible for
tual relative risk. every language or reasonable for every study, it
is appropriate in this non-emergent situation.
Answer C is incorrect. Prevalence is a mea-
sure of how many cases of a given disease exist Answer A is incorrect. With limited knowl-
in a population that is at risk for that disease. edge of Spanish, the doctor will unlikely be
This is not the best answer in this case, be- able to address all the important issues delin-
cause there are no data to judge whether this eated in the consent form.
group of 200 women represents the true preva- Answer B is incorrect. Having someone other
lence of alcoholism during pregnancy in the than an interpreter translate will be invading
community. patient privacy, incomplete, and not perfectly
Answer D is incorrect. The statistic described accurate/reliable.
in this answer is the population attributable Answer C is incorrect. In a non-emergent set-
risk (PAR), which helps us understand, in a ting, the best approach is to allow the patient/
given population, how much less common a family to view a translated copy of the consent
disease (fetal abnormality) would be if a given and consider all their options in an unbiased
risk factor (alcohol consumption during preg- manner. The use of an interpreter, however,
nancy) were completely eliminated. To calcu- would be invaluable in an emergent setting.
late PAR, the attributable risk is multiplied by
High-Yield Principles
Chapter 1: Behavioral Science Answers 15

Answer E is incorrect. The patient is too ently more or less logical explanation for an
young to give consent (<18 years). act or decision actually produced by uncon-
scious impulses. This patients assertion that he
16. The correct answer is A. Heart disease is the feels fine, anyway may be a form of rational-
leading cause of death among the elderly (65 ization, but the primary ego defense mecha-
years old and older), as well as the leading nism that he is using is denial.
cause of death if all ages are combined. The
Answer E is incorrect. Repression is the un-
patient is at a particularly high risk for subse-
conscious exclusion of a painful or anxiety-
quent cardiac events due to his previous history
provoking thought, impulse, or memory from
of myocardial infarction. Other major risk fac-
awareness.
tors for cardiac events are high blood pressure,
hypercholesterolemia, and diabetes mellitus.
18. The correct answer is E. This is a typical
Answer B is incorrect. Cancer is the second well-child visit. Other milestones reached at

Behavioral Science
most common cause of death. It ranks after approximately this age include stacking nine
heart disease, but before stroke. blocks, riding a tricycle, and beginning to en-
gage in group play. Riding a tricycle at 3 years
Answer C is incorrect. Motor vehicle crashes,
is easy to remember because a tricycle has
and accidents in general, are leading causes of
three wheels. The number of blocks stacked
death. However, they are the most common
between ages 2 and 4 years is about three times
cause of death among children (1-14 years
the childs age in years; that is, a 2-year-old can
old) and adolescents (15-24 years old) and not
stack six blocks, whereas a 3-year-old can stack
among the elderly.
nine blocks.
Answer D is incorrect. Stroke is the third most
Answer A is incorrect. Engaging in coopera-
common cause of death among the elderly, be-
tive play is achieved between 4 and 5 years of
hind heart disease and then cancer.
age.
Answer E is incorrect. Suicide is not the lead-
Answer B is incorrect. Imaginary friends are
ing cause of death in the elderly. It is a com-
typically present between 4 and 5 years of age.
mon cause of death among adolescents.
Answer C is incorrect. Hopping on one foot is
17. The correct answer is A. The mechanism of typical of a 4-year-old child.
denial is when one fails to recognize the obvi-
Answer D is incorrect. Reading is most often
ous implications or consequences of a thought,
learned at 5-6 years of age and older.
act, or situation. This ego defense mechanism
is often seen in patients with recently diag- Answer F is incorrect. Children at 2 years of
nosed HIV or cancer. age can usually stack six blocks, whereas chil-
dren at 3 years can stack nine blocks.
Answer B is incorrect. Displacement is a de-
fense mechanism whereby ideas and feelings
19. The correct answer is B. A retrospective co-
that a patient wishes to avoid are transferred
hort study includes a group of subjects who
to another person or object; for example, a pa-
had a certain condition or received a certain
tient who yells at the nurse because he is angry
treatment at some time in the past and com-
at news he has just received from the doctor.
pares their outcomes to those of another group
Answer C is incorrect. Projection is the pro- (a control group) made up of subjects who did
cess of attributing ones thoughts or impulses, not have this condition or receive the treat-
usually ones that are unacceptable or undesir- ment. In this study the risk factor is the pres-
able, to another person. ence of diabetes in the mothers and the out-
come is LGA babies. The incidence of LGA
Answer D is incorrect. Rationalization pro-
births in women with diabetes is four times
duces a more socially acceptable and appar-
that in women without diabetes. Relative risk is
High-Yield Principles
16 Section I: General Principles Answers

defined as the incidence rate of some outcome Answer A is incorrect. Cluster B personality
in those exposed to a risk factor divided by the disorders include antisocial, borderline, histri-
incidence rate of those not exposed. This defi- onic, and narcissistic types. Patients with anti-
nition gives the factor at which the incidence social personality disorder show a disregard for
rate of LGA among women with diabetes is and often violate the rights of others. These in-
larger than the incidence rate of LGA among dividuals often have a criminal history. This is
women without diabetes. the only personality disorder with an age limit
(18 years). Minors with similar behavior are
Answer A is incorrect. This choice describes
classified as having conduct disorder.
the correct type of risk analysis but describes
the relationship in reverse. Answer B is incorrect. Cluster C personal-
ity disorders are characterized by anxiety and
Answer C is incorrect. This choice reverses
include avoidant, obsessive-compulsive, and
the findings of the study, which shows that
Behavioral Science

dependent personality types. Individuals with


the incidence of LGA is four times more in
avoidant personality disorder are sensitive to
women with diabetes.
rejection, are socially inhibited, and have over-
Answer D is incorrect. This choice incorrectly whelming feelings of inadequacy.
uses odds rather than incidence rates and also
Answer D is incorrect. Patients with schiz-
describes the relationship of the findings of the
oid personality disorder exhibit voluntary so-
study in reverse.
cial withdrawal (unlike avoidant patients) and
Answer E is incorrect. This choice describes have limited emotional expressions. They lack
an odds ratio for a case-control study. A case- strange beliefs and thoughts of the schizotypal
control study evaluates the presence of risk personality disorder.
factors in people with and without a disease.
Answer E is incorrect. Schizophrenia is a
Although this is the opposite of a cohort study,
chronic psychiatric condition. It affects 1% of
the results are still reported in terms of disease
the population and usually begins before age
presence with respect to risk factors; that is, the
25. The Diagnostic and Statistical Manual
presence or absence of disease is categorized
of Mental Disorders, Fourth Edition, specifies
in the group with risk factors and compared to
the active phase of the disease and requires
the group without risk factors. The difference,
that at least two of the following symptoms be
however, is that odds are used rather than inci-
present during a one-month period: delusions,
dence. The incidence rate is a percentage (eg,
hallucinations, disorganized speech, grossly
50 out of 100). Odds are calculated by dividing
disorganized or catatonic behavior, and nega-
those with disease by those without (50 to 50,
tive symptoms (eg, flat affect, lack of motiva-
or 1 to 1).
tion, or poverty of speech). Moreover, signs of
20. The correct answer is C. Delusional disor- the disturbance must be present for at least six
der is diagnosed following one month of non- months, such as one of the above symptoms in
bizarre delusions that are usually focused an attenuated form (eg, magical thinking, so-
around a particular topic, in this case, the fi- cial withdrawal, or other negative symptoms).
delity of the patients wife. The delusions are Answer F is incorrect. Schizophreniform dis-
not attributable to another psychiatric disorder order is similar to schizophrenia except that
such as schizophrenia. Delusional disorder its symptoms have lasted between one and six
does not markedly impair the persons func- months. In contrast, patients with schizophre-
tioning in daily activities. The ramifications nia must have had symptoms for longer than
are limited to the delusional content. six months.
Chapter 2

Biochemistry

17
High-Yield Principles
18 Section I: General Principles Questions

Q u e st i o n s

1. A 6-year-old boy presents to his pediatrician 3. A 54-year-old woman complains of fatigue,


with skin lesions all over his body. For several difficulty climbing stairs, and weight loss. Her
years he has been very sensitive to sunlight. medical history is notable for hypertension.
Neither the boys parents nor his siblings have She takes no medications. Her skin is moist
the same skin lesions or sun sensitivity. Biop- and she has a prominent stare. The patients vi-
sies of several of the boys lesions reveal squa- tal signs are:
mous cell carcinoma. Which mutation would
Heart rate: 112/min
one expect to see in this patients DNA?
Blood pressure: 143/90 mm/Hg
(A) Methylation of the gene Respiratory rate: 14/min
(B) Missense mutation in the gene Oxygen saturation: 98% on room air
(C) Nonsense mutation in the middle of the
Biochemistry

Laboratory tests reveal markedly elevated levels


gene
of a specific hormone. What is the first mole-
(D) Point mutation within the enhancer region
cule produced within a cell in response to this
(E) Point mutation within the operator region
hormone?
(F) Point mutation within the promoter region
(G) Thymidine dimers (A) Carbohydrate
(B) DNA
2. A metabolic process is pictured below. Which (C) Fatty acid
intermediate in this process inhibits the rate- (D) Protein
limiting enzyme of glycolysis and activates the (E) RNA
rate-limiting enzyme of fatty acid synthesis?
4. A 35-year-old man presents to the physician
Pyruvate
with arthritic pain in both knees along with
back pain. He states that the pain has been
Acetyl-CoA present for months. In an effort to obtain re-
lief, he has taken only aspirin, but this has
D B been of little benefit. The patient is afebrile,
NADH
cis-aconitate
and his slightly swollen knee joints are neither
hot nor tender to palpation; however, the pain
C Isocitrate
does restrict his motion. The cartilage of his
CO2 + NADH
Fumarate ears appears slightly darker than normal. No
FADH2
A tophi are present. A urine specimen is taken
CO2 + NADH for analysis of uric acid content and turns
Succinate
GTP black in the laboratory while standing. A de-
+
CoA E fect in which of the following is the most likely
underlying cause of the patients condition?
Reproduced, with permission, from USMLERx.com. (A) a-Ketoacid dehydrogenase
(B) Galactokinase
(C) Homogentisic acid oxidase
(A) A
(D) Orotate phosphoribosyl transferase
(B) B
(E) Phenylalanine hydroxylase
(C) C
(D) D
(E) E
High-Yield Principles
Chapter 2: Biochemistry Questions 19

5. A patient who is a carrier of sickle cell trait 6. A 57-year-old woman visits her primary care
presents to the clinic. The single base-pair mu- physician. Laboratory studies reveal an LDL of
tation for sickle cell anemia destroys the MstII 194 mg/dL and HDL of 41 mg/dL. Her phy-
restriction enzyme recognition site represented sician begins therapy with a drug that inhibits
by an asterisk in the image. The restriction production of mevalonic acid. Which of the
enzyme-binding sites are shown as arrows on following is a common side effect of this ther-
the map. DNA from this patient is treated with apy?
MstII and run on an electrophoresis gel. The
(A) Hepatomegaly without elevations in aspar-
DNA is then hybridized with a labeled probe
tate aminotransferase or alanine amino-
that binds to the normal gene in the posi-
transferase
tion shown on the map. In the Southern blot
(B) Muscle injury clinically similar to myositis
shown in the image, which lane represents the
(C) Spontaneous abortion of a pregnancy
patient?
(D) Suicidality and homicidality in patients
with bipolar disorder

Biochemistry
A Globin gene (E) Tonic-clonic seizures
MstII Probe MstII MstII
A B C D E F 7. A nucleic acid fragment is added to four dif-
1.15 Kb 0.2 Kb 1.35 Kb ferent tubes along with a polymerase, a radio-
MstII MstII 1.15 Kb labeled primer, and deoxynucleotides. Each
0.2 Kb
* tube also contains one of the four bases as
S Globin gene dideoxynucleotides. The four tubes are then
run on electrophoresis gel and visualized by
Reproduced, with permission, from USMLERx.com.
autoradiography. For which of the following
purposes would the described laboratory tech-
(A) A nique be utilized?
(B) B (A) To amplify DNA fragments
(C) C (B) To create an allele-specific oligonucleotide
(D) D probe
(E) E (C) To decipher the order of nitrogenous bases
(F) F in the human genome
(D) To determine the base pairing of a seg-
ment of DNA with a DNA probe
(E) To determine the base pairing of a seg-
ment of RNA with a DNA probe
(F) To establish the presence of a given pro-
tein
(G) To show the presence of a specific anti-
body in plasma
High-Yield Principles
20 Section I: General Principles Questions

8. A 45-year-old white woman presents to her regulated both across the cell membrane and
physician complaining of several months of within the cell via sequestration in the en-
worsening shortness of breath. Previously she doplasmic reticulum and mitochondria. In
was told she had asthma because she was hav- which of the following ways does increased
ing intermittent episodes of wheezing com- intracellular calcium concentration cause the
bined with a productive cough and difficulty most cell damage?
catching her breath. She used to run two miles
(A) Enzyme activation
every morning but can no longer walk more
(B) Free radical generation
than 10 city blocks without stopping. She has
(C) Increased membrane permeability
never smoked. On physical examination she is
(D) Inhibition of glycolysis
using her accessory muscles to assist with res-
(E) Inhibition of oxidative phosphorylation
piration. Pulmonary examination is notable
for an increased decreased FEV1/FVC ratio, 10. A scientist working in a research laboratory has
decreased air movement with each breath, and been examining different agonists of serotonin
Biochemistry

increased resonance upon percussion. X-ray of receptor 1B (5-HT1B), a G-protein-coupled re-


the chest is shown in the image. Which of the ceptor. Compound A has a much higher affin-
following is the most likely underlying cause ity for 5-HT1B than compound B. Both com-
for this patients disease? pounds have a higher affinity for the receptor
than serotonin. Which of the following de-
scribes the relationship between compound A
and compound B when considering the guan
ine-nucleotide exchange activity of 5-HT1B?
(A) Km for the exchange reaction with com-
pound A is higher than that with com-
pound B
(B) Km for the exchange reaction with com-
pound A is lower than that with compound
B
(C) Km values with compounds A and B are
the same
(D) The maximum reaction rate with com-
pound A is greater than that with com-
Courtesy of Dr. James Heilman. pound B
(E) The maximum reaction rate with com-
pound B is greater than that with com-
(A) A genetic mutation resulting in deficient pound A
levels of a protease
(B) A genetic mutation resulting in deficient 11. A mother brings her 6-month-old son to the
levels of a protease inhibitor pediatrician. She has noticed that he seems
(C) A mutation in the p53 gene afraid of light and, after some Internet re-
(D) A mutation of the CFTR gene, which en- search, she is concerned that he might be an
codes a regulated chloride channel albino. Laboratory analysis reveals uropor-
(E) Airway inflammation, airflow obstruction, phyrin in his urine. The child most likely has
and bronchial hyperresponsiveness which of the following conditions?
(A) Deficiency of coproporphyrinogen oxidase
9. As increased intracellular calcium is detrimen-
(B) Deficiency of porphobilinogen deaminase
tal to the cell, calcium homeostasis is tightly
(C) Deficiency of uroporphyrinogen decarbox-
ylase
High-Yield Principles
Chapter 2: Biochemistry Questions 21

(D) Inhibition of ferrochelatase and (A) 3-Hydroxy-3-methylglutaryl coenzyme A


-aminolevulinic acid dehydrase reductase
(E) Overexpression of porphobilinogen deami- (B) Adenosine deaminase
nase (C) Aldose reductase
(D) Galactose-1-phosphate uridyltransferase
12. A 48-year-old woman of Mediterranean de- (E) Hexokinase
scent presents because of fatigue, arthralgias, (F) Insulin-like growth factor
discomfort in her right upper abdominal quad-
rant, and polyuria. Laboratory tests are remark- 14. Acquired mutation in the p53 gene is the most
able for elevated glucose level, elevated biliru- common genetic alteration found in human
bin, low hemoglobin, elevated reticulocytes, cancer (> 50% of all cancers). A germline
and increased transferrin saturation. Cardiac mutation in p53 is the causative lesion of Li-
testing shows moderate restrictive cardiomyop- Fraumeni familial cancer syndrome. In many
athy. She frequently has required blood trans- tumors, one p53 allele on chromosome 17p is

Biochemistry
fusions throughout her life. Which hereditary deleted and the other is mutated. What type of
disorder does this patient most likely have? protein is encoded by the p53 gene?
(A) Absence of the hemoglobin a-chain (A) Caspase
(B) Absence of the hemoglobin b-chain (B) DNA repair enzyme
(C) Mutation resulting in increased absorption (C) Membrane cell adhesion molecule
of dietary iron (D) Serine phosphatase
(D) Mutations in the gene encoding ankyrin (E) Telomerase
(E) Mutations resulting in copper accumula- (F) Transcription factor
tion (G) Tyrosine kinase

13. A 52-year-old man with a 12-year history of 15. A segment of DNA is isolated and added to a
poorly controlled diabetes mellitus presents to mixture of four deoxynucleotides, two specific
his physician complaining of changes in his vi- oligonucleotide sequences, and heat-stable
sion. Physical examination reveals opacities on DNA polymerase. The mixture is then heated
the lens of the eye similar to those seen in this to denature the DNA, cooled, and reheated
image. Which enzyme most likely contributed in a number of cycles. Which of the following
to this complication? laboratory techniques does this describe?
(A) Enzyme-linked immunosorbent assay
(B) Gel electrophoresis
(C) Northern blot
(D) Polymerase chain reaction
(E) Sequencing
(F) Southern blot
(G) Western blot

Courtesy of Dr. Rakesh Ahuja.


High-Yield Principles
22 Section I: General Principles Questions

16. A 32-year-old woman presents to her physician (C) Microorganisms ability to produce b-lacta-
for the third time in six months. She has been mase
feeling very tired and depressed, and has come (D) Mutation in terminal amino acid of micro-
to talk about starting antidepressants. She also organisms cell wall component
complains of a 4.5-kg (10-lb) weight gain over (E) Mutation in the microorganisms penicil-
the past three months. During her physical lin-binding protein
examination the physician notices that she is
wearing a sweater and a coat, despite the room 18. A 2-year-old boy presents to the pediatrician
being at a warm temperature. Problems with with fever, facial tenderness, and a green, foul-
the thyroid are suspected, and a biopsy is per- smelling nasal discharge. The patient is diag-
formed (see image). This woman may have a nosed with sinusitis, and the physician notes
human leukocyte antigen subtype that also in- that he has a history of recurrent episodes of
creases her risk of which disease? sinusitis. X-ray of the chest is ordered because
of the fever; it reveals some dilated bronchi
Biochemistry

and shows the heart situated on the right side


of his body. A congenital disorder is diagnosed.
Which other finding would this patient be
most likely to have?
(A) Defective chloride transport
(B) Elevated blood sugar
(C) Infertility
(D) Reactive airway disease
(E) Tetralogy of Fallot

19. A 5-day-old boy is brought to the emergency


department after a tonic-clonic seizure at
home. The infant is the product of a full-term,
uneventful pregnancy, and was normal until
Reproduced, with permission, from USMLERx.com. two days prior to presentation. The mother re-
ports irritability and poor feeding at home, and
the infant was difficult to rouse this morning
(A) Multiple sclerosis
before suffering the seizure. On physical ex-
(B) Pernicious anemia
amination, the infant is tachypneic to 75/min,
(C) Psoriasis
has icteric sclerae, and has poor muscle tone
(D) Steroid-responsive nephrotic syndrome
throughout. Laboratory studies show the fol-
lowing levels: plasma ammonia, 300 mol/L
17. A 65-year-old woman who has been in the hos-
(normal = 10-40 mol/L); blood urea nitro-
pital for three weeks receiving cefotaxime to
gen, 1.5 mg/dL; and creatinine, 0.4 mg/dL.
treat Klebsiella pneumonia develops a urinary
A plasma amino acid analysis fails to detect
tract infection. Urine cultures are positive for
citrulline. Urine amino acids demonstrate el-
Enterococcus faecium. Treatment with vanco-
evated orotic acid levels. This patient suffers
mycin is attempted but is unsuccessful. Which
from a deficiency of which of the following en-
of the following aided in this microorganisms
zymes?
ability to persist despite vancomycin treat-
ment? (A) a-Galactosidase A
(B) Aldose B
(A) Alteration of microorganisms gyrase
(C) Galactose 1-phosphate uridylyltransferase
(B) Methylation of microorganisms rRNA at a
(D) Lysosomal a-glucosidase
ribosome-binding site
(E) Ornithine transcarbamylase
High-Yield Principles
Chapter 2: Biochemistry Questions 23

20. A 42-year-old woman presents to her physician gin. X-ray of the chest reveals cardiomegaly.
with generalized itching. Physical examination He has a difficult time sitting upright and
reveals scleral icterus. Laboratory tests show: cannot squeeze the physicians fingers or the
ring of his pacifier with any noticeable force.
Total bilirubin: 2.7 mg/dL
Despite a number of interventions, the childs
Conjugated bilirubin: 2.4 mg/dL
symptoms continue to worsen until his death
Alkaline phosphatase: 253 U/L
two weeks later. On autopsy, it is likely that this
Aspartate aminotransferase: 36 U/L
patients cells will contain an accumulation of
Alanine aminotransferase: 40 U/L
which of the following substances?
What is the most likely mechanism underlying
(A) Glucose
this patients jaundice?
(B) Glycogen
(A) Absence of UDP-glucuronyl transferase (C) Oxaloacetate
(B) Decreased levels of UDP-glucuronyl trans- (D) Pyruvate
ferase (E) Urea

Biochemistry
(C) Extravascular destruction of the patients
RBCs 23.
After consumption of a carbohydrate-rich
(D) Intrahepatic or extrahepatic biliary ob- meal, the liver continues to convert glucose to
struction glucose-6-phosphate. The livers ability to con-
(E) Intravascular destruction of the patients tinue this processing of high levels of glucose
RBCs is important in minimizing increases in blood
glucose after eating. What is the best explana-
21. A 5-year-old boy was playing outside during tion for the livers ability to continue this con-
recess when he began to experience difficulty version after eating a carbohydrate-rich meal?
breathing. He was brought to his physician,
(A) The hepatocyte cell membranes permea-
because his symptoms seemed to be getting
bility for glucose-6-phosphate
worse. On examination, the physician notes
(B) The high maximum reaction rate of gluco-
that the boy is struggling to breathe and hears
kinase
diffuse wheezing bilaterally. The boys heart
(C) The high maximum reaction rate of hexo-
rate is 98/min, respiratory rate is 24/min, and
kinase
oxygen saturation is 90%. His medical history
(D) The high Michaelis-Menten constant of
is significant only for seasonal allergies and
hexokinase
mild eczema. Which type of medication will
(E) The low Michaelis-Menten constant of
alleviate this patients respiratory symptoms?
glucokinase
(A) b1 Antagonist
(B) b1 Agonist 24. A 30-year-old man is diagnosed with type I fa-
(C) b2 Agonist milial dyslipidemia. Recent laboratory studies
(D) Histamine1 agonist show an elevated triglyceride level but normal
(E) Histamine2 agonist LDL and HDL cholesterol levels. Which of
the following explains the pathophysiology of
22. An 8-month-old boy is brought to the pediatri- this disease?
cian by his parents because he has recently lost
(A) Apolipoprotein E deficiency
the ability to crawl or hold his toys. On exami-
(B) LDL cholesterol receptor deficiency
nation the patient is tachypneic and breathing
(C) Lipoprotein lipase deficiency
with considerable effort; the liver is palpable
(D) VLDL cholesterol clearance deficiency
five finger widths below the right costal mar-
(E) VLDL cholesterol overproduction
High-Yield Principles
24 Section I: General Principles Questions

25. A 59-year-old woman with history of morbid cheeks. He has arachnodactyly, pes cavus,
obesity, hypercholesterolemia, and diabetes and bilaterally dislocated lenses, and demon-
mellitus presents to the emergency depart- strates developmental delay with mild mental
ment with complaints of substernal chest pain retardation. His mother is told that her child
lasting two hours. An ECG reveals ST eleva- might benefit from folic acid supplementation.
tions in the lateral leads. The troponin level Which is the most appropriate test to confirm
at admission is extremely elevated, and a cre- the diagnosis?
atine kinase-myocardial bound test is pend-
(A) Enzymatic assay for the enzyme HGPRT
ing. Which of the following is a key cell me-
(B) Genetic studies demonstrating a mutation
diator in the pathogenesis of an atherosclerotic
in type I collagen
plaque?
(C) Genetic studies indicating >200 copies of
(A) -Interferon the CGG trinucleotide repeat on the X
(B) Complement chromosome
(C) Interleukin-6 (D) Nitroblue tetrazolium test
Biochemistry

(D) Natural killer cells (E) Nitroprusside cyanide test


(E) Platelet-derived growth factor
28. A 6-year-old boy is brought to his pediatricians
26. A 53-year-old man presents to his physician, office by his parents, who report that the child
because he has blood in his urine and some has been unusually thirsty for the past week.
low back pain. A gross specimen of kidneys He also has increased urinary frequency and
from a patient with the same condition is has wet the bed three times in the past two
shown in the image. Which of the following weeks. A random blood glucose level is 215
also is associated with this disorder? mg/dL. The pediatrician suspects that the
child has type 1 diabetes mellitus caused by
autoimmune destruction of insulin-producing
pancreatic b cells. Which of the following is
the transporter for glucose to enter pancreatic
b cells?
(A) GLUT 1
(B) GLUT 2
(C) GLUT 4
(D) Simple diffusion

29. Hemoglobin consists of four polypeptide sub-


units: two a subunits and two b subunits. The
arrangement of these subunits shifts between
a taut and relaxed conformation, resulting in
Reproduced, with permission, from USMLERx.com. changes in hemoglobins oxygen affinity. At a
given partial pressure of oxygen, which of the
following will decrease hemoglobins affinity
(A) Astrocytomas
for oxygen?
(B) Berry aneurysm
(C) Ectopic lens (A) Decreasing the partial pressure of carbon
(D) Optic nerve degeneration dioxide
(E) Squamous cell carcinoma (B) Increasing the amount of 2,3-bisphospho-
glycerate in RBCs
27. At a routine check-up, a 7-year-old boy is (C) Increasing the number of oxygen mole-
found to have osteoporosis. The patient is tall cules bound to a hemoglobin from one to
and thin with pale skin, fair hair, and flushed three
High-Yield Principles
Chapter 2: Biochemistry Questions 25

(D) Increasing the pH by moving from periph- (A) Adenosine deaminase


eral tissue to lung (B) Homogentisic acid oxidase
(E) The presence of excess carbon monoxide (C) Lysosomal a-1,4-glucosidase
(D) Ornithine transcarbamylase
30. A 15-year-old boy presents with prolonged fa- (E) Porphobilinogen deaminase
tigue and mild jaundice following a serious
infection. Blood tests reveal hemoglobin of 33. A 2-year-old boy is brought by his parents to
10.5 g/dL and an elevated reticulocyte count. the emergency department after the discovery
A peripheral blood smear reveals Heinz bodies. of blood in a wet diaper. The physician pal-
Which of the following best describes the nor- pates an abdominal mass in the right flank. CT
mal action associated with this patients meta- of the abdomen reveals a large tumor invading
bolic defect? the right kidney; the gross specimen is shown
in the image. Cytogenetic analysis of the tu-
(A) To generate glucose-6-phosphate in all
mor cells reveals a deletion of chromosome
cells

Biochemistry
11p. Which of the following is the most likely
(B) To generate glucose-6-phosphate in RBCs
diagnosis?
only
(C) To generate mucopolysaccharides
(D) To regenerate reduced nicotinamide ade-
nine dinucleotide phosphate in all cells
(E) To regenerate reduced nicotinamide ade-
nine dinucleotide phosphate in RBCs only

31. Hyperparathyroidism is a common manifesta-


tion of several distinct genetic disorders that
predispose to endocrine gland neoplasia and
cause hormone excess syndromes. Which of
the following is a consequence of parathyroid
hormone?
(A) Increase calcium absorption in the small
intestine
(B) Inhibit the production of 1,25-dihydroxyvi-
tamin D
(C) Promote calcium excretion in the renal tu-
bules
(D) Stimulate further secretion of parathyroid
hormone
(E) Stimulate phosphate reabsorption in the
renal tubules

32. A 22-year-old woman presents to the hospital


with severe abdominal pain, abdominal dis- Reproduced, with permission, from USMLERx.com.
tention, and ileus, along with peripheral neu-
ropathy. Her boyfriend notes that she has been
(A) Adrenocortical adenoma
acting strange lately, and that she seems like
(B) Neuroblastoma
a different person. Which of the following en-
(C) Renal cell carcinoma
zymes is deficient in this patient?
(D) Transitional cell carcinoma
(E) Wilms tumor
High-Yield Principles
26 Section I: General Principles Questions

34. A 6-year-old boy is diagnosed with a worsening 37. A term child is delivered by spontaneous vagi-
ataxic gait and a cardiac dysrhythmia. His un- nal delivery without complications. Upon
cle also has this condition, but his symptoms physical examination the child has bilateral
did not appear until he was 12 years of age. hip dislocations, restricted movement in shoul-
What is the molecular mechanism of this dis- der and elbow joints, and coarse facial features.
ease? Laboratory studies show that the activities of
b-hexosaminidase, iduronate sulfatase, and
(A) Unstable repeats affect protein folding
arylsulfatase A are deficient in cultured fibro-
(B) Unstable repeats affect protein splicing
blasts, but are 20 times normal in the patients
(C) Unstable repeats cause an amino acid sub-
serum. The primary abnormality in this disor-
stitution
der is associated with which of the following
(D) Unstable repeats impede protein transla-
organelles?
tion
(E) Unstable repeats result in a truncated pro- (A) Golgi apparatus
tein (B) Lysosomes
Biochemistry

(C) Ribosomes
35. A 3-month-old child is brought to his pediatri- (D) Rough endoplasmic reticulum
cians office for a check-up. On examination, (E) Smooth endoplasmic reticulum
the physician notices that he has a social smile,
but does not hold his head up on his own or 38. Patients with albinism appear white-pink (skin
make noises. The infant also has pale skin, ec- color), have white hair, and have nonpig-
zema, odd odor, and hyperreflexia. What is the mented or blue irises. In many cases, these
most appropriate treatment for the condition individuals may have melanocytes, but lack
the infant most likely has? melanin in their skin. What is the most use-
ful advice to give to a guardian of a child diag-
(A) A diet low in isoleucine and leucine
nosed with albinism?
(B) A diet low in phenylalanine
(C) A diet low in tyrosine (A) To avoid foods with lactose
(D) A high-protein diet (B) To avoid foods with phenylalanine
(E) Recombinant enzyme therapy (C) To avoid strenuous activity
(D) To give growth hormone to help the child
36. A 63-year-old man who is an alcoholic is grow to a normal height
brought into the emergency department by his (E) To wear clothing and sunscreen that pro-
daughter. She states that the patients memory tect from the sun when outside
has been very poor, and he constantly creates
elaborate yet untrue stories. Physical examina- 39. A 65-year-old African-American man presents
tion reveals ataxia and bilateral horizontal nys- to his physician because of jaundice. He says
tagmus. Wernicke-Korsakoff syndrome, caused that in the past few months he has not had
by a water-soluble vitamin deficiency, is sus- much of an appetite and has lost 13.6 kg (30
pected. Which of the following conditions is lb). Physical examination is notable for a gall-
also a result of a water-soluble vitamin defi- bladder that is palpable. What set of character-
ciency? istics is expected in this patient?
(A) Increased erythrocyte hemolysis
(B) Neonatal hemorrhage
(C) Night blindness
(D) Osteomalacia
(E) Pellagra
High-Yield Principles
Chapter 2: Biochemistry Questions 27

Type of Urine Urine


Na+: 135 mEq/L
Choice
hyperbilirubinemia bilirubin urobilinogen K+: 4.5 mEq/L
conjugated normal
Cl-: 95 mEq/L
A
HCO3-: 9 mEq/L
conjugated
B
Glucose: 40 mEq/L
C unconjugated
Serum pH: 6.8
D unconjugated Lactate: 9.5 mmoL/L
E unconjugated
What metabolic process induced this patients
current condition?
Reproduced, with permission, from USMLERx.com.
(A) Decreased levels of glycerol 3-phosphate
(B) Elevated pyruvate levels
(A) A (C) Inappropriate induction of gluconeogene-
(B) B sis

Biochemistry
(C) C (D) Overproduction of reduced nicotinamide
(D) D adenine dinucleotide
(E) E (E) Thiamine deficiency

40. A 3-year-old boy recently developed weak- 42. A 78-year-old man with asthma presents to his
ness of his lower extremity and uses his arms primary care physician for an annual check-
to stand up even though his lower legs appear up. The physician performs a physical exami-
quite muscular. Laboratory tests reveal a cre- nation and orders routine blood work, which
atine kinase level of 20,000 U/L. A DNA test reveals a macrocytic anemia. Subsequent
confirms the working diagnosis. What is the laboratory tests show an elevated serum meth-
function of the altered gene product in this pa- ylmalonic acid level. A peripheral blood smear
tient? is shown in the image. If this patients vitamin
(A) Exocytosis of acetylcholine at the neuro- deficiency is not corrected, what neurological
muscular junction symptoms is he most likely to experience?
(B) Linking actin filaments to laminin
(C) Promoting actin-myosin cross-bridge cy-
cling
(D) Receptor for acetylcholine
(E) Release of calcium from the sarcoplasmic
reticulum

41. A 55-year-old man is found unresponsive and


breathing rapidly in his apartment. His daugh-
ter found him while stopping by to visit. She
stated that she was concerned after he told her
on the phone that he was drowning his sor-
rows, having been fired from his job earlier
that day. He has no significant medical history Reproduced, with permission, from USMLERx.com.
other than moderate hypertension, for which
he takes a b-blocker. Relevant laboratory find-
(A) Confusion and confabulation
ings are:
(B) Deficiency in this vitamin does not cause
neurological symptoms
(C) Dysarthria and diplopia
(D) Paresthesias and ataxia
(E) Syncope and lethargy
High-Yield Principles
28 Section I: General Principles Questions

43. A young woman currently being treated for is notable only for the ocular findings shown
HIV is brought to the emergency department in the image. Deficiency of which enzyme is
because of a headache and cyanosis of her nail responsible for this disease?
beds and lips. She also reports feeling dizzy.
The resident on call immediately places her
on supplemental oxygen and draws blood for
arterial blood gas analysis. While drawing the
blood, he notes that the arterial blood has a
dark brown color. Blood gas analysis reveals a
pH of 7.39, partial oxygen pressure of 96 mm
Hg, partial carbon dioxide pressure of 35 mm
Hg, and oxygen saturation of 82% on room air.
What enzyme is primarily responsible for pre-
venting this condition in the normal adult?
Biochemistry

(A) ATPase
(B) Flavin adenine dinucleotide reductase
(C) GTPase Reproduced, with permission, from USMLERx.com.
(D) Lactase
(E) Nicotinamide adenine dinucleotide reduc-
tase (A) a-Galactosidase A
(F) Pyruvate kinase (B) Arylsulfatase A
(C) Hexosaminidase A
44. A mass is felt in the groin of an infant girl dur- (D) Iduronate sulfatase
ing a physical examination. Surgical resection (E) Lysyl hydrolase
shows that it is a testicle. The baby is diag-
nosed with testicular feminization syndrome. 46. A pediatrician examines a baby with a defi-
In this syndrome, androgens are produced but ciency in fructose metabolism. Upon adminis-
cells fail to respond to the steroid hormones tration of a fructose bolus, the child becomes
because they lack appropriate intracellular re- symptomatic and blood glucose levels begin to
ceptors. After binding intracellular receptors, decrease. Which of the following will also oc-
steroids regulate the rate of which of the fol- cur after the administration of a fructose bolus
lowing? in this patient?

(A) Initiation of protein synthesis (A) A fall in serum phosphate levels


(B) mRNA degradation (B) A rise in cellular ATP levels
(C) mRNA processing (C) A sustained rise in serum fructose levels
(D) Protein translation (D) An increase in the serum pH
(E) Transcription of genes (E) Large amounts of fructose in the urine

45. The wife in an Ashkenazi Jewish family brings


her 1-year-old daughter to the pediatrician.
Her previous pregnancy was uneventful and
resulted in a full-term healthy girl who is now
4 years old. Her younger daughter, however,
has demonstrated a progressive series of behav-
iors over the first year of life. Her motor skills
have diminished and she demonstrates an in-
creased startle reaction. Physical examination
High-Yield Principles
Chapter 2: Biochemistry Questions 29

47. A 28-year-old African-American man is re- 50. A 28-year-old woman is trying to conceive a
ceiving primaquine therapy for treatment of child. She has a nephew with fragile X syn-
malaria, which he contracted while visiting drome (a genetic disorder characterized by
Asia. He presents to his physician after noting trinucleotide repeat expansion) and she would
blood in his urine. Physical examination is sig- like to assess her risk as a carrier for the disease.
nificant for scleral icterus, and urinalysis shows Blood is drawn, and DNA is extracted and cut
hemoglobinuria. A peripheral blood smear by restriction enzymes that flank the CGG
shows spherocytes, bite cells, and Heinz bod- repeat region. The DNA is then treated with
ies. Which of the following is the most likely a labeled probe that binds the affected region
diagnosis? of the gene. The woman is found to carry one
normal X chromosome and one X chromo-
(A) Alkaptonuria
some with some expansion of the CGG se-
(B) Cystinuria
quence. However, the number of CGG repeats
(C) Glucose-6-phosphate dehydrogenase defi-
in this X chromosome is not sufficient to alter
ciency

Biochemistry
phenotype. Which lane on the Southern blot
(D) Hereditary fructose intolerance
represents this womans genotype?
(E) Hereditary spherocytosis
(F) Lactase deficiency
Affected Unaffected
48. A neonate born at 28 weeks gestation is having nephew husband A B C D E
difficulty breathing. On physical examination, _
the neonates heart rate is 120/min, blood pres-
sure is 100/60 mm Hg, and respiratory rate is
55/min. He has nasal flaring and subcostal re-
tractions. Which of the following components
+
is deficient in this infant?
(A) Dipalmitoyl phosphatidylcholine Reproduced, with permission, from USMLERx.com.
(B) Elastase
(C) Functional cilia
(D) Phosphatidylglycerol (A) A
(E) Sphingomyelin (B) B
(C) C
49. A group of scientists at a pharmaceutical com- (D) D
pany are conducting in vitro experiments to in- (E) E
vestigate the effects of an antineoplastic drug.
Under the microscope, it appears that with
treatment, the majority of the cells are arrested
at a stage in which their chromosomes are
aligned in the vertical axis of the cells. Which
antineoplastic agent has a mechanism of ac-
tion similar to the one described?
(A) 5-Fluorouracil
(B) Cyclophosphamide
(C) Etoposide
(D) Methotrexate
(E) Vincristine
High-Yield Principles
30 Section I: General Principles Answers

An s w e r s

1. The correct answer is G. This patient has xe- Answer E is incorrect. Succinyl-CoA down-
roderma pigmentosa, an autosomal recessive regulates its own synthesis by inhibiting the
disease characterized by a defect in excision enzyme responsible for dehydrogenation of
repair. This disease results in an inability to a-ketoglutarate.
repair thymidine dimers that can form in the
presence of ultraviolet light. This can lead to 3. The correct answer is E. Characteristic symp-
the development of skin cancer and photosen- toms of hyperthyroidism include tachycardia,
sitivity. heat intolerance, weight loss, weakness, tremu-
lousness, and diarrhea. This patient also displays
Answer A is incorrect. Methylation of a partic-
another symptom of elevated thyroid hormone
ular gene does not cause xeroderma pigmento-
levels, exophthalmos. Thyroid hormone enters
sum.
Biochemistry

target cells through carrier-mediated transport


Answer B is incorrect. A missense mutation or possibly diffusion, and binds to nuclear re-
does not cause xeroderma pigmentosum. ceptors. The hormone-receptor complex then
binds DNA and acts as a transcription factor,
Answer C is incorrect. A nonsense mutation
regulating the transcription of genes. Tran-
does not cause xeroderma pigmentosum.
scription results in the production of RNA,
Answer D is incorrect. A mutation in the en- specifically messenger RNA.
hancer region of a gene does not cause xero-
Answer A is incorrect. Carbohydrate is pro-
derma pigmentosum.
duced by the joining of sugar molecules dur-
Answer E is incorrect. A mutation in the oper- ing cellular metabolism; for example, glycogen
ator region of a gene does not cause xeroderma is produced from the linkage of glucose mol-
pigmentosum. ecules by glycogen synthase.
Answer F is incorrect. A mutation in the pro- Answer B is incorrect. DNA binding occurs
moter region of a gene does not cause xero- when the thyroid hormone molecule enters
derma pigmentosum. the nucleus and binds on nuclear receptors.
However, this leads to the transcription of
2. The correct answer is B. Citrate, formed from RNA from DNA, not production of new DNA
oxaloacetate and acetyl CoA by the enzyme or DNA replication.
citrate synthase, inhibits phosphofructokinase
and allosterically activates acetyl CoA carbox- Answer C is incorrect. Fatty acid is synthe-
ylase. Citrate synthase regenerates a molecule sized from acetyl-coenzyme A (CoA) in the
of CoA and is an important regulator of the tri- cell cytoplasm via the action of acetyl-CoA car-
carboxylic acid cycle. It is inhibited by adeno boxylase and other enzymes.
sine triphosphate. Answer D is incorrect. Protein may be pro-
Answer A is incorrect. a-Ketoglutarate is not duced from the RNA template but is not the
an important regulator of the tricarboxylic acid first molecule produced in response to thyroid
cycle, but it is an important intermediate in hormone.
protein metabolism.
4. The correct answer is C. The patient has al-
Answer C is incorrect. Malate is not an impor- kaptonuria, a condition corresponding to the
tant regulator of the tricarboxylic acid cycle, one described in the stem. A deficiency of the
but it is important in the malate shuttle. enzyme homogentisic acid oxidase leads to de-
Answer D is incorrect. Oxaloacetate is not an position of homogentisic acid in the joints and
important regulator of the tricarboxylic acid cartilage, giving them a dark color (ochronosis)
cycle, but it is important in glyconeogenesis. and resulting in degenerative changes. Clas-
High-Yield Principles
Chapter 2: Biochemistry Answers 31

sically, the urine of these patients turns black sickle cell anemia. The b-A-globin gene re-
on contact with air or when the urine is made sults in a 1.15-kb fragment of DNA cut by the
alkaline. The associated defect is on chromo- MstII restriction enzyme. The b-S-globin gene
some 3. results in a 1.35-kb band because the single
base-pair mutation responsible for sickle cell
Answer A is incorrect. A deficiency in a-keto-
anemia eliminates an MstII restriction site. A
acid dehydrogenase causes maple syrup urine
heterozygote will have two bands indicating
disease, a metabolic disorder of autosomal re-
one normal allele with an intact MstII site
cessive inheritance that affects the metabo-
(two fragments), and a mutant allele with a
lism of branched-chain amino acids (leucine,
missing MstII site (one fragment).
isoleucine, and valine) and causes the urine
of affected patients to smell like maple syrup. Answer A is incorrect. The band in lane A is
The urine does not, however, turn black upon from a sickle cell anemia patient with two cop-
standing. The disease is not classically associ- ies of the b-S-globin gene. This gene results
ated with arthritis in middle-aged individuals. in a 1.35-kb band because the single base-pair

Biochemistry
mutation responsible for sickle cell anemia
Answer B is incorrect. A deficiency in galac-
eliminates an MstII restriction site.
tokinase causes galactosemia and galactosuria,
but is otherwise a fairly benign condition and Answer C is incorrect. The band in lane C
would not present with any of the symptoms is from an unaffected patient with two copies
seen in this patient. Other symptoms would of the b-A-globin gene. The gene results in a
be cataracts in affected children, owing to the 1.15-kb fragment of DNA cut by the MstII re-
accumulation of galactitol, a by-product of ga- striction enzyme.
lactose metabolism when galactokinase is not
Answer D is incorrect. The bands in lane D
present.
could not result from any patient. The labeled
Answer D is incorrect. Orotate phosphoribo DNA probe does not bind to the 0.2-kb DNA
syltransferase is an enzyme involved in pyrimi- fragment and therefore would not be visual-
dine synthesis. Deficiencies in this enzyme or ized on the Southern blot.
in orotidine 5-monophosphate decarboxylase
Answer E is incorrect. The bands in lane E
(an enzyme involved in the same pathway
could not result from any patient. The labeled
and located on the same chromosome) cause
DNA probe does not bind to the 0.2-kb DNA
a very rare disorder called hereditary orotic ac-
fragment and therefore would not be visual-
iduria. Symptoms include poor growth, mega-
ized on the Southern blot.
loblastic anemia, and orate crystals in urine.
Treatment involves cystidine or uridine to by- Answer F is incorrect. The bands in lane F
pass this step in pyrimidine synthesis and also could not result from any patient. The labeled
to negatively downregulate orotic acid produc- DNA probe does not bind to the 0.2-kb DNA
tion. fragment and therefore would not be visual-
ized on the Southern blot. A heterozygote will
Answer E is incorrect. A congenital deficiency
have two bands indicating one normal allele
of phenylalanine hydroxylase causes phenyl-
with an intact MstII site (two fragments), and
ketonuria. This enzyme converts phenylala-
a mutant allele with a missing MstII site (one
nine to tyrosine, and a deficit of this enzyme
fragment).
leads to a deficiency of tyrosine and a build-up
of phenylketones in the urine. It is associated 6. The correct answer is B. This patient was
with mental retardation and with the presence started on an 3-hydroxy-3-methylglutaryl co-
of phenylketones in the urine (which do not enzyme A (HMG CoA) reductase inhibi-
classically turn black upon standing). tor (statin), which prevents the conversion of
HMG CoA to mevalonic acid, the rate-limiting
5. The correct answer is B. Lane B represents
step in cholesterol biogenesis. HMG CoA is
the Southern blot of a heterozygous carrier of
High-Yield Principles
32 Section I: General Principles Answers

formed from three acetyl CoA molecules and the DNA more than a million times. Dideoxy-
is a precursor to sterols and ketone bodies. nucleotides are not used in PCR techniques.
Muscle pain or injury resembling myositis has
Answer B is incorrect. Allele-specific oligo-
been known to occur with statins. Although
nucleotide probes are short, labeled DNA
the mechanism is unknown, it may be related
sequences complementary to an allele of in-
to a decrease in muscle tissue synthesis of
terest. These probes can be used to detect the
ubiquinone, a coenzyme used in muscle cell
presence of disease-causing mutations.
metabolism.
Answer D is incorrect. In a Southern blot pro-
Answer A is incorrect. Another common side
cedure, DNA is separated with electrophoresis,
effect of statins is transient elevation of trans-
denatured, transferred to a filter, and hybrid-
aminases. Alanine aminotransferase and aspar-
ized with a labeled DNA probe. Regions on
tate aminotransferase elevations are usually
the filter that base-pair with the labeled DNA
seen within 12 weeks after the onset of therapy
probes can be identified when the filter is ex-
and may be persistent. No studies have demon-
Biochemistry

posed to film that is sensitive to the radiola-


strated an adverse affect of this transaminitis.
beled probe.
Hepatomegaly, however, is not a known side
effect. Answer E is incorrect. In a Northern blot
procedure, RNA is separated by electrophore-
Answer C is incorrect. The teratogenicity of
sis, denatured, and transferred to a filter. RNA
statins is unknown. Fetal toxicity has been
is hybridized to a labeled radioactive DNA
demonstrated at high enough concentrations
probe. The hybridized RNA/DNA strand is ra-
to adversely affect the mother, but the conse-
dioactive and visualized when the filter is ex-
quence of standard doses is unknown. Statins
posed to film.
have not been shown to induce spontaneous
abortions. Answer F is incorrect. In a Western blot pro-
cedure, protein is separated by electrophore-
Answer D is incorrect. Statins have also been
sis and labeled antibodies are used as a probe.
implicated as causes of irritability and depres-
This technique can be used to detect the exis-
sion, specifically in patients with major depres-
tence of an antibody to a particular protein.
sion, but this relationship has not been con-
firmed. Homicidality is not caused by statins. Answer G is incorrect. Enzyme-linked immu-
nosorbent assay (ELISA) is an immunologic
Answer E is incorrect. Seizures are not a com-
technique used to determine whether a par-
mon side effect of statin therapy.
ticular antibody is present in a patients blood.
Labeled antibodies are used to detect whether
7. The correct answer is C. Sequencing is a
the serum contains antibodies against a spe-
laboratory technique that uses dideoxynucleo-
cific antigen precoated on an ELISA plate.
tides to randomly terminate growing strands of
DNA. Gel electrophoresis is used to separate
8. The correct answer is B. This patient has
the varying lengths of DNA. The DNA se-
a1-antitrypsin deficiency, a genetic disease
quence can then be read based on the position
characterized by a deficiency in the serine
of the bands on the gel.
protease inhibitor a1-antitrypsin. This protein
Answer A is incorrect. Polymerase chain reac- normally functions to inhibit neutrophil elas-
tion (PCR) is a laboratory technique used to tase in the lung. When deficient, there is over-
produce many copies of a segment of DNA. In abundant activity of elastase, which destroys
the procedure, DNA is mixed with two specific elastin and collagen in the alveolar walls, pro-
primers, deoxynucleotides and a heat-stable gressing to emphysema. Most patients with
polymerase. The solution is heated to denature a1-antitrypsin deficiency are homozygous for
the DNA and then cooled to allow synthesis. the Z allele. Clinically, a1-antitrypsin defi-
Twenty cycles of heating and cooling amplify ciency can affect the lung, liver, and less com-
High-Yield Principles
Chapter 2: Biochemistry Answers 33

monly the skin. In the lung, the most com- radiographic findings are more consistent with
mon manifestation is early onset panacinar emphysema.
emphysema, which is more prominent at the
lung bases than apices. Slowly worsening dysp 9. The correct answer is A. Calcium is main-
nea is the most common symptom, although tained in high concentrations outside of the
patients may initially complain of cough, spu- cell and in discrete compartments within the
tum production, or wheezing. As in this case, cell (eg, in mitochondria). Free intracellu-
patients who present early complaining of lar calcium can activate several enzymes the
episodes of wheezing and productive cough cumulative effect of which is to induce sig-
may be told they have asthma. Although treat- nificant cell injury. A few important enzyme
ment for asthma may initially improve symp- classes include ATPases, which decrease the
toms, it does not slow the progression of the ATP supply; phospholipases, which decrease
disease. Her x-ray of the chest shows a pattern membrane stability; endonucleases, which in-
typical for this disease; hyperinflated lungs, a duce DNA damage; and several proteases, re-

Biochemistry
flattened diaphragm, and hyperlucent lungs sponsible for protein breakdown.
due to decreased lung markings (it is difficult Answer B is incorrect. Free radical generation
to see at this resolution due to the overlying is a common mechanism of cell injury, but
breast tissue, but we expect that the lung mark- calcium excess does not induce free radical
ings would be especially absent at the bases). generation.
a1-Antitrypsin deficiency can also cause cir-
rhosis of the liver and panniculitis of the skin. Answer C is incorrect. Activation of proteases
and phospholipases induces the breakdown of
Answer A is incorrect. a1-Antitrypsin defi- necessary components of cell membranes.
ciency is characterized by low levels of a prote-
ase inhibitor. This leads to elevated activity of Answer D is incorrect. ATP depletion, result-
the protease elastase and increased destruction ing from the activation of ATPases, can con-
of elastin. tribute to the inhibition of glycolysis.
Answer C is incorrect. Mutations in the tu- Answer E is incorrect. Inhibition of oxidative
mor suppressor gene p53 lead to uncontrolled phosphorylation is an effect of ATP depletion
cellular proliferation. Such mutations are caused by enzyme activation. Although this
commonly seen in the lung cancers associated may contribute to cell damage, it is not the
with smoking (small cell and squamous cell), best answer. The enzyme activation resulting
and they have been found in many non-small from calcium excess is the root cause of the
cell types. This patients history and x-ray find- cell damage, and thus would be the primary
ings do not suggest cancer. insult responsible for the majority of cell dam-
age.
Answer D is incorrect. Mutations in the gene
encoding the cystic fibrosis transmembrane 10. The correct answer is B. G-protein coupled
conductance regulator (CFTR) on chromo- receptors exist in an equilibrium between their
some 7 lead to the disease cystic fibrosis (CF). active and inactive states that is dependent on
CF is a multisystem disease that affects the res whether ligand is present, and the affinity of the
piratory tract, digestive tract, sweat glands, and ligand for the receptor. When active, these re-
reproductive tract. This patient does not pre ceptors catalyze guanine-nucleotide exchange
sent with symptoms characteristic of CF. (GTP for guanosine diphosphate) of their asso-
Answer E is incorrect. Airway inflamma- ciated G proteins. The Michaelis-Menten con-
tion, airway obstruction, and bronchial hyper- stant (Km) for any enzyme-catalyzed reaction
responsiveness are characteristic of asthma. is inversely proportional to the affinity of the
While this patients presentation mimicked enzyme for its substrate. Therefore, the Km for
that of asthma, her history, physical exam, and compound A will be lower than that for com-
pound B because compound A has a higher
High-Yield Principles
34 Section I: General Principles Answers

affinity for the receptor than compound B. porphobilinogen. Lack of this enzyme causes
The maximum rate of reaction (Vmax) will be porphobilinogen and -aminolevulinic acid to
reached at a lower concentration of A than it accumulate in the urine. Patients with acute
would for B, although the Vmax is unchanged. intermittent porphyria are not photosensitive,
but they do experience symptoms of painful
Answer A is incorrect. The Km of compound
abdomen, polyneuropathy, and psychological
A will be lower than that of compound B.
disturbances. They also have pink coloration of
Answer C is incorrect. Given that compounds their urine.
A and B have different affinities for the recep-
Answer D is incorrect. Ferrochelatase and
tor, their Michaelis-Menten constant values
-aminolevulinic acid (ALA) dehydrase are
cannot be the same.
sensitive to inhibition by lead. Thus, lead poi-
Answer D is incorrect. Vmax is directly propor- soning leads to an accumulation of copropor-
tional to the enzyme concentration, and is un- phyrin and ALA in the urine. Lead poisoning
affected by the concentration of substrates or is a problem seen in children who live in old
Biochemistry

competitive inhibitors. houses with chipped paint (lead was used in


Answer E is incorrect. Vmax is directly propor- paint manufacturing until the 1970s). Inges-
tional to the enzyme concentration, and is un- tion of large quantities of lead can cause lines
affected by the concentration of substrates or on the gingiva and epiphyses of long bones,
competitive inhibitors. encephalopathy, erythrocyte basophilic stip-
pling, abdominal colic, sideroblastic ane-
11. The correct answer is C. This individual suf- mia, and neuropathy leading to foot and wrist
fers from porphyria cutanea tarda. The por- drops. It is not associated with photosensitivity.
phyrias are diseases resulting from enzymatic The first line of treatment is dimercaprol and
deficiencies in heme biosynthesis, and por- EDTA to bind up the free lead in the serum.
phyria cutanea tarda is the most common Answer E is incorrect. Porphobilinogen deam-
form. This disorder is caused by deficiency of inase deficiency, not excess, results in acute in-
uroporphyrinogen decarboxylase, the hepatic termittent porphyria. One would expect to find
enzyme that catalyzes the formation of copro- -aminolevulinic acid and porphobilinogen in
porphyrinogen III from uroporphyrinogen III. the urine and no photosensitivity.
Lack of this enzyme results in uroporphyrin
accumulation in the urine (giving the urine 12. The correct answer is B. This woman suffers
a tea-colored appearance) and uroporphy- from b-thalassemia major, the most severe
rinogen accumulation systemically. This com- form of b-thalassemia, in which the b-chain is
pound absorbs light and releases heat, causing absent. Clinically b-thalassemia major mani-
extreme photosensitivity. fests as severe hemolysis and ineffective eryth-
Answer A is incorrect. Hereditary copropor- ropoiesis. These individuals are transfusion
phyria is a disease due to the deficiency of dependent and frequently develop iron over-
coproporphyrinogen oxidase, the enzyme that load. The consequences of iron overload due
catalyzes the formation of protoporphyrinogen to transfusion dependency or secondary hemo-
from coproporphyrinogen III. Coproporphy- chromatosis are described in the stem. These
rinogen III accumulates in the urine. Patients manifestations are due to iron deposition in
with this condition tend to be photosensitive. various tissues including the pancreas, heart,
and skin. b-Thalassemia is more common
Answer B is incorrect. Acute intermittent por- among Mediterranean populations, whereas
phyria is caused by a deficiency in porphobi- b-thalassemia is more common among Asian
linogen deaminase (also called uroporphyrino- and African populations.
gen 1 synthetase), the enzyme that catalyzes
the formation of pre-uroporphyrinogen from Answer A is incorrect. This answer describes
the most severe form of a-thalassemia, a disease
High-Yield Principles
Chapter 2: Biochemistry Answers 35

in which a fetus is unable to make any func- drug is currently approved to inhibit aldose re-
tional hemoglobin aside from the 4-tetramer ductase, but aldose reductase inhibitors such
(Hb Bart). Clinically a-thalassemia manifests as epalrestat and ranirestat are currently being
as congestive heart failure, anasarca, and intra tested.
uterine fetal death.
Answer A is incorrect. 3-Hydroxy-3-methyl-
Answer C is incorrect. This answer describes glutaryl coenzyme A (HMG CoA) reductase
hereditary hemochromatosis, a disease caused catalyzes the conversion of HMG CoA into
by iron overload due to an intrinsic defect in mevalonate and eventually into cholesterol. In-
the bodys ability to control the absorption of hibition of this enzyme is commonly affected
iron. Clinically this disease manifests in a man- by statin drugs to reduce cholesterol levels, but
ner similar to that of secondary hemochroma- it would not help prevent the development of
tosis. However, the laboratory picture in hered- cataracts.
itary hemochromatosis is not characterized by
Answer B is incorrect. Adenosine deaminase
hemolysis.

Biochemistry
inhibition would result in problems in the pu-
Answer D is incorrect. This answer describes rine salvage pathway. Disrupting this pathway
hereditary spherocytosis, a disease in which would result in excess ATP and dATP via feed-
mutations in either the ankyrin or spectrin back inhibition of ribonucleotide reductase.
gene contribute to instability of the RBC This excess ATP prevents DNA synthesis and
plasma membranes. This condition is charac- thus affects lymphocyte development. Congen-
terized by extravascular hemolysis. Clinically ital deficiency of this enzyme results in severe
this disease manifests as gallstones, anemia, combined immunodeficiency. Inhibition of
jaundice, and splenomegaly. The definitive this enzyme would not prevent the develop-
treatment is splenectomy, thus obviating any ment of cataracts.
need for chronic blood transfusion.
Answer D is incorrect. Galactose-1-phosphate
Answer E is incorrect. This answer describes (G-1-P) uridyltransferase is important in the
Wilson disease, a disease in which failure of breakdown of galactose; it catalyzes the for-
copper to enter the circulation in the form of mation of glucose-1-phosphate from G-1-P.
ceruloplasmin results in copper accumulation Hereditary deficiency of this enzyme leads to
in the liver, brain, and cornea. Clinically this hepatosplenomegaly, mental retardation, jaun-
disease manifests as parkinsonian symptoms, dice, and cataract formation. Inhibition of this
Kayser-Fleischer rings, asterixis, and dementia. enzyme in an adult would certainly not pre-
vent the development of cataracts.
13. The correct answer is C. Aldose reductase
Answer E is incorrect. Hexokinase is the en-
catalyzes the breakdown of glucose into sorbi-
zyme that catalyzes the first step in the catab-
tol. Sorbitol is then metabolized to fructose, a
olism of glucose, converting glucose to glu-
process that is relatively slow. In patients with
cose-6-phosphate. It is stimulated by insulin.
hyperglycemia, as would be present in this pa-
Inhibition of hexokinase would not prevent the
tient with poorly controlled diabetes, sorbitol
development of cataracts in this patient. Con-
accumulation with the cells of the lens leads
genital hexokinase deficiency is a rare autoso-
to a rise in intracellular osmolality, causing
mal recessive condition that results in severe
water movement into the cells. This results in
hemolysis. Inhibition of hexokinase would
cellular swelling and osmotic damage. It also
likely have a similar, albeit less severe, result.
leads to a decrease in intracellular myoinositol,
interfering with cellular metabolism. Swelling Answer F is incorrect. Insulin-like growth fac-
of lens fiber cells can lead to rupture and cata- tor (IGF) is a product synthesized in the liver
ract formation. Inhibition of aldose reductase that mediates many of the physiologic effects
could decrease sorbitol accumulation in the of growth hormone (GH). Its name refers to a
lens and thus prevent cataract formation. No high degree of structural similarity to insulin,
High-Yield Principles
36 Section I: General Principles Answers

and it is even capable of binding to the insu- Answer G is incorrect. Tyrosine kinase prod-
lin receptor directly, although with lower affin- ucts play a role in cell signaling through phos-
ity than insulin. Its effects include increased phorylation. The p53 gene product is not a ty-
protein synthesis, and IGF levels are especially rosine kinase.
high during puberty. Inhibition of IGF would
not help prevent the development of cataracts. 15. The correct answer is D. This question de-
scribes the polymerase chain reaction (PCR).
14. The correct answer is F. The p53 gene protein PCR is a laboratory technique used to produce
product is a transcription factor that regulates many copies of a segment of DNA. In the pro-
apoptosis. It acts as a cell-cycle regulator, pre- cedure, DNA is mixed with two specific prim-
venting cells from undergoing division. Muta- ers, deoxynucleotides and a heat-stable poly-
tions in p53 cause uncontrolled cell division, merase. The solution is heated to denature
leading to various types of tumors. Another the DNA and then cooled to allow synthesis.
example of a cell-cycle regulator is the retino- Twenty cycles of heating and cooling amplify
Biochemistry

blastoma gene. the DNA over a million times.


Answer A is incorrect. The p53 gene product Answer A is incorrect. Enzyme-linked immu-
is involved in apoptosis induced by DNA dam- nosorbent assay (ELISA) is an immunologic
age and other stimuli, but it is not a caspase technique used to determine whether a par-
protein. ticular antibody is present in a patients blood.
Labeled antibodies are used to detect whether
Answer B is incorrect. p53 is involved in cell
the serum contains antibodies against a spe-
cycle regulation but not direct DNA repair ac-
cific antigen precoated on an ELISA plate.
tivity. DNA repair products are produced by
This is not the technique described above.
genes such as BRCA1 (chromosome 17) and
BRCA2 (chromosome 13), among others. Answer B is incorrect. Gel electrophoresis
uses an electric field to separate molecules
Answer C is incorrect. Membrane cell adhe-
based on their sizes.
sion products are produced by the APC gene
found on chromosome 5. Mutations in the Answer C is incorrect. Northern blots are sim-
APC gene lead to colon cancer. ilar to Southern blots except that in Northern
blotting, mRNA is separated by electrophoresis
Answer D is incorrect. p53 is not a G-protein
instead of DNA. This is not the technique de-
product. G proteins such as ras can be in-
scribed above.
volved in oncogenesis. Mutations in ras can
lead to cancer in the lungs, pancreas, and co- Answer E is incorrect. Sequencing is a labo-
lon as well as leukemia. ratory technique that utilizes dideoxynucleo-
tides to randomly terminate growing strands of
Answer E is incorrect. DNA polymerase is un-
DNA. Gel electrophoresis is used to separate
able to replicate at the end of chromosomes
the varying lengths of DNA. The DNA se-
(telomeres), resulting in the loss of DNA with
quence can then be read based on the position
each replication cycle. Telomerase is an en-
of the bands on the gel. This is not the tech-
zyme that adds repeats onto the 3ends of chro-
nique described above.
mosomes to protect them from being recog-
nized as broken or damaged DNA. Although Answer F is incorrect. In a Southern blot pro-
most normal somatic cells do not express cedure, DNA is separated with electrophoresis,
enough telomerase to prevent telomerase attri- denatured, transferred to a filter, and hybrid-
tion with each cell division, telomerase is often ized with a labeled DNA probe. Regions on
reexpressed in cancer cells. However, p53 is the filter that base-pair with the labeled DNA
not involved in the process of adding nucleo- probes can be identified when the filter is
tides to telomeres. exposed to film that is sensitive to the radio-
High-Yield Principles
Chapter 2: Biochemistry Answers 37

labeled probe. This is not the technique de- enzymes that convert the D-ala D-ala peptide
scribed above. bridge to D-ala D-lac, preventing vancomycin
from binding. Vancomycin resistance is much
Answer G is incorrect. In a Western blot pro-
more common with Enterococcus faecium than
cedure, protein is separated by electrophore-
with Enterococcus faecalis. High-dose ampicil-
sis and labeled antibodies are used as a probe.
lin, often in combination with gentamicin, is
This technique can be used to detect the exis-
generally first-line treatment in urinary tract
tence of an antibody to a particular protein.
infections due to vancomycin-resistant Entero-
16. The correct answer is B. This woman has coccus.
symptoms of Hashimoto thyroiditis, an auto- Answer A is incorrect. Microorganisms be-
immune disorder resulting in hypothyroidism come resistant to quinolones through the al-
(also known as myxedema), although there teration of their gyrase.
may be a transient hyperthyroidism at the very
Answer B is incorrect. Microorganisms be-
onset of disease when follicular rupture occurs.

Biochemistry
come resistant to macrolides through the
It is a type IV hypersensitivity associated with
methylation of its rRNA at a ribosome-binding
autoantibodies to thyroglobulin, thyroid per-
site.
oxidase, and the thyroid-stimulating hormone
receptor itself. The most common presenting Answer C is incorrect. b-Lactamases are en-
symptoms of Hashimoto thyroiditis are those zymes produced by microorganisms that cleave
seen in this patient, as well as constipation b-lactam antibiotics, deactivating them. To
and dry skin. Histologic characteristics include overcome resistance, b-lactams are usually
massive infiltrates of lymphocytes with germi- given with b-lactamase inhibitors such as cla-
nal cell formation. Hashimoto thyroiditis is as- vulanic acid, tazobactam, and sulbactam.
sociated with the DR5 human leukocyte anti-
Answer E is incorrect. b-Lactam antibiotics
gen subtype, as is pernicious anemia, a disease
bind to penicillin-binding proteins (enzymes
that leads to vitamin B12 deficiency caused by
that synthesize peptidoglycan, a major com-
atrophic gastritis and destruction of parietal
ponent of bacterial cell walls), preventing cell
cells.
wall synthesis by the microorganism. Microor-
Answer A is incorrect. Multiple sclerosis is as- ganisms such as methicillin-resistant Staphy-
sociated with the DR2 human leukocyte an- lococcus aureus and penicillin-resistant Strep-
tigen subtype. It is not associated with Hashi- tococcus pneumoniae have alterations in their
moto thyroiditis. penicillin-binding proteins that result in low
affinity and thus resistance to these b-lactams.
Answer C is incorrect. Psoriasis is associated
b-Lactam antibiotics include penicillins, ceph-
with the B27 human leukocyte antigen sub-
alosporins, monobactams, and carbapenems
type. It is not associated with Hashimoto thy-
(not vancomycin).
roiditis.
Answer D is incorrect. Steroid-responsive ne- 18. The correct answer is C. Kartagener syn-
phrotic syndrome is associated with the DR7 drome, or immotile cilia, is caused by a defect
human leukocyte antigen subtype. It is not as- in dynein that prevents effective movement of
sociated with Hashimoto thyroiditis. cilia. The full syndrome is characterized by si-
nusitis, bronchiectasis, situs inversus, and male
17. The correct answer is D. Vancomycin is a gly- infertility. Cilia play an important role in mov-
copeptide antibiotic that is effective in fighting ing mucus along the airway and clearing de-
only gram-positive bacteria. It binds tightly to bris; the absence of this function contributes to
a cell wall precursor that contains the termi- the pulmonary findings of the syndrome. Cilia
nal amino acid sequence D-ala D-ala and pre- are also very important for leukocyte move-
vents cell wall synthesis. Resistance to vanco- ment and phagocytosis. Infertility is present in
mycin is transferred via plasmids and encodes most patients due to immotile cilia.
High-Yield Principles
38 Section I: General Principles Answers

Answer A is incorrect. Defective chloride opacities, acroparesthesias, and vascular dis-


transport is the cause of cystic fibrosis. Cystic ease of the kidney, heart, and brain. Labora-
fibrosis frequently causes bronchiectasis, but it tory results show diminished a-galactosidase A
is not associated with situs inversus. activity in plasma, leukocytes, or cultured fi-
broblasts. Enzyme replacement therapy is now
Answer B is incorrect. Patients with diabetes
available for patients, and renal transplant and
are predisposed to developing chronic fungal
long-term hemodialysis are mainstays of treat-
sinusitis. However, the bronchiectasis and situs
ment.
inversus are not consistent with diabetes.
Answer B is incorrect. Hereditary fructose in-
Answer D is incorrect. Mucus plugging in
tolerance is caused by the inability of aldose B
reactive airway disease can cause atelectasis
to split fructose 1-phosphate, resulting in its
at the lung bases. An x-ray film of the chest of
accumulation along with inhibition of glucose
a patient with reactive airway disease would
production. Patients are usually asymptom-
likely reveal hyperinflated lungs with areas of
atic until they begin ingesting food contain-
Biochemistry

atelectasis, not bronchiectasis.


ing fructose, sucrose, or sorbitol after weaning
Answer E is incorrect. Tetralogy of Fallot is a from breastfeeding. Symptoms include nausea,
congenital heart defect, but it is not associated vomiting, pallor, sweating, and trembling with
with infections or cardiac inversion. Patients fructose ingestion; continued ingestion can
with this condition develop early cyanosis be- lead to seizure and coma.
cause of the malformed right-to-left shunt. The
Answer C is incorrect. Absent function of ga-
four components of the tetralogy are (1) ven-
lactose-1-phosphate uridylyltransferase in galac-
tricular septal defect, (2) overriding aorta, (3)
tosemia results in the accumulation of galactose
infundibular pulmonary stenosis, and (4) right
and galactose-1-phosphate. Galactose-1-phos-
ventricular hypertrophy.
phate has direct toxic effects on renal, hepatic,
19. The correct answer is E. This child is suffer- and neuronal cells. The disorder is character-
ing from an inherited form of hyperammone- ized by onset of clinical symptoms within the
mia as a result of a defect in ornithine trans- first few days of life: vomiting, diarrhea, failure
carbamylase (OTC). In the urea cycle, OTC to thrive, and hypotonia. Patients who undergo
combines carbamoyl phosphate and ornithine early galactose restriction may still have devel-
to make citrulline. When OTC is deficient, opmental delays, ataxia, and apraxia. Labora-
excess carbamoyl phosphate enters the py- tory findings include an elevated blood galac-
rimidine synthesis pathway to cause increased tose level, low glucose, and galactosuria.
orotic acid in the blood, which distinguishes Answer D is incorrect. Pompe disease is
OTC deficiency from other urea cycle dis- caused by absent function of lysosomal
orders. A defect in OTC causes an excess of a-glucosidase, characterized by generalized
ammonia in circulation, which leads to men- hypotonia, muscle weakness, and hypertrophic
tal retardation, seizures, and ultimately death. cardiomegaly. Patients usually have cardiores
Some patients with OTC deficiency also ex- piratory failure by 1 year of age with the early
hibit a very low blood urea nitrogen, but this onset form of the disorder. Laboratory findings
is not enough to make a conclusive diagnosis. include significantly elevated serum creatinine
Unlike the rest of the urea cycle disorders that kinase.
are autosomal recessive, deficiency of OTC is
X-linked. 20. The correct answer is D. This patient has ob-
structive jaundice, causing her pruritus and
Answer A is incorrect. Fabry disease is caused
scleral icterus. In this situation conjugated
by mutations in the a-galactosidase A gene,
bilirubin cannot be excreted, and its levels are
resulting in the accumulation of ceramide tri-
therefore elevated in the serum. The unconju-
hexoside. Patients classically have angiokera-
tomas, hypohidrosis, corneal and lenticular
High-Yield Principles
Chapter 2: Biochemistry Answers 39

gated bilirubin level, however, is not elevated. heart contraction) and chronotropy (increased
Alkaline phosphatase is usually elevated in heart rate).
cases of obstructive jaundice.
Answer D is incorrect. Activation of hista-
Answer A is incorrect. This is seen in Crigler- mine1 receptors results in pruritus, broncho-
Najjar syndrome type I, which leads to kernic- constriction, and increased nasal and bron-
terus and is diagnosed during childhood. Ex- chial mucus production. Histamine1-receptor
tremely high levels of unconjugated bilirubin antagonists are primarily used in the treatment
would be expected in this case. of seasonal allergy symptoms.
Answer B is incorrect. This is seen in Gilbert Answer E is incorrect. Activation of hista-
syndrome, which does not have any clinical mine2 receptors leads to increased gastric acid
consequence. This syndrome is more common production. Therefore, histamine2-receptor
in men, the jaundice is typically associated antagonists such as cimetidine are used in the
with stress or exercise, and alkaline phospha- treatment of gastroesophageal reflux disease.

Biochemistry
tase levels are normal.
22. The correct answer is B. This patient has
Answer C is incorrect. Extravascular hemo-
Pompe disease, a glycogen storage disorder.
lysis (eg, hereditary spherocytosis) would lead
Pompe disease is an autosomal recessive dis-
to increased levels of unconjugated bilirubin.
ease that is characterized by a deficiency or
Hemoglobinuria would not be observed in
defect in lysosomal a-1,4-glucosidase. This
these patients.
enzyme is necessary for the dissolution of the
Answer E is incorrect. Intravascular hemo- polymer linkages in glycogen. In its absence,
lysis (eg, due to mechanical injury to RBCs, glycogen accumulates to toxic levels in both
defective cardiac valves, toxic injury to RBCs) the cytoplasm and lysosomes.
would lead to an increase in unconjugated
Answer A is incorrect. Glucose is stored as gly-
bilirubin, which is not the case in this patient.
cogen in the cells and is also present in blood.
Also, levels of alkaline phosphatase would not
However, hyperglycemia is not responsible for
be elevated in a patient with increased RBC
the symptoms observed in this patient.
destruction. Hemoglobinuria would be ex-
pected in these patients. Answer C is incorrect. Oxaloacetate is the first
intermediate in the Krebs cycle. It is regener-
21. The correct answer is C. This patient is expe- ated with each turn of the cycle but is not pres-
riencing an acute asthma attack. Treatment is ent in excessive amounts in the cell.
targeted at relieving bronchoconstriction and
Answer D is incorrect. Pyruvate is a compo-
inflammation. This patient should be treated
nent of the cellular respiration pathway and
with a b2 agonist such as albuterol. When ac-
an intermediate in gluconeogenesis. It is not
tivated with an agonist, the b2 receptor will
stored in cells in any significant quantity.
cause bronchodilation.
Answer E is incorrect. Disorders of the urea
Answer A is incorrect. b1 Blockers inhibit
cycle lead to nitrogen accumulation in the
sympathetic stimulation of b1 receptors by
body and result in progressive lethargy and
epinephrine. b1 Blockers reduce the effect of
coma. They do not cause the myopathy seen
excitement/physical exertion on heart rate and
in this patient.
force of contraction; they also add to the dila-
tion of blood vessels, some opening of bronchi, 23. The correct answer is B. Glucokinase catalyzes
and also reduction of tremor. the initial step of glycolysis, which is the phos-
Answer B is incorrect. b1 Agonists work on the phorylation of glucose to glucose-6-phosphate.
heart more than the lungs. Activation of b1- In most other tissues, this process is catalyzed by
receptor agonists leads to inotropy (increased hexokinase. Both enzymes are found in the liver.
Glucokinase has a higher Michaelis-Menten
High-Yield Principles
40 Section I: General Principles Answers

constant and a higher Vmax than hexokinase; cholesterol levels rise, which causes an in-
it thus has a low affinity for glucose but large crease in plasma cholesterol; triglyceride levels
capacity of activity. Importantly, it is not inhib- remain normal.
ited by glucose-6-phosphate, as is hexokinase.
Answer D is incorrect. Mixed hypertriglyc-
Answer A is incorrect. The hepatocyte cell eridemia (type V) is a dyslipidemia character-
membrane is permeable to glucose, which ized by extremely high triglyceride levels and
is trapped in the cell after phosphorylation to visibly foamy plasma. Unlike type I, type V is
glucose-6-phosphate. characterized by elevated VLDL cholesterol
levels and is thought to be related to a VLDL
Answer C is incorrect. Hexokinase has a
cholesterol clearance problem.
high affinity (low Michaelis-Menten constant,
Km) for glucose and processes glucose to glu- Answer E is incorrect. VLDL cholesterol over-
cose-6-phosphate at lower levels of glucose. production is another characteristic of type V
At higher glucose levels, hexokinase is over- dyslipidemias, as well as type IIb combined hy-
Biochemistry

whelmed (low Vmax), and sufficient substrate is perlipidemia.


available for glucokinase to process the excess
glucose despite its higher Km. 25. The correct answer is E. Following endothe-
lial injury, the subendothelial space accumu-
Answer D is incorrect. Hexokinase has a rela-
lates lipoproteins. Next, chemical modifica-
tively low Michaelis-Menten constant.
tion (eg, glycation or oxidation) of lipoproteins
Answer E is incorrect. Glucokinase has a rela- occurs that recruits monocytes to the vessel
tively high Michaelis-Menten constant. wall. Monocytes are converted to macrophages
upon entry into the subendothelial space, and
24. The correct answer is C. Type I dyslipidemia unregulated macrocytosis of modified LDL
(or familial lipoprotein lipase deficiency) is cholesterol occurs, yielding foam cells. At this
caused by a deficiency of lipoprotein lipase. point, various cell mediators, most notably
This enzyme exists in capillary walls of adipose platelet-derived growth factor, tumor necrosis
and muscle tissue and cleaves triglycerides into factor, and interleukin-1, recruit platelets and
free fatty acids and glycerol. The enzyme is ac- smooth muscle to the intimal lining, where
tivated by apolipoprotein C-II, which is found proliferation and production of extracellular
on VLDL cholesterol and chylomicrons. matrix leads to the development of a fibrous
Type I dyslipidemia is characterized by an ac- plaque.
cumulation of triglyceride-rich lipoproteins in
Answer A is incorrect. -Interferon is secreted
the plasma. Deficiency in apolipoprotein C-II
by T-helper cells and stimulates macrophages.
produces a similar result.
This mediator does not play a prominent role
Answer A is incorrect. VLDL cholesterol in the pathogenesis of atherosclerotic plaque.
remnants are removed from the circula-
Answer B is incorrect. Complement defends
tion by apolipoprotein E receptors. Thus,
against gram-negative bacteria and is activated
apolipoprotein E deficiency (dysbetalipopro-
by IgG or IgM in the classic pathway, and acti-
teinemia) results in an elevated VLDL choles-
vated by molecules on the surface of microbes
terol, triglyceride, and cholesterol levels. Often
in the alternate pathway. Complement has not
this disorder manifests with other conditions
been shown to be an active participant in the
that cause hyperlipidemia such as diabetes.
pathogenesis of atherosclerotic plaque.
Xanthomas are often present.
Answer C is incorrect. Interleukin-6 (IL-6) is
Answer B is incorrect. LDL cholesterol recep-
secreted by T-helper cells and macrophages,
tor dysfunction is characteristic of familial hy-
and is responsible for stimulating the produc-
perbetalipoproteinemia, also known as type II
tion of acute-phase reactants and immuno-
hyperlipidemia. In these cases, plasma LDL
High-Yield Principles
Chapter 2: Biochemistry Answers 41

globulins. IL-6 does not play a prominent role mocysteine, which is then excreted in urine.
in the pathogenesis of atherosclerotic plaque. In this condition, cysteine becomes an essen-
tial amino acid. Clinically, homocystinuria is
Answer D is incorrect. Natural killer cells are
manifested by mental retardation, osteoporo-
a form of cytotoxic lymphocytes and constitute
sis, tall stature, kyphosis, lens subluxation, and
a major component of the innate immune sys-
atherosclerosis (causing premature stroke and
tem. These cells play a major role in the host
myocardial infarction). Diagnosis is based on
rejection of both tumors and virally-infected
a positive nitroprusside cyanide test. Marfan
cells, and do not play a prominent role in the
syndrome is the primary differential diagno-
pathogenesis of atherosclerotic plaque.
sis. Clinical features of homocystinuria, such
26. The correct answer is B. This patient has as ectopia lentis, tall and thin body habitus,
adult polycystic kidney disease, an autosomal and chest and spinal deformities, are similar
dominant condition characterized by mas- to the features found in patients with Marfan
sive bilateral cysts in the kidneys, asymptom- syndrome. However, generalized osteoporosis,

Biochemistry
atic hepatic and pancreatic cysts, mitral valve arterial and venous thrombosis, premature ath-
prolapse, and berry aneurysms. All disease erosclerosis, changes in hair, and the disorders
manifestations are believed to be secondary to of mental development are absent in patients
abnormal epithelial cell differentiation, most with Marfan syndrome.
likely caused by a mutation in the polycystic Answer A is incorrect. Lesch-Nyhan syndrome
genes. The renal cysts eventually progress to is an X-linked recessive condition caused by
end-stage renal disease. Berry aneurysms tend a defect in the purine salvage pathway due to
to increase in size with age, thus increasing the the absence of HGPRT (hypoxanthine guan
risk of rupture and intracranial hemorrhage. ine phosphoribosyl transferase), which con-
Answer A is incorrect. Astrocytomas are seen verts hypoxanthine to inosine monophosphate
in patients with tuberous sclerosis, an autoso- and guanine to guanosine monophosphate.
mal dominant disorder affecting the tuberin As a result, excess uric acid accumulates and
and hamartin proteins, which regulate cellular causes hyperuricemia and gout. Patients also
growth and differentiation. present with mental retardation, self-mutilating
behavior, aggression, and choreoathetosis.
Answer C is incorrect. Ectopic lens is seen
in Marfan syndrome, an autosomal dominant Answer B is incorrect. Osteogenesis im-
connective tissue disorder associated with slen- perfecta is an autosomal dominant disorder
der body habitus and aortic dissection. caused by a variety of gene defects that result
in abnormal synthesis of type I collagen. Clini-
Answer D is incorrect. Optic nerve degen- cally, it is characterized by multiple fractures
eration can be seen in Leber hereditary optic occurring with minimal trauma (brittle bone
neuropathy, a condition in which patients de- disease), blue sclerae due to the translucency
velop a rapid loss of central vision. of connective tissue over the choroid, hearing
Answer E is incorrect. Increased incidence of loss due to abnormal middle ear bones, and
squamous cell carcinoma is seen in patients dental imperfections due to lack of dentition.
with xeroderma pigmentosum, an autosomal Answer C is incorrect. Fragile X results from
recessive disease caused by a deficiency in an expansion of the CGG trinucleotide repeat
DNA repair of thymine dimers. on the FMR-1 locus of the X chromosome.
Methylation of these trinucleotide repeats will
27. The correct answer is E. Homocystinuria is result in nonproduction of the FMR-1 protein,
an autosomal recessive condition caused by resulting in a phenotype that includes mental
deficiencies of various enzymes involved in retardation, an elongated face, protruding ears,
the pathway that converts methionine to cys- macro-orchidism, and low muscle tone. While
teine. This results in the accumulation of ho- children suffering from fragile X might exhibit
High-Yield Principles
42 Section I: General Principles Answers

the same developmental delays and mild re- lower affinity for oxygen. The taut form is sta-
tardation as the child in this vignette, they will bilized by the processes that result in increased
not have pes cavus, arachnodactyly, and dislo- oxygen unloading, including binding of car-
cated lenses, and folic acid supplementation bon dioxide, low pH, and increased levels of
will not help them. 2,3-BPG in RBCs. Therefore, by decreasing
the partial pressure of carbon dioxide, one in-
Answer D is incorrect. Chronic granuloma-
creases hemoglobins affinity for oxygen.
tous disease is an X-linked recessive condition
caused by a lack of reduced nicotinamide ad- Answer C is incorrect. Binding of oxygen mol-
enine dinucleotide phosphate oxidase activity ecules is the major cause of the shift of hemo-
within neutrophils. As a result, neutrophils can globin from its taut structure to the relaxed
ingest bacteria but cannot kill them due to a form. The oxygen molecule disrupts the weak
defective oxidative burst. Patients present with polar bonds and opens up the molecule for
a marked susceptibility to opportunistic infec- more oxygen to bind.
tions with bacteria, especially Staphylococcus
Biochemistry

Answer D is incorrect. The Bohr effect comes


aureus, Escherichia coli, and Aspergillus. Di-
from an increase in protons, which subse-
agnosis is confirmed with a negative nitroblue
quently stabilize the taut form of hemoglo-
tetrazolium test.
bin preferentially. In addition, an increase in
protons means an increase in carbon dioxide
28. The correct answer is B. Glucose enters pan-
because of the bicarbonate buffer present in
creatic b cells via GLUT 2 channels. GLUT
blood. Remember, though, that increasing the
2 transporters are insulin-dependent glucose
pH means a decrease in protons.
channels that are present on pancreatic b cells
when glucose levels are low. Answer E is incorrect. Carbon monoxide sta-
bilizes the relaxed form of hemoglobin so that
Answer A is incorrect. GLUT 1 transport-
the dissociation curve shifts dramatically to the
ers are found in RBCs and the brain. GLUT
left; thus oxygen cannot be unloaded.
2 transporters are found in pancreatic b cells,
liver, and kidney.
30. The correct answer is D. Glucose-6-phosphate
Answer C is incorrect. GLUT 4 transporters dehydrogenase (G6PD) deficiency often mani-
are found in adipose tissue and skeletal mus- fests in young adulthood or adolescents after
cle. a serious infection. Genetic mutation variants
have been described, including the common
Answer D is incorrect. Glucose cannot simply
G6PDA and G6PD Mediterranean, both of
diffuse across membranes; it requires transport-
which are X-linked. Normal G6PD generates
ers.
reduced nicotinamide adenine dinucleotide
29. The correct answer is B. 2,3-Bisphosphoglyc- phosphate (NADPH) from oxidized nico-
erate (BPG) promotes oxygen unloading by tinamide adenine dinucleotide phosphate
binding to a pocket formed by the two a sub- (NADP+), which is used to reduce glutathi-
units. It can bind only when they are close to- one. Reduced glutathione is used to detoxify
gether, such as in the taut form. It is essential oxidizing agents. Oxidizing agents are found
to add inosine to stored blood for transfusions at times of infection, as with certain drugs
to prevent the loss of 2,3-BPG. Any change such as primaquine, and with ingestion of fava
that enhances the taut form of hemoglobin beans (called favism when symptomatic).
will decrease hemoglobins affinity for oxygen. Answer A is incorrect. Glucose-6-phosphate
Answer A is incorrect. Hemoglobin carries is generated from glucose by hexokinase in
oxygen better when it is in the relaxed form, all cells. High levels of glucose are processed
which has a higher affinity for oxygen. Con- by glucokinase in liver cells and pancreatic B
versely, the taut form of hemoglobin has a cells.
High-Yield Principles
Chapter 2: Biochemistry Answers 43

Answer B is incorrect. Glucose-6-phosphate Answer B is incorrect. PTH stimulates the


is generated from glucose by hexokinase in all production of 1,25-dihydroxyvitamin D, which
cells. in turn increases calcium and phosphate ab-
sorption from the gut. It does not inhibit
Answer C is incorrect. Hunter disease is an X-
1,25-dihydroxyvitamin D production.
linked mucopolysaccharidosis that results from
a deficiency of mucopolysaccharide break- Answer C is incorrect. PTH promotes cal-
down. It is not associated with this patients cium reabsorption in the renal tubules, not
presentation. calcium excretion.
Answer E is incorrect. The conversion of Answer D is incorrect. PTH inhibits the fur-
glucose-6-phosphate (G6P) to 6-phosphoglu- ther release of PTH as part of a negative feed-
conate (6PG) is the first step in the pentose- back loop; it does not induce further release of
phosphate pathway (also known as the hexose- PTH.
monophosphate shunt). This particular step
Answer E is incorrect. PTH inhibits phos-

Biochemistry
produces NADPH (reduced NADP+), which
phate reabsorption in the renal tubules and,
is used to maintain a reduced pool of gluta-
in fact, promotes phosphate excretion. Think
thione. It is also used to synthesize fatty acids
PTH: Phosphate Trashing Hormone.
and steroids, to generate the cytochrome P450
(CYP450) enzyme system, and in phagocytosis. 32. The correct answer is E. Deficiency of por-
6PG can be converted to ribose-5-phosphate phobilinogen deaminase (also known as uro-
for use in DNA synthesis. These processes oc- porphyrinogen I synthetase) causes acute
cur in all cells, but deficiency of G6P has the intermittent porphyria (AIP), a disease char-
greatest effect on RBCs, which have no alter- acterized by acute attacks of gastrointestinal,
nate means of reducing oxidizing toxins. neurologic/psychiatric, and cardiovascular
symptoms. A deficiency in porphobilinogen
31. The correct answer is A. Parathyroid hormone
deaminase leads to a deficiency in heme syn-
(PTH) plays a key role in the regulation of cal-
thesis, in turn causing a build-up of intermedi-
cium and phosphate balance. When the serum
ary products such as aminolevulinic acid and
calcium level falls, PTH is rapidly released from
porphobilinogen, which cause the symptoms
the parathyroid glands and acts to restore serum
of the disease. Age at onset is almost always af-
calcium levels to normal through the following
ter puberty, it is more common in women, and
mechanisms: (1) increasing calcium absorption
symptoms often are precipitated by drugs that
in the small intestine; (2) promoting calcium
induce heme-containing CYP450. Because of
reabsorption in the renal tubules; (3) inhibiting
the intermittent nature of attacks, AIP can be
phosphate reabsorption in the renal tubules; (4)
difficult to diagnose. These patients often will
inhibiting the further release of PTH as part of
present with urine that turns a dark color when
a negative feedback loop; and (5) stimulating
exposed to air.
the production of 1,25-dihydroxyvitamin D.
Primary hyperparathyroidism is one of the most Answer A is incorrect. A deficiency in adeno
common forms of hypercalcemia, whereby a sine deaminase (ADA) can cause severe com-
parathyroid adenoma spontaneously produces bined immunodeficiency disorder. It presents
excess PTH, leading to hypercalcemia and hy- with recurrent viral, bacterial, fungal, and
pophosphatemia. Secondary PTH is caused by protozoal infections. ADA normally functions
excess PTH in response to renal failure or other to convert adenosine to inosine in the purine
situations like 1,25-dihydroxyvitamin D defi- salvage pathway. Deficiency of this enzyme
ciency (rickets or osteomalacia), in which low causes an excess of ATP and dATP that im-
calcium and high phosphate levels detected by balances nucleotide synthesis through nega-
the body lead to excess PTH production. tive feedback, thus preventing DNA synthesis
and decreasing lymphocytes. ADA deficiency
would not be associated with the symptoms
High-Yield Principles
44 Section I: General Principles Answers

seen in this patient, nor would it become clini- deletion of WT1, a tumor suppressor gene lo-
cally apparent at the age of 22 years. cated on chromosome 11p.
Answer B is incorrect. Congenital deficiency Answer A is incorrect. Adrenocortical adeno-
of homogentisic acid oxidase, an enzyme in mas are usually asymptomatic and are often in-
the degradative pathway of tyrosine, results in cidentally found at autopsy or on CT. They are
a disease called alkaptonuria. This deficiency usually smaller tumors, nodular lesions <2.5
leads to the accumulation of homogentisate, cm in diameter. They rarely cause pathology.
forming polymers that cause urine to darken
Answer B is incorrect. Neuroblastoma is the
on standing. This disease is generally innocu-
most common extracranial solid tumor in chil-
ous but may cause arthritis with darkening of
dren. They can present retroperitoneally, often
the joints. It would not be associated with the
involving the adrenal medulla, as they arise
systemic symptoms described in this patient.
from the neural crest cells; they would not typ-
Answer C is incorrect. Lysosomal a-1,4- ically be of renal origin. Neuroblastoma is as-
Biochemistry

glucosidase deficiency causes a rare glycogen sociated with the N-myc oncogene, located on
storage disease called Pompe disease, which chromosome 2p.
is transmitted in an autosomal recessive man-
Answer C is incorrect. Renal cell carcinoma
ner. It presents with cardiomegaly along with
is the most common renal cancer in adults. It
weakness and hypotonia in the first six months
usually presents in older adults after the fifth
of life. It is often fatal by age 2 years. Pompe
decade of life and is uncommon in children.
disease would not be associated with the symp-
toms seen in this patient. Answer D is incorrect. Transitional cell carci-
noma can involve any part of the urothelium.
Answer D is incorrect. Ornithine transcarba-
In the kidney, it usually involves the renal pel-
mylase deficiency, an X-linked disorder, is the
vis. Transitional cell carcinoma accounts for
most common genetic deficiency of the five
5%-10% of primary renal tumors.
enzymes of the urea cycle. Failure to synthe-
size urea, and therefore break down ammo- 34. The correct answer is D. This child and his
nia, leads to hyperammonemia during the first uncle appear to have Friedreich ataxia, a tri-
weeks of life and can lead to mental retarda- nucleotide repeat disease. Like other trinucle-
tion. Treatment includes limiting protein in- otide repeat diseases, illness occurs because
take in the diet and administering compounds the unstable microsatellite regions on certain
like phenylbutyrate, which help bind to amino chromosomes have triplet codons that expand,
acids and promote their excretion. This disor- typically worsening from generation to genera-
der would not present with the symptoms seen tion (and often making the age of onset earlier
in this patient, nor would it normally present for each successive generation). These regions
at age 22 years. of massively expanded triplet repeats (most
commonly between 600 and 1200 in Fried-
33. The correct answer is E. The patient is a
reich ataxia) cause a decrease in the product of
young boy presenting with an abdominal mass
a gene, frataxin, at the translation stage.
involving the kidney. The most common re-
nal tumor in young children is Wilms tumor, Answer A is incorrect. The triplet repeats in
which accounts for approximately 6% of pe- Friedreich ataxia typically do not affect protein
diatric malignancies. Wilms tumor typically folding because the gene product does not usu-
presents with a palpable mass, and about 25% ally get to that stage.
of patients present with gross or microscopic Answer B is incorrect. The triplet repeats in
hematuria. It is an embryonal neoplasm that Friedreich ataxia typically do not affect protein
tends to occur between ages 1 and 3 years, splicing.
with most cases occurring before the age of 7
years. Wilms tumor is often associated with the
High-Yield Principles
Chapter 2: Biochemistry Answers 45

Answer C is incorrect. The triplet repeats in glycogen storage diseases. In particular, high
Friedreich ataxia typically do not cause a sub- protein plus creatinine supplementation may
stitution, such as that which occurs in sickle be recommended in McArdle disease, a glyco-
cell disease. gen storage disease that primarily affects skele-
tal muscle. This disease causes painful muscle
Answer E is incorrect. The triplet repeats in
cramps and myoglobinuria with strenuous ex-
Friedreich ataxia typically do not contain a
ercise.
stop codon.
Answer E is incorrect. Recombinant enzyme
35. The correct answer is B. The clinical vignette therapy has not been developed for PKU. This
strongly suggests phenylketonuria (PKU). PKU technology has been used to develop a treat-
results most commonly from a deficiency of ment for the adult-onset form of Gaucher dis-
phenylalanine hydroxylase, the first enzyme ease, a lysosomal storage disorder. This disor-
in the breakdown pathway for phenylala- der is characterized by hepatosplenomegaly,
nine. The product of this reaction is tyrosine, aseptic necrosis of the femur, and bone crisis.

Biochemistry
a nonessential amino acid in healthy patients.
Infants with PKU have inappropriately high 36. The correct answer is E. Pellagra is caused by
blood phenylalanine levels. High phenylala- vitamin B3 (niacin) deficiency. Patients clas-
nine levels are neurotoxic, so this may lead sically present with diarrhea, dermatitis, and
to mental retardation if untreated. Other dementia (and beefy glossitis). Other water-
symptoms include hypopigmentation (due to soluble vitamins include riboflavin (B2), niacin
impaired melanin synthesis), musty odor, ec- (B3), biotin, folate, and cobalamin (B12).
zema, and hyperreflexia. Treatment includes
Answer A is incorrect. Increased erythrocyte
a diet low in phenylalanine with tyrosine sup-
hemolysis is the result of vitamin E deficiency,
plementation (since it is now essential). It is
which results in increased fragility of RBCs.
most effective if instituted before the child is 3
Vitamin E is an antioxidant that protects RBCs
weeks old. Most infants in North America are
from hemolysis. It is fat-soluble.
currently routinely screened for PKU.
Answer B is incorrect. Neonatal hemorrhage
Answer A is incorrect. A diet low in the
is due to vitamin K deficiency. Vitamin K cata-
branched-chain amino acids leucine and iso-
lyzes -carboxylation of glutamic acid residues
leucine is used to treat patients with maple
on various proteins concerned with blood clot-
syrup urine disease. These patients lack a
ting. It is a fat-soluble vitamin.
branched-chain dehydrogenase, and thus
have inhibited breakdown of leucine, isoleu- Answer C is incorrect. Night blindness is a
cine, and valine. Infants with this disorder consequence of vitamin A (retinol) deficiency.
would have an odd smell to their urine. They Vitamin A is a constituent of visual pigments
can have severe central nervous system de- and is a fat-soluble vitamin.
fects. They do not typically have pale skin, as Answer D is incorrect. Osteomalacia is due to
branched chain amino acids, unlike phenylala- vitamin D deficiency. Vitamin D is a fat-soluble
nine, are not involved in the melanin synthesis vitamin.
pathway.
Answer C is incorrect. A diet low in tyrosine 37. The correct answer is A. This patient suffers
would cause harm to a patient with PKU, who from I-cell disease, which is caused by a fail-
cannot make this amino acid. ure of addition of mannose-6-phosphate by
GlcNAc phosphotransferase on the Golgi ap-
Answer D is incorrect. A high-protein diet paratus. Without mannose-6-phosphate, lyso-
would not be recommended in a patient with somal enzymes cannot be properly directed for
PKU, as it would lead to high levels of amino inclusion into lysosomes and will instead be
acids including phenylalanine. High-protein excreted by the cell. Thus lysosomal enzymes,
diets may be used in therapy of some of the
High-Yield Principles
46 Section I: General Principles Answers

including hexosaminidase, iduronate sulfa- are a few of the many ophthalmologic prob-
tase, and arylsulfatase A, will be found in the lems such patients can have.
extracellular, but not intracellular, space. I-cell
Answer A is incorrect. Lactose intolerance is
disease is characterized by skeletal abnormali-
not associated with albinism.
ties, restricted joint movement, coarse facial
features, and severe psychomotor impairment. Answer B is incorrect. Children with phenyl-
Death usually occurs in the first decade of life. ketonuria should avoid foods with phenylala-
nine.
Answer B is incorrect. Although lysosomes
may be abnormal in I-cell disease, that ab- Answer C is incorrect. Avoiding strenuous ac-
normality results from defective trafficking of tivity may be useful for patients with certain
intracellular proteins caused by an abnormal rare cardiac diseases, but is not necessary for
Golgi apparatus, not from an intrinsic lyso- children with albinism.
somal abnormality. This is proven by the find- Answer D is incorrect. Patients with Turner
ing that cultured cells from patients with I-cell
Biochemistry

syndrome will be very short at full growth (<5


disease are capable of incorporating lysosomal feet tall) unless GH is given in childhood.
enzymes if properly tagged with mannose- Children with albinism have normal growth
6-phosphate. and development.
Answer C is incorrect. Ribosomes are primar-
ily responsible for ensuring the proper match- 39. The correct answer is B. The patient most
ing of messenger RNA with transport RNA, likely has pancreatic adenocarcinoma that is
therefore ensuring protein synthesis. The ri- located at the head of the pancreas, leading to
bosomes of patients with I-cell disease are not obstruction of the common bile duct. Weight
abnormal. loss, painless jaundice, and a palpable gallblad-
der (Courvoisier sign) can occur in pancreatic
Answer D is incorrect. Rough endoplasmic cancer. The obstruction from the growing tu-
reticulum (RER) typically translates proteins mor results in conjugated hyperbilirubinemia,
meant for extracellular use. The RER in I-cell increased urine bilirubin levels, and decreased
disease is not abnormal. urine urobilinogen levels. The majority of
Answer E is incorrect. Smooth endoplasmic bilirubin results from the breakdown of heme
reticulum (SER) is the site of cell lipid synthesis groups in senescent RBCs. After cellular re-
and processing of protein. The SER of patients lease, bilirubin binds to albumin, which deliv-
with I-cell disorder is not abnormal and does ers the molecule to the liver. Hepatocellular
not play a role in the addition of 6-mannose- uptake and glucuronidation in the endoplas-
phosphate. mic reticulum generate conjugated bilirubin,
which is water soluble and excreted in the bile.
38. The correct answer is E. Patients with congen- Gut bacteria deconjugate the bilirubin and de-
ital albinism have problems producing mela- grade it to urobilinogens. The urobilinogens
nin. This can be due to a deficiency in the are excreted in the feces, with some reabsorp-
tyrosine (precursor to melanin) transporters or tion and excretion into urine. Based on this
a deficiency in the tyrosinase enzyme. Either metabolic schema, the laboratory values in ob-
way, patients will have generalized decreased structive liver disease become evident. Failed
pigmentation in the skin, eyes, and hair. With- excretion of conjugated bilirubin leads to a
out aggressive photoprotection, most albinism direct bilirubinemia. Failure of urobilinogen
patients will eventually develop skin cancer. production by gut flora leads to low levels of
The other major problems are ocular, as the urine urobilinogen. The urine bilirubin level
lack of melanin causes poor development of is elevated secondary to the increased plasma
the retinal pigment epithelium. The lack of concentration of direct bilirubin, which under-
pigment in the iris also causes problems. Nys- goes renal excretion.
tagmus, strabismus, and impaired visual acuity
High-Yield Principles
Chapter 2: Biochemistry Answers 47

Answer A is incorrect. Conjugated hyperbili- including laminin. The legs look muscular,
rubinemia, increased urine bilirubin levels, but are actually pseudohypertrophic due to
and normal urine urobilinogen levels can massive interstitial fibrosis.
be seen in patients with hepatocellular jaun-
Answer A is incorrect. Dystrophin has no in-
dice. The urine urobilinogen level is normal
volvement with signaling at the neuromuscular
because, unlike in obstructive jaundice, gut
junction.
bacteria have the opportunity to synthesize
urobilinogen. The clinical presentation and Answer C is incorrect. Actin-myosin cross-
physical findings presented here supports a bridge cycling is promoted by calcium binding
diagnosis of pancreatic adenocarcinoma, not to troponin C, which causes a conformational
hepatocellular jaundice. change that allows tropomyosin to move so
that actin-myosin cycling can occur.
Answer C is incorrect. Unconjugated hyper-
bilirubinemia, increased urine bilirubin lev- Answer D is incorrect. Dystrophin is not an
els, and decreased urine urobilinogen levels acetylcholine receptor.

Biochemistry
can occur with hepatocellular disease if there Answer E is incorrect. The ryanodine receptor
is also concurrent conjugated hyperbilirubine- and the dihydropyridine receptor are involved
mia. However, a pure obstructive condition is in the control of exocytosis of calcium from
not characterized by unconjugated hyperbili- the sarcoplasmic reticulum.
rubinemia.
Answer D is incorrect. Unconjugated hyper- 41. The correct answer is D. This patient pre
bilirubinemia, decreased urine bilirubin lev- sents with altered mental status, hyperventila-
els, and increased urine urobilinogen levels is tion, and lactic acidosis with hypoglycemia.
a classic pattern seen in hemolytic jaundice. This presentation is consistent with ethanol-
In this case the bilirubin level rises due to in- induced hypoglycemia. Oxidation of ethanol
creased heme turnover and may overwhelm produces the reduced form of nicotinamide
the livers ability to conjugate it. These fea- adenine dinucleotide (NADH) in the liver via
tures would not be seen in obstructive liver two key enzymes: alcohol dehydrogenase and
disease. Patients with certain diseases that in- acetaldehyde dehydrogenase. A high ratio of
crease RBC turnover, such as sickle cell dis- NADH to oxidized nicotinamide adenine di-
ease, spherocytosis, and glucose-6-phoshate nucleotide (NAD) induces pyruvate metabo-
dehydrogenase deficiency, may have hemolytic lism to lactic acid, which leads to lactic aci-
jaundice. The clinical presentation and physi- dosis. Note the anion gap and the high lactate
cal findings here point to a diagnosis of pancre- level. This elevated NADH / NAD ratio limits
atic adenocarcinoma, not hemolytic jaundice. the supply of pyruvate needed for gluconeo-
genesis, hence hypoglycemia ensues.
Answer E is incorrect. Unconjugated hyper-
bilirubinemia, decreased urine bilirubin, and Answer A is incorrect. Glycerol 3-phosphate
decreased urine urobilinogen are very unlikely levels are increased (rather than decreased) as
to occur simultaneously in any given condi- a result of the low pyruvate levels. Incidentally,
tion. it is important to understand that this leads to
increased very low density lipoprotein levels
40. The correct answer is B. This boy suffers from and hyperlipidemia.
Duchenne muscular dystrophy, an X-linked Answer B is incorrect. Pyruvate is not overpro-
recessive disorder caused by a frameshift mu- duced; rather, it is metabolized to lactate.
tation that deletes the dystrophin gene and
causes accelerated muscle breakdown (in- Answer C is incorrect. Gluconeogenesis is in-
creases creatine kinase). Dystrophin normally hibited (note the low glucose level) during lac-
links actin filaments to a group of transmem- tic acidosis as a result of the pyruvate conver-
brane glycoproteins in the extracellular space, sion to lactic acid.
High-Yield Principles
48 Section I: General Principles Answers

Answer E is incorrect. Thiamine (vitamin B1) Neither of these symptoms is typically associ-
deficiency can cause lactic acidosis, because ated with a vitamin deficiency.
it is a cofactor in the pyruvate dehydrogenase
complex; this causes pyruvate accumulation, 43. The correct answer is E. This patient is suf-
which induces lactic acid production. How- fering from methemoglobinemia, in which
ever, this patient has not been drinking for a symptoms typically develop as the percentage
long time, so he is less likely to be vitamin B1 of circulating hemoglobin that is instead met-
deficient. hemoglobin rises above 3%. Methemoglobin
contains Fe3+ (as opposed to the Fe2+ of circu-
42. The correct answer is D. Vitamin B12 is a nec- lating hemoglobin) and is formed by nonoxy-
essary cofactor in the regeneration of folate for gen oxidizing agents. One such agent known
methyl group donation in DNA synthesis. For to cause this is dapsone, which is used for toxo-
this reason, vitamin B12 and folate deficiencies plasmosis prophylaxis in HIV-positive patients.
each present with megaloblastic anemia and The Fe3+ of methemoglobin is unable to bind
Biochemistry

hypersegmented neutrophils, as all blood cell oxygen, and so cannot deliver it to the cells of
lines are affected by the defect in DNA syn- the body and the patient becomes cyanotic.
thesis. However, only vitamin B12 deficiency Nicotinamide adenine dinucleotide reductase
increases serum methylmalonic acid levels (NADH) converts Fe3+ into Fe2+ by simulta-
and impairs myelin synthesis. This myelin de- neously oxidizing NADH to the oxidized form
fect primarily impacts the posterior and lateral of nicotinamide adenine diphosphatase, and
spinal columns, causing paresthesias and im- so oxygen-carrying capacity is restored. This
paired proprioception. Thus, neurologic ab- system may be overwhelmed in the presence
normality in the context of megaloblastic ane- of oxidizing agents such as dapsone. Of note,
mia is a USMLE-favorite hint that vitamin B12, the arterial blood gas of patients with methe-
rather than folate, is deficient. moglobinemia will show a normal partial oxy-
gen pressure of because the level of dissolved
Answer A is incorrect. Confusion, confabula-
oxygen is normal; it is only the level of hemo-
tion, and ataxia are typical of Wernicke-Korsakoff
globin-bound oxygen that is reduced, hence,
syndrome, a disorder of thiamine (vitamin B1)
reduced oxygen saturation. The patient may
deficiency typical in alcoholics.
be acidotic secondary to lactic acidosis from an
Answer B is incorrect. Folate and vitamin oxygen deficit at the tissue level.
B12 deficiencies present similarly, but folate
Answer A is incorrect. ATPase, the enzyme re-
deficiency does not manifest with an elevated
sponsible for releasing a phosphate group from
methylmalonic acid level or neurologic prob-
ATP, is not responsible for converting met-
lems. In the absence of increased serum meth-
hemoglobin to hemoglobin. It is involved in
ylmalonate levels, therefore, the physician
many other reactions in the body and is often
would diagnose folate deficiency, and no neu-
used to provide energy for an energetically un-
rologic symptoms would be expected.
favorable but necessary reaction.
Answer C is incorrect. Concurrent onset of
Answer B is incorrect. Flavin adenine dinu-
dysarthria (defective articulation) and diplo-
cleotide (FADH2) reductase is not responsible
pia may indicate that a transient ischemic epi-
for converting methemoglobin to hemoglobin,
sode or cerebrovascular accident has occurred.
but instead returns FADH2 to its reduced form
These symptoms are not typical of any vitamin
so that it can accept electrons in the Krebs cy-
deficiency.
cle.
Answer E is incorrect. Syncope may be a sign
Answer C is incorrect. GTPase, the enzyme
of vasovagal stimulation, low blood pressure,
responsible for releasing a phosphate group
arrhythmia, and other cardiovascular disorders.
from GTP, is not responsible for converting
Lethargy is a sign of decreased consciousness.
methemoglobin to hemoglobin. It is used in
High-Yield Principles
Chapter 2: Biochemistry Answers 49

many second messenger pathways and can trophy, a syndrome that consists of central and
help provide energy for an energetically unfa- peripheral demyelination, ataxia, and demen-
vorable but necessary reaction. tia.
Answer D is incorrect. Lactase, the enzyme Answer D is incorrect. Hunter syndrome is a
responsible for cleaving lactose into its mono- lysosomal storage disease that is characterized
saccharide constituents, is not responsible for by developmental delay, aggressive behav-
converting methemoglobin to hemoglobin. ior, and airway obstruction. It is due to a defi-
ciency of iduronate synthase.
Answer F is incorrect. Pyruvate kinase, the en-
zyme responsible for converting phosphoenol- Answer E is incorrect. Mutations in lysyl hy-
pyruvate to pyruvate at the end of glycolysis, is droxylase have been found in certain forms of
not responsible for converting methemoglobin Ehlers-Danlos syndrome. These mutations re-
to hemoglobin. duce the content of hydroxylysine in collagen
and reduce the content of collagen cross-links.

Biochemistry
44. The correct answer is E. Steroid hormones These defects are believed to decrease the ten-
enter cells and bind to receptor proteins. The sile strength of collagen and account for the
receptor-hormone complex binds to specific symptoms of Ehlers-Danlos syndrome.
response elements, or the regulatory region of
DNA, and activates gene transcription. 46. The correct answer is A. This patient has fruc-
tose intolerance caused by a deficiency in al-
Answer A is incorrect. Steroid hormones do
dolase B. Aldolase B catalyzes the reaction in
not regulate the initiation of protein synthesis.
which fructose-1-phosphate is metabolized to
Answer B is incorrect. Steroid hormones do dihydroxyacetone-phosphate and glyceralde-
not regulate mRNA degradation. hyde. If there is a deficiency in aldolase B, the
Answer C is incorrect. Steroid hormones do reactant fructose-1-phosphate accumulates in
not regulate mRNA processing. the liver. This depletes the livers stores of free
phosphate, which inhibits the production of
Answer D is incorrect. Steroid hormones reg- glucose through gluconeogenesis and causes a
ulate gene transcription, not translation. fall in cellular ATP levels. The common pre-
ceding event to the drop in glucose and ATP
45. The correct answer is C. Tay-Sachs disease levels is a decrease in free phosphate levels.
results from a deficiency of hexosaminidase A
activity. This disorder is inherited as an autoso- Answer B is incorrect. ATP will not be in-
mal recessive trait and has a carrier frequency creased, because much of the free phosphate
of 1:25 in the Ashkenazi Jewish population. needed to combine with adenosine diphos-
Findings include loss of motor skills, increased phate to form ATP is already bound to fruc-
startle reaction, macular pallor, and a cherry- tose.
red spot on the macula (as shown in the im- Answer C is incorrect. When a patient with
age). Diagnosis is confirmed by the quantifica- aldolase B deficiency is challenged with fruc-
tion of hexosaminidase level in isolated WBCs tose, glucose levels will fall and a lactic acido-
in the blood. Future at-risk pregnancies can be sis will ensue. Therefore the pH will decrease,
monitored via prenatal diagnosis by either am- not increase.
niocentesis or chorionic villus sampling.
Answer D is incorrect. Rough endoplasmic
Answer A is incorrect. Fabry disease occurs in reticulum (RER) typically translates proteins
a-galactosidase A deficiency. This disease is meant for extracellular use. The RER in I-cell
characterized by symptoms of peripheral neu- disease is not abnormal.
ropathy, cardiovascular, and renal disease.
Answer E is incorrect. In aldolase B defi-
Answer B is incorrect. Arylsulfatase A defi- ciency fructose can be converted to fructose-
ciency characterizes metachromatic leukodys- 1-phosphate and become trapped intracellu-
High-Yield Principles
50 Section I: General Principles Answers

larly. Thus there should not be a significant phate leads to inhibition of gluconeogenesis
rise in urinary fructose excretion as occurs in and glycogenolysis. Patients present with jaun-
fructokinase deficiency. dice, cirrhosis, hypoglycemia, and scleral ic-
terus. Hepatosplenomegaly is often seen on
47. The correct answer is C. Glucose-6-phosphate physical examination. It is usually diagnosed
dehydrogenase (G6PD) deficiency is charac- in early childhood, when children are weaned
terized by acute episodes of hemolytic anemia from formula to regular table food.
following administration of certain medica-
Answer E is incorrect. Hereditary spherocyto-
tions, infection, or ingestion of fava beans.
sis is caused by a variety of molecular defects
G6PD is the first and rate-limiting enzyme of
in genes that code for spectrin, ankyrin, pro-
the pentose phosphate pathway, which pro-
tein 4.1, and other RBC membrane proteins.
duces two reducing equivalents that keep glu-
The structural defect makes the RBCs more
tathione in its reduced state. Reduced glutathi-
fragile and they take on a spherical shape,
one is necessary to detoxify peroxides and free
hence the name spherocytes. Spherocytes
Biochemistry

radicals that can accumulate within RBCs and


are recognized as abnormal and destroyed
cause damage to various cellular structures.
in the spleen, resulting in severe anemia and
Heinz bodies are small round inclusions seen
splenomegaly. Splenectomy curbs the anemia;
within RBCs that comprise hemoglobin and
however, the RBCs will continue to be spheri-
other protein precipitates. G6PD deficiency is
cal in shape.
most common in people who are black, people
of Mediterranean descent, and people from Answer F is incorrect. Lactase deficiency can
tropical Africa and Asia. be due to either an inherited intolerance or
an age-dependent acquired intolerance of the
Answer A is incorrect. Alkaptonuria is a rare
sugar lactose. Acquired lactase deficiency (de-
genetic disorder in which patients present
creased expression with increased age) is more
with urine that darkens on exposure to air.
common in Africans and Asians. Patients pre
These patients cannot breakdown the amino
sent with osmotic diarrhea, abdominal cramps,
acid tyrosine, which results in the accumula-
and bloating.
tion of a by-product called homogentisic acid.
Homogentisic acid builds up in the skin and
48. The correct answer is A. At 28 weeks, this neo
connective tissues and is excreted in the urine,
nates lungs have not had the opportunity to
causing the dark color. Patients typically have
fully develop, and are deficient in dipalmitoyl
a good prognosis, although many suffer from
phosphatidylcholine, also known as surfactant.
arthritis as well as heart disease and kidney/
Surfactant, synthesized by type II pneumo-
prostate stones.
cytes, is essential in stabilizing air-expanded
Answer B is incorrect. Cystinuria is caused alveoli by decreasing surface tension, thus pre-
by a defect in an amino acid transporter in the venting lung collapse during expiration. Sur-
renal tubules. This is an inherited defect that factant is usually made most abundantly after
affects the absorption of four amino acids: cys- the 35th week of gestation. The most com-
tine, ornithine, lysine, and arginine. Cystine mon way to determine lung maturity is by the
kidney stones can form as a result of excess lecithin:sphingomyelin ratio of the amniotic
cystine in the urine. This disorder is not associ- fluid. If this ratio is >2.0, then the risk of de-
ated with the jaundice or hematologic abnor- veloping neonatal respiratory distress syndrome
malities seen in this patient. (NRDS) is significantly decreased.
Answer D is incorrect. Hereditary fructose Answer B is incorrect. Elastase is an endog-
intolerance is an autosomal-recessive inher- enous proteolytic enzyme in the lung that is
ited disease due to a deficiency of aldolase B, normally broken down by antitrypsin. In pa-
which causes an accumulation of fructose- tients with a1-antitrypsin deficiency, there is an
1-phosphate. The decrease in available phos- increased level of elastase, which leads to lung
High-Yield Principles
Chapter 2: Biochemistry Answers 51

tissue destruction and emphysema. Liver cir- nently cross-linking DNA strands, cyclophos-
rhosis also occurs as a result of the increased phamide causes breaks in double-stranded
level of elastase in the liver. DNA during cellular repair efforts, leading to
apoptosis.
Answer C is incorrect. Cilial dysfunction may
result in decreased mucus clearance from the Answer C is incorrect. Etoposide acts in the
lungs and may predispose patients to recurrent growth 2 (G2) and synthesis (S) phases of the
respiratory infections. In Kartagener syndrome, cell cycle, by inhibiting topoisomerase II and
cilia are immotile because of a dynein arm de- thereby inhibiting DNA synthesis. In the G2
fect. This results in infertility, bronchiectasis, and S phases, the chromosomes are not verti-
and recurrent sinusitis. cally aligned in the cell.
Answer D is incorrect. This neonate has signs Answer D is incorrect. Methotrexate acts
and symptoms consistent with NRDS second- in the synthesis (S) phase of the cell cycle. It
ary to his prematurity. NRDS is caused by a binds to dihyrofolate reductase and thereby

Biochemistry
deficiency of dipalmitoyl phosphatidylcholine, inhibits formation of purine nucleotides and
not phosphatidylglycerol. Phosphatidylglycerol thymidylate so that DNA synthesis cannot take
is a compound measured in amniotic fluid to place. In the S phase the chromosomes are not
determine fetal lung maturity, and is used in vertically aligned in the cell.
conjunction with the lecithin:sphingomyelin
ratio. 50. The correct answer is C. Fragile X syndrome
is a complex genetic disorder that most closely
Answer E is incorrect. Sphingomyelin is
follows an X-linked dominant pattern of inheri-
found primarily in the brain and nervous tis-
tance. It is caused by a trinucleotide repeat ex-
sue. Although it is measured to help in de-
pansion (CGG). The disease is characterized
termining fetal lung maturity, deficiency of
by mental retardation and physical features
sphingomyelin does not lead to NRDS.
such as macroorchidism (large testicles), long
face, large mandible, and large, everted ears.
49. The correct answer is E. The cells described
The number of CGG repeats in patients with
above are in metaphase of the mitosis (M)
the full mutation average around 230-4000. In
phase of the cell cycle, which is character-
the normal population, this sequence repeats
ized by chromosomes migrating and lining up
an average of 29 times. Patients with premu-
in the middle of the cell. In metaphase, the
tations have from 52 to 230 repeats and lack
nuclear envelope has disintegrated and the mi-
the disease phenotype. Differences in the size
totic spindle moves into the nuclear area. The
of CGG repeats can be shown on a Southern
chromosomes then become arranged in the
blot. Shorter fragments of DNA migrate more
plane of the spindle equator. Vincristine acts
rapidly through a gel toward the positive elec-
by binding to tubulin and blocking formation
trode. Therefore, patients with full mutations
of microtubules, which are required to form
(who have longer strands of DNA) will have a
the mitotic spindle.
sluggish band that stays toward the top of the
Answer A is incorrect. 5-Fluorouracil acts gel, the normal population will show a band at
in the synthesis (S) phase of the cell cycle. It the bottom of the gel, and patients with a pre-
works by complexing to folic acid, which in- mutation will have a band in the middle. Lane
hibits thymidylate synthesis and therefore C would best represent the Southern blot of a
DNA synthesis. In the S phase the chromo- woman who carries a premutation for fragile X
somes are not vertically aligned in the cell and one normal X.
Answer B is incorrect. Cyclophosphamide Answer A is incorrect. Lane A on the South-
is an alkylating agent, a class of cell cycle- ern blot shows two bands. The band at the top
nonspecific antineoplastic drugs. By perma- of the gel represents a large fragment of DNA
High-Yield Principles
52 Section I: General Principles Answers

and an amplification of the CGG region to a Answer D is incorrect. The DNA band on
full-blown mutation. The band at the middle lane D represents a patient with no trinucleo-
of the gel represents a medium-sized fragment tide repeat expansion.
of DNA or a premutation.
Answer E is incorrect. Lane E on the South-
Answer B is incorrect. Lane B represents a ern blot shows two bands. The band at the bot-
patient with the full fragile X mutation. The tom of the gel represents a short fragment of
DNA band is located at the top of the gel and DNA and thus a normal-sized CGG repeat re-
represents a large fragment of DNA and an gion. The band at the top of the gel represents
amplification of the CGG region to a full- a large fragment of DNA and an amplification
blown mutation. of the CGG region to a full-blown mutation.
Biochemistry
Chapter 3

Embryology

53
High-Yield Principles
54 Section I: General Principles Questions

Q u e st i o n s

1. A physician is asked to evaluate a 5-year-old (D) Incomplete fusion of urethral (urogenital)


girl who has developed a mass in her neck. folds
During the interview, he learns that the mass (E) Patency of the processus vaginalis
appeared within the past few months and has
been enlarging; however, it causes no pain or 4. Ensuring adequate maternal intake of a spe-
discomfort. The mass is in the midline of the cific nutrient is especially important in reduc-
neck just inferior to the hyoid bone. Labora- ing the incidence of the congenital anomaly
tory tests reveal a triiodothyronine level of 150 shown in the image. A deficiency of this nu-
ng/dL, a thyroxine level of 8.0 g/dL, and a trient, when present in an adult, is associated
thyroid-stimulating hormone level of 1 U/ with which of the following conditions?
mL. A CT scan of the neck is performed and
the doctor recommends surgery. Which of the
Embryology

following is the most likely diagnosis?


(A) Branchial cleft cyst
Subarachnoid
(B) Dermoid cyst space
(C) Ectopic thyroid gland
(D) Enlarged pyramidal lobe of the thyroid
(E) Lipoma
(F) Thyroglossal duct cyst

2. A 5-year-old girl is brought to her pediatri-


cian because her mother says she is frequently
bumping into stationary objects while playing.
Visual field examination shows bilateral pe-
ripheral vision defects. CT of the head reveals
Reproduced, with permission, from USMLERx.com.
calcifications in the pituitary fossa. Which of
the following is the most likely origin of this
childs brain tumor? (A) Confabulation and anterograde amnesia
(A) Adenohypophyseal lactotrophs (B) Diarrhea, dermatitis, and dementia
(B) Fourth ventricle neuroectoderm (C) Megaloblastic anemia
(C) Rathke pouch (D) Megaloblastic anemia with neurologic
(D) Vascular endothelium symptoms
(E) Ventricular lining (E) Microcytic anemia
(F) Polyneuritis and cardiac pathology
3. A 6-week-old boy is brought to the clinic be- (G) Swollen and bleeding gums, easy bruising,
cause of fever. Urinalysis is positive for WBCs. and poor wound healing
Physical examination reveals the boys urethral
opening to be displaced to the ventral (infe-
rior) aspect of the penis. Which of the follow-
ing is the embryologic cause of this congenital
abnormality?
(A) Abnormal expansion of the ureteric bud
(B) Abnormal positioning of genital tubercle
(C) Failure of the mesonephric (wolffian) duct
to regress
High-Yield Principles
Chapter 3: Embryology Questions 55

5. A 1-year-old girl presents to the pediatrician


because of increasing neuromuscular irritabil-
ity and tetany over the past few weeks. She has
also had recurrent viral and fungal infection
since birth, and was born full term. Results of
physical examination are within normal lim-
its. X-ray of the chest reveals the absence of a
thymic shadow. Thorough laboratory testing
reveals a T-lymphocyte deficiency. What other
findings are most likely in this child?
(A) Elevated parathyroid hormone levels
(B) Enlarged thymus gland
(C) Enlarged thyroid gland
(D) Low serum calcium levels Reproduced, with permission, from USMLERx.com.

Embryology
(E) Low serum phosphorus levels

6. A 13-month-old child is brought to the emer- (A) Cardiac tamponade


gency room after his parents found blood in (B) Coarctation of the aorta
his stool. They state that he did not appear dis- (C) Diaphragmatic eventration
tressed at the time, although he now displays (D) Mediastinal shift
some tenderness to abdominal pressure. Other (E) Pulmonary hypoplasia
than this tenderness, there are no significant
findings on physical examination. After per- 8. A 5-month-old girl is brought to the emer-
forming radionuclide imaging using 99mTc gency department by her parents because she
pertechnetate, the doctor makes a diagnosis is turning blue. She is cyanotic, weak, and
and recommends surgery to correct the prob- dyspneic. Her parents state that she has expe-
lem. What is the probable source of this childs rienced similar episodes in the past, but never
condition? this severe. Physical examination reveals the
lungs are clear to auscultation, with no wheez-
(A) Blockage of the intestine due to folding of ing, rales, or rhonchi. Cardiac examination
the distal ileum into the proximal colon reveals a regular rate and rhythm, normal S1,
(B) Breakdown of the stomach mucosal bar- single S2, a grade III rough systolic murmur
rier, with erosion of the underlying mu- at the left sternal border in the third intercos-
cosa tal space, and a palpable right ventricular lift.
(C) Damage to the intestinal epithelium due Echocardiography demonstrates unusual posi-
to ingestion of coins tioning of the aorta, which overrides both the
(D) Ectopic gastric epithelium in a persistent left and right ventricles in the long axis view.
omphalomesenteric duct In this condition, the primary developmental
(E) Incomplete bowel rotation resulting in ob- defect occurs in which portion of the primitive
struction of the superior mesenteric artery heart?
7. The x-ray shown in the image is from a child (A) Bulbus cordis
with a congenital condition. Which of the fol- (B) Conal septum
lowing is the most common cause of death in (C) Left and right horns of the sinus venosus
infants with this condition? (D) Primitive atria
(E) Primitive ventricle
High-Yield Principles
56 Section I: General Principles Questions

9. Spermatogenesis, the process of forming sper- (C) Failure of the midgut to return to the ab-
matozoa, occurs in the seminiferous tubules of dominal cavity after physiological midgut
the testes. As the cells proceed through the dif- herniation
ferent stages of spermatogenesis, they contain (D) Hypertrophy of the pyloric muscles
varying numbers of chromosomes and varying (E) Incomplete separation of the esophagus
amounts of DNA. A laboratory investigator is and laryngotracheal tube
observing, under the microscope, cells under-
going this process. He has focused on a group 12. A 16-year-old pregnant girl has not received
of cells that recently gained an acrosome and prenatal care. At 17 weeks, she noted some
tail. Which of the following best describes the painless vaginal spotting (bleeding) which
amount of DNA and the number of chromo- prompted her to seek medical attention. On
somes that exist in those cells? arrival at the hospital, pelvic examination
showed fetal parts in the cervical os and the
(A) 23, 1n
patient was told that a miscarriage was inevi-
(B) 23, 2n
Embryology

table. The products of conception as delivered


(C) 46, 1n
are shown in the image. What is the most
(D) 46, 2n
likely pathogenesis of this condition?
(E) 46, 4n

10. During embryonic development of the uri-


nary system, a portion of the bladder extends
into the umbilical cord. Failure of this vestigial
structure to degenerate may lead to which of
the following complications?
(A) Bladder exstrophy
(B) Bladder adenocarcinoma
(C) Meckel diverticulum
(D) Polycystic kidney disease
(E) Renal agenesis

11. A 4-year-old boy is brought to the pediatrician


by his mother, who says that he has been hav-
ing problems eating. She says he quickly be- Reproduced, with permission, from USMLERx.com.
comes full and often vomits following a meal.
When questioned, the boy says his stomach
hurts when he eats. The mother says that the (A) Ethanol toxicity
boy ate well up until about six months ago, (B) Malrotation
when the current problems began; he expe- (C) Maternal folate deficiency
rienced no abnormal vomiting as an infant. (D) Omphalomesenteric vessel occlusion
X-ray of the abdomen is remarkable for a dis- (E) ToRCHeS infection
tended, air-filled stomach that narrows at the
level of the proximal duodenum and then di- 13. Immediately following delivery, a newborn is
lates again in the distal duodenum. Which of observed to have multiple abnormalities, in-
the following developmental abnormalities is cluding a small lower jaw, abnormal feet, and
most likely responsible for this patients condi- hands that are clenched into fists. Treatment
tion? is started for a congenital heart condition. The
survival of a patient with this condition is most
(A) Abnormal rotation of the ventral pancre- similar to that of a person affected by which of
atic bud around the duodenum the following genetic abnormalities?
(B) Failure of duodenal recanalization
High-Yield Principles
Chapter 3: Embryology Questions 57

(A) An F508 deletion in the CFTR gene (D) Migration of neural crest cells to the distal
(B) CAG tandem repeats colon
(C) CGG tandem repeats (E) Recanalization of the duodenum
(D) Trisomy of chromosome 13
(E) Trisomy of chromosome 21 17. A 34-year-old man complains of dry mouth
and difficulty swallowing. He has no other
14. A neonate is found to have a congenital heart complaints. Physical examination is begun in
defect. Physical examination reveals that the the head and neck region. The eye examina-
patient is not cyanotic, but a harsh holosystolic tion is grossly benign. The nasal sinus appears
murmur is heard at the left lower sternal bor- unremarkable. The patients oral cavity is then
der. No other murmurs are heard on ausculta- examined. To enable evaluation of the palatal
tion. From which of the following congenital elevation, the patient is asked to say ah. The
heart defects is this neonate most likely suffer- muscles used to perform palatal elevation are
ing? derived from which of the following embryo-
logic structures?

Embryology
(A) Atrial septal defect
(B) Tetralogy of Fallot (A) Branchial arches 1 and 2
(C) Transposition of the great arteries (B) Branchial arches 3 and 4
(D) Truncus arteriosus (C) Branchial arches 4 and 6
(E) Ventricular septal defect (D) Branchial clefts 1 and 2
(E) Branchial pouches 3 and 4
15. A scientist creates a model of fetal circulation
in order to study blood flow during this stage 18. A child has a unilateral notch of the upper lip
of development. During one experiment, he (see image). What is the most likely etiology of
measures the partial oxygen pressure in various this lip malformation?
fetal vessels. His results are as follows:
Vessel A: 20 mm Hg
Vessel B: 27 mm Hg
Vessel C: 35 mm Hg
Vessel D: 12 mm Hg
The vessel labeled C will develop into which
structure in the adult?
(A) Falciform ligament
(B) Ligamentum teres hepatis
(C) Ligamentum venosum
(D) Medial umbilical ligament
(E) Median umbilical ligament

16. A baby boy dies several hours after birth. He


was born with wrinkled skin, deformed limbs, Courtesy of Dr. James Heilman.
and abnormal facies. The mothers pregnancy
was complicated by oligohydramnios. Which
(A) Abnormal fusion of the maxillary and me-
of the following embryologic processes most
dial nasal processes
likely failed in this child?
(B) Altered development of the third and
(A) Development of the ureteric buds fourth branchial pouches
(B) Closure of the rostral neural tube (C) Flaws in the mandibular and maxillary
(C) Formation of the tracheoesophageal sep- bones
tum (D) Incomplete development of the third pha-
ryngeal arch
High-Yield Principles
58 Section I: General Principles Questions

19. A 3-week-old boy presents to his pediatrician 20. Over the course of embryologic development,
because his mother has noticed that he looks the predominant location of hematopoiesis
yellow. On questioning, she elaborates that changes several times. When the uterine fun-
the jaundice began several days after birth and dus is palpable above the umbilicus, where is
has been associated with dark urine and clay- the main location of hematopoiesis in the fe-
colored stools. Laboratory studies show a direct tus?
bilirubin level of 5.0 mg/dL and a total biliru-
(A) Bone marrow
bin level of 5.5 mg/dL. Which of the following
(B) Liver
is characteristic of the most likely diagnosis?
(C) Pancreas
(A) Caused by a genetic mutation in a pro- (D) Thymus
moter region (E) Yolk sac
(B) Caused by deficiency in uridine 5-diphos-
phoglucuronosyltransferase
(C) Commonly treated with phototherapy
Embryology

(D) Inherited in an autosomal dominant pat-


tern
(E) Untreated, it leads to cirrhosis by six
months of age
High-Yield Principles
Chapter 3: Embryology Answers 59

An s w e r s

1. The correct answer is F. The thyroid gland thyroid gland before surgery is performed on a
originates as the thyroid diverticulum on thyroglossal duct cyst.
the floor of the pharynx. It descends into the
Answer D is incorrect. Hypertrophy of the
neck during development, but remains con-
pyramidal lobe of the thyroid is not the most
nected to the tongue by the thyroglossal duct.
likely cause of midline neck swelling in a
The thyroglossal duct eventually disappears,
young child. Furthermore, hypertrophic thy-
leaving a small cavity (the foramen cecum)
roid tissue would most likely alter thyroid hor-
at the base of the tongue. The pyramidal lobe
mone and TSH levels.
of the thyroid can be thought of as the caudal
part of the duct. Occasionally, part of the duct Answer E is incorrect. Lipomas may cause
epithelium persists in the neck and may form neck swelling, but the location of this mass
cysts. Thyroglossal duct cysts are usually pain- and the age of the patient make a thyroglossal

Embryology
less or slightly tender and appear in the mid- duct cyst much more likely. Lipomas tend to
line of the neck. They often appear over or just be very superficial, with poorly defined edges.
below the hyoid, but may appear anywhere be-
tween the base of the tongue and the thyroid. 2. The correct answer is C. The visual-field de-
If a normal thyroid gland is present, surgery fect described is a bitemporal hemianopia, typ-
to remove the thyroglossal duct cyst is recom- ically caused by lesions in the sella turcica im-
mended to prevent infection. In this case, the pinging on the optic chiasm. In children the
presence of a normal thyroid is demonstrated most common tumor in this location is a cra-
by normal triiodothyronine, thyroxine, and niopharyngioma, derived from the remnants
thyroid-stimulating hormone (TSH) levels and of Rathke pouch. This embryologic structure
is confirmed by CT scan. buds from the roof of the mouth to form the
anterior pituitary. Bitemporal hemianopia is
Answer A is incorrect. Branchial cleft cysts typically accompanied by severe headaches
can also occur in the neck but are not always and poor pituitary function. Treatment in-
in the midline. Unlike thyroglossal duct cysts, cludes surgery, radiotherapy, or both.
they are often associated with fistulas or sinus
tracts. Answer A is incorrect. Pituitary adenomas,
derived from secretory cells of the adenohy-
Answer B is incorrect. Dermoid cysts are the pophysis, can cause bitemporal hemianopia
second most common cause of midline neck and headaches, as they are also sella turcica
masses, after thyroglossal duct cysts. They tend tumors. However, they are more common
to be more superficial than thyroglossal duct in older patients, and are unlikely in a child.
cysts and more mobile relative to underlying Also, pituitary adenomas tend to secrete pi-
structures. tuitary hormones. The three most common
Answer C is incorrect. Ectopic thyroid glands forms of pituitary adenoma are prolactino-
are often seen in the presence of a thyroglos- mas (which are derived from lactotrophs and
sal duct cyst. An ectopic thyroid gland occurs secrete prolactin, causing galactorrhea and
when the thyroid fails to descend during devel- amenorrhea), growth hormone-secreting tu-
opment; in contrast, ectopic thyroid tissue may mors (somatotrophs, causing acromegaly), and
occur along the path of the thyroglossal duct ACTH-producing tumors (corticotrophs, caus-
in the presence of a normal thyroid gland. Un- ing Cushing disease). In this case, the only
like this patient, who has normal thyroid lev- data making this an incorrect answer are the
els, about one third of patients with an ectopic patients age and the lack of secretory action.
gland are hypothyroid. A CT scan is usually Answer B is incorrect. Medulloblastoma arises
performed to confirm the presence of a normal from primitive neuroectoderm in the fourth
High-Yield Principles
60 Section I: General Principles Answers

ventricle. It does not cause the visual symp- Answer B is incorrect. Abnormal positioning
toms seen in this patient, but the tumor may of the genital tubercle may result in epispadias,
compress the fourth ventricle to cause hydro- a condition in which the urethral opening is
cephalus and symptoms consistent with in- located on the dorsal (superior) surface of the
creased intracranial pressure such as morning penis. This condition is less common than hy-
headache and vomiting. An additional, specific pospadias and is associated with exstrophy of
sign of this posterior fossa tumor is a head tilt. the urinary bladder.
Treatment consists of surgery, chemotherapy,
Answer C is incorrect. The mesonephric
and radiation. When in doubt, remember that
(wolffian) duct develops into the seminal vesi-
medulloblastoma is the most common malig-
cles, epididymis, ejaculatory duct, and ductus
nant brain tumor in children.
deferens in the male. Regression of this duct
Answer D is incorrect. Hemangioblastomas might lead to an absence of these reproductive
are vascular tumors of the central nervous structures rather than hypospadias.
system that usually occur in the cerebellum
Embryology

Answer E is incorrect. Patency of the proces-


and spinal cord and thus would be unlikely
sus vaginalis allows fluid to flow from the peri-
to cause the visual field defects described in
toneum into the tunica vaginalis, resulting in a
this case. Symptoms include cerebellar ataxia,
hydrocele of the testes. This would not cause
motor weakness, and sensory dysfunction. He-
hypospadias, an abnormality in which the ure-
mangioblastomas can occur sporadically or
thra opens on the ventral surface of the penis.
in patients with von Hippel-Lindau disease,
which is an autosomal dominant disease in 4. The correct answer is C. The image shows a
which patients develop cerebellar and reti- meningomyelocele, a neural tube defect in
nal hemangioblastomas, pancreatic cysts, and which the meninges and spinal cord herniate
pheochromocytomas. through a defect in the spinal canal. Folate,
Answer E is incorrect. Ependymomas form if given to a mother early in pregnancy, low-
from the cells lining the ventricles and most ers the risk of developing neural tube defects
often occur in the fourth ventricle. Like me- (spina bifida occulta, meningocele, or menin-
dulloblastomas, ependymomas can block the gomyelocele). In the adult, folate deficiency
flow of cerebrospinal fluid and cause hydro- produces a megaloblastic anemia without neu-
cephalus. These patients, however, do not rologic symptoms. Folate deficiency is seen in
have the visual disturbances of the patient in alcoholics, pregnant women, patients with he-
this vignette. molytic anemia, and those taking drugs such
as methotrexate that inhibit folate metabolism.
3. The correct answer is D. This vignette de- Folate can be found in uncooked vegetables
scribes a urinary tract infection in an infant and fruits. A deficiency of vitamin B12 also
with hypospadias, a congenital abnormality in causes a megaloblastic anemia, but produces
which the urethra opens on the ventral (infe- neurologic symptoms as well. Such symptoms
rior) aspect of the penis. It occurs as a result include distal neuropathy and loss of position
of a failure of the urethral folds (also known as sense due to demyelination of the posterior
the urogenital folds) to fuse fully. Infants with and lateral columns of the spinal cord and of
hypospadias should undergo surgery to prevent the peripheral nerves.
urinary tract infections.
Answer A is incorrect. Confabulation and
Answer A is incorrect. The ureteric bud devel- anterograde amnesia, chronic neurologic se-
ops into the upper urinary system (collecting quelae of thiamine (vitamin B1) deficiency, are
duct, calices, renal pelvis, and ureters) and is seen in Wernicke-Korsakoff syndrome. This is
unrelated to the lower urinary system. Its ab- commonly seen in alcoholics.
normal expansion is not associated with known
urogenital anomalies.
High-Yield Principles
Chapter 3: Embryology Answers 61

Answer B is incorrect. Diarrhea, dermatitis, Answer C is incorrect. DiGeorge syndrome


and dementia are characteristic of pellagra, can less frequently involve the clear cells of the
caused by a deficiency of niacin (vitamin B3). thyroid gland, but would not be expected to
cause an enlarged thyroid.
Answer D is incorrect. Megaloblastic anemia
with neurologic symptoms is a result of vita- Answer E is incorrect. With hypoparathyroid-
min B12 (cobalamin) deficiency. Typically, ism, an increased serum phosphorus level is
neurologic symptoms result from demyelin- anticipated.
ation of the posterior and lateral columns of
the spinal cord and of peripheral nerves. Sym- 6. The correct answer is D. The child has a
metric numbness or burning in the extremities Meckel diverticulum, which describes the
and loss of position sense are common. Unlike persistence after birth of part of the omphalo-
folate deficiency, this is not associated with mesenteric duct (vitelline duct or yolk stalk).
congenital neural tube defects. Cobalamin de- Meckel diverticulum is usually found in the
ficiency can manifest as dementia as well. mid to distal ileum, and may end blindly or

Embryology
connect to the umbilicus. It is described by
Answer E is incorrect. Microcytic anemia is
the rule of 2s: It is about 2 inches long, is
caused by iron deficiency as well as lead poi-
located 2 feet proximal to the ileocecal valve,
soning and the thalassemias.
occurs in about 2% of the population in a
Answer F is incorrect. Polyneuritis and car- 2:1 male:female ratio, often presents before 2
diac pathology are signs of beriberi, which re- years of age (60% of cases), and may contain
sults from thiamine (vitamin B1) deficiency. 2 types of epithelium (gastric or pancreatic).
Ectopic gastric epithelium is present in about
Answer G is incorrect. Scurvy is a disorder of
half of cases and can cause ulcers and pain-
swollen and bleeding gums, easy bruising, and
less bleeding, but does not generally cause se-
poor wound healing seen in vitamin C (ascor-
vere pain unless inflammation occurs. In the
bic acid) deficiency. Vitamin C is an essential
half of Meckel diverticulum patients with no
cofactor for the hydroxylation of proline and
ectopic gastric epithelium, there is no bleed-
lysine residues. Hydroxyproline and hydroxyly-
ing. 99mTechnetium (99mTc) pertechnetate is
sine allow crosslinking of collagen, giving con-
absorbed preferentially by gastric mucosa, and
nective tissue adequate tensile strength.
thus may be used to detect ectopic gastric mu-
5. The correct answer is D. This child has Di- cosa in the diverticulum.
George syndrome, which is associated with Answer A is incorrect. Intussusception is the
defective development of the third and fourth telescoping of the distal ileum into the proxi-
pharyngeal pouches. These structures typi- mal colon. It usually presents in the first two
cally give rise to the thymus and parathyroid years of life, and a Meckel diverticulum may
glands. Their absence explains the typical predispose to this condition. However, intus-
T-lymphocyte immunodeficiency and hypo- susception typically has an abrupt and severe
parathyroidism seen in these patients, and evi- presentation, with paroxysmal bouts of scream-
denced by the hypocalcemia in this case. Most ing, vomiting, diarrhea, and bloody bowel
patients also display congenital cardiac defects. movements occurring within 24 hours of on-
Answer A is incorrect. With hypoparathyroid- set. A sausage-shaped mass in the abdomen
ism from underdeveloped parathyroid glands, may be palpable on physical exam.
a decreased parathyroid hormone level would Answer B is incorrect. Breakdown of the mu-
be expected. cosal barrier of the stomach and erosion of
Answer B is incorrect. DiGeorge syndrome is the underlying mucosal epithelium describes
characterized by thymic hypoplasia, not hyper- the pathology of a peptic ulcer. Peptic ulcers
plasia. may present at any age, but are more com-
mon in patients 12-18 years than in very young
High-Yield Principles
62 Section I: General Principles Answers

children. Additionally, it is not diagnosed by compromise breathing. Similarly to congeni-


99mTc-pertechnetate scanning, but would be tal diaphragmatic hernias, this can also cause
diagnosed by endoscopy. pulmonary hypoplasia, although usually not as
severe.
Answer C is incorrect. Ingestion of foreign
objects occurs frequently in young children Answer D is incorrect. Mediastinal shift does
and may cause mechanical damage to the in- occur in congenital diaphragmatic hernia, as
testinal lining. However, these tears are not de- the bowel invades the thorax and pushes the
tected with 99mTc-pertechnetate scanning. mediastinum to the right. However, this in it-
self is not a cause of death.
Answer E is incorrect. Abnormal or incom-
plete rotation of the intestine as it returns to
8. The correct answer is B. This patient has te-
the abdomen after physiologic herniation can
tralogy of Fallot (TOF). TOF is the most
trap and twist loops of bowel; twisting of these
common congenital cyanotic lesion and is
loops (volvulus) can result in obstruction of
characterized by four congenital cardiac ab-
Embryology

circulation and potentially lead to gangrene


normalities: (1) pulmonary stenosis, (2) ven-
of the affected segment of intestine. Most af-
tricular septal defect (VSD), (3) overriding
fected infants present within the first three
(right-arched) aorta, and (4) right ventricular
weeks of life with bile-containing vomit or
hypertrophy (due to outflow blockage). The
bowel obstruction. Bloody stool is not a princi-
severity of the condition is determined by the
pal sign of malrotation or volvulus.
degree of cyanosis, which is, in turn, most de-
pendent on the degree of pulmonary stenosis.
7. The correct answer is E. Pulmonary hypo-
In the most severe cases patients are cyanotic
plasia is the most common cause of death in
at birth, but most infants with TOF present
infants born with congenital diaphragmatic
at 4-6 months of age with recurrent bouts of
hernia. When the pleuroperitoneal folds fail
hypoxemia and cyanosis. The primary devel-
to fuse with the other components of the dia-
opmental defect is an abnormal anterior and
phragm during development, a hole is created
cephalad displacement of the conal septum,
that allows bowel into the thorax. The physical
resulting in an enlarged aorta and obstructed
compression of the bowels on the lung buds
pulmonary artery.
then prevents full development of the respira-
tory system (pulmonary hypoplasia). This leads Answer A is incorrect. The bulbus cordis be-
to a common presentation of dyspnea and cya- comes the smooth parts of the left and right
nosis and, unless it can be repaired surgically, ventricles, which are not primarily involved in
eventually leads to death. this lesion.
Answer A is incorrect. Cardiac tamponade is Answer C is incorrect. The left horn of the
most frequently associated with a pericardial sinus venosus gives rise to the coronary sinus.
effusion. This is not a common complication The right horn of the sinus venosus gives rise
of congenital diaphragmatic hernia. to the smooth part of the right atrium. Neither
of these structures is primarily involved in this
Answer B is incorrect. Cardiac abnormalities
lesion.
such as ventriculoseptal defects, vascular rings,
and coarctation of the aorta are associated with Answer D is incorrect. The primitive atria
congenital diaphragmatic hernias; however, become the trabeculated parts of the left and
they are not the most common cause of death. right atria, which are not primarily involved in
this lesion.
Answer C is incorrect. Eventration of the
diaphragm is a disorder in which all or part Answer E is incorrect. The primitive ventricle
of the diaphragmatic muscle is replaced by becomes the trabeculated parts of the left and
fibroelastic tissue. The weakened hemidia- right ventricles, which are not primarily in-
phragm is displaced into the thorax, which can volved in this lesion.
High-Yield Principles
Chapter 3: Embryology Answers 63

9. The correct answer is A. Spermiogenesis is These cysts are potential sites of bladder ade-
the series of post-meiotic morphologic changes nocarcinomas.
that marks the final maturation of the sperm.
Answer A is incorrect. Bladder exstrophy is a
Spermatids are the 23, 1n cells that result from
congenital developmental anomaly resulting
secondary spermatocyte meiosis II comple-
from failure of the abdominal wall to close
tion. They undergo morphologic changes to
during embryogenesis. This causes the poste-
become mature sperm that include acrosome,
rior bladder wall to protrude through the lower
head, neck, and tail.
abdominal wall. It is not a complication of a
Answer B is incorrect. Secondary spermato- patent urachus.
cytes are 23, 2n cells that result from primary
Answer C is incorrect. Meckel diverticulum
spermatocytes completing meiosis I. Each pri-
is the most frequent congenital anomaly found
mary spermatocyte forms two secondary sper-
in the gastrointestinal tract, and it is caused by
matocytes, each going on to form two sperma-
persistence of the omphalomesenteric duct.
tids.
It is often asymptomatic but can present with

Embryology
Answer C is incorrect. At no point during rectal bleeding, volvulus, intussusception, and
male gametogenesis is there a haploid cell obstruction. Meckel diverticulum can be re-
with 46 chromosomes. membered by the rule of 2s: found in 2%
of the population, commonly presents around
Answer D is incorrect. Both primordial germ
age 2 years, measures 2 inches long, can be
cells in the testes, which are dormant until
found 2 feet from the ileocecal valve, and of-
puberty, and type A spermatogonia, which de-
ten contains 2 types of epithelia (gastric and
velop at puberty, are 46, 2n cell types. A type A
pancreatic).
spermatogonium perpetuates itself to provide a
constant supply of sperm cells; it also differen- Answer D is incorrect. Polycystic kidney dis-
tiates into type B spermatogonia. ease is a hereditary disease characterized by
bilateral development of multiple cysts in the
Answer E is incorrect. Primary spermatocytes
renal parenchyma, ultimately leading to re-
are 46, 4n cells that result from the DNA repli-
nal failure. There are two forms of polycystic
cation of type B spermatogonia.
kidney disease: adult autosomal dominant
10. The correct answer is B. The portion of the (ADPKD) and childhood autosomal reces-
bladder that extends into the umbilical cord is sive (ARPKD). They are caused by distinct
the allantois, an extraembryonic cavity within genes. ADPKD has been mapped to the PKD1
the body stalk that projects onto the cloaca and PKD2 genes, which code for the integral
(the future bladder), and regresses prior to membrane proteins polycystin-1 and poly-
birth as the bladder descends into the pelvis. cystin-2, respectively. ARPKD is caused by
It gives rise to the urachus, which later degen- mutations in the PKHD1 gene, which codes
erates into a fibrous structure running along for a large protein called fibrocystin. Neither
the anterior abdominal wall extending to the ADPKD nor ARPKD is a complication of a
umbilicus known as the median umbilical patent urachus.
ligament. Failure of the urachus to completely Answer E is incorrect. Ectopic kidney is a
degenerate (persistent urachus) results in a condition that arises from development of a
number of clinical complications, depending kidney at an unusual anatomic location. Most
on the degree of patency of the urachus. A to- ectopic kidneys are found either within the
tally patent urachus creates a fistulous urinary pelvis or just above the pelvic brim. Function-
tract between the bladder and the umbilicus. ally, these kidneys are normal; however, the
At other times, only the umbilical end, the ureter may kink, leading to urinary flow stagna-
bladder end, or the central urachal region re- tion that predisposes to recurrent bacterial in-
mains patent, which gives rise to urachal cysts. fections. Ectopic kidney is not a complication
of a patent urachus.
High-Yield Principles
64 Section I: General Principles Answers

11. The correct answer is A. This patient most Answer E is incorrect. Incomplete separation
likely has an annular pancreas. Normally the of the esophagus and laryngotracheal tube re-
ventral bud of the pancreas rotates around the sults in a tracheoesophageal fistula. In its most
duodenum to fuse with the dorsal bud. The common form, the tracheoesophageal septum
ventral bud forms the uncinate process and is deviated posteriorly and the esophagus ends
part of the head of the pancreas, and the duct in a blind pouch connected to the trachea.
of the ventral bud becomes the main pancre- The fetus cannot swallow amniotic fluid and
atic duct. Rarely, a bifid ventral bud grows polyhydramnios may occur during pregnancy.
around the duodenum in both directions, Newborns appear healthy at first and swallow
forming a ring. Especially in the setting of in- normally, but quickly begin regurgitating fluid
flammation or malignancy, this ring can block through the nose and mouth and enter respira-
movement of food through the duodenum; tory distress. The defect can be repaired surgi-
such blockage causes epigastric pain, postpran- cally with high success rates.
dial fullness, nausea, and vomiting. Onset of
Embryology

symptoms can occur any time between infancy 12. The correct answer is B. The patient has an
and adulthood, or not at all. Blockage is also omphalocele, which results from failure of
associated with the double-bubble sign in closure of the anterior abdominal wall. In
the radiograph: the stomach is dilated proximal this midline abdominal wall defect, the herni-
to the blockage point and the duodenum is di- ated viscera are covered by a membrane con-
lated distal to it. sisting of the amniotic membranes, Wharton
jelly, and peritoneum. Between 50% and 70%
Answer B is incorrect. During normal devel-
of children with omphalocele have additional
opment, the lumen of the duodenum is ob-
congenital anomalies (including cardiac de-
structed by overgrowth of endothelial cells and
fects and genitourinary malformations such
then restored as these cells recede. Failure of
as bladder exstrophy), which are also thought
this process results in duodenal atresia. The
to be related to ventral closure defects. The
signs and symptoms of duodenal atresia are
pathogenesis of omphalocele is believed to be
very similar to those seen with an annular pan-
sporadic defective closure of the abdominal
creas, but they always present within hours af-
wall secondary to malrotation of the midgut
ter birth. Vomit containing bile and the radio-
derivatives during the 10th week of embryonic
graphic double bubble sign are indicative of
development. Alternative theories include ab-
duodenal atresia in an infant.
normal persistence of the primitive body stalk
Answer C is incorrect. Physiological midgut and the failure of body wall closure secondary
herniation occurs at the beginning of the sixth to incomplete lateral body wall migration. The
week of embryogenesis, when the midgut her- incidence of omphalocele is 1:5000 live births,
niates into the proximal umbilical cord. Nor- and it is most commonly associated with ex-
mally, it returns to the abdomen during the tremes of maternal age (<20 or >40 years of
tenth week. Failure to return to the abdomen age). It may be associated with a chromosomal
results in omphalocele, in which a portion of abnormality if there is only herniation of the
the newborns abdominal contents remain out- small bowel or the liver.
side the abdomen, covered by the umbilical
Answer A is incorrect. Ethanol toxicity is not
cord epithelium. This condition requires im-
associated with abdominal wall defects. Etha-
mediate surgical repair.
nol exposure during embryogenesis is associ-
Answer D is incorrect. Hypertrophy of the py- ated with fetal alcohol syndrome, which in-
loric muscles results in blockage of the diges- cludes mental retardation and a typical facies
tive pathway. Infants with congenital hyper- characterized by a smooth philtrum, thin up-
trophic pyloric stenosis generally present with per lip, and small palpebral fissures.
nonbilious projectile vomiting soon after birth.
Answer C is incorrect. Maternal folate defi-
ciency is not associated with abdominal wall
High-Yield Principles
Chapter 3: Embryology Answers 65

defects. Folate deficiency has been associated Answer A is incorrect. F508 deletion in the
with a number of neural tube defects, includ- CFTR gene is the most common cause of cys-
ing anencephaly and spina bifida. A myelo- tic fibrosis. Patients with cystic fibrosis have
meningocele would be located at the posterior frequent pulmonary infections, impaired mu-
side (superior if using fetal terminology). cous clearance, and poor growth secondary to
pancreatic involvement. Survival can extend
Answer D is incorrect. Omphalomesenteric
into the fourth and fifth decades in these pa-
vessel occlusion and consequent ischemia is
tients.
believed to be the cause of gastroschisis, an-
other congenital abdominal wall defect. This Answer B is incorrect. CAG tandem repeats
condition is a full-thickness defect in the ab- are found in Huntington disease, among oth-
dominal wall, and there is no protective mem- ers. Huntington is asymptomatic until the
brane with a variable amount of herniation patients third or fourth decade and is caused
of the intestines and parts of other abdominal by degeneration of the caudate and putamen.
organs. Unlike omphalocele, gastroschisis her- Patients present with gradually worsening cho-

Embryology
niation occurs to the right of the umbilicus, reiform (dance-like) movements, but not the
and is rarely associated with other congenital birth defects found in this patient.
anomalies. Children with this defect should be
Answer C is incorrect. This is fragile X syn-
given a warm moist occlusive dressing and re-
drome. Associated with CGG tandem repeats,
ceive immediate surgical intervention.
this syndrome is characterized by mental retar-
Answer E is incorrect. The ToRCHeS infec- dation, a large jaw, and large testes. Children
tions include Toxoplasmosis, Rubella, Cyto- with fragile X syndrome typically survive be-
megalovirus (CMV), Herpesvirus/HIV, and yond one year of age.
Syphilis. Congenital infection with one of the
Answer E is incorrect. Down syndrome can
ToRCHeS viruses is not associated with ab-
cause mental retardation and characteris-
dominal wall defects. Instead, common mani-
tic physical findings that include microge-
festations include fevers, hepatosplenomeg-
nia (a small chin), macroglossia, epicanthal
aly, jaundice, poor feeding, and intrauterine
folds, and a round face, but clenched fists and
growth restriction. Other specific signs include
rocker-bottom feet are classic for trisomy 18.
chorioretinitis, cataracts, and neural deafness
The survival of a child affected by Down syn-
(rubella); intracranial calcifications (toxoplas-
drome is approximately 50 years.
mosis); rhinitis, blueberry-muffin skin le-
sions, and interstitial keratitis (syphilis); cere- 14. The correct answer is E. This individual is
bral calcifications (CMV); and vesicular skin most likely suffering from a VSD. Infants with
lesions (herpes simplex virus). VSDs are generally not cyanotic at birth, but
can become cyanotic if a large defect is left
13. The correct answer is D. This newborn has
untreated. The majority of small VSDs involv-
Edwards syndrome, or trisomy 18. Affected
ing the membranous portion of the septum
children are born with clenched fists, rocker-
resolve on their own. With larger defects in-
bottom feet, micrognathia (a small lower jaw),
volving the muscular portion of the septum,
congenital heart disease, and mental retar-
higher pressures in the left ventricle initially
dation. The survival rate of <1 year is similar
cause a shunt of blood from the left ventricle
to that of trisomy 13 (Patau syndrome), from
to the right ventricle during systole. Over time,
which it should be distinguished. Trisomy of
due to the volume and pressure overload on
chromosome 13, or Patau syndrome, is charac-
the right-sided circulation, the child will de-
terized by a constellation of findings including
velop increased resistance in the pulmonary
mental retardation, microphthalmia, micro-
circulation (termed pulmonary hypertension),
cephaly, cleft lip/palate, abnormal forebrain
which increases the pressure in the right ven-
structures, polydactyly, and congenital heart
tricle to a point at which the shunt reverses
disease.
High-Yield Principles
66 Section I: General Principles Answers

and blood flows from the right ventricle to the of deoxygenated blood with oxygenated blood,
left through the VSD. This shunt reversal is causing cyanosis in the neonate. The cyanosis
termed Eisenmenger syndrome. As described is not as pronounced as in transposition of the
in the vignette, these children present early great arteries, and greatly depends on the anat-
with a harsh holosystolic murmur at the left omy of the individuals defect.
lower sternal border. The intensity of the mur-
mur is inversely proportional to the size of the 15. The correct answer is B. The vessel labeled
defect. C is most likely the umbilical vein, which has
the highest oxygen saturation level in the fe-
Answer A is incorrect. Atrial septal defect
tus. It carries blood enriched in oxygen from
(ASD) is a communication between the right
the placenta to the fetus. Its oxygen satura-
and left atria. Patients may remain asymptom-
tion is typically between 30 and 35 mm Hg.
atic or manifest symptoms of right-sided heart
Soon after birth, the umbilical vein becomes
failure, depending on the size of the defect.
dysfunctional as the neonate makes the tran-
Cyanosis may occur if there is a patent fora-
Embryology

sition from fetal circulation to that found in


men ovale with right-to-left shunting, but is
adult anatomy. In place of this vein is a fibrous
not systematically seen. On exam, patients
structure, the ligamentum teres hepatis, or the
with ASD have an ejection systolic murmur
round ligament of the liver. It extends from the
with fixed splitting of S2.
umbilicus to the transverse fissure of the liver,
Answer B is incorrect. Tetralogy of Fallot is where it joins the ligamentum venosum, thus
characterized by pulmonary artery stenosis, effectively separating the liver into its right and
right ventricular hypertrophy, an overriding left lobes. Recanalization of this vein occurs
aorta, and a VSD. Infants with cardiac defects under the pathologic condition of portal hy-
are typically cyanotic at birth. The pulmo- pertension associated with liver cirrhosis.
nary artery stenosis reduces the caliber of the
Answer A is incorrect. The falciform ligament
outflow tract, causing the pressure in the right
is a developmental remnant of the ventral mes-
ventricle to be unusually high. As a result, de-
entery of the fetus, thus it is a peritoneal fold
oxygenated blood is shunted from the right to
enclosing the round ligament of the liver an-
the left side of the heart through the VSD.
teriorly and the ligamentum venosum posteri-
Answer C is incorrect. Transposition of the orly.
great arteries is a congenital defect in which
Answer C is incorrect. The ligamentum veno-
the pulmonic artery exits from the left ventri-
sum is a fibrous structure that is derived from
cle and the aorta exits from the right ventricle.
the ductus venosus in the fetal circulatory sys-
In this defect there are essentially two closed
tem. The ductus venosus is a shunt that con-
circuits with no way for oxygenated blood to
ducts oxygen-rich blood from the umbilical
reach the systemic circulation outside of the
vein into the inferior vena cava. It may be as-
patent ductus arteriosus (PDA). Efforts to keep
sociated with the round ligament of the liver,
the PDA open are necessary to keep the baby
coursing through the fissure that demarcates
alive so it can be taken to the operating room
the boundaries between the left and caudate
to have the defect corrected. Neonates with
lobes of the liver. Most often, it is found at-
this condition are typically cyanotic at birth,
tached to the left branch of the portal vein in
have shortness of breath, and feed poorly.
the porta hepatis.
Since the defect is so severe, it is typically dis-
covered in the first week of life. Answer D is incorrect. There are two medial
umbilical ligaments in the adult. They course
Answer D is incorrect. Truncus arteriosus is
longitudinally on the deep surface of the an-
a congenital defect in which there is a large
terior abdominal wall underneath the medial
VSD and a common trunk that eventually sep-
umbilical folds. The medial umbilical liga-
arates into the aorta and pulmonary arteries.
ments represent vestigial remnants of the fetal
Due to the anatomy there is significant mixing
High-Yield Principles
Chapter 3: Embryology Answers 67

umbilical arteries. The paired umbilical arter- Answer D is incorrect. This describes the de-
ies have a very low oxygen saturation level (ves- fect in Hirschsprung disease, which manifests
sel D), as they carry blood depleted of oxygen as severe constipation and an inability to pass
from the fetus back to the placenta. meconium. Hirschsprung disease would not
account for the symptoms described in this
Answer E is incorrect. The median umbilical
scenario.
ligament is a single ligament that runs longi-
tudinally on the deep surface of the anterior Answer E is incorrect. A failure of duodenal
abdominal wall between the medial umbili- recanalization may give rise to duodenal atre-
cal ligaments in the adult, extending from the sia. Duodenal atresia is associated with Down
apex of the bladder to the umbilicus. It is a ves- syndrome, and it is often marked by a double
tigial remnant of the embryonic urachus. bubble sign on abdominal radiographs. Duo-
denal atresia would result in polyhydramnios
16. The correct answer is A. The presentation rather than oligohydramnios.
described here is consistent with Potter syn-

Embryology
drome, one cause of which is bilateral renal 17. The correct answer is B. The muscles that ele-
agenesis. The renal parenchyma (except for vate the palate are derived from branchial arch
the nephrons) is derived from the ureteric bud 3 (the stylopharyngeus) and branchial arch 4
(recall that the nephrons arise from mesoderm (the levator veli palatini). These are innervated
surrounding the ureteric bud). A failure of ure- by cranial nerves IX and X, respectively.
teric bud maturation would result in a fetus
Answer A is incorrect. The first branchial arch
without kidneys. An absence of kidneys would
generates M muscles: muscles of Mastica-
lead to oligohydramnios, as the fetus would
tion (teMporalis, Masseter, Medial and lateral
be unable to excrete urine into the amniotic
pterygoids) and the Mylohyoid. The second
sac. This, in turn, would lead to compression
arch gives rise to S muscles: Stapedius, Stylo-
of the fetus by the uterine wall, causing limb
hyoid, and facial expression muscles. None of
deformities, abnormal facies, and wrinkly skin.
these muscles is involved in palatal elevation.
Death would occur shortly after birth unless
an appropriate kidney donor could be found. Answer C is incorrect. Although branchial
arch 4 does give rise to the levator veli pala-
Answer B is incorrect. Anencephaly may re-
tini, branchial arch 6 gives rise to the intrinsic
sult from a failure of the rostral neural tube
muscles of the larynx (except the cricothyroid,
to close. Anencephalic infants are born with a
which is a fourth arch derivative). These mus-
marked reduction in fetal brain tissue and usu-
cles are not involved in elevating the palate.
ally an absence of the overlying skull. These
infants are unable to swallow amniotic fluid in Answer D is incorrect. The first branchial
utero, so their mothers pregnancies are usu- cleft gives rise to the external auditory meatus,
ally marked by polyhydramnios (too much am- and the second, third, and fourth clefts are
niotic fluid) rather than oligohydramnios (too obliterated during development. The clefts are
little). formed from ectoderm and could not give rise
to muscles, which are derived from mesoderm.
Answer C is incorrect. Failure of development
of the tracheoesophageal (TE) septum is the Answer E is incorrect. Branchial pouch 3
cause of a TE fistula. There are several variants gives rise to the thymus (ventral wings) and in-
of TE fistula, the most common of which is a ferior parathyroid glands (dorsal glands), and
blind upper esophagus with the lower esopha- the fourth branchial pouch gives rise to the su-
gus having an anomalous connection to the perior parathyroids. These are not involved in
trachea. TE fistulas commonly result in poly- palatal elevation. Remember that pouches give
hydramnios rather than oligohydramnios, and rise to endoderm-derived tissue, and arches
they are unlikely to cause the other findings in give rise to mesoderm-derived tissue such as
this infant. muscle. Use the mnemonic CAP to remem-
High-Yield Principles
68 Section I: General Principles Answers

ber that Clefts, Arches, and Pouches give rise the promoter region of uridine 5-diphospho-
to ecto-, meso-, and endoderm, respectively. glucuronosyltransferase, leading to diminished
expression of the gene. Patients with Gilbert
18. The correct answer is A. This child has a cleft syndrome develop a mild unconjugated hyper-
lip, which is most often caused by failure of bilirubinemia but usually are asymptomatic
the maxillary prominence to fuse with the me- and have a normal life expectancy.
dial nasal prominence. Cleft lip may occur
Answer B is incorrect. Crigler-Najjar syn-
unilaterally or bilaterally and represents the
drome type 1 is caused by a complete defi-
most common congenital malformation of the
ciency in uridine 5-diphosphoglucuronosyl-
head and neck. This commonly occurs with a
transferase, the hepatic enzyme necessary to
cleft palate.
conjugate bilirubin. This disorder produces
Answer B is incorrect. Abnormal development a severe unconjugated (indirect) hyperbiliru-
of the third and fourth branchial pouches gives binemia that causes death within the first few
rise to DiGeorge syndrome, which results in years of life. The patient in this case, however,
Embryology

thymic aplasia and failure of parathyroid devel- has a conjugated hyperbilirubinemia, suggest-
opment. ing an obstructive cause and ruling out Cri-
Answer C is incorrect. The mandibular and gler-Najjar syndrome.
maxillary bones are typically normally devel- Answer C is incorrect. Physiologic jaundice
oped in a cleft lip. Abnormal development of refers to the mild unconjugated (indirect)
these bones typically causes various facial dys- hyperbilirubinemia that affects nearly all
ostoses. newborns because of the greater turnover of
Answer D is incorrect. The third pharyngeal neonatal RBCs and the decreased bilirubin
arch forms the hyoid bone, stylopharyngeus clearance in the first few weeks of life. The
muscle, and glossopharyngeal nerve, which are peak total serum bilirubin occurs between 72
not altered in a simple cleft lip. and 96 hours of age and resolves within the
first few weeks of life. Often phototherapy is
19. The correct answer is E. The patient is pre- used to hasten resolution. This patient has a
senting with congenital extrahepatic biliary severe conjugated hyperbilirubinemia that
atresia. Descriptions of a pure elevation in di- cannot be explained by normal neonatal physi-
rect (conjugated) bilirubin strongly suggest ologic jaundice.
an obstructive etiology, as the liver is able to Answer D is incorrect. Biliary atresia is a rare
effectively conjugate bilirubin but fails to ex- condition whose cause is not entirely known; it
crete it into the small intestine. The absence of is not inherited in an autosomal dominant pat-
bilirubin in the small bowel results in acholic tern. Hereditary spherocytosis is an example
stools, whereas increased renal excretion of of an autosomal dominant condition that can
conjugated bilirubin causes a darkening of the cause jaundice and hyperbilirubinemia sec-
urine. Congenital extrahepatic biliary atresia ondary to hemolytic anemia. This autosomal
occurs when the developing bile ducts close dominant condition is due to mutations in
completely and fail to recanalize. Surgical spectrin or ankyrin causing RBC membrane
therapy of biliary atresia involves anastomosis defects that make the cells more fragile to he-
of the small bowel directly to intrahepatic bile molysis. Peripheral blood smears show small
ducts, a maneuver known as Kasais procedure, RBCs without central pallor, and diagnosis can
which is appropriate for the 10% of patients be confirmed with the osmotic fragility test.
with limited disease. Liver transplantation con- Unlike this case, hereditary spherocytosis usu-
tinues to be the best chance of survival for the ally presents later in life, with a mixed hyper-
remaining patients. bilirubinemia and normal stools.
Answer A is incorrect. Gilbert syndrome is
a benign disorder caused by a mutation in
High-Yield Principles
Chapter 3: Embryology Answers 69

20. The correct answer is B. The uterine fundus Answer C is incorrect. The pancreas produces
is palpable above the umbilicus at 20 weeks insulin, glucagon, and digestive enzymes. It
gestational age. Another landmark to keep plays no role in hematopoiesis.
in mind is that the uterine fundus is palpable
Answer D is incorrect. The thymus is the site
above the pubic symphysis at 12 weeks gesta-
of early development of the immune system; it
tional age. The liver is the predominant site of
is not a site of hematopoiesis.
hematopoiesis at weeks 6-30 of gestation.
Answer E is incorrect. The yolk sac is the pre-
Answer A is incorrect. The bone marrow is
dominant site of hematopoiesis between fetal
the predominant site of hematopoiesis begin-
weeks three and eight.
ning around week 28 and remains so through-
out adult life.

Embryology
This page intentionally left blank
Chapter 4

Microbiology

71
High-Yield Principles
72 Section I: General Principles Questions

Q u e st i o n s

1. A 30-year-old sexually active woman presents (A)


Blastomyces dermatitidis
with a painful vesicle on her external genita- (B)
Coccidioides immitis
lia and bilateral inguinal lymphadenopathy. A (C)
Cryptococcus neoformans
Tzanck smear from the vesicle is negative, and (D)
Histoplasma capsulatum
a Venereal Disease Research Laboratory assay (E)
Paracoccidioides brasiliensis
is also negative. Which of the following medi-
cations would be most appropriate for this pa- 3. A 17-year-old boy visits his physician with com-
tient? plaints of recurrent bouts of dizziness, palpita-
tions, and joint pain. He went on a summer
(A) Acyclovir
hiking trip in eastern Massachusetts about six
(B) Ceftriaxone
months ago but does not recall getting a tick
(C) Foscarnet
Microbiology

bite and notes no rashes. The ECG is shown


(D) Ribavirin
in the image. What is the most likely diagnosis
(E) Vancomycin
of this patients symptoms?
2. A 51-year-old man living near St. Louis, Mis- (A) Brugada syndrome
souri presents to his primary care physician (B) Chagas disease
with recent-onset productive cough, pleuritic (C) Hypertrophic cardiomyopathy
chest pain, and a fever of 39.1C (102.4F). (D) Lyme disease
He recently returned from a business trip to (E) Third-degree heart block
Phoenix, Arizona. A sample of the mans puru-
lent sputum is sent for analysis, which reveals 4. A 30-year-old woman complains of a nonpro-
yeast cells up to 15 m in diameter. The pa- ductive cough that has developed over the past
thologist is able to identify several dividing 10 days. She reports feeling achy, and having
yeast organisms. Direct fluorescent antibody a sore throat and headaches. X-ray of the chest
staining (see image) is notable for large, broad- demonstrates patchy bilateral interstitial infil-
based budding from mother cells. What fungal trates. After work-up, the patient is diagnosed
species is responsible for this mans illness? with Mycoplasma pneumoniae pneumonia.
Which of the following is associated with the
causative organism?
(A) Growth on buffered charcoal yeast extract
media
(B) IgM cold agglutinins
(C) Phyocyanin production
(D) Polysaccharide capsule
(E) Reticulate bodies

Courtesy of Dr. William Kaplan, Centers for Disease Control


and Prevention.
High-Yield Principles
Chapter 4: Microbiology Questions 73

5. A homeless 37-year-old woman with HIV in-


fection comes to the clinic with a four-week
history of worsening hemiparesis, visual field
deficits, and cognitive impairment. The pa-
tients CD4+ count is 22/mm3. MRI shows
several hyperintensities on T2-weighted im-
ages that do not enhance with contrast and are
not surrounded by edema. A lumbar puncture
shows a normal opening pressure, and cerebro-
spinal fluid analysis shows a mildly elevated
protein level and the presence of myelin basic
protein, with a mild mononuclear pleocytosis.
Which of the following entities is most likely Courtesy of the Centers for Disease Control and Prevention.
responsible for this patients clinical picture?

Microbiology
(A) Cortical tuberculoma
(B) Cytomegalovirus encephalitis (A) Inhibition of cell wall synthesis
(C) JC virus (B) Inhibition of DNA polymerase
(D) Primary central nervous system lymphoma (C) Inhibition of genome uncoating
(E) Toxoplasmosis (D) Inhibition of nucleoside reverse transcrip-
tase
6. A family who recently emigrated from Roma- (E) Inhibition of protein synthesis
nia brings their 7-year-old child to the pedia-
trician with complaints of conjunctivitis and 8. A 38-year-old man comes to the emergency
periorbital swelling. The child has had cough- department complaining of cyclic fevers and
ing with a runny nose and high fever for three headaches. The fevers began about one week
days. Small lesions with blue-white centers are ago; two weeks ago the patient returned from
seen in his oral cavity. Which of the following a trip to Africa. Physical examination reveals
is the most likely cause of this childs symp- hepatosplenomegaly. Imaging of the brain
toms? shows signs of significant cerebral involve-
ment. Which of the following parasites most
(A) Diphtheria likely caused this patients symptoms?
(B) Pertussis
(C) Roseola (A)
Plasmodium falciparum
(D) Rubella (B)
Plasmodium malariae
(E) Rubeola (C)
Plasmodium ovale
(D)
Plasmodium vivax
7. A 5-year-old girl is brought to her pediatrician (E)
Plasmodium knowlesi
because of an eight-day history of a painful
rash confined to her flank. Physical examina-
tion reveals the crusted lesion shown in the
image. Which of the following describes the
mechanism of action of the treatment for this
lesion?
High-Yield Principles
74 Section I: General Principles Questions

9. A 15-year-old boy presents to the pediatrician 11. Influenza virus type A usually produces a mild,
with a two-day history of fever and headache. self-limited febrile illness in the general popu-
The patient is unable to touch his chin to his lation. However, worldwide epidemics have
chest when asked to do so. He also asks that occurred at different times in history due to
the lights in the room be turned down. In ad- rapid changes in viral genetic makeup. Which
dition to performing a lumbar puncture to ob- of the following is the most important reason
tain cerebrospinal fluid (CSF), the physician why these sporadic worldwide epidemics oc-
begins empiric treatment. The CSF is sent for cur?
analysis and culture. The patients condition
(A) Antigenic drift
improves over the next week. In the meantime,
(B) Antigenic shift
bacterial and fungal culture results are nega-
(C) Hemagglutinin develops the ability to de-
tive. Which of the following is the most likely
stroy a component of mucin, becoming
result of the CSF analysis?
more infectious
(D) Neuraminidase develops the ability to at-
Microbiology

Choice Pressure Lymphocyte Protein Sugar


tach to sialic acid receptors, becoming
count more infectious
A normal normal normal normal
(E) RBCs agglutinate with certain strains
B normal normal normal
C normal or normal normal 12. A 66-year-old woman who recently emigrated
D from Mexico comes to the physician be-
E cause she has begun to have seizures. A test
for anticysticercal antibodies is positive. A T1
Reproduced, with permission, from USMLERx.com. weighted, non-contrast MRI of the head is
shown in the image below. Which of the fol-
lowing organs or tissues is most likely to have
(A) A
similar lesions?
(B) B
(C) C
(D) D
(E) E

10. Oncogenic viruses act through a variety of


mechanisms. Some introduce oncogenes di-
rectly into host cells, while others force cells to
repeatedly undergo cycles of proliferation that
eventually become unregulated. Still others in-
troduce oncogenic potential by manipulating
chromosomal structure through deletions or
translocations. Which of the following viruses
causes neoplasia by inactivating tumor sup-
pressor genes such as p53 and Rb?
(A) Epstein-Barr virus
(B) Hepatitis C virus Courtesy of Dr. Per-Lennart Westesson, University of Roches-
(C) Human immunodeficiency virus ter Medical Center.
(D) Human papillomavirus
(E) Human T-cell lymphotropic virus type 1
High-Yield Principles
Chapter 4: Microbiology Questions 75

(A) Bladder 15. A 27-year-old woman presents to her physi-


(B) Bone cian complaining of fever, chills, and flu-like
(C) Kidney cortex symptoms. A sputum culture at 25C (77F) is
(D) Skeletal muscle shown in the image. Which of the following is
(E) Small bowel most likely to be elicited on further question-
ing?
13. A young girl living in rural New Mexico is
brought to her pediatrician with complaints
of fever, cough, and fatigue for the past two
weeks. The physician notices that the patient
is having intermittent bouts of many coughs in
a single breath, followed by a deep inspiration.
The parents report that this pattern of cough-
ing had started in the past two days. The phy-

Microbiology
sician informs them that their daughter will
most likely recover with only supportive care.
However, she wants to confirm his diagnosis. A
throat swab is sent for culture for a specific or-
ganism. Which of the following culture media
will be used?
(A) Bordet-Gengou medium
(B) Charcoal yeast extract with iron and cyste- Courtesy of Dr. Hardin, Centers for Disease Control and
Prevention.
ine
(C) Chocolate agar with factors V and X
(D) Loeffler medium (A) A recent trip to Namibia
(E) Thayer-Martin medium (B) A recent trip to New Mexico
(C) A recent trip to Ohio
14. A worried mother brings her infant to the
(D) Recent hiking in wooded areas
emergency department because he appears to
(E) Recent work in her large rose garden
be unable to swallow and continues to choke
on his formula. On physical examination, the 16. At birth, a newborn is noted to be unrespon-
physician notes generalized muscle weakness. sive to verbal stimulation from the doctors,
On further questioning, the patients mother nurses, and his parents. A routine physical ex-
says that she recently started sweetening the amination of the child reveals a split S2 heart
babys food with honey. Which of the follow- sound with an accentuated P2 component.
ing is a characteristic of the organism most The newborn has bounding pulses with a wide
likely responsible for this infants symptoms? pulse pressure. After a week the newborns par-
(A) Production of IgA protease ents notice that he has developed shortness of
(B) Production of exotoxin A breath and respiratory distress. What pathogen
(C) Production of lecithinase did the mother contract during her pregnancy
(D) Production of lipopolysaccharide that could explain the newborns current con-
(E) Production of spores that can only be dition?
killed by autoclaving (A) Cytomegalovirus
(B) Herpes simplex virus 2
(C) Rubivirus
(D) Toxoplasma gondii
(E) Treponema pallidum
High-Yield Principles
76 Section I: General Principles Questions

17. A 45-year-old man presents to the clinic com- (C) Erythromycin


plaining of several weeks of vague abdominal (D) Prompt replacement of water and electro-
discomfort and early satiety. The physician or- lytes; tetracyclines shorten the diseases
ders upper GI endoscopy as part of his workup. course
During the study, mucosal rigidity and hyper- (E) Supportive care only, without antibiotics
plasia are seen in the stomach, and a biopsy
is taken from the affected area. Microscopic 19. A 65-year-old man with a history of viral hepa-
analysis of the biopsy specimen shows sheets of titis presents to his primary care physician with
atypical lymphocytes. The organism believed complaints of early satiety, a 4.5-kg (10-lb)
to be associated with this condition is best de- weight loss over three months, upper abdomi-
scribed by which set of laboratory results? nal pain, and yellowing of his eyes. The pa-
tient says he has lived in Rochester, New York
(upstate) for his entire life, has not traveled
Choice Urease Catalase Oxidase outside of the country, and received two blood
Microbiology

A negative negative negative


transfusions in the early 1970s following an au-
tomobile accident. Work-up reveals extensive
B negative negative positive macronodular cirrhosis with a 2-2-cm mass
C negative positive
in his liver. Which of the following viral in-
negative
fections is most likely to result in this patients
D negative positive positive current presentation?
E positive negative negative (A) Cytomegalovirus
F
(B) Hepatitis A
positive positive negative
(C) Hepatitis C
G positive positive positive (D) Hepatitis E
(E) HIV
Reproduced, with permission, from USMLERx.com.
20. A neonate with purulent umbilical discharge
for one day presents with fever, irritability, and
(A) A diffuse flushing. One day later she is covered
(B) B in large, fluid-filled blisters that rupture easily,
(C) C leaving raw red areas beneath. Blood cultures
(D) D are taken, which within 24 hours grow an or-
(E) E ganism that is subsequently Gram stained with
(F) F the results shown below. The skin symptoms
(G) G observed in this case are due to the involve-
ment of which of the following intercellular
18. A 36-year-old man comes to the physician structures?
because he is experiencing abdominal pain,
vomiting, and a non-bloody diarrhea. He last
ate chicken and rice about four hours ago at
a Chinese restaurant. He has no other symp-
toms. Which of the following treatments
should this man receive?
(A) Bismuth subsalicylate, metronidazole, and
amoxicillin
(B) Ciprofloxacin
High-Yield Principles
Chapter 4: Microbiology Questions 77

Courtesy of Dr. Richard Facklam, Centers for Disease Control Courtesy of Drs. E. Arum and N. Jacobs, Centers for Disease

Microbiology
and Prevention. Control and Prevention.

(A) Desmosomes (A) Azithromycin


(B) Gap junctions (B) Ceftriaxone
(C) Hemidesmosomes (C) Fluconazole
(D) Intermediate junctions (D) Penicillin
(E) Tight junctions (E) Vancomycin

21. A 5-year-old boy develops diarrhea after eat- 23. A 47-year-old woman comes to the clinic com-
ing at a fast-food restaurant. The following plaining of fever and malaise. She reports hav-
day, his mother notices that he seems lethargic ing severe headaches associated with some
and brings him to the urgent care center. His nausea and vomiting, over the past few days.
blood pressure is 150/90 mm Hg. Laboratory Her urine has been exceptionally dark for the
tests show a hemoglobin level of 9 g/dL, plate- past few days. The patient is mildly jaundiced
let count of 40,000/mm3, and creatinine level with scleral icterus. Based on these symptoms
of 2.8 mg/dL. What is the most likely cause of the physician suspects hepatitis B and draws
this patients condition? blood for serologic testing for hepatitis B mark-
ers. If the patient had unprotected intercourse
(A) Campylobacter
during this infection, the presence of which of
(B) Escherichia coli
the following would be most concerning for
(C) Rotavirus
her partner?
(D) Shigella
(E) Vibrio cholerae (A) Hepatitis B e antibody
(B) Hepatitis B e antigen
22. A 32-year-old man presents to his doctor with (C) Hepatitis B surface antibody
painful urination and a purulent urethral dis- (D) IgG hepatitis B core antibody
charge. The discharge material is cultured, (E) IgM hepatitis B core antibody
and a sample from the culture is stained with
Giemsa and is shown in the image. Which of
the following is the treatment of choice for this
infection?
High-Yield Principles
78 Section I: General Principles Questions

24. A 1-year-old girl presents to the emergency (C) Hageman factor


room because of a three-day history of cough- (D) C5a
ing attacks that are occasionally followed by (E) Interleukin-1
episodes of vomiting. Her parents are espe- (F) Nitric oxide
cially concerned because sometimes she be-
comes blue after an episode. She has markedly 27. A 30-year-old man from Mexico comes to the
injected sclera but no discharge. She is afe- physician because of a two-day history of a fe-
brile and has no other symptoms. Laboratory ver of 38.8 C (101.8 F), a sore throat, and
tests show a WBC count of 25,000/mm3 with shortness of breath. On physical examination,
marked lymphocytosis. A bacterial infection is the patient is found to have cervical adenopa-
diagnosed. Which of the following is a result of thy and a thick, gray, tissue-like material cover-
the exotoxin produced by the organism caus- ing his tonsils. Which of the following types of
ing this childs symptoms? culture should be used to determine the organ-
ism infecting this patient?
(A) Blocked release of acetylcholine into the
Microbiology

synaptic cleft (A) Lwenstein-Jensen agar


(B) Formation of a pore in the plasma mem- (B) Bordet-Gengou agar
brane (C) Chocolate agar with factors V and X
(C) Inactivation of elongation factor 2, a pro- (D) Loeffler medium, blood agar, and tellurite
tein involved in translation plate
(D) Inhibition of G proteins to increase cAMP (E) Thayer-Martin media
(E) Release of lipopolysaccharide-lipid A
28. A 12-year-old boy presents to the emergency
25. A 50-year-old man develops profuse, non- room five days after returning from a camping
bloody, watery diarrhea while working as trip in Virginia. He complains of a fever, head-
an aid worker in Bangladesh. He arrived in ache, and muscle aches for several days, and
the area two days ago. A stool smear shows recently developed a rash on his wrists, palms,
no WBCs. His mucous membranes are dry, and legs that has since spread to his trunk, as
and his skin shows signs of tenting. He subse- seen in the image. Which of the following is
quently develops electrolyte abnormalities that the most appropriate treatment?
lead to cardiac and renal failure. What is the
mechanism of action of the exotoxin produced
by the most likely causative organism?
(A) Cleaves host cell rRNA
(B) Directly acts as an adenylate cyclase
(C) Inactivates elongation factor 2
(D) Permanently inactivates Gi
(E) Permanently activates Gs

26. A biotechnology company is developing a


small protein to block the cascade by which
allergens can cause shock. Patients often die
from vasodilation and massive edema; there-
fore, the new protein could lead to a life-saving
Courtesy of the Centers for Disease Control and Prevention.
drug. Which of the following molecules is the
most promising target to block the anaphylac-
tic pathway? (A) Ceftriaxone
(A) Interferon (B) Doxycycline
(B) IgE surface receptors
High-Yield Principles
Chapter 4: Microbiology Questions 79

(C) Gentamicin
(D) Nystatin
(E) Penicillin

29. A 53-year-old obese man with poorly con-


trolled noninsulin-dependent diabetes mel-
litus presents with fever to 39.6C (103.2F),
jaundice, hypotension, and acute onset of right
upper quadrant pain. Right upper quadrant
imaging shows multiple gallstones and chole-
cystitis. Urgent cholecystectomy is performed,
and subsequent gall bladder fluid and blood
cultures grow aerobic, nonlactose-fermenting,
Courtesy of the Centers for Disease Control and Prevention.
oxidase-positive, gram-negative rods. Blood

Microbiology
tests show:
Hematocrit: 29% (A) Bloody and foul-smelling vaginal discharge
WBC count: 14,700/mm3 (B) Pelvic pain
Platelet count: 76,000/mm3 (C) Profuse, frothy vaginal discharge
International Normalized Ratio: 3.2 (D) Thick, white, cottage cheese-like vaginal
D-dimer: 8500 ng/mL discharge
Fibrinogen levels: low (E) Thin, gray-white, fishy-smelling vaginal
discharge
Microscopic inspection of peripheral blood
smear shows schistocytes and multiple helmet 31. A 40-year-old man goes on a camping vaca-
cells. Clinically, there is no evidence of active tion with his family. One day after swimming
bleeding. What is the most appropriate treat- in a freshwater lake near the campsite, he de-
ment for this patients coagulopathy? velops nausea and vomiting and starts to be-
(A) Amoxicillin have irrationally. His family takes him to the
(B) Aztreonam emergency department, where blood samples
(C) Fresh frozen plasma are taken and a spinal tap is performed. He is
(D) Vancomycin diagnosed with a rapidly progressing meningo-
(E) Vitamin K encephalitis and dies shortly thereafter. Which
of the following protozoa was most likely the
30. A 16-year-old girl complains of abnormal vagi- cause of the mans illness?
nal discharge as well as itching, tenderness, (A)
Cryptosporidium species
and burning in the vulvovaginal area. On ex- (B)
Entamoeba histolytica
amination there is vulvar and vaginal erythema (C)
Leishmania donovani
and colpitis macularis. Results of a wet mount (D)
Naegleria fowleri
examination are shown in the image. Which (E)
Plasmodium falciparum
additional symptom would most likely be seen
in this patient?
High-Yield Principles
80 Section I: General Principles Questions

32. A mother brings her 12-year-old daughter to an (C) Mosquito bites


outpatient clinic. The child complains of ach- (D) Saliva and respiratory secretions
ing pain localized to the joints of the extremi- (E) Sexual contact
ties. The mother recalls her daughter was sick
with a sore throat about a month ago, but re- 34. While hospitalized for treatment of an episode
covered completely without medical attention. of aspiration pneumonia, a 45-year-old man
The girl is admitted to the hospital for further begins to have episodes of severe non-bloody
examination and testing. A tissue biopsy is diarrhea and lower abdominal pain. Tempera-
taken, and the abnormal results are seen in the ture is 38C (100.4F). CT of the abdomen
image. Given the most likely diagnosis, what and pelvis with oral and intravenous contrast
finding would be expected in this patient on demonstrates marked diffuse colonic thicken-
cardiac physical examination as an adult? ing (see image). What is the pathophysiology
of the most likely cause of this patients condi-
tion?
Microbiology

Courtesy of Dr. Ed Uthman.

(A) A friction rub heard throughout the pre- Reproduced, with permission, from USMLERx.com.
cordium
(B) A harsh crescendo-decrescendo early sys-
tolic murmur heard at the right upper ster- (A) Directly damages the microvilli of the en-
nal border with radiation to the carotids terocytes but does not invade
(C) A late diastolic murmur heard best at the (B) Produces an exotoxin that can induce cyto-
apex kine release and cause hemolytic uremic
(D) A midsystolic click heard best at the apex syndrome
(E) An S4 gallop heard at the apex (C) Produces an exotoxin that increases the se-
cretory activity of enterocytes
33. A 23-year-old man from Kenya presents with (D) Produces an exotoxin that kills enterocytes
night sweats, fevers, oliguria, and a large sub- (E) Produces both heat-stable and labile toxins
mandibular mass. Biopsy of the mass shows an that promote secretions in the intestines
aggressive tumor with sheets of lymphocytes
staining positive for CD20, as well as very high 35. A 56-year-old man presents with sharp subster-
levels of nuclear c-myc with interspersed mac- nal pain radiating to his back and arms. The
rophages. What is the mode of transmission of patient is seated and leaning forward. He states
the virus associated with this malignancy? that the pain is less severe in this position, and
worsens when he lies down and takes a deep
(A) Blood products
breath. He recently recovered from a febrile
(B) Fecal-oral transmission
illness. On physical examination a scratchy,
High-Yield Principles
Chapter 4: Microbiology Questions 81

leathery sound is heard at the left lower sternal cutaneous needle biopsy. A Gram stain of this
border. An ECG shows diffuse ST-segment el- sample is most likely to show which of the fol-
evation. Which of the following describes the lowing?
microorganism that is the most likely cause of
(A) Acid-fast bacilli
this condition?
(B) Catalase-negative, gram-positive cocci in
(A) Catalase- and coagulase-positive cocci chains
(B) Double-stranded, linear, enveloped, icosa- (C) Coagulase-negative, gram-positive cocci in
hedral DNA virus clusters
(C) Double-stranded, segmented RNA virus (D) Coagulase-positive, gram-positive cocci in
(D) Positive, single-stranded, helical RNA virus clusters
(E) Small, naked, single-stranded RNA virus (E) Oxidase-negative, gram-negative bacilli

36. A 28-year-old man complains of increasing 38. A 28-year-old woman presents to her primary
muscle weakness and numbness that began care physician complaining of a generalized

Microbiology
in his legs and feet three days ago and that body rash, especially on the inside of her wrists
now involves his arms and hands. The patient and ankles, and lesions on her genitals (see im-
reports recently experiencing a self-limited age). Physical examination reveals generalized
episode of gastroenteritis. Which organism is lymphadenopathy and a mild fever. Which of
commonly associated with this patients neuro- the following could be used to confirm the di-
logic symptoms? agnosis?
(A) a-Hemolytic, encapsulated, gram-positive
cocci that produce an IgA protease
(B) Comma-shaped, oxidase-positive, gram-
negative bacteria that can be grown at
42C
(C) Non-lactose-fermenting, oxidase-positive,
gram-negative, aerobic bacilli
(D) Rod-shaped, gram-positive, spore-forming
anaerobe that produces a heat-labile toxin
(E) Spiral-shaped bacteria with axial filaments,
visualized using dark-field microscopy

37. An otherwise healthy 15-year-old boy sustains


a deep puncture wound in his left heel while Courtesy of Dr. J. Pledger, Centers for Disease Control and
playing in a junkyard. Four days later, his fa- Prevention.
ther brings him to the emergency department
because the boy has become lethargic and has
developed shaking chills. He refuses to bear (A) Culture on Thayer-Martin agar
weight on his left foot. The patients tempera- (B) Tzanck preparation
ture is 39.7C (103.4F). Physical examination (C) Venereal Disease Research Laboratory test
shows a warm, swollen, and extremely tender (D) Weil-Felix reaction
area around the puncture wound. A specimen (E) Ziehl-Neelsen stain
through uninfected tissue is obtained via per-
High-Yield Principles
82 Section I: General Principles Questions

39. A 43-year-old HIV-positive man presents to his 40. An 8-day-old infant has developed fever, ir-
physician complaining of recent-onset abdomi- ritability, decreased level of consciousness,
nal pain and diarrhea, along with an increased apnea, and a full anterior fontanelle. Prenatal
level of general fatigue and occasional night laboratory tests results are not available, as the
sweats. Physical examination is significant for infants mother received no prenatal care and
a fever of 37.8C (100.1F), bilateral cervical delivered at home at 36 weeks gestation. What
adenopathy, and a weight loss of 4.5 kg (10 lb) routine prophylactic intrapartum antibiotic
compared to his last physicians visit. A blood could the mother have been treated with in or-
sample is taken, which when cultured shows der to eradicate the likely cause of the infants
the presence of nonbranching bacilli that stain illness?
positively for Ziehl-Neelsen stain. His CD4+
(A) Fluconazole
cell count is 50/mm3. Which of the following
(B) Metronidazole
is the most worrisome for causing the patients
(C) Moxifloxacin
recent symptoms?
(D) Penicillin
Microbiology

(A)
Actinomyces israelli (E) Vancomycin
(B)
Mycobacterium avium-intercellulare
(C)
Mycobacterium marinum
(D)
Mycobacterium tuberculosis
(E)
Nocardia asteroides
High-Yield Principles
Chapter 4: Microbiology Answers 83

An s w e r s

1. The correct answer is B. The differential diag- quired the illness and/or the morphology of
nosis of a genital ulcer in a sexually active pa- the organism. In this case, one cannot reach a
tient should include primary syphilis (though conclusion based on location. The man lives
these ulcers are usually painless), genital her- near the Mississippi River basin (where his-
pes, and chancroid. Because the Tzanck smear toplasmosis and blastomycosis are endemic),
(which looks for multinucleated giant cells and he has recently traveled to the Southwest
typical of herpes infection), is negative, as is (where coccidioidomycosis is endemic). Only
the VDRL test for syphilis, chancroid becomes paracoccidioidomycosis (endemic to Central
most likely. Chancroid is a bacterial infection and South America) can be eliminated as a
caused by Haemophilus ducreyi, which pre likely answer by location. Rather, the morphol-
sents typically as a painful genital ulcer with ogy of the yeast is the key to reaching the cor-

Microbiology
associated inguinal lymphadenopathy. It is typ- rect conclusion. In the lower-right portion of
ically treated with ceftriaxone given as a one- the image, an example of broad-based budding
time, 250-mg, intramuscular injection, or with can be seen, which is most consistent with
azithromycin as a single 1000-mg dose. blastomycosis. A common mnemonic regard-
ing the appearance of Blastomyces is that it is a
Answer A is incorrect. Acyclovir is an antiviral
Big, Broad-Based, Budding organism.
agent used to treat herpes infections. It is acti-
vated by viral thymidine kinase, whereupon it Answer B is incorrect. The distinguishing
inhibits the herpes viral polymerase. It can be morphologic feature of Coccidioides immitis,
used to treat herpes simplex virus types 1 and which is endemic to the southwestern United
2, varicella-zoster virus, and Epstein-Barr virus States, is its tendency to form large (up to 70
infections. m in diameter) spherules filled with endo-
spores.
Answer C is incorrect. Foscarnet inhibits viral
DNA polymerase without the need of activa- Answer C is incorrect. Unlike the other an-
tion by thymidine kinase. It is used to treat cy- swer choices, Cryptococcus neoformans most
tomegalovirus (CMV) retinitis, but it can also commonly causes fungal meningitis (with
be used to treat acyclovir-resistant herpes sim- pneumonia as the second most common mani-
plex virus. festation) in the immunocompromised. Like
Blastomyces, it is a budding organism, but is
Answer D is incorrect. Ribavirin is used to
distinguishable morphologically by a thick
treat respiratory syncytial virus. It functions by
capsule that may be visualized with India ink
inhibiting inosine monophosphate dehydro-
stain.
genase, thus blocking the synthesis of guanine
nucleotides. Answer D is incorrect. Histoplasma capsula-
tum, which is endemic to the Mississippi and
Answer E is incorrect. Vancomycin is a bac-
Ohio River valleys, is unique among the an-
tericidal antibiotic used for multidrug-resistant
swer choices in that it can live as an intracel-
gram-positive organisms such as Staphylococ-
lular pathogen. Microscopic evaluation of a le-
cus aureus and Clostridium difficile. It func-
sion can show numerous small (1-5 m) yeast
tions by binding to mucopeptide precursors,
forms within an individual macrophage.
preventing formation of the bacterial cell wall.
Answer E is incorrect. Paracoccidioides brasil-
2. The correct answer is A. This patient is suf- iensis, which is endemic to rural Latin Amer-
fering from a fungal pneumonia. In USMLE- ica, is often described as having a captains-
style questions, students are often asked to wheel or Mickey-Mouse-head appearance.
differentiate between candidate yeast species This is due to several smaller daughter cells
based on the location where the patient ac-
High-Yield Principles
84 Section I: General Principles Answers

that are simultaneously budding from a single Answer C is incorrect. Hypertrophic cardio-
mother cell. myopathy is the most common cause of death
in young athletes in the United States. It is
3. The correct answer is D. Lyme disease is characterized by an asymmetric hypertrophic,
caused by infection with the spirochete Bor- nondilated left ventricle. Histopathologically,
relia burgdorferi, and is transmitted by the bite the myocardial architecture is disorganized
of the Ixodes tick. Initially, the disease presents and scarred. The typical ECG shows repolar-
with constitutional symptoms such as fever and ization changes or frank hypertrophy.
malaise, as well as a rash surrounding the bite
Answer E is incorrect. Classic third-degree
site. However, the bite site often goes unno-
heart block is complete, which means that
ticed, and erythema chronicum migrans is not
the atria and the ventricles beat independently
necessarily present in every case. Early dissem-
of each other, with the P waves and the QRS
inated disease presents four-six weeks after the
waves bearing no relation to one another. Se-
initial infection and is characterized by cardiac
vere bradycardia is usually present, and sudden
Microbiology

and neurologic abnormalities. Cardiac abnor-


death is a possibility. This condition is usually
malities include myocarditis, arrhythmias, and
treated with a pacemaker.
conduction disturbances. Lyme arthritis is a
late-stage finding, occurs in about 60% of pa-
4. The correct answer is B. The gradual onset
tients months to years later, and is associated
of her symptoms, together with the radiologic
with pain and swelling of large joints, most of-
findings of diffuse interstitial infiltrates, sug-
ten in one or both knees. Lyme disease is most
gests atypical pneumonia. Atypical pneumo-
prevalent in the northeast Atlantic Coast states,
nia is caused most commonly by Mycoplasma
but cases have been reported throughout the
pneumoniae, Legionella pneumophila, Chla-
United States.
mydia pneumoniae, and viruses; however, IgM
Answer A is incorrect. Brugada syndrome is cold agglutinin production is seen only with
a conductive heart disease that usually affects Mycoplasma infection.
young men and carries an increased risk of
Answer A is incorrect. Culture on buffered
sudden cardiac death. The disease has been as-
charcoal yeast extract medium is performed to
sociated with sodium ion channel abnormali-
diagnose L pneumophila pneumonia. L pneu-
ties. The typical ECG pattern is a right bun-
mophila causes atypical pneumonia that is
dle-branch block and ST-segment elevation on
seen most commonly in older individuals who
leads V1-V3.
smoke and abuse alcohol. Although Legionella
Answer B is incorrect. Chronic Chagas dis- is transmitted through environmental water
ease usually manifests during its earliest phase sources, infection does not imply aspiration.
with arrhythmias (eg, heart block and ven-
Answer C is incorrect. Phyocyanins, a product
tricular tachycardia). Dilated cardiomyopathy,
of Pseudomonas aeruginosa, lead to the blue-
megacolon, and megaesophagus occur later in
green color of the organisms. Pseudomonas can
the course of the disease. The disease presents
cause pneumonia but typically in patients who
acutely after the transfer of Trypanosoma cruzi
have cystic fibrosis or are severely immuno-
(found in the southern United States, Mexico,
compromised.
and Central and South America) by the redu-
viid bug (also called the kissing bug). Trans- Answer D is incorrect. Polysaccharide cap-
mission is associated with a hardened red area sules are a characteristic of Streptococcus pneu-
or chagoma. This is followed by fever, malaise, moniae and other organisms including certain
lymphadenopathy, tachycardia, and menin- strains of Haemophilus influenzae, Neisseria
goencephalitis that resolve within one month. meningitidis, and Escherichia coli. S pneu-
The patients ECG tracing is classic for Mobitz moniae is the cause of typical lobar pneumo-
type II heart block. Chagas disease would be a nia, which is characterized by sudden onset of
rare diagnosis in the northern United States. fever, chills, cough, and pleuritic pain. X-ray
High-Yield Principles
Chapter 4: Microbiology Answers 85

of the chest usually shows focal lung consoli- Answer B is incorrect. CMV encephalitis can
dation rather than diffuse infiltrates, as seen in mimic the appearance of PML, but would
this case. be associated with enhancing periventricular
white matter lesions in cortical and subepen-
Answer E is incorrect. Reticulate bodies are
dymal regions. CMV encephalitis also is asso-
the intracellular form of Chlamydia species,
ciated typically with more systemic signs and
including C pneumoniae. C pneumoniae can
symptoms. Polymerase chain reaction analysis
cause atypical pneumonia that presents simi-
of CSF would be positive for CMV, and histo-
larly to Mycoplasma pneumonia. It is difficult
logic exam shows giant cells with eosinophilic
to distinguish between the two based on symp-
inclusions in both the cytoplasm and the nu-
toms and presentation, so treatment usually is
cleus.
designed to cover both organisms. Mycoplasma
infection, however, is much more common. Answer D is incorrect. Central nervous system
(CNS) lymphoma typically affects those with
5. The correct answer is C. The clinical picture CD4+ cell counts <50/mm3. MRI will dem-

Microbiology
and imaging are consistent with progressive onstrate one or more enhancing lesions (50%
multifocal leukoencephalopathy (PML) sec- are multiple and 50% are single) that typically
ondary to reactivation of latent JC virus infec- are surrounded by edema, and can produce a
tion, which can occur with CD4+ counts <50/ mass effect. CNS lymphoma can present with
mm3. It typically presents with rapidly progres- polymerase chain reaction findings positive for
sive focal neurologic deficits without signs of Epstein-Barr virus on CSF.
increased intracranial pressure. Ataxia, apha-
Answer E is incorrect. Space-occupying le-
sia, and cranial nerve deficits also may occur.
sions due to toxoplasmosis infection represent the
Lumbar puncture is nondiagnostic and fre-
most common cause of cerebral mass lesions in
quently demonstrates mild elevations in pro-
HIV-infected patients, and typically present with
tein and WBCs. Cerebrospinal fluid (CSF)
multiple enhancing lesions on MRI. The le-
analysis can reveal the presence of myelin
sions typically are located at the corticomedullary
basic protein, which is due to demyelination
junction, and are surrounded by edema that fre-
caused by the JC virus. PML typically presents
quently produces a mass effect and distinguishes
as multiple nonenhancing T2-hyperintense
its appearance from PML. Positive Toxoplasma
lesions. When it is suspected, stereotactic bi-
serologies can assist in diagnosis, and clinical
opsy is required for definitive diagnosis, but a
improvements will result from treatment with
positive CSF polymerase chain reaction for JC
sulfadiazine/pyrimethamine or trimethoprim/
virus is diagnostic in the appropriate clinical
sulfamethoxazole.
setting. Histology of the lesions shows nuclear
inclusions in oligodendrocytes. Although there
6. The correct answer is E. Rubeola, also called
is no definitive treatment, clearance of JC virus
measles, is a relatively rare illness in the
DNA can be observed with response to highly
United States because of the ubiquity of the
active antiretroviral therapy.
measles/mumps/rubella (MMR) vaccine. It
Answer A is incorrect. Uncommon in the de- presents with the prodrome described in this
veloped world, but presenting with increased patient. The rash that spreads from head to
risk in homeless and HIV patients, cortical toe over a three-day period develops one or
tuberculomas are caseating foci within the two days after the appearance of Kopliks spots,
cortical parenchyma occurring from previous which are red oral lesions with blue-white cen-
hematogenous mycoplasma bacillemia. The ters.
clinical presentation may be similar to that
Answer A is incorrect. Diphtheria is an ill-
of the current patient; however, presentation
ness virtually unknown in the United States
would include enhancing nodular lesions on
because of the prevalence of the diphtheria/
imaging and elevated protein and low glucose
tetanus/pertussis (DTaP) vaccine. It is caused
on CSF examination.
High-Yield Principles
86 Section I: General Principles Answers

by Corynebacterium diphtheriae and is charac- zolid, erythromycin, tetracycline & doxycy-


terized by a membranous pharyngitis. cline, and the aminoglycosides. Doxycycline is
the main treatment for both Rickettsia rickettsii
Answer B is incorrect. Pertussis, or whooping
(Rocky Mountain spotted fever) and Borrelia
cough, is also rare due to widespread vaccina-
burgdorferi (Lyme disease) infections. The rash
tions. It is a respiratory infection of children
of Rocky Mountain spotted fever is typically
that characteristically produces coughing
petechial and begins around the wrists and an-
spasms followed by a loud inspiratory whoop.
kles, although it may begin on the trunk or dif-
Answer C is incorrect. Roseola is a febrile dis- fusely. The rash of Lyme disease may be solid
ease of very young children that begins with a red or may form a ring or multiple rings with a
high fever and progresses to a rash similar to bulls-eye appearance.
measles. Infants and young children are most
at risk. It is believed to be caused by human 8. The correct answer is A. Four members of the
herpesvirus 6. Plasmodium genus of protozoa commonly in-
Microbiology

fect humans and cause malaria. All are spread


Answer D is incorrect. Rubella, also known
by the female Anopheles mosquito; diagnosis is
as German measles, is a less severe viral ex-
made through a blood smear. The species that
anthem. Many infections are subclinical, but
causes cerebral involvement is P falciparum,
rubella can cause severe birth defects when in-
which is almost entirely responsible for the se-
fection occurs during the prenatal period.
vere cases of disease that proceed to coma and
7. The correct answer is B. Based on the derma- death.
tomal and unilateral distribution of this rash, Answer B is incorrect. Plasmodium malariae
the patient most likely has shingles. This is a infection causes a 72-hour cyclic fever. P ma-
focal reactivation of a prior varicella-zoster vi- lariae, however, does not cause cerebral ma-
rus (VZV) infection. Most patients who de- laria.
velop shingles have a two- to three-day pro-
Answer C is incorrect. Plasmodium ovale in-
drome of pain, tingling, or burning in the
fection causes a 48-hour cyclic fever. A unique
involved dermatome, followed by the devel-
feature of P vivax and P ovale organisms is that
opment of a vesicular rash. The treatment of
they can form hypnozoites that can remain
choice for herpesvirus infections is acyclovir,
dormant in the liver for long periods, only to
ganciclovir, and (for VZV specifically) fam-
resurface later. However, P ovale does not
ciclovir, which work by inhibiting viral DNA
cause cerebral malaria.
polymerase.
Answer D is incorrect. Plasmodium vivax in-
Answer A is incorrect. Bacteria, not viruses,
fection causes a 48-hour cyclic fever. A unique
have cell walls. Inhibition of cell wall synthe-
feature of both P vivax and P ovale organisms
sis is accomplished by the penicillin family of
is that they can form hypnozoites that can re-
antibiotics.
main dormant in the liver for long periods,
Answer C is incorrect. The antiviral medica- only to resurface later. However, P vivax does
tion amantadine, used only in the treatment of not cause cerebral malaria.
influenza A virus infection, works by inhibiting
Answer E is incorrect. Plasmodium knowlesi is
viral genome uncoating in the host cell.
a simian malaria parasite that primarily infects
Answer D is incorrect. Nucleoside reverse macaques, although it has been reported to
transcriptase inhibitors are first-line medica- infect humans in southeast Asia. There are re-
tions for treating HIV infection. ports of cerebral involvement in monkeys, and
Answer E is incorrect. Inhibition of protein of isolated fatal human cases.
synthesis is achieved by five types of antibiot-
9. The correct answer is C. These lab results and
ics: chloramphenicol & clindamycin, line-
the clinical presentation (fever, headache, nu-
High-Yield Principles
Chapter 4: Microbiology Answers 87

chal rigidity, and photophobia) are typical of are associated with an increased risk of devel-
viral meningitis. Because the cultures are neg- oping hepatocellular carcinoma. The liver has
ative, a viral cause should be considered. This a high regenerative potential, but if this pro-
patient would have recovered without compli- cess is overused, the chance of an oncogenic
cations with only symptomatic support. Viral mutation occurring during the regeneration of
aseptic meningitis usually is caused by entero- cells increases.
viruses and runs a milder course than bacterial
Answer C is incorrect. HIV as a direct onco-
meningitis.
genic agent is being intensely researched, but
Answer A is incorrect. This profile does not it is already known that immune suppression
suggest meningitis. However, because the clin- and dysregulation caused by HIV infection
ical presentation strongly suggests meningitis, give rise to lymphomas and Kaposi sarcoma.
it is not likely that the CSF analysis would be
Answer E is incorrect. Human T-cell lym-
completely normal.
photropic virus causes adult T-cell leukemia,

Microbiology
Answer B is incorrect. In this profile, only the and although the mechanism of oncogenesis
CSF sugar level is elevated. This does not sug- remains unclear, there is some evidence that
gest bacterial meningitis, in which sugar levels integration into the host genome at locations
would decrease. This profile may suggest sys- near cellular growth genes may play a role.
temic hyperglycemia, such as in uncontrolled
diabetes. 11. The correct answer is B. Influenza virus has
both hemagglutinin (HA) and neuramini-
Answer D is incorrect. This is a typical profile
dase (NA) molecules on its surface. These
of fungal or mycobacterial meningitis. Note
two molecules are responsible for the ability
that it is the same profile as that of bacterial
of the virus to be absorbed and penetrate the
meningitis, except the increase in WBCs is
host cells. After a human is infected with the
due to lymphocytes, not neutrophils. Fungal
influenza virus, that person will be immune
and mycobacterial meningitis also have a more
to infection by the same virus because of an-
subacute presentation than has bacterial men-
tibodies created against HA and NA. If either
ingitis.
HA or NA is changed, as can be the case if two
Answer E is incorrect. This is a typical profile different influenza viruses infect the same cell
of bacterial meningitis, in which neutrophils and exchange RNA, antigenic shift can occur.
predominate over lymhocytes. This creates a new virus that has never been
exposed to the human immune system before,
10. The correct answer is D. Human papillomavi- with potentially catastrophic consequences.
rus (HPV) causes carcinoma (usually cervical) This type of mixing is most commonly thought
by inactivating tumor suppressor genes such to be between a human and an avian strain
as p53 and Rb through the actions of viral pro- mixing in an intermediary porcine host, thus
teins E6 and E7, respectively. leading to the term avian flu.
Answer A is incorrect. Epstein-Barr virus Answer A is incorrect. Antigenic drift de-
(EBV) is associated with Burkitt lymphoma (a scribes mutations that can occur in hemag-
B-lymphocyte lymphoma) and nasopharyngeal glutinin and neuraminidase, making them
carcinoma. The t(8;14) translocation is consis- less antigenic to the preexisting antibod-
tently associated with Burkitt lymphoma, but ies in the human host. Since this results in
the translocation alone is not responsible for small changes in viral toxicity, it will lead to
the neoplasm and is not found in nasopharyn- a slightly different strain, but it is not likely to
geal carcinomas. The other factors that deter- lead to a global epidemic.
mine oncogenesis of EBV remain unclear.
Answer C is incorrect. Hemagglutinin has the
Answer B is incorrect. Both hepatitis C ability to attach to sialic acid receptors, which
(HCV) and hepatitis B virus (HBV) infections
High-Yield Principles
88 Section I: General Principles Answers

activates fusion of the virus to the cell. All in- Answer B is incorrect. Bone is an extremely
fectious influenza viruses have this molecule. unlikely source for cysticerci due to its rela-
tively low blood flow.
Answer D is incorrect. Neuraminidase has the
ability to destroy neuraminic acid, a compo- Answer C is incorrect. The kidney can be a
nent of mucin. This helps break down the bar- location for cysticerci but is much less likely
rier to the upper airways and aids in infectivity. than cysts involving muscle tissue.
Answer E is incorrect. RBCs agglutinate in Answer E is incorrect. While the small bowel
the presence of hemagglutinin; hence the is the site of infection of primary hosts like the
name. This does not affect the infection rate of pig, secondary hosts (humans) do not develop
the influenza virus. an adult tapeworm infection.

12. The correct answer is D. The image shows 13. The correct answer is A. This patient is pre-
multiple lesions throughout the brain paren- senting with a classic case of whooping cough
Microbiology

chyma and subarachnoid space, which are caused by Bordetella pertussis. The initial
characterized by ring-shaped regions of low T1 phase is characterized by flu-like symptoms
intensity consistent with calcification. This ap- for the first one-two weeks. During this time,
pearance is most consistent with the nodular erythromycin is an effective treatment. The
calcified stage of neurocysticercosis and is seen second phase, the paroxysmal stage, is marked
only in individuals with long-standing, chronic by bouts of multiple coughs in a single breath
infection from endemic areas. Although this followed by a deep inspiration (the classic
patients presentation is highly suspicious for whooping cough). Treatment during this phase
malignancy, the image provided and labora- does not change the disease course, so only
tory data confirm a diagnosis of neurocysticer- supportive care is indicated and the infection
cosis, which is caused by infection with Taenia ought to pass in otherwise healthy individu-
solium, a pork tapeworm. It is the most com- als. In the United States, the diptheria/tetanus/
mon parasitic infection of the CNS worldwide, pertussis (DTaP) vaccine is supposed to be
and is particularly endemic to Central and given to all infants and protects them against
South America, Eastern Europe, and some diphtheria, tetanus, and pertussis. Infants who
parts of Asia. After humans ingest the tape- are not vaccinated are at risk for infection.
worms eggs, the eggs hatch and the larvae B pertussis can only be cultured on Bordet-
invade the wall of the small intestine and dis- Gengou medium.
seminate hematogenously. Cysticerci may be
Answer B is incorrect. Charcoal yeast extract
found in any organ, but are most commonly
when buffered with increased levels of iron
found in the brain, muscles, skin, and heart.
and cysteine is used to culture Legionella
Since we know that this patient is already suf-
pneumophila.
fering from cysts in her brain, the most likely
additional location would be her muscles. Answer C is incorrect. Chocolate agar with
Fortunately, the disease rarely results in death factor V and X is used to culture Haemophilus
and patients are often asymptomatic; however, influenzae.
when the disease does result in neurologic se- Answer D is incorrect. Loeffler medium is
quelae, specific symptoms depend on the loca- needed to culture Corynebacterium diphthe-
tion of the cysts. Cysticercosis is treated with riae.
administration of albendazole.
Answer E is incorrect. Thayer-Martin me-
Answer A is incorrect. Although the cysticerci dium is used to culture Neisseria gonorrhoeae.
may be found in virtually any organ, they al-
most never involve the urinary bladder. Schis- 14. The correct answer is E. This describes all

tosomiasis is a parasite that commonly invades spore-forming bacteria, which include Bacil-
the bladder. lus anthracis, Bacillus cereus, and Clostridium.
High-Yield Principles
Chapter 4: Microbiology Answers 89

However, only Clostridium botulinum pro- common fungal infection in the US. About
duces the symptoms seen in this baby and 60% of these infections cause no symptoms,
also fits the mode of transmission. C botuli- and in the remaining 40% of cases, the symp-
num causes botulism via the production of a toms can range from mild to severe. Severe
heat-labile toxin that inhibits the release of forms of the infection can present with blood-
acetylcholine into the neuromuscular junc- tinged sputum, loss of appetite, weight loss,
tion. Infants may initially become constipated a painful red rash on the legs, and change in
and then develop generalized muscle weak- mental status. Cultures from sputum samples
ness (floppy baby). The organism is spread or biopsy show a dimorphic fungus seen as hy-
through the ingestion of contaminated canned phae at 25C (77F) and spherules filled with
or bottled food. Additionally, fresh honey has endospores at 37C (98.6F). Treatment with
been shown to harbor the organism. amphotericin B or fluconazole is usually re-
quired only in severe, disseminated disease.
Answer A is incorrect. IgA protease is pro-
duced by some bacteria so they can cleave Answer A is incorrect. In a patient with fever,

Microbiology
secretory IgA and colonize mucosal areas; chills, and flu-like symptoms who has recently
Neisseria gonorrhoeae, Neisseria meningitidis, returned from Namibia, there is concern for
Streptococcus pneumoniae, and Haemophilus infection by Plasmodium species, which cause
influenzae are the most well known. However, malaria. Malaria is transmitted by the female
none of these are typically transmitted via food, Anopheles mosquito. The time course and pat-
namely honey. tern of symptoms depend on the Plasmodium
species with which the patient is infected.
Answer B is incorrect. Exotoxin A is produced
Treatment is tailored to the geographic area
by Pseudomonas aeruginosa as well as some
of infection and the Plasmodium species in-
Streptococcus species. Exotoxin A has been as-
volved; agents include chloroquine, hydroxy-
sociated with toxic shock syndrome and scarlet
chloroquine, and atovaquone-proguanil. Ma-
fever. However, none of these organisms pro-
larial infection would be evident on a blood
duce the symptoms seen in this case or is trans-
smear.
mitted by honey ingestion.
Answer C is incorrect. Sickness after travel
Answer C is incorrect. Lecithinase is pro-
to the Mississippi and Ohio River valleys is
duced by Clostridium perfringens and is re-
suggestive of histoplasmosis. Although histo-
sponsible for the development of gas gangrene,
plasmosis typically does not present symptom-
cellulitis, and diarrhea. This organism is associ-
atically, some patients experience a flu-like
ated with contaminated wounds, which is not
illness with fever, cough, headaches, and myal-
a part of this babys history.
gias. Histoplasmosis can result in lung disease
Answer D is incorrect. Lipopolysaccharide, resembling tuberculosis (TB) and widespread
also called endotoxin, is produced by gram- disseminated infection affecting the liver,
negative bacteria and Listeria. It is highly anti- spleen, adrenal glands, mucosal surfaces, and
genic and can cause sepsis in severe infections. meninges. On microscopy, histoplasmosis ap-
However, generalized muscle weakness is not pears as spherules filled with endospores, as
characteristic of sepsis. opposed to the hyphae and spherules observed
in the sputum of those with coccidiomycosis.
15. The correct answer is B. This patients history
and sputum culture are suggestive of coccidi- Answer D is incorrect. Recent hiking in
oidomycosis, a fungal infection caused by the wooded areas carries the risk of contracting
inhalation of Coccidioides immitis or Coccidi- tick-borne illnesses, such as those carried by
oides posadasii. These organisms are found in the Ixodes tick: Babesia microti, a protozoon
soil in dry areas of the southwestern United that causes babesiosis; Borrelia burgdorferi, a
States, Mexico, and Central and South Amer- spirochete that causes Lyme disease; and Ehr
ica. Coccidioidomycosis is the second most lichia chaffeensis, a rickettsial bacterium that
High-Yield Principles
90 Section I: General Principles Answers

causes erlichiosis. None of these organisms ap- valve, such as physiologic split and, in this
pears as hyphae on microscopy. case, a large PDA, we hear the split S2 sound.
Answer E is incorrect. A wound while garden- Answer A is incorrect. Congenital CMV in-
ing, such as a thorn prick, can cause inocula- fection is marked most commonly by pete-
tion with Sporothrix schenckii. This fungus can chial rashes, jaundice, hepatosplenomegaly,
be found in various environments, including and sensorineural hearing loss. Cardiovascular
sphagnum moss, decaying vegetation, hay, abnormalities are not features of congenital
and soil. When S schenckii is introduced into CMV infection.
the skin, it causes a local pustule or ulcer with
Answer B is incorrect. Congenital herpes in-
nodules along the draining lymphatics (as-
fection most often either affects skin, eyes, and
cending lymphangitis). S schenckii is a dimor-
mouth or presents as localized CNS infection.
phic fungus, existing as hyphae at 25C (77F)
Symptoms usually develop within four weeks
and as a budding yeast form at 37C (98.6F).
of birth. CNS symptoms can include tempera-
Itraconazole or potassium iodide is used for
Microbiology

ture instability, respiratory distress, poor feed-


treatment. On microscopy, one would not ex-
ing, and lethargy. Herpes simplex virus type 2
pect to see spherules.
is also one of the most common causes of neo-
natal encephalitis.
16. The correct answer is C. All five answers

are part of ToRCHeS (Toxoplasmosis, Ru- Answer D is incorrect. Congenital toxoplas-
bella, Cytomegalovirus, Herpesvirus/HIV, mosis infection most often is asymptomatic ini-
and Syphilis) infections, the group of infec- tially. The class triad of symptoms that develop
tions for which every newborn is tested. If the include chorioretinitis, hydrocephalus, and
mother becomes infected during pregnancy, intracranial calcifications. Early symptoms can
the pathogens can cross the placenta and in- include a maculopapular rash, jaundice, and
fect the fetus. Rubivirus causes rubella in hepatomegaly. Most complications develop if
adults. The virus crosses the placenta in the the infection is not treated soon after birth.
first trimester and causes congenital abnor-
Answer E is incorrect. Newborns with con-
malities that range from deafness to cataracts
genital syphilis normally are asymptomatic
to cardiovascular abnormalities. The abnormal
at birth. When symptoms develop, the babies
heart exam findings in this newborn are clas-
often have hearing problems (based on cra-
sic for a patent ductus arteriosus (PDA) with
nial defect VIII) and cutaneous lesions that
delayed symptoms of heart failure. A PDA is
normally appear on the palms and soles first.
the most common cardiovascular abnormal-
More serious symptoms include anemia, jaun-
ity seen in congenital rubella syndrome. A
dice, and hepatomegaly. Patent ductus arterio-
PDA results from the failure of the ductus ar-
sus is not found with congenital syphilis.
teriosus to close in the first days of life. This
results in a left-to-right shunt from the aorta to 17. The correct answer is G. This patient is likely
the pulmonary artery. In a substantial shunt, presenting with a mucosa-associated lymphoid
deoxygenated blood returning from the body tissue (MALT) lymphoma. This type of indo-
to the heart bypasses the lung via the PDA to lent lymphoma is believed to be associated
the aorta. Because blood is shunted, there is a with infection by the organism Helicobacter
widening of pulse pressure (the difference be- pylori. H pylori is commonly identified by the
tween systolic and diastolic). A split S2 sound presence of urease, catalase, and oxidase. Erad-
occurs in PDA because of the increased flow ication of the infection with antibiotics and
through the pulmonary artery. The S2 sound is proton-pump inhibitors is often sufficient to
a composite of two distinct heart valves. Nor- cause regression of the lymphoma.
mally, the aortic valve closes just before the
pulmonary valve. When the pulmonary valve Answer A is incorrect. This pattern is seen in
is forced to stay open longer than the aortic benign flora such as the lactobacilli.
High-Yield Principles
Chapter 4: Microbiology Answers 91

Answer B is incorrect. This pattern would be Moreover, an invasive process by the organism
commonly seen in streptococcal species such would likely take >4 hours to produce symp-
as Streptococcus pneumoniae. toms.
Answer C is incorrect. This pattern of results Answer D is incorrect. Vibrio cholerae causes
is commonly seen in facultative anaerobes large-volume, watery diarrhea. Treatment in-
such as Escherichia coli. volves prompt replacement of water and elec-
trolytes. Although antibiotics are not needed
Answer D is incorrect. This pattern represents
for treatment, tetracyclines have been shown
Pseudomonas aeruginosa, an opportunistic
to reduce the course of the disease. However,
lung pathogen.
there is nothing about this patients history to
Answer E is incorrect. This represents a pat- suggest that he has been exposed to cholera.
tern common of true anaerobes in the Bacter Rather, the history indicates a food-related
oides family. cause.

Microbiology
Answer F is incorrect. This pattern is seen in
19. The correct answer is C. This patient presents
Proteus mirabilis, a common cause of urinary
with classic symptoms of hepatocellular carci-
tract infection.
noma. Approximately 10%-30% of people in-
18. The correct answer is E. Food poisoning is fected with HCV will develop cirrhosis of the
the major cause of illness in this patient, and liver. Approximately 1%-5% of these patients
the most likely cause in this case is preformed develop hepatocellular carcinoma. HCV is
exotoxin from Bacillus cereus secreted into the transmitted via blood or blood transfusions
gastrointestinal (GI) tract. These exotoxins are and, rarely, by sexual contact. This patient is
fast acting, so the symptoms of food poisoning more likely to have HCV infection due to his
(nausea, vomiting, diarrhea) are usually rapid lack of travel, history of blood transfusion prior
in onset (within four-eight hours of ingestion). to the availability of sensitive screening meth-
Other major causes of food poisoning resulting ods, and extensive macronodular cirrhosis. Up
in nonbloody diarrhea include Staphylococcus to 90% of HCV-related hepatocellular carcino-
aureus, Clostridium perfringens, and entero- mas occur in patients with cirrhosis. Onset of
toxigenic Escherichia coli, which cause trav- hepatocellular carcinoma occurs on average
elers diarrhea. These organisms are typically 30 years after initial infection with HCV.
found in specific types of food, and B cereus is Answer A is incorrect. In the immunocom-
found in reheated rice. Because the food poi- petent host, CMV infection is often asymp-
soning in B cereus infection is caused by pre- tomatic, or it may produce a mononucleosis
formed enterotoxins, antibiotic treatment will syndrome. Disease manifestations are more
not help and supportive care is recommended. common in the immunocompromised host,
Answer A is incorrect. Bismuth subsalicylate, and include CMV colitis and CMV retinitis.
metronidazole, and amoxicillin are used to Patients with symptomatic CMV infection
treat Helicobacter pylori infection, which does may have subclinical transaminitis; however,
not result in the symptoms seen in this patient. there is no association with chronic hepatitis.

Answer B is incorrect. Fluoroquinolones Answer B is incorrect. Hepatitis A is transmit-


can be used to treat severe Shigella infection, ted via the fecal-oral route and causes an acute
which causes a bloody diarrhea. self-limited GI infection. It may rarely result
in fulminant hepatic failure requiring liver
Answer C is incorrect. Campylobacter jejuni transplantation, but it does not cause a chronic
enterocolitis can be treated with erythromy- hepatitis or cirrhosis.
cin or ciprofloxacin. Infection with this organ-
ism is not associated with eating reheated rice Answer D is incorrect. Hepatitis E is transmit-
and would typically result in bloody diarrhea. ted via the fecal-oral route and has been linked
to fatalities in pregnant women. It does not
High-Yield Principles
92 Section I: General Principles Answers

cause chronic hepatitis except very rarely in 21. The correct answer is B. This boy is suffering
patients who have previously received solid or- from the classic hemolytic-uremic syndrome
gan transplants. (HUS) caused most often by the endotoxin
of Escherichia coli O157:H7 contracted from
Answer E is incorrect. HIV is transmitted via
undercooked beef. This disease is caused by
bodily fluids and causes the death of CD4+ T
endothelial injury and platelet aggregation
lymphocytes, resulting in an immunocompro-
that lead to the classic triad of microangio-
mised state and increased susceptibility to op-
pathic hemolytic anemia, thrombocytopenia,
portunistic infections. It does not cause hepa-
and acute renal injury. Up to 75% of cases of
titis.
classic HUS occur as a result of infection with
20. The correct answer is A. The image shows
E coli O157:H7.
gram-positive cocci in clusters. Staphylococcal Answer A is incorrect. Campylobacter in-
scalded skin syndrome (SSSS) is caused by the fections can cause diarrheal illnesses and
release of two exotoxins (epidermolytic toxins have been implicated in the development of
Microbiology

A and B) from Staphylococcus aureus. Des- Guillain-Barr syndrome, but would not be ex-
mosomes (also called macula adherens) are pected to cause HUS.
responsible for binding epithelial cells to one
Answer C is incorrect. Rotavirus is a common
another to form a coherent whole. The exotox-
cause of infantile gastroenteritis. It is caused
ins that are released bind to a molecule within
by a double-stranded virus (reovirus). It is typi-
the desmosome called desmoglein 1, thereby
cally spread throughout daycare centers but
disrupting cell adhesion. In SSSS, the epider-
does not cause HUS.
mis separates at the stratum granulosum due to
the binding of exotoxins to desmosomes in this Answer D is incorrect. Shigella is known to
layer. Clinically, this results in bullous lesions cause bloody diarrhea. It can cause HUS, but
and a positive Nikolsky sign. this is less common than E coli-induced HUS.
Answer B is incorrect. Gap junctions are cir- Answer E is incorrect. Vibrio cholerae causes
cular intercellular contact areas that permit massive watery diarrhea by secreting cholera
the passage of small molecules between adja- toxin. Vibrio infections are not implicated in
cent cells, allowing communication to facili- classic HUS. This bacterium is generally asso-
tate electrotonic and metabolic function. ciated with contaminated water sources rather
than ill-prepared food.
Answer C is incorrect. Hemidesmosomes are
present on the basal surface of epithelial cells
22. The correct answer is A. These symptoms are
adjacent to the basement membrane, and
typical of urethritis. The most common causes
serve to connect epithelial cells to the underly-
of urethritis in males are Chlamydia tracho-
ing extracellular matrix.
matis and Neisseria gonorrhoeae. The image
Answer D is incorrect. Intermediate junctions shows intracellular inclusions consistent with
lie deep to tight junctions, comprised of actin infection by C trachomatis. While they may be
filaments forming a continuous band around difficult to differentiate, C trachomatis infec-
the cell, providing structural support just be- tion induces a predominantly immunologic
low tight junctions. reaction, with only a few polymorphonuclear
leukocytes (PMNs), while N gonorrhoeae in-
Answer E is incorrect. Tight junctions are lo-
duces predominantly nonimmunologic in-
cated beneath the luminal surface of simple
flammation, with a PMN-rich infiltrate. The
columnar epithelium (eg, intestinal lining)
antibiotic of choice for chlamydia urethritis is
and seal the intercellular space to prevent dif-
azithromycin (macrolide) or doxycycline (tet-
fusion between cells.
racycline).
High-Yield Principles
Chapter 4: Microbiology Answers 93

Answer B is incorrect. Ceftriaxone is an effec- tor of recent disease, given that IgM is the first
tive treatment for gonorrhea, but the cephalo- antibody produced in response to an antigen.
sporin class of antibiotics is relatively ineffec-
tive against Chlamydia trachomatis. 24. The correct answer is D. This patient likely
has pertussis, or whooping cough, which is
Answer C is incorrect. Fluconazole inhibits
caused by the gram-negative rod Bordetella
fungal steroid synthesis. It is used in the treat-
pertussis. This organism has four virulence fac-
ment of fungal infections, such as Candida al-
tors, including pertussis toxin. The A subunit
bicans.
of this exotoxin inhibits membrane-bound
Answer D is incorrect. Penicillin has been Gai proteins, which ultimately results in the
shown to suppress chlamydial multiplication. accumulation of cAMP. The effects of this ac-
However, it does not eradicate the organ- cumulation include histamine sensitization,
ism and thus is not the best treatment for this increased insulin synthesis, lymphocytosis, and
type of infection. Penicillin is the treatment of inhibition of phagocytosis.

Microbiology
choice for syphilis.
Answer A is incorrect. The botulinum toxin
Answer E is incorrect. Vancomycin has not released by Clostridium botulinum prevents
been shown to be effective in the treatment of the release of acetylcholine into the synaptic
chlamydial infection. It is used to treat drug- cleft, resulting in muscle weakness and paraly-
resistant Staphylococcus aureus and Clostrid- sis.
ium difficile.
Answer B is incorrect. The alpha toxin of
Staphylococcus aureus binds to the plasma
23. The correct answer is B. HBV is transmit-

membrane of host cells, forming a pore in
ted via parenteral, sexual, or maternal-fetal
the membrane that allows ions and small
routes. Of the markers listed, only hepatitis B
molecules to enter the cell. This leads to cell
e antigen (HBeAg) signifies active viral replica-
swelling and eventual lysis. Streptolysin O of
tion, and would therefore make transmission
Streptococcus pyogenes functions in a similar
of HBV to a partner more likely. HBeAg and
manner.
hepatitis B core antigen (HBcAg) are antigenic
markers of the virus core. They can be de- Answer C is incorrect. The exotoxin of Cory-
tected two-four months after exposure. nebacterium diphtheriae functions via the inac-
tivation of elongation factor 2, causing pharyn-
Answer A is incorrect. Hepatitis B e anti-
gitis and the formation of a pseudomembrane
body (HBeAb) is an antibody directed against
in the throat. Pseudomonas aeruginosa exo-
HBeAg. Its presence indicates low transmissi-
toxin A also works via this mechanism.
bility. HBeAb can be detected five months af-
ter exposure to HBV and one month after the Answer E is incorrect. Lipopolysaccharide-
detection of HBeAg. lipid A is an endotoxin released only by gram-
negative bacteria, with the exception of Liste-
Answer C is incorrect. Hepatitis B surface an-
ria monocytogenes, a gram-positive bacteria
tibody (HBsAb) provides immunity to HBV in-
responsible for meningitis in neonates and
fection. It can be detected in former carriers of
immunosuppressed patients. Endotoxins are
HBV or in patients immunized with the HBV
a normal part of the bacterial membrane re-
vaccine.
leased upon lysis of the cell.
Answer D is incorrect. IgG HBcAb is an indi-
cator of chronic disease. 25. The correct answer is E. Vibrio cholerae

causes watery stools, often called rice-water
Answer E is incorrect. Hepatitis B core anti-
stool. This illness is not accompanied by ab-
body (HBcAb) is produced in response to hep-
dominal pain, but the symptoms are due to
atitis core antigen (HBcAg). IgM is an indica-
dehydration, which leads to electrolyte imbal-
ances. Cholera toxin binds to the GM1 entero-
High-Yield Principles
94 Section I: General Principles Answers

cyte receptor via the pentameric B subunit. mechanism of shock through anaphylaxis is
Once inside the cell, the toxin must undergo not related to DIC.
cleavage of the active, A1 component, which
Answer D is incorrect. The C5a component
goes on to constitutively activate the Gs protein
of the complement cascade, activated by en-
through ADP ribosylation. This results in high
dotoxin, functions in neutrophil chemotaxis.
cyclic AMP levels, which activate the CFTR
This is not the mechanism involved in anaphy-
(cystic fibrosis transmembrane conductance
laxis.
regulator) channel, leading to a large efflux
of chlorine and other ions into the GI lumen. Answer E is incorrect. The cytokine
This results in extremely watery diarrhea ac- interleukin-1, released by macrophages acti-
companied by electrolyte imbalances. vated by endotoxin, causes fever. Fever is ab-
sent in anaphylaxis.
Answer A is incorrect. This is a characteristic
of Shiga toxin, which typically leads to bloody Answer F is incorrect. Nitric oxide, released
diarrhea. by macrophages activated by endotoxin, causes
Microbiology

hypotension (shock). However, this is not the


Answer B is incorrect. Bacillus anthracis pro-
mechanism of anaphylactic shock.
duces a toxin that acts as an adenylate cyclase
(edema factor) but is not associated with severe 27. The correct answer is D. Loeffler medium,

watery diarrhea. blood agar, and tellurite plate are used to cul-
Answer C is incorrect. Diphtheria toxin and ture a throat swab from patients with suspected
exotoxin A from Pseudomonas inactivate elon- Corynebacterium diphtheriae infection. This
gation factor 2, but neither is a likely cause of organism causes symptoms of pseudomembra-
watery diarrhea. nous pharyngitis (thick gray membrane) and
lymphadenopathy. A possible complication of
Answer D is incorrect. Bordetella pertussis
this disease is the extension of the membrane
produces an exotoxin that increases cAMP lev-
into the larynx and trachea, resulting in airway
els by inactivating the inhibitory Gi. However,
obstruction. Rapid treatment with diphtheria
pertussis causes whooping cough, not severe
antitoxin, penicillin, or erythromycin and the
watery diarrhea.
DTP vaccine is indicated in this patient
26. The correct answer is B. Anaphylactic shock Answer A is incorrect. Lwenstein-Jensen agar
is a life-threatening disorder that occurs when is used to culture Mycobacterium tuberculosis,
an allergen overactivates mast cells and ba- the bacterium that causes TB.
sophils, leading to widespread release of his-
Answer B is incorrect. Bordet-Gengou agar is
tamines, serotonins, and other compounds
used to culture Bordetella pertussis, the etio-
stored in the granules of these immune cells.
logic agent responsible for whooping cough.
These compounds lead to vasodilation and
leaky capillaries. The crosslinking of IgE re- Answer C is incorrect. Chocolate agar with
ceptors present on these cells causes the activa- factors V and X is used to culture Haemophilus
tion of these cell types. By blocking this cross influenzae. This organism typically causes up-
reaction, the anaphylactic pathway can be sty- per respiratory infections but is not responsible
mied. for pseudomembranous pharyngitis.
Answer A is incorrect. Interferon is pro- Answer E is incorrect. Neisseria gonorrhoeae
duced by T lymphocytes and, among other is cultured on Thayer-Martin media. This bac-
functions, activates tumoricidal macrophages. terium can cause gonorrhea, septic arthritis,
neonatal conjunctivitis, and pelvic inflamma-
Answer C is incorrect. Endotoxin can directly
tory disease.
activate Hageman factor, activating the coagu-
lation cascade and leading to disseminated in-
travascular coagulation (DIC). However, the
High-Yield Principles
Chapter 4: Microbiology Answers 95

28. The correct answer is B. This patient presents treonam is a b-lactamase-resistant monobac-
with Rocky Mountain spotted fever (RMSF) tam that interferes with cell wall biosynthesis
caused by Rickettsia rickettsii, a small, gram- by binding to penicillin-binding protein 3. Az-
negative bacterium carried by the American treonam is a potent antipseudomonal agent in-
dog tick (Dermacentor variabilis). Despite dicated for pseudomonal sepsis.
its name, RMSF is more common in the
Answer A is incorrect. Amoxicillin is an ami-
southeastern United States than in the Rocky
nopenicillin antibiotic that interferes with cell
Mountains. Patients often present first with
wall synthesis. Although amoxicillin has an
severe headache, fever (>38.9C or >102F),
extended spectrum compared with penicillin
and myalgias followed by a petechial rash on
(covering Haemophilus influenzae, Escherichia
the palms and soles (or wrists and ankles) that
coli, Listeria, Proteus, Salmonella, and Entero-
spreads to the trunk. The Weil-Felix assay re-
cocci), it does not provide antipseudomonal
action is the classic test for rickettsial disease.
coverage.
The treatment of choice for adults with RMSF

Microbiology
is doxycycline; chloramphenicol is also used Answer C is incorrect. Use of fresh frozen
but has more significant adverse effects. plasma (FFP) is reserved for patients with co-
agulopathy and signs of active, life-threatening
Answer A is incorrect. Cephalosporins (cef-
bleeding. Although provision of FFP will tem-
triaxone) are not effective against Rickettsia
porarily reverse some of this patients labo-
rickettsii. They are generally used to treat neo-
ratory signs of DIC (elevated International
natal/infant sepsis or gonorrhea, as well as bac-
Normalized Ratio, decreased fibrinogen),
terial meningitis.
treatment of the underlying cause (ie, Pseudo-
Answer C is incorrect. Aminoglycosides (gen- monas sepsis) is most important.
tamicin) are not effective against Rickettsia
Answer D is incorrect. Vancomycin is an an-
rickettsii. Aminoglycosides are effective against
tibiotic used for serious multidrug-resistant,
many gram-negative bacteria and some strains
gram-positive infections. Major uses are for
of Staphylococcus aureus. It is also used as
methicillin-resistant Staphylococcus aureus
broad-spectrum therapy when combined with
and moderate to severe Clostridium difficile in-
a penicillin or metronidazole.
fections. Its mechanism of action is to inhibit
Answer D is incorrect. Nystatin is used in the cell wall mucopeptide formation by binding
treatment of fungal infections such as oral can- the D-ala-D-ala portion of cell wall precursors.
didiasis.
Answer E is incorrect. Coagulopathy caused
Answer E is incorrect. Penicillin is not effec- by warfarin overdose is reversed by pharma-
tive against Rickettsia rickettsii. Penicillin is cologic administration of vitamin K. This pa-
still the treatment of choice for syphilis. Other tients coagulopathy is caused by Pseudomonas
derivatives that are used more frequently in- sepsis, so vitamin K therapy plays no role here.
clude oxacillin, cloxacillin, dicloxacillin, and
amoxicillin when Staphylococcus and Strepto- 30. The correct answer is C. Trichomoniasis is

coccus species prove sensitive. caused by Trichomonas vaginalis. Symptoms
include a profuse, frothy discharge that is as-
29. The correct answer is B. This patient has leu- sociated with vulvovaginal pruritus, tender-
kocytosis and Charcots triad (fever, jaundice, ness, and burning. The vulva and vagina are
right upper quadrant pain), along with the frequently inflamed. The cervix and vagina
ominous sign of hypotension, a clear clini- may develop small, red, punctate lesions, caus-
cal picture of cholecystitis. In addition, he ing the classic strawberry appearance. Diag-
has Pseudomonas aeruginosa sepsis and DIC. nosis is made by wet mount, on which small,
Gram-negative rod sepsis is the clear cause of pear-shaped, flagellated organisms can be seen
this patients DIC, and antipseudomonal cov- moving around.
erage with aztreonam is most appropriate. Az-
High-Yield Principles
96 Section I: General Principles Answers

Answer A is incorrect. Bloody and foul- Answer B is incorrect. Entamoeba histolytica


smelling vaginal discharge suggest a vaginal infection presents with bloody diarrhea (dysen-
foreign body. tery), abdominal cramps with tenesmus, and
pus in the stool. It can also cause right upper
Answer B is incorrect. Pelvic or lower ab-
quadrant pain and liver abscesses. E histolyt-
dominal pain with an abnormal, foul-smelling
ica is transmitted via cysts in water (fecal-oral
vaginal discharge is suggestive of pelvic inflam-
transmission). On microscopy, one observes
matory disease, which can involve the endo-
amebas with ingested RBCs. Treatment for
metrium, fallopian tubes, ovaries, and peri-
E histolytica infection includes metronidazole
toneum. Fever, nausea, and vomiting may be
and iodoquinol.
present. The typical organisms involved are
Neisseria gonorrhoeae and Chlamydia tracho- Answer C is incorrect. Leishmania donovani
matis. infection presents with hepatomegaly and sple-
nomegaly, malaise, anemia, and weight loss.
Answer D is incorrect. Candida species typi-
L donovani is transmitted via the sandfly. Mi-
Microbiology

cally cause intense pruritus and a thick, odor-


croscopically, macrophages containing amas-
less, white, cottage cheese-like vaginal dis-
tigotes are observed. Sodium stibogluconate is
charge. Erythema, edema, dysuria, and urinary
used to treat L donovani infection.
frequency may be present. Budding yeasts and
hyphae are seen on a wet mount. Answer E is incorrect. The Plasmodium falci-
parum parasite is responsible for causing ma-
Answer E is incorrect. Bacterial vaginosis
laria. It is spread by the Anopheles mosquito.
typically presents with an unpleasant fishy-
Diagnosis of Plasmodium falciparum infection
smelling discharge that is thin, gray-white, and
is made through a blood smear.
homogeneous. Pruritus and inflammation are
unusual in bacterial vaginosis, thus the term
32. The correct answer is C. This image of the
vaginosis rather than vaginitis. On a wet
mitral valve reveals Aschoffs nodule, which
mount, one will see clue cells that are formed
is pathognomonic for rheumatic fever. Rheu-
from bacteria-coated epithelial cells.
matic fever is caused by group A streptococci.
Years after a bout of rheumatic fever, rheu-
31. The correct answer is D. Naegleria fowleri

matic heart disease can develop due to calcifi-
presents with a rapidly progressing meningoen-
cation of warty vegetations on fibrotic healing,
cephalitis that can progress to coma or death
most commonly on the mitral valve. As a re-
within six days. Other symptoms include nau-
sult, it most commonly causes mitral stenosis,
sea, vomiting, and irrational behavior. Trans-
which in mild disease causes a late diastolic
mission occurs through swimming in fresh-
murmur heard best at the apex. In the US, the
water lakes. Microscopic analysis will reveal
incidence of this mitral stenosis secondary to
amebas in the spinal fluid. Unfortunately,
rheumatic fever is low given the widespread
there is no treatment for N fowleri.
use of antibiotics. However, rheumatic mitral
Answer A is incorrect. Cryptosporidium spe- stenosis is prevalent in immigrant populations.
cies infection presents with severe diarrhea in
Answer A is incorrect. A friction rub heard
HIV-positive patients and mild watery diarrhea
throughout the precordium would correspond
in HIV-negative patients. Cryptosporidium spe-
to pericarditis, an inflammation of the pericar-
cies are transmitted via cysts in water (fecal-
dial sac that leads to friction with an expanding
oral transmission). Microscopically, acid-fast
and contracting myocardium. It is not a long-
staining cysts are found. Unfortunately, there
term complication of rheumatic fever. Rather,
is no treatment available for Cryptosporidium
a friction rub may be associated with malig-
species infection; however, in healthy patients,
nancy, uremia, active infections such as viral
cryptosporidiosis is self-resolving.
or tuberculous, and other rare causes.
High-Yield Principles
Chapter 4: Microbiology Answers 97

Answer B is incorrect. Aortic stenosis is repre- munoglobulin heavy chain enhancer. There
sented by a harsh crescendo-decrescendo early is a strong association between Burkitt lym-
systolic murmur heard best at the right upper phoma and Epstein-Barr virus (EBV). In en-
sternal border with radiation to the carotids. demic regions, children are typically infected
Rheumatic heart disease can lead to calcifica- with EBV by the age of three years, compared
tion of the aortic valve, which leads to aortic with infection during adolescence in other re-
stenosis, but for unclear reasons, this occurs gions. EBV, the cause of infectious mononu-
much less frequently than on the mitral valve. cleosis, is spread by saliva and respiratory secre-
An aortic stenosis murmur in a middle-aged tions.
woman should raise the suspicion for a calci-
Answer A is incorrect. HBV and HCV are
fied bicuspid aortic valve (remember the fish
spread by blood-borne contacts. Although
mouth).
these viruses are associated with hepatocellu-
Answer D is incorrect. A systolic click heard lar carcinoma, there is no association between
best at the apex corresponds to mitral valve HBV or HCV and Burkitt lymphoma.

Microbiology
prolapse, which is a relatively common and
Answer B is incorrect. Hepatitis A virus (HAV)
benign finding in middle-aged women. It oc-
is transmitted by the fecal-oral route. There is
curs when an abnormally thickened mitral
no association between HAV and Burkitt lym-
valve leaflet displaces into the left atrium dur-
phoma.
ing ventricular systole. It is not related to rheu-
matic heart disease. It may lead to mitral regur- Answer C is incorrect. Arboviruses and flavi-
gitation and ultimately valve surgery may be ruses can be transmitted through mosquito
required, but typically it is followed by a car- bites. These viruses cause tropical diseases
diologist with serial exams and echocardiogra- such as dengue fever and yellow fever, but not
phy. Burkitt lymphoma.
Answer E is incorrect. An S4, which is heard Answer E is incorrect. Viruses such as HIV,
best at the apex and is associated with concen- herpes simplex virus type 2, and human her-
tric left ventricular hypertrophy, is indicative of pesvirus type 8 are spread by sexual contact.
either chronic extensive afterload (ie, from un- None of these pathogens is associated with
controlled hypertension) or long-standing aor- Burkitt lymphoma.
tic stenosis. It also can be caused by diastolic
heart failure because the left ventricle is not as 34. The correct answer is D. This patients con-
compliant as it should be. The exam finding is stellation of symptoms and prior hospitaliza-
due to turbulent blood flow caused by blood tion points toward pseudomembranous coli-
filling a stiff ventricle. An S4 is not associated tis. Clostridium difficile proliferation causes
with rheumatic heart disease. the severe non-bloody diarrhea associated
with pseudomembranous colitis by produc-
33. The correct answer is D. This patient has
ing an exotoxin that kills enterocytes. Antibi-
Burkitt lymphoma, a lymphoma endemic otic treatments suppress the normal flora of
to Africa. Clinically, Burkitt lymphoma of- the GI tract, allowing C difficile to multiply.
ten presents with B symptoms (fever, night Clindamycin was the first antibiotic associated
sweats, weight loss), signs of tumor lysis syn- with C difficile gastroenteritis and is used of-
drome such as oliguria, and solitary jaw ten to treat anaerobic infections above the dia-
masses. Histopathologically, Burkitt lymphoma phragm, such as aspiration pneumonia. How-
typically assumes a starry sky appearance ever, many antibiotics have been implicated
with sheets of lymphocytes interspersed with since then, especially cephalosporins and am-
occasional macrophages. The cytogenetic ab- picillin. Always consider C difficile in patients
normality associated with Burkitt lymphoma is with gastroenteritis and recent antibiotic use.
a t(8;14) translocation in which the oncogene
c-myc is placed under the expression of the im-
High-Yield Principles
98 Section I: General Principles Answers

Answer A is incorrect. This describes how the drome in young adults similarly characterized
Norwalk virus can cause gastroenteritis charac- by fever and pharyngitis. Both cause pericardi-
terized by nausea, vomiting, and diarrhea that tis only rarely.
resolves spontaneously within 12-24 hours.
Answer C is incorrect. Reoviridae is the only
Answer B is incorrect. This describes the exo- double-stranded RNA virus. Members of this
toxin produced by Shigella species, which can family include rotavirus, which is responsible
cause a bloody and mucus-rich diarrhea. for diarrhea in children, and reovirus, which
causes Colorado tick fever.
Answer C is incorrect. This describes the
exotoxin produced by Vibrio cholerae, which Answer D is incorrect. This answer choice de-
causes a large volume of watery diarrhea de- scribes the structure of Coronaviridae. Coro-
void of RBCs or WBCs (sometimes called rice- navirus (CoV) is a common virus that causes
water stool). It is not associated with prior anti- a self-limited cold-like syndrome. SARS-CoV,
biotic use. however, has been identified as the cause of se-
Microbiology

vere acute respiratory syndrome.


Answer E is incorrect. This describes Esch-
erichia coli, which causes the abrupt onset of
36. The correct answer is B. Guillain-Barr syn-
profuse watery diarrhea.
drome (GBS) is a common cause of acute
peripheral neuropathy that results in progres-
35. The correct answer is E. The patient presents
sive weakness over a period of days. Labora-
with classic signs and symptoms of pericardi-
tory abnormalities associated with GBS in-
tis, including precordial chest pain. This pain
clude elevated gamma-globulin, decreased
is relieved when leaning forward and worsens
nerve conduction velocity indicative of demy-
with inspiration. On physical exam the patient
elination, and albuminocytologic dissociation
has a pericardial friction rub, which accounts
(CSF shows increased protein concentration
for the scratchy, leathery sound heard during
with normal cell count in the setting of nor-
both systole and diastole. Classic ECG find-
mal glucose). Although one third of patients
ings include diffuse ST-segment elevation and
report no history of an infection, the other
depression of the PR segment. Pericarditis is
two thirds will have recently experienced an
frequently preceded by a viral upper respira-
acute GI or influenza-like illness prior to de-
tory infection. Although many viruses may
veloping the neuropathy. The most common
cause pericarditis, coxsackie B is the most
epidemiologic associations involve infections
common cause of inflammation of the pericar-
with Campylobacter jejuni, a comma-shaped,
dial membrane. Coxsackievirus is a picornavi-
oxidase-positive, gram-negative bacterium that
rus, the smallest of the RNA viruses. They are
can be grown at 42C. C jejuni causes a gas-
positive, single-stranded, naked, icosahedral
troenteritis that often presents with bloody di-
RNA viruses.
arrhea. Although a recent history of C jejuni
Answer A is incorrect. Staphylococcus au- enteritis is epidemiologically linked with GBS,
reus is a gram-positive, catalase-positive, and the infection does not directly cause GBS. The
coagulase-positive bacterium. Infection with proposed mechanism of GBS is that a preced-
S aureus may lead to acute bacterial endocar- ing infection incites an immune response that
ditis from seeding secondary to bacteremia. cross-reacts with peripheral nerve components,
The bacterium rarely causes pericarditis. leaving them susceptible to damage also.
Answer B is incorrect. This describes the Answer A is incorrect. Streptococcus pneu-
structure of Herpesviridae. Herpesvirus is char- moniae is an a-hemolytic, encapsulated, gram-
acterized by multinucleated giant syncytial positive coccus that produces an IgA protease.
cells with intranuclear inclusion bodies. Mem- Pneumococcal pneumonia can result in bac-
bers of this family include CMV and Epstein- teremia, meningitis, osteomyelitis, or septic
Barr virus. Both cause a mononucleosis syn-
High-Yield Principles
Chapter 4: Microbiology Answers 99

arthritis, but is not associated with the develop- Group A streptococci can cause cellulitis, nec-
ment of GBS syndrome. rotizing fasciitis, and streptococcal toxic shock
syndrome. Group B streptococci are a com-
Answer C is incorrect. Pseudomonas aeru-
mon cause of neonatal bacterial meningitis.
ginosa is a non-lactose-fermenting, oxidase-
Group D streptococci (Enterococcus) are a fre-
positive, gram-negative, aerobic bacillus that
quent cause of urinary tract infections and sub-
can cause otitis externa, urinary tract infection,
acute bacterial endocarditis.
pneumonia, and sepsis in immunocompro-
mised hosts. It is not associated with GBS syn- Answer C is incorrect. Staphylococcus epider-
drome or other neurologic conditions. midis is a coagulase-negative, gram-positive
coccus that grows in clusters. It is common
Answer D is incorrect. Clostridium botulinum
skin flora. It can be a cause of osteomyelitis,
is a rod-shaped, gram-positive, spore-forming,
but this is more common after implantation
anaerobe that produces a heat-labile toxin that
with orthopedic appliances.
inhibits acetylcholine release at the neuromus-

Microbiology
cular junction, causing flaccid paralysis. Botu- Answer E is incorrect. Salmonella species are
lism, therefore, does not lead to sensory find- oxidase-negative, gram-negative bacilli. Salmo-
ings, and is not associated with increased CSF nella osteomyelitis is often associated with pa-
protein on lumbar puncture. tients who have sickle cell disease.
Answer E is incorrect. Treponema pallidum,
38. The correct answer is C. The patient is now
the causative agent of syphilis, is a spiral-
in the secondary stage of a syphilis infection,
shaped bacterium with axial filaments, visu-
characterized by wart-like lesions known as
alized using dark-field microscopy. Tertiary
condylomata lata, generalized rash, and sys-
syphilis causes sensory deficits rather than
temic symptoms such as lymphadenopathy,
muscle weakness and is preceded by a painless
weight loss, and fever. The fluorescent trepo-
chancre and maculopapular rash. Neurologic
nemal antibody absorption (FTA-ABS) test,
findings develop after years, not weeks, of un-
the Venereal Disease Research Laboratory
treated infection.
(VDRL) test, and the rapid plasma reagin test
approach 100% sensitivity for detecting syphi-
37. The correct answer is D. This teenager most
lis.
likely has osteomyelitis secondary to a contigu-
ous focus of infection, such as bites, puncture Answer A is incorrect. Thayer-Martin agar is
wounds, and open fractures. Most of these used to culture Neisseria gonorrhoeae.
cases are caused by Staphylococcus aureus, a
Answer B is incorrect. Tzanck preparation
gram-positive, coagulase-positive coccus that
using Giemsa stain reveals multinucleated gi-
occurs in clusters. This organism expresses re-
ant cells indicative of herpes simplex virus
ceptors for bone matrix components, such as
(HSV) or vesicular stomatitis virus infection.
collagen, which help it to attach to and infect
Although HSV can cause genital lesions, they
bone. When compared to hematogenous os-
are usually painful and come in clusters.
teomyelitis, continguous-focus infections are
more likely to also include gram-negative and Answer D is incorrect. The Weil-Felix re-
anaerobic bacteria. action assay tests for antirickettsial antibod-
ies. This test would be positive if the patient
Answer A is incorrect. Acid-fast bacilli such
were infected with Rickettsia rickettsii (Rocky
as Mycobacterium tuberculosis are found in
Mountain spotted fever). Rocky Mountain
patients with TB. Infection of the bone by TB
spotted fever can also present with a rash on
is known as Pott disease, but its usual presenta-
the palms and soles but would not present with
tion is vertebral osteomyelitis.
genital lesions.
Answer B is incorrect. Streptococcus species
are catalase-negative, gram-positive cocci.
High-Yield Principles
100 Section I: General Principles Answers

Answer E is incorrect. Ziehl-Neelsen stain is 40. The correct answer is D. This infant is show-
used to stain acid-fast mycobacteria such as ing signs of neonatal sepsis and meningitis.
Mycobacterium tuberculosis. The most common cause of neonatal sep-
sis and meningitis is group B Streptococcus
39. The correct answer is B. The first step in
(GBS), which frequently colonizes the genito-
answering this question is to recognize that urinary tract of women and can be passed to
Ziehl-Neelsen stain is what is used for the the infant during delivery. Penicillin G would
acid-fast test. The presence of acid-fast rods have provided adequate coverage for the moth-
in the blood indicates that this man has a dis- ers likely colonization with GBS.
seminated mycobacterial infection. In order of
Answer A is incorrect. Fluconazole, an an-
prevalence, the three main candidate organ-
tifungal agent that interferes with fungal er-
isms in patients with HIV are: (1) M avium-
gosterol synthesis, would not have been an
intracellulare (MAC), (2) Mycobacterium tu-
appropriate antibiotic for GBS prophylaxis.
berculosis, and (3) Mycobacterium kansasii.
Fluconazole has good coverage against fungal
Microbiology

Disseminated MAC infection can present


infections.
with generalized symptoms (such as fatigue,
night sweats, fever, and weight loss) as well as Answer B is incorrect. Metronidazole, a dis-
organ-specific symptoms, and occurs when the ruptor of nucleic acid structure, would not
patients CD4+ cell count has dropped to <50/ have been an appropriate antibiotic for GBS
mm3. It can include gut pain (from mycobac- prophylaxis. Metronidazole has good activity
terial enteritis), pulmonary symptoms, or ad- against protozoans and anaerobic organisms.
enopathy. Although M tuberculosis infection
Answer C is incorrect. Moxifloxacin, a DNA
is frequently seen in HIV-infected patients, it is
gyrase inhibitor, would not have been an ap-
rare to recover it from blood cultures.
propriate antibiotic for GBS prophylaxis.
Answer A is incorrect. Actinomyces israelii is a Fluoroquinolones have good coverage against
bacterial pathogen with a fungal-like morphol- gram-negative and select gram-positive organ-
ogy. Unlike Nocardia, it is not acid-fast. isms, and are often used to treat urinary tract
infections and community-acquired pneumo-
Answer C is incorrect. Mycobacterium mari-
nia. Additionally, fluoroquinolones are a class
num is a species native to fresh-water and salt-
C substance, as they have the potential to
water environments. It is a rare cause of cuta-
cause teratogenic or embryocidal effects. Giv-
neous wound infection in anglers, swimmers,
ing fluoroquinolones during pregnancy is not
and aquarium owners. It is not commonly as-
recommended unless the benefits justify the
sociated with disseminated infection in immu-
potential risks to the fetus.
nocompromised patients.
Answer E is incorrect. Vancomycin, a cell
Answer D is incorrect. M tuberculosis could
wall synthesis inhibitor, would not have been
be a causative agent for the symptoms found
an appropriate antibiotic for GBS prophylaxis
in this patient, except that his CD4+ count
in this case. While vancomycin has good cov-
is <50/mm3, which makes infection with
erage against GBS, its use is reserved for cases
M avium-intracellulare most likely.
of known resistance. Vancomycin could have
Answer E is incorrect. Nocardia is eliminated been used if the mother were known to harbor
as the correct answer by the given morphology GBS that was resistant to other first-line antibi-
of the observed bacteria. Although Nocardia otics, or had an allergy that prevented the use
can stain weakly acid-fast, they demonstrate of other agents.
a branching filamentous morphology that re-
sembles fungal hyphae.
Chapter 5

Immunology

101
High-Yield Principles
102 Section I: General Principles Questions

Q u e st i o n s

1. A 48-year-man with chronic renal failure un- flammatory cytokines. Which of the following
derwent a cadaveric renal transplant. The op- opposes the action of cytokines?
eration was a success, and the transplanted kid-
(A) Interferon-
ney started producing urine on the operating
(B) Interleukin-7
table. However, one week later, the patients
(C) Transforming growth factor-b
creatinine level begins to rise and his urine
(D) Tumor necrosis factor-a
output drops. He does not experience dysuria,
(E) Tumor necrosis factor-b
and urinalysis shows no bacteria or crystals.
A biopsy taken from the transplanted kidney 4. The image depicts a cell that is activated by
shows a cellular infiltrate. Which of the follow- bacterial products, upregulates costimulatory
ing would most likely be found on the surface molecules, and migrates to the draining lymph
Immunology

of the cells responsible for this patients current node. Which of the following types of cells is
condition? shown in this image, and of which type of im-
(A) CD20 mune cell is it a specialized form?
(B) CD27
(C) CD34
Ag
(D) CD4 Ag
Ag
(E) CD8 TNF Ag
CD40L Ag
MCM Ag
2. An infant boy experiences multiple bacterial, LPS Ag
viral, and fungal infections during his first Ag

year of life. He has also been suffering diar- Ag Ag

rhea since birth. Tests are performed to deter-


Ag
mine the likely cause of his symptoms. Serum Ag Ag
calcium levels are normal, and the patients
white blood cells change nitroblue tetrazolium Reproduced, with permission, from USMLERx.com.
from clear to bright blue; however, his B- and
T-lymphocyte counts are very low. What is a
possible mechanism accounting for his symp- (A) Kupffer cell, dendritic cell
toms? (B) Kupffer cell, macrophage
(C) Langerhans cell, dendritic cell
(A) Defective interleukin-2 receptors (D) Langerhans cell, macrophage
(B) Failure of the third and fourth pharyngeal (E) Microglia, dendritic cell
pouches to descend
(C) Inability of helper T lymphocytes to switch 5. To assess the risk of erythroblastosis fetalis dur-
classes ing the future pregnancy of an Rh-negative
(D) Lack of NADPH oxidase activity woman, a clinician sends a sample of serum
(E) X-linked tyrosine kinase defect for detection of anti-Rh blood group anti-
bodies. The laboratory performs an indirect
3. A 45-year-old woman presents to her fam- Coombs test by mixing the patients serum
ily physician with complaints of two months with Rh-positive RBCs and then adding an
of joint stiffness and pain that is worst in the anti-IgG antibody. In doing so, the laboratory
morning. Physical examination reveals swell- technician observes agglutination of the RBCs.
ing of the left metacarpophalangeal joints and After receiving this test result, the clinician
of the wrists bilaterally. She is diagnosed with a would be correct to conclude which of the fol-
condition associated with the release of proin- lowing?
High-Yield Principles
Chapter 5: Immunology Questions 103

(A) The laboratory performed the test incor- 7. A 1-year-old child whose parents just emi-
rectly; it should have mixed the patients grated from Mexico presents to the emergency
serum with Rh-negative rather than Rh- room with stridor. The child is in obvious dis-
positive RBCs tress and is drooling. Examination of the phar-
(B) The patient has had previous pregnancies ynx reveals a cherry-red mass at the base of
and all of her children are Rh-negative the tongue. The vaccine that could have pre-
(C) The patient is currently pregnant with an vented this childs illness contains two parts:
Rh-positive fetus purified bacterial capsule and mutant diphthe-
(D) The presence of anti-Rh antibodies in the ria toxoid. Which of the following characteris-
patients serum suggests that she has been tics of the causative organism makes necessary
pregnant with an Rh-positive fetus the addition of the diphtheria toxoid to the vac-
(E) The results of the test cannot be used to cine?
determine the Rh status of a current fetus;
(A) Attachment pili
the results only assess the presence of anti-
(B) Gram-negative rod

Immunology
bodies in the mother. To determine fetal
(C) IgA protease
Rh status, direct typing of fetal blood must
(D) Polyribitol-ribose phosphate capsule
be done.
(E) Protein A
6. A 68-year-old woman has been hospitalized
8. A type B blood group, Rh-positive recipient
for three days after an exacerbation of emphy-
mistakenly receives a kidney from a type A
sema. Her clinical course progresses well un-
blood group, Rh-negative donor. Which of
til the fourth hospital day, when she develops
the following best describes the mechanism of
shortness of breath, fatigue, and cough produc-
transplant rejection that is most likely to ensue
tive of yellow sputum. Her oxygen saturation
in this recipient?
drops by 10%, and she is started on vancomy-
cin and gentamicin via rapid infusion. Thirty (A) Pre-formed recipient antibodies
minutes after the initiation of antibiotics, the (B) Macrophages
patient develops erythema of the face and (C) Pre-formed donor antibodies
neck, itchiness, and hypotension. The patient (D) Donor T lymphocytes
has no known drug allergies and has not been (E) Recipient T lymphocytes
treated with vancomycin prior to this hospital-
ization. Which of the following is the mecha- 9. A 3-year-old boy is admitted to the hospital
nism of this reaction? with aspergillosis. He has had multiple admis-
sions for viral and fungal infections previously.
(A) Binding of antibody-complement to target His serum calcium level is 7.8 mg/dL. Biopsy
cells of one of this patients lymph nodes would
(B) Cross-linking of IgE by Fc receptors on most likely reveal which of the following ab-
mast cells normalities?
(C) Deposition of antibody-drug immune com-
plexes (A) Decreased number of follicles
(D) Release of cytokines by activated T lym- (B) Hypocellular paracortex
phocytes (C) Hypocellular medullary sinuses
(E) Release of histamine by mast cells (D) Enlarged follicles throughout the entire
lymph node
(E) Increased number of the medullary cords
High-Yield Principles
104 Section I: General Principles Questions

10. A 60-year-old postmenopausal woman presents the following symptoms is this patient most
with fatigue, mild jaundice, and tingling in the likely experiencing?
lower extremities. Laboratory studies show ele-
(A) Episodic palpitations, sweating, and head-
vated serum levels of homocysteine and meth-
aches with no apparent trigger
ylmalonic acid, and mild thrombocytopenia. A
(B) Intermittent ischemia of fingers and toes
peripheral blood smear supports the diagnosis.
associated with pallor and pain
In which of the following disorders would a pe-
(C) Joint pain, dry eyes and mouth
ripheral blood smear be similar to the one seen
(D) Urethritis
in this case?
(E) Widespread tightening of the skin
(A) Acute blood loss
(B) Anemia of chronic disease 13. A 10-month-old boy is brought to the pedia-
(C) Iron deficiency anemia trician by his parents because of fever, cough,
(D) Pernicious anemia and difficulty breathing. A profile of the pa-
(E) Pyridoxine deficiency tients immunoglobulin isotypes shows low
Immunology

IgA, low IgG, and markedly elevated IgM lev-


11. The image below depicts a series of steps in an els. The number of T and B lymphocytes is
immunologic activation pathway. This path- normal. Which of the following is the most
way is most important for which activity of the likely etiology of the increased level of IgM in
immune system? this patient?
(A) A defect in DNA repair enzymes
(B) A defect in LFA-1 adhesion proteins on
phagocytes
(C) A defect in the CD40 ligand on CD4 T
helper cells
(D) Failure of interferon- production
(E) Failure of the thymus and parathyroid
glands to develop

14. A 40-year-old man presents to his physician


with numbness and tingling on the dorsal sur-
face of his right hand and forearm, and raised
varicose veins that are firm to the touch
along the same distribution. He also complains
of weight loss. His serum creatinine level is 2.0
Reproduced, with permission, from USMLERx.com. mg/dL. He has no previous medical history
of significance. An immune complex disease
is suspected, and assays for autoantibodies in-
(A) Antigen presentation and destruction of in-
side neutrophils are conducted. What diseases
tracellular pathogens
are associated with the identification of anti-
(B) Defense against parasites by eosinophils
myeloperoxidase and anti-proteinase-3 antibod-
(C) Immediate allergic hypersensitivity reac-
ies, respectively?
tion
(D) Neutrophil chemotaxis (A) Kawasaki disease, Buerger disease
(B) Microscopic polyangiitis, Wegener granu-
12. A 35-year-old woman presents to the clinician lomatosis
with symptoms suggestive of an autoimmune (C) Polyarteritis nodosa, Buerger disease
etiology. A biopsy is sent for immunofluores- (D) Takayasu arteritis, Wegener granulomato-
cent staining, and the results indicate the pres- sis
ence of anticentromere antibodies. Which of
High-Yield Principles
Chapter 5: Immunology Questions 105

(E) Takayasu arteritis, Buerger disease (C) Patients with juvenile rheumatoid arthritis
(F) Temporal arteritis, Wegener granulomato- are more likely to have large-joint involve-
sis ment, but the likelihood of concurrent sys-
temic symptoms is the same
15. A 24-year-old woman presents with a four- (D) Patients with juvenile rheumatoid arthritis
month history of fever, night sweats, and are more likely to have systemic symptoms
weight loss. X-ray of the chest reveals enlarged and high levels of serum rheumatoid factor
mediastinal lymph nodes. The biopsy of one (E) Patients with juvenile rheumatoid arthritis
such lymph node is shown in the image. From are more likely to have systemic symptoms
which of the following cell types is the cell and large-joint involvement
with the bilobed nucleus derived?
17. A 6-month old boy is noted at his well-child
visit to have very poor growth and weight gain
since his last visit. His mother states that he

Immunology
was hospitalized for pneumococcal pneumo-
nia, and has had several bad colds with pu-
rulent nasal discharge since he was born. His
physician suspects an immunodeficiency, and
laboratory results indeed reveal deficiency of a
complement protein. Which of the following
antibodies functions in the same manner as
the missing complement protein in this child?
(A) IgA
(B) IgD
(C) IgE
(D) IgG
Reproduced, with permission, from USMLERx.com.
(E) IgM

18. A 29-year-old intravenous drug user has suf-


(A) B lymphocyte
fered from recurrent pneumonias, fungal
(B) Fibroblast
infections in the axillae, and a recent ear in-
(C) Macrophage
fection. He now presents with a cough and
(D) Neutrophil
painful swallowing. Physical examination re-
(E) T lymphocyte
veals a patchy, white oral lesion. Cells with
16. Patients who share similar clinical symptoms which of the following markers are most likely
and disease pathology may nevertheless pre to be deficient in this patient?
sent differently based on age at disease onset. (A) CD4
How does the presentation of the disease evi- (B) CD8
dent in the image differ between juvenile and (C) CD20
adult-onset disease? (D) CD40
(A) Juvenile rheumatoid arthritis is simply the (E) CD56
presence of rheumatoid arthritis that be-
gins before the age of 21 years
(B) Patients with juvenile rheumatoid arthritis
are less likely to have systemic symptoms,
but the likelihood of high levels of serum
rheumatoid factor is the same
High-Yield Principles
106 Section I: General Principles Questions

19. A 2-year-old girl with a lifelong history of mal- tient does not have tonsils. His mother denies
absorptive and foul-smelling diarrhea, weak- a previous tonsillectomy. Analysis of the boys
ness, and general failure to thrive has just un- serum would most likely yield which of the fol-
dergone a small intestine biopsy (see image). lowing results?
Her parents believe her problems began at 6
(A) < 200/mm3 CD4 T lymphocytes
months of age, when she started eating solid
(B) Absence of T lymphocytes
foods, but have significantly worsened over
(C) IgA, IgG, and IgM levels normal
the past few months. The only recent change
(D) IgG and IgM levels markedly decreased,
in her diet is that she eats a bowl of cereal ev-
no IgA
ery morning with her parents before they go to
(E) IgG and IgM levels normal, IgA markedly
work. She tried a dairy-free diet a month ago,
decreased
but it did not improve her symptoms. Which
of the following is the most likely diagnosis? 21. A 26-year-old woman presents to the clinic
with joint pain in her hands and wrists, diffi-
Immunology

culty breathing, and redness over her cheeks


and nose. She also notes that her fingertips
change color from white to blue to red when
she is cold. Which of the following describes
the renal pathology commonly associated with
this patients condition?
(A) Histopathology reveals glomerulonephritis
with subendothelial immune deposits evi-
dent on immunofluorescence electron mi-
croscopy
(B) It has a railroad track or tram track ap-
pearance on light microscopy
(C) It is a homogeneous renal disease
Reproduced, with permission, from USMLERx.com. (D) It is associated with elevated serum com-
plement levels
(E) It is immune mediated by anti-mitochon-
(A) Abetalipoproteinemia drial antibodies
(B) Celiac sprue
(C) Lactase deficiency 22. A clinician is concerned that an Rh-negative
(D) Viral enteritis mother may be pregnant with an Rh-positive
(E) Whipple disease fetus. The potential pathology that the clini-
cian is concerned about is classified as which
20. A pediatrician becomes concerned after learn- of the following immune reactions?
ing about the family and the medical history
(A) Graft-versus-host disease
of an 18-month-old child who is currently suf-
(B) Type I hypersensitivity
fering from pneumonia, with a presumed diag-
(C) Type II hypersensitivity
nosis of Streptococcus pneumoniae infection.
(D) Type III hypersensitivity
Over the past year, the patient has suffered
(E) Type IV hypersensitivity
from erysipelas as well as a previous bout of
pneumococcal pneumonia; both were treated 23. A 14-year-old boy presents to the physician
successfully with antibiotics. The patients with recurrent pyogenic infections. Physical
mother says that her sons maternal uncle also examination shows that the boy has pruritic
suffered from repeated bacterial infections and papulovesicular dermatitis. Laboratory tests
was successfully treated with antibiotics. On show low serum IgM level and a normal serum
physical examination, it appears that the pa-
High-Yield Principles
Chapter 5: Immunology Questions 107

IgG level. Which of the following laboratory (A) Lyme disease


abnormalities is most likely to also be present? (B) Pneumonia
(C) Sarcoidosis
(A) Hypocalcemia
(D) Systemic lupus erythematosus
(B) Low IgA level
(E) Tuberculosis
(C) Low IgE level
(D) Lymphopenia
25. A 58-year-old man presents to his physician be-
(E) Thrombocytopenia
cause of fatigue, edema, and worsening kidney
function. After extensive laboratory work-up,
24. A 30-year-old woman presents to the emer-
his physician decides to perform a kidney bi-
gency department with a right-sided facial
opsy. The pathologist notes numerous green-
droop and bilateral swelling on the face near
colored, proteinaceous deposits when he uses
the angles of the mandible. She reports that
polarized light microscopy to view the sample.
these signs occurred suddenly while she was at
Which of the following is most likely abnormal
home. On further questioning she says that for

Immunology
in this patient?
the past few weeks she has been feeling short
of breath and tired, and has had a dry cough. (A) C2
She denies any recent exposure to wooded (B) CD8
areas. Her temperature is 38.4C (101.2F), (C) Fab fragment
heart rate is 93/min, blood pressure is 110/85 (D) Ig light chain
mm Hg, respiratory rate is 22/min, and oxygen (E) Major histocompatibility complex II
saturation is 93% on room air. Physical exami-
nation reveals red, tearing eyes; smooth, non- 26. A 7-year-old boy is brought to the physician by
tender bulging of both cheeks; a right-sided his parents because of recurrent sinus infec-
drooping of the mouth; cervical nodes; and tions. The parents state that the boy also has
bilateral dry rles. Results of a purified protein had multiple lung infections and intermittent
derivative test are negative. X-ray of the chest diarrheal infections since birth. Which of the
is shown in the image. What process is most following results would most likely be found
likely to be causing this patients symptoms? on further testing?
(A) A high IgE level
(B) A low IgA level
(C) A low IgM level, with increased IgA
(D) A negative nitroblue tetrazolium dye test
(E) A normal immunoglobulin level for all iso-
types

27. A patient is administered a tuberculin test.


Which of the following types of hypersensitiv-
ity reaction is being tested, and which cells
would be expected to mediate a positive test re-
sult?
(A) Type I hypersensitivity, mast cells
(B) Type II hypersensitivity, cytotoxic T lym-
Reproduced, with permission, from USMLERx.com. phocytes
(C) Type IV hypersensitivity, mast cells
(D) Type IV hypersensitivity, T-helper 1 cells
(E) Type IV hypersensitivity, T-helper 2 cells
High-Yield Principles
108 Section I: General Principles Questions

28. A 24-year-old, previously healthy woman pre (A) A noninflamed skin abscess
sents to the outpatient clinic with a two-week (B) A repaired cleft palate
history of drooping eyelids and difficulty rising (C) Frequent falls
from a chair. Stimulation with a reversible ace- (D) Skin granulomas
tylcholinesterase inhibitor leads to the resolu- (E) Visual hallucinations
tion of her symptoms. Which of the following
is most responsible for the three-dimensional 30. A 50-year-old man comes to the physician with
structure of the key mediator in this womans hemoptysis and diffuse joint pain. He states
condition? that both his father and cousin had similar
symptoms and were diagnosed with micro-
(A) Disulfide bonds
scopic polyangiitis, a disease affecting me-
(B) Hydrogen bonds
dium- to small-sized arteries that is believed to
(C) Ionic bonds
have an autoimmune component to its patho-
(D) Triple covalent bonds
genesis. Antibody levels were measured to con-
(E) Van der Waals forces
Immunology

firm the diagnosis. What other disease is most


closely correlated with the same type of auto-
29. A 3-year-old boy is brought to his pediatrician
antibodies as present in this patient?
because of worsening cough and rhinorrhea.
His parents state that he has had multiple simi- (A) Churg-Strauss syndrome
lar episodes over the past year with two brief (B) CREST variant of scleroderma
hospitalizations for pneumonia. Physical ex- (C) Sjgren syndrome
amination of the skin reveals the lesion seen (D) Systemic lupus erythematosus
in the image. Laboratory tests show very low (E) Wegener granulomatosis
serum levels of IgA. Which of the following is
most likely to also be seen in this child?

Reproduced, with permission, from Wolff K, et al, Fitzpatricks


Color Atlas & Synopsis of Clinical Dermatology, 6th edition.
New York: McGraw-Hill, 2009.
High-Yield Principles
Chapter 5: Immunology Answers 109

An s w e r s

1. The correct answer is E. This patient suffers viral, and fungal infections. Treatment in-
from rejection of his recently transplanted cludes bone marrow transplantation.
organ. There are three types of rejection: hy-
Answer B is incorrect. Failure of the third
peracute, acute, and chronic. A hyperacute
and fourth pharyngeal pouches to descend is
rejection is mediated by pre-formed antibod-
known as DiGeorge syndrome, and results in
ies to the transplanted organ. In most cases,
no thymus or parathyroid glands. Chromo-
it can be observed while still in the operating
some 22q11 deletions are associated with Di-
theater. Acute rejection can occur at any time
George syndrome. Tetany from hypocalcemia
but is most likely in the first three months after
and viral and fungal infections are common
transplantation. It is due to human leukocyte
due to the lack of T lymphocytes, while nor-
antigen discrepancies between host and graft,
mal B lymphocytes are present.
and is more common in highly vascular organs

Immunology
such as the liver or kidney. Finally, chronic re- Answer C is incorrect. A CD40 ligand defect
jection is a slow process that leads to fibrosis of causes hyper-IgM syndrome, because the CD4
the transplanted tissue due to increased fibro- T-helper cells are unable to switch classes from
blast activity. This patient experienced acute IgM. Although these patients present with
rejection, which is mediated by cytotoxic T multiple infections such as pneumonia, sinus-
cells (CD8). itis, infectious diarrhea, and central nervous
system (CNS) infections, the most common
Answer A is incorrect. CD20 is a B-cell
laboratory finding is neutropenia, not low lev-
marker. Because they are a precursor to plasma
els of lymphocytes.
cells, they would only be indirectly involved in
hyperacute rejection. Answer D is incorrect. The lack of reduced
NADPH oxidase activity results in chronic
Answer B is incorrect. CD27 is a marker of
granulomatous disease. Staphylococcus aureus,
plasma cells. Plasma cells are responsible for
Escherichia coli, and Aspergillus are common
antibody production and therefore would be
pathogens. The nitroblue tetrazolium dye re-
the culprit in hyperacute rejections.
duction test shows no activity in these patients.
Answer C is incorrect. CD34 is a fibrocyte Because the question stem says that the ni-
marker. Fibrocytes leave the bloodstream and troblue tetrazolium dye test turned blue, this
differentiate into fibroblasts in the transplanted patient must have normal NADPH oxidase
organ. They are the cell type that leads to activity, and thus cannot have chronic granulo-
chronic rejection of the graft. matous disease.
Answer D is incorrect. CD4 is the marker of Answer E is incorrect. An X-linked tyrosine
T-helper cells. They do not attack pathogens kinase defect causes Bruton agammaglobulin-
or tissues and are not implicated in the pathol- emia, resulting in decreased levels of all im-
ogy of acute rejection and negative selection. munoglobulin molecules. Infections begin to
occur after the maternal IgG antibodies de-
2. The correct answer is A. Severe combined cline, typically after six months of life.
immunodeficiency can be caused by multiple
factors: failure to synthesize major histocom- 3. The correct answer is C. This patient has
patibility complex II antigens, defective inter- signs and symptoms of rheumatoid arthritis, a
leukin-2 receptors, or adenosine deaminase disorder of immune dysregulation. Many par-
deficiency. This defect in early stem cell differ- allel and sequential events occur within the
entiation results in a lack of T and B lympho- synovium to cause joint destruction, includ-
cytes. Without T and B lymphocytes, patients ing activation of T lymphocytes and release
are at significantly increased risk of bacterial, of many proinflammatory cytokines such as
High-Yield Principles
110 Section I: General Principles Answers

interleukin (IL) 1. Transforming growth fac- Answer B is incorrect. Kupffer cells are tissue-
tor-b plays a role in dampening the immune resident macrophages; the image depicts a
response, and in the case of rheumatoid ar- Langerhans cell.
thritis works as a reparative agent by inhibit-
Answer D is incorrect. Langerhans cells are
ing T lymphocyte activation and proliferation,
specialized, tissue-resident dendritic cells, not
inhibiting biosynthesis of metalloproteinases,
macrophages.
protecting cartilage from degradation by IL-1,
and inhibiting tumor necrosis factor secretion Answer E is incorrect. Microglia are tissue-
by macrophages. resident macrophages within the CNS.
Answer A is incorrect. Interferon- is secreted 5. The correct answer is D. When an Rh-
by helper T lymphocytes and helps stimulate negative mother gives birth to an Rh-positive
macrophages. fetus, fetal RBCs may enter the mothers circu-
Answer B is incorrect. IL-7 is secreted by mac- lation, and the body may recognize the Rh an-
Immunology

rophages and is one of the main cytokines in- tigen as foreign and produce antibodies against
volved in mounting an acute phase response. it. As maternal IgG freely crosses the placenta,
IL-7 has been shown to stimulate bone erosion any subsequent Rh-positive fetus is at risk for
in rheumatoid arthritis. hemolytic disease. Thus, the indirect Coombs
test is an important laboratory tool to monitor
Answer D is incorrect. Tumor necrosis
for Rh incompatibilities that may complicate
factor-a is one of the main cytokines involved
fetal health. The test result given in this ques-
in mounting an acute-phase response; it is se-
tion indicates that the patient possesses anti-Rh
creted by macrophages.
antibodies in her serum. Therefore, it would
Answer E is incorrect. Tumor necrosis fac- be logical for the clinician to suspect previous
tor-b has functions similar to tumor necrosis pregnancy with an Rh-positive fetus.
factor-a in that it helps mount an acute-phase
Answer A is incorrect. The laboratory protocol
response. However, it is secreted by activated T
described in the question stem is correct. Rh-
lymphocytes instead of macrophages.
positive RBCs must be added because the test
is assaying for the presence anti-Rh antibodies,
4. The correct answer is C. Dendritic cells arise
which will bind the Rh antigen on the RBCs.
from both myeloid and lymphoid bone mar-
row precursors and then establish sites of resi- Answer B is incorrect. The presence of anti-
dence within the peripheral tissues. Immature Rh antibodies within the patients serum sug-
dendritic cells located within the epidermis are gests that she has been exposed to the blood of
named Langerhans cells, and they are highly at least one Rh-positive fetus.
phagocytic. The exact function of Birbeck
Answer C is incorrect. The results of the test
granules is unknown, but they are present only
cannot be used to determine the Rh status of a
with Langerhans cells. Upon antigen encoun-
current fetus; only direct typing of fetal blood
ter, Langerhans cells upregulate costimulatory
can determine its Rh status.
molecules (such as major histocompatibil-
ity complex class II) and then migrate to the Answer E is incorrect. The test yielded a
draining lymph node, where they play an in- positive result. Agglutination occurs when the
tegral part in the activation of T lymphocytes anti-IgG antibody binds to the anti-Rh antibod-
and the subsequent induction of an adaptive ies that are already bound to the Rh-positive
immune response. RBCs.
Answer A is incorrect. Kupffer cells are tissue- 6. The correct answer is E. Vancomycin can
resident macrophages within the liver. cause two types of hypersensitivity reactions:
anaphylaxis, which is a type I hypersensitiv-
ity reaction, and the red man syndrome
High-Yield Principles
Chapter 5: Immunology Answers 111

(RMS), which is an anaphylactic reaction. 7. The correct answer is D. This child is suffer-
This patient most likely has RMS due to rapid ing from acute epiglottitis, caused by Hae-
infusion of vancomycin. Although her symp- mophilus influenzae type B (HiB). The inci-
toms also may be consistent with anaphylaxis, dence of this illness has decreased drastically
the patient has never been exposed to vanco- in recent years because of immunization ef-
mycin; therefore, she would not have pre- forts. The HiB vaccine consists of two parts:
formed IgE antibodies against the drug. By the bacterial capsule antigen and diphtheria
contrast, a vancomycin-induced anaphylactic toxoid protein. Because the bacterial capsule
reaction involves histamine release from mast is a polysaccharide, it alone will not generate a
cells and basophils without binding of pre- sufficient immune response. Therefore, a pro-
formed IgE antibodies to Fc receptors. RMS tein (the toxoid) is added to the vaccine in or-
can be prevented by slow infusion of vanco- der to generate an antibody response.
mycin, which is preferable to discontinuing
Answer A is incorrect. Whereas attachment
the drug. Another method of prevention is pre-
pili are an important virulence factor of H in-

Immunology
treatment with antihistamine.
fluenzae, they are not the reason why the vac-
Answer A is incorrect. Type II hypersensitiv- cine must contain a toxoid protein.
ity reactions are characterized by IgM or IgG
Answer B is incorrect. Whereas H influenzae
molecules binding to an antigen on a cell,
is a gram-negative rod, its Gram stain charac-
which leads to destruction of the cell via ac-
teristics do not play a role in the bodys ability
tivation of the complement cascade. Exam-
to generate antibodies against it.
ples include autoimmune hemolytic anemia,
Goodpasture syndrome, rheumatic fever, and Answer C is incorrect. IgA protease is an im-
Graves disease. portant virulence factor in H influenzae. It
functions to cleave IgA, which allows the bac-
Answer B is incorrect. Type I hypersensitivity
teria to colonize the mucosa. It does not, how-
reactions are mediated by pre-formed IgE anti-
ever, play a role in vaccination.
bodies that bind a particular antigen to which
the patient has already been exposed. Binding Answer E is incorrect. H influenzae does not
of the antigen-IgE complexes to Fc receptors generate protein A. This is a virulence factor
on mast cells results in degranulation and re- found in Staphylococcus aureus that binds the
lease of vasoactive substances such as hista- Fc portion of IgG and thus helps prevent opso-
mine. The reaction occurs rapidly after anti- nization.
gen exposure. Examples include anaphylaxis,
asthma, hives, wheals, and flare. 8. The correct answer is A. This clinical scenario
would result in hyperacute rejection (within
Answer C is incorrect. Type III hypersensitiv- minutes of transplantation; clinical presenta-
ity reactions involve antibodies binding to an- tion within minutes to hours) mediated by
tigen in plasma, leading to antibody-antigen pre-formed anti-donor antibodies in the recipi-
immune complexes. Examples include polyar- ent. The recipient would possess anti-type A
teritis nodosa, immune complex glomerulone- antibodies, which react to the A antigen pres-
phritis, lupus, rheumatoid arthritis, serum sick- ent not only on RBCs but on most other cell
ness, and the Arthus reaction (local complex types. Hyperacute rejection occurs almost im-
deposition). mediately, as the anti-donor antibodies bind
Answer D is incorrect. Type IV hypersensitiv- directly to vascular endothelial cells, initiating
ity reactions involve sensitized T lymphocytes complement and clotting cascades and result-
that encounter the antigen and release lym- ing in hemorrhage and necrosis of the trans-
phokines. Examples include a tuberculosis planted kidney. It should be noted that it is not
(TB) skin test, transplant rejection, and con- only ABO blood group mismatches but any
tact dermatitis (poison oak, poison ivy). anti-donor antibodies possessed by the recipi-
ent that can lead to hyperacute rejection; thus,
High-Yield Principles
112 Section I: General Principles Answers

it is important to carefully cross-match donor Answer D is incorrect. This pattern is charac-


and recipient. teristic of follicular lymphoma, not DiGeorge
syndrome.
Answer B is incorrect. Macrophages provide
a secondary immune response in this situation Answer E is incorrect. The medullary cords
but are not initially involved in acute or hyper- contain lymphocytes and plasma cells, and are
acute reactions. not usually affected in DiGeorge syndrome.
Answer C is incorrect. Hyperacute rejection
10. The correct answer is D. The smear would
is typically mediated by pre-formed anti-donor
have a hypersegmented neutrophil, classically
antibodies that are possessed by the recipient.
associated with vitamin B12 deficiency or fo-
Answer D is incorrect. Graft-versus-host dis- late deficiency. In this patients case, symptoms
ease (GVHD) is a serious adverse effect of and laboratory findings suggest a deficiency
bone marrow transplantation mediated by in vitamin B12, most likely resulting in perni-
donor-derived T lymphocytes. Acute GVHD cious anemia, given the patients age. Autoim-
Immunology

usually occurs within the first three months af- mune gastritis/pernicious anemia is associated
ter an allogeneic bone marrow transplantation, with two forms of autoantibodies: (1) antibod-
whereas chronic GVHD usually develops after ies directed against the transmembrane proton
the third month post-transplant. pumps of parietal cells (the cells that secrete
gastric acid and intrinsic factor [IF]) and (2)
Answer E is incorrect. Acute rejection is cell-
antibodies directed against IF itself. Parietal
mediated and occurs within weeks after trans-
cell autoantibodies lead to their destruction,
plantation of an organ that is major histocom-
thereby decreasing IF and acid production
patibility (MHC)-mismatched; rejection is the
(which then hinders vitamin B12 release from
result of cytotoxic T lymphocytes reacting to
food). IF autoantibodies, on the other hand,
foreign MHC molecules. In this scenario, hy-
prevent either the binding of vitamin B12 to IF,
peracute rejection would be expected to occur
or the binding of the vitamin B12-IF complex
first (within the first few hours after transplant).
to its receptor in the distal ileum. Symptoms of
9. The correct answer is B. This patients recur- vitamin B12 deficiency include fatigue, pallor,
rent viral and fungal infections and hypocalce- mild to moderated jaundice, glossitis (a pain-
mia are consistent with DiGeorge syndrome. ful, beefy tongue), and neuropathies (particu-
This condition is caused by the failure of de- larly of the lower extremities due to atrophy of
velopment of the third and fourth pharyngeal the posterior and lateral columns in the spi-
pouches, and thus the thymus and parathyroid nal cord). Serum levels of homocysteine and
glands. The recurrent viral and fungal infec- methylmalonic acid can be elevated, and a
tions are caused by a T-lymphocyte deficiency. complete blood cell count can show thrombo-
In lymph nodes, T lymphocytes are found in cytopenia. Vitamin B12 deficiency also causes
the paracortical region, thus this region is of- a megaloblastic anemia with hypersegmented
ten underdeveloped in patients with DiGeorge neutrophils on peripheral blood smear. Folate
syndrome. deficiency also results in a similar megaloblas-
tic anemia, although is not accompanied by
Answer A is incorrect. Follicles are areas of neurologic symptoms.
mostly B-lymphocyte aggregation, and are not
usually affected in DiGeorge syndrome. Answer A is incorrect. Acute blood loss would
result in a normocytic normochromic anemia.
Answer C is incorrect. The medullary sinuses However, this patient shows signs of vitamin
contain macrophages and communicate with B12 deficiency, which would result in a macro-
lymphatics. cytic anemia with polysegmented neutrophils
on peripheral blood smear.
High-Yield Principles
Chapter 5: Immunology Answers 113

Answer B is incorrect. Anemia of chronic dis- chemicals. IL-12 and IFN are not directly in-
ease results in a microcytic, hypochromic ane- volved.
mia (late manifestation) on peripheral blood
Answer D is incorrect. IFN-, IL-8, and C5a
smear with decreased serum iron levels and
are major chemotactic factors for neutrophils.
decreased total iron-binding capacity. This
Neutrophils are not antigen-presenting cells
patient shows signs of vitamin B12 deficiency,
and would not secrete IL-12.
which would result in a macrocytic anemia
with polysegmented neutrophils. 12. The correct answer is B. This patient is likely
Answer C is incorrect. Iron deficiency ane- suffering from one of the two major types of
mia can result in hypersegmented neutrophils scleroderma, known as CREST syndrome.
but also results in a microcytic, hypochromic The CREST acronym indicates the major
anemia (late manifestation) on peripheral symptoms: Calcinosis, Raynaud phenomenon,
blood smear with decreased serum iron and Esophageal dysmotility, Sclerodactyly, and
increased total iron-binding capacity. This Telangiectasia. Often, CREST syndrome pa-

Immunology
patient shows signs of vitamin B12 deficiency, tients test positive for anticentromere antibod-
which would result in a macrocytic anemia ies. The answer describes Raynaud phenom-
with polysegmented neutrophils. enon, which may be triggered by cold weather
or even emotional stimuli.
Answer E is incorrect. Pyridoxine deficiency
(vitamin B6), often caused by isoniazid ther- Answer A is incorrect. These symptoms are
apy, results in an acquired sideroblastic anemia not usually associated with CREST syndrome.
(often macrocytic, anisocytosis). However, this Answer C is incorrect. These symptoms are
patient shows signs of vitamin B12 deficiency, suggestive of Sjgren syndrome, not CREST
which would result in a macrocytic anemia syndrome.
with polysegmented neutrophils on peripheral
blood smear. Answer D is incorrect. This is not a symptom
usually associated with CREST syndrome.
11. The correct answer is A. The cell on the left Note that urethritis, conjunctivitis/anterior
is a macrophage and the cell on the right is uveitis, and arthritis make up the classic triad
a helper T cell. The image depicts a macro- in Reiter syndrome.
phage secreting interleukin-12 (IL-12), which Answer E is incorrect. This is not usually a
causes the nave helper T cell to differentiate hallmark of CREST syndrome but rather of
into a Th1 cell. In turn, the T cell secretes diffuse scleroderma. Note that diffuse sclero-
interferon- (IFN-), stimulating the macro- derma is associated with anti-Scl-70 antibody.
phage to increase antigen presentation and ly
sosome production. This series of events is an 13. The correct answer is C. This patient most
important mechanism for increasing killing of likely has hyper-IgM syndrome, which is
intracellular pathogens such as mycobacteria. caused by a defect in the CD40 ligand on
Answer B is incorrect. Eosinophils do not CD4 T helper cells. This defect leads to an in-
present antigens to Th1 cells and are not clasi- ability to class switch between the different im-
cally thought to secrete IL-12. Plasma levels munoglobulin isotypes. Since IgM is initially
of eosinophils increase in hypersensitivity dis- created and subsequently switched to the other
eases such as asthma and in parasitic infection. isotypes, an inability to do so leads to elevated
IgM levels and low levels of all other isotypes.
Answer C is incorrect. Basophils and mast Two prominent clinical problems are Pneumo-
cells are the primary mediators of the immedi- cystis jiroveci and neutropenia.
ate allergic, or type I, hypersensitivity reaction.
These cells are activated by attached IgE and Answer A is incorrect. Ataxia-telangiectasia
produce histamine and other inflammatory is caused by a defect in DNA repair enzymes.
The disease is associated with an IgA defi-
High-Yield Principles
114 Section I: General Principles Answers

ciency. The typical presentation of the disease body titer is usually a good indicator of disease
is given away by the name, as symptoms in- severity, particularly in Wegener granulomato-
clude cerebellar problems (ataxia) and spider sis, for which specificity and sensitivity of anti-
angiomas (telangiectasia). body testing are both >90%.
Answer B is incorrect. Leukocyte adhesion Answer A is incorrect. Kawasaki disease is not
deficiency syndrome is caused by a defect in associated with serum P-ANCA, and Buerger
the LFA-1 adhesion protein on the surface of disease is not associated with serum C-ANCA.
neutrophils. The disease usually presents with
Answer C is incorrect. Classic polyarteri-
marked leukocytosis and localized bacterial
tis nodosa is not associated with P-ANCA,
infections that are difficult to detect until they
and Buerger disease is not associated with
have progressed to an extensive life-threatening
C-ANCA.
level. Since neutrophils are unable to adhere
to the endothelium and transmigrate into tis- Answer D is incorrect. Takayasu arteritis is not
sues, infections in patients with leukocyte ad- associated with serum P-ANCA.
Immunology

hesion deficiency syndrome act similarly to Answer E is incorrect. Takayasu arteritis


those observed in neutropenic patients. is not associated with serum P-ANCA, and
Answer D is incorrect. Job syndrome in- Buerger disease is not associated with serum
volves the failure of helper T lymphocytes to C-ANCA.
produce interferon- (IFN-). Because IFN- Answer F is incorrect. Temporal arteritis is not
is a potent activator of phagocytic cells, a de- associated with serum P-ANCA.
crease in its production leads to a failure of
neutrophils to respond to chemotactic stimuli. 15. The correct answer is A. The image reveals
Job syndrome presents with recurrent staphy- Reed-Sternberg cells, which are found in
lococcal abscesses, eczema, and high levels of Hodgkin lymphoma and can be identified by
IgE. their distinctive owls eye bilobular nuclei.
Answer E is incorrect. In thymic aplasia (Di- Most studies support a B-lymphocyte origin for
George syndrome), the third and fourth pha- Reed-Sternberg cells. Evidence supporting this
ryngeal pouches, and thus the thymus and includes rearrangements at immunoglobulin
parathyroid glands, fail to develop. The disease gene loci and the expression of MHC class II
often presents with many congenital defects, and B7 molecules. Additionally, they are CD
such as cardiac abnormalities, cleft palate, and 30+ and CD 15+, but CD45-.
abnormal facies. Thymic aplasia can also pre Answer B is incorrect. Fibroblasts are elevated
sent with tetany due to hypocalcemia. in chronic inflammation and in granulation
tissue. Tumors that are derived from fibroblasts
14. The correct answer is B. Patients suffering are called fibrosarcomas.
from microscopic polyangiitis often have au-
toantibodies against the enzyme myeloperoxi- Answer C is incorrect. Activated macrophages
dase, which stains in a perinuclear pattern and tend to form granulomas, which are groups
is therefore commonly called P-ANCA (peri- of epithelial-like macrophages that are sur-
nuclear anti-neutrophil cytoplasmic antibody). rounded by a collar of mononuclear lympho-
Wegener granulomatosis is a vasculitis charac- cytes and plasma cells. They lack the owls-
terized by necrotizing granuloma formation eyes nuclei that characterize Reed-Sternberg
in the lungs and kidneys. These patients often cells.
have autoantibodies specific for proteinase-3, Answer D is incorrect. Neutrophil levels are
which stains in a cytoplasmic distribution and elevated in acute infection and inflammation.
is therefore commonly called C-ANCA (cyto- Their appearance is characterized by a three-
plasmic anti-neutrophil cytoplasmic antibody). to four-lobed nucleus and basophilic granules.
In both of these diseases, the patients autoanti-
High-Yield Principles
Chapter 5: Immunology Answers 115

Answer E is incorrect. T lymphocytes are el- immune system. Opsonins adhere to microor-
evated in T-lymphocyte leukemias such as ganisms and promote leukocyte chemoattrac-
T-cell acute lymphocytic leukemia and T-cell tion, antigen binding and phagocytosis, and
chronic lymphocytic leukemia. activation of macrophage and neutrophil kill-
ing mechanisms. The antibody IgG is also an
16. The correct answer is E. Juvenile rheumatoid opsonin, and C3b and IgG are the two primary
arthritis (JRA) may appear with a different pre- opsonins responsible for defense against bacte-
sentation than adult-onset rheumatoid arthritis ria.
(RA). By definition, JRA begins before age 16
Answer A is incorrect. IgA patrols mucosal
years and must include arthritis in at least one
barriers and prevents attachment of bacteria
joint for at least six weeks. Additionally, the
and viruses. It does not fix complement, nor is
morphologic joint pathology is similar to that
it an opsonin.
of adult-onset RA. However, there are several
signs and symptoms that occur more com- Answer B is incorrect. IgD is found on the

Immunology
monly in JRA than in adult-onset RA, includ- surface of many B lymphocytes and in the se-
ing an increased likelihood of systemic onset rum, but its function is unclear.
(with symptoms including high fevers, lymph-
Answer C is incorrect. IgE mediates immedi-
adenopathy, and hepatomegaly), large-joint in-
ate (type I) hypersensitivity and immunity to
volvement, and anti-nuclear antibody seroposi-
helminths by facilitating the activation of eo-
tivity. Furthermore, JRA patients are less likely
sinophils.
to have rheumatoid nodules and rheumatoid
factor. Answer E is incorrect. IgM fixes (activates)
complement but does not function by opso-
Answer A is incorrect. There are several signs
nization. It exists as a monomer on the surface
and symptoms that occur more commonly
of B lymphocytes, or as a pentamer in the se-
in JRA than in adult-onset RA, including in-
rum.
creased likelihood of systemic onset, increased
likelihood of large-joint involvement, and in- 18. The correct answer is A. This patient has be-
creased likelihood of anti-nuclear antibody se- come susceptible to opportunistic disease
ropositivity. Age at onset is <16 years. due to infection with HIV. Risk factors for
Answer B is incorrect. Systemic symptoms are contracting HIV include high-risk sexual be-
more likely, but high levels of serum rheuma- havior and intravenous drug use. HIV pref-
toid factor are less likely, in patients with JRA. erentially infects T-helper cells, which stain
positive for CD3 and CD4. However, CD3
Answer C is incorrect. Both systemic symp-
stains all T lymphocytes, while CD4 is spe-
toms and large-joint involvement are more
cific for T-helper cells. At this point in time,
likely in patients with JRA.
the patient can be diagnosed with AIDS based
Answer D is incorrect. Systemic symptoms are on the presence of AIDS-defining opportunis-
more likely, but high levels of serum rheuma- tic infections or by a CD4+ cell count <200/
toid factor are less likely, in patients with JRA. mm3. This patient should be started on highly
active antiretroviral therapy, which commonly
17. The correct answer is D. This patient has al- includes the nucleoside reverse transcriptase
ready had several bacterial infections, most inhibitor zidovudine.
notably an infection with Streptococcus pneu-
Answer B is incorrect. CD8 is specific for
moniae. Complement, part of the innate im-
cytotoxic T lymphocytes. HIV affects only
mune system, is a group of serum proteins that
T-helper cells and does not affect cytotoxic
work with antibody activity to eliminate patho-
T lymphocytes.
gens. Specifically, the protein C3b is respon-
sible for the opsonization of bacteria, and is Answer C is incorrect. CD20 is a marker that
likely the protein that is missing in this childs is specific for B lymphocytes, which are activated
High-Yield Principles
116 Section I: General Principles Answers

by T-helper cells. A person with HIV infec- 20. The correct answer is D. The infants fam-
tion will not be deficient in B lymphocytes. In ily history is suggestive of a trait with X-linked
fact, individuals with HIV may produce a large inheritance, and the preponderance of bacte-
amount of antibodies from B lymphocytes. rial infections suggests a defect in the humoral
(antibody-mediated) immune response. These
Answer D is incorrect. CD40 is found on B
two clues are most suggestive of a diagnosis of
lymphocytes. Costimulation with T lympho-
Bruton X-linked agammaglobulinemia. The
cytes occurs via the CD40 ligand and is re-
molecular defect occurs in a signaling mol-
quired for activation of B lymphocytes. CD40
ecule named BTK (Bruton tyrosine kinase),
is not found on T lymphocytes
leading to maturing arrest of developing B
Answer E is incorrect. CD56 is a marker that cells at the pre-B-cell stage. Arrest at the pre-
is specific for natural killer cells, which are un- B-cell stage would result in an inability to
affected in HIV infection. It should be noted produce immunoglobulins; thus, the patient
that natural killer cells are an important part of would have very low levels of all immunoglob-
Immunology

the bodys defense against tumors. ulins in his serum. In the first several months
of life, the infant can get by without problems
19. The correct answer is B. Celiac sprue is also because of the mothers IgG (still present).
known as gluten-sensitive enteropathy, non- Indeed, it should be noted that these patients
tropical sprue, and celiac disease. It is due to a are particularly susceptible to extracellular
sensitivity to gluten, which is found in wheat, pyogenic bacterial infections with organisms
grains, and many cereals. Biopsy shows marked such as Haemophilus influenzae, Streptococ-
atrophy, total loss, or flattening of the villi of cus pyogenes, Staphylococcus aureus, and
the small bowel. Streptococcus pneumoniae. The only physical
Answer A is incorrect. Abetalipoproteinemia finding for Bruton patients is the absence, or
is an autosomal recessive disease that causes a near absence, of tonsils and adenoids, which
defect in the synthesis and export of lipids by are B-cell-rich tissues. Patients diagnosed with
mucosal cells because of the inability to syn- Bruton will need to be treated with replace-
thesize apolipoprotein B. These patients usu- ment immunoglobulin.
ally have acanthocytes (or spur cells, RBCs Answer A is incorrect. A CD4 T-lymphocyte
that have spiny projections) and do not have count <200/mm3 suggests a diagnosis of AIDS,
any characteristic features of the intestine not an inherited genetic defect. Without any
found in celiac disease. indication that his mother has HIV, there
Answer C is incorrect. Lactase deficiency would be no reason to suspect HIV for the boy.
causes osmotic diarrhea from the inability to AIDS patients have a defect in cell-mediated
break down lactose into glucose and galactose. immunity, but the repeated bacterial infections
in this case indicate the patient has a defect in
Answer D is incorrect. Viral enteritis, usually humoral immunity.
caused by a rotavirus, is common in children
and can cause diarrhea. However, the clinical Answer B is incorrect. Absence of T lympho-
time course, suggested gluten sensitivity, and cytes would result in a defect in cell-mediated
findings on biopsy make viral enteritis unlikely. immunity, and the patient would be more
highly susceptible to viral and intracellular
Answer E is incorrect. Whipple disease usu- bacterial pathogens. Decreased T cells are
ally presents in middle-aged men who have seen in DiGeorge syndrome because of ab-
malabsorptive diarrhea, and the hallmark is the sence of thymus.
presence of periodic acid-Schiff-positive mac-
rophages in the intestinal mucosa. Rod-shaped Answer C is incorrect. The physical exami-
bacilli of the causal agent, Tropheryma whip- nation and family and patient history are all
pelii, are found on electron microscopy. highly suggestive of an immunoglobulin defi-
ciency.
High-Yield Principles
Chapter 5: Immunology Answers 117

Answer E is incorrect. Low serum IgA levels 22. The correct answer is C. This clinician is
are suggestive of selective IgA deficiency, the concerned that the fetus may have erythro-
most common inherited immunodeficiency blastosis fetalis (hemolytic disease of the new-
in the European population and, interestingly born). This disease is mediated by maternally
enough, one that appears to have no striking derived IgG anti-Rh antibodies developed in
disease associations. These patients may pro- Rh-negative mothers that are directed at the
duce autoantibodies to IgA that make them Rh antigen present on the fetal RBCs of a Rh+
susceptible to anaphylactic reactions when fetus in a previous pregnancy. If the mother
transfused with normal blood products con- possesses the antibodies developed from a pre-
taining IgA. vious exposure to an Rh+ fetus, they may cross
the placenta (antibodies of the IgG isotype
21. The correct answer is A. Systemic lupus ery- readily cross the placenta) and coat the fetal
thematosus (SLE) is a chronic autoimmune RBCs of a Rh+ fetus if the mother is now preg-
disease that affects multiple organ systems, nant with another Rh+ child. Antibody coating

Immunology
including the kidney. It presents with a vari- of the RBCs leads to phagocytosis of RBCs (via
ety of symptoms including arthropathy, malar Fc receptors) and/or destruction of the RBCs
rash, Raynaud phenomenon, and pleural and by the complement system and potentially fa-
pericardial effusions. SLE affects young adults tal anemia. This antibody-mediated cytotoxic
(women almost three times more than men) reaction is an example of a type II hypersensi-
and usually presents with a combined ne- tivity reaction.
phritic and nephrotic picture. Lupus nephrop-
Answer A is incorrect. Graft-versus-host dis-
athy is a heterogeneous renal disease that is a
ease is a potentially lethal side effect of bone
consequence of immune complexes deposited
marrow transplantation.
in the glomerulus. Anti-dsDNA antibodies and
low serum complement levels are markers for Answer B is incorrect. Type I hypersensitivity
renal involvement in lupus. Histologic sec- reactions are antibody-mediated but require
tions of biopsies from an SLE-affected kidney antigen binding to IgE, which is prebound to
have a peculiar wire-loop appearance with sub the surface of mast cells. Mast cell degranula-
endothelial basement membrane deposits. In tion then ensues. Examples include anaphy-
general, immunosuppressants are used to mini- laxis, asthma, hives, and local wheal and flare.
mize the inflammatory effects of lupus on the
Answer D is incorrect. Type III hypersensitiv-
kidney.
ity reactions are immune complex-mediated.
Answer B is incorrect. A tram track appear- Examples include polyarteritis nodosa, glomer-
ance is typically seen in membranoprolifera- ulonephritis, rheumatoid arthritis, and SLE.
tive glomerulonephritis.
Answer E is incorrect. Type IV hypersensitiv-
Answer C is incorrect. Lupus nephritis is con- ity reactions are a group of T-cell-mediated
sidered a heterogeneous renal disease that can pathologies. Examples include the tuberculin
have a variety of presentations including active skin test, transplant rejection, and contact der-
or inactive diffuse, segmental, or global glo- matitis.
merulonephritis.
23. The correct answer is E. This patient has
Answer D is incorrect. Immune complex de-
Wiskott-Aldrich syndrome, an X-linked disor-
position causes complement activation and
der resulting in the bodys inability to mount
leads to low serum complement levels.
an IgM response to bacteria. Recurrent pyo-
Answer E is incorrect. SLE is associated with genic infections, eczema, and thrombocytope-
anti-dsDNA and anti-Smith antibodies, not an- nia are the typical triad of symptoms. Wiscott-
timitochondrial antibodies. Aldrich syndrome does not present with any
specific enzyme abnormality.
High-Yield Principles
118 Section I: General Principles Answers

Answer A is incorrect. Hypocalcemia is char- infected bite, patients may develop erythema
acteristic of thymic aplasia (DiGeorge syn- migrans at the site of the bite and additional
drome), in which the third and fourth pha- annular lesions. They may also display symp-
ryngeal pouches, and thus the thymus and toms of cardiac and neurologic involvement,
parathyroid glands, fail to develop. As a result including first-degree heart block, myopericar-
patients may experience tetany. Thymic apla- ditis, meningitis, cerebellar ataxia, and seventh
sia often presents with congenital defects such nerve facial palsy. In addition, patients often
as cardiac abnormalities, cleft palate, and ab- experience a migratory musculoskeletal pain.
normal facies. They do not, however, experience respiratory
or ocular symptoms.
Answer B is incorrect. IgA levels are elevated
in Wiskott-Aldrich syndrome. They are low Answer B is incorrect. Pneumonia is an infec-
in hyper-IgM syndrome, ataxia-telangiectasia, tion of the lung involving the alveoli, intersti-
and in selective IgA deficiency. tia, and distal airways whereupon the alveoli
become consolidated with WBCs, RBCs, and
Immunology

Answer C is incorrect. IgE levels are elevated


fibrin. The patient with pneumonia may have
in Wiskott-Aldrich syndrome. They are low
fever, cough, and an increased respiratory
in hyper-IgM syndrome, in which B cells are
rate, as this patient does. However, physical
unable to class switch because of a defect in
exam would display findings of dullness to per-
helper T cells; these patients have high levels
cussion in a lobar distribution in addition to
of IgM and low IgG, IgA and IgE levels.
other breath sounds such as wheezes or rles,
Answer D is incorrect. Wiskott-Aldrich syn- and findings would be unlikely to be bilateral.
drome is characterized by thrombocytopenia Coughing often produces sputum.
and small platelets, rather than lymphopenia.
Answer D is incorrect. SLE is an autoimmune
Lymphopenia is typical of patients with severe
disease in which circulating antibodies and
combined immunodeficiency, who also have
immune complexes cause systemic damage
reduced levels of all immunoglobulin isotypes
to the body. SLE is most prevalent in women
and are infected early in life by opportunistic
and African-American people. Symptoms can
pathogens.
affect all organ systems and cause polyarthri-
24. The correct answer is C. Sarcoidosis is a sys- tis, malar rash, nephritis, vascular occlusions,
temic inflammatory process that involves an and pericarditis. Neurologic symptoms include
exaggerated Th1 immune response of un- headache, cognitive dysfunction, seizures, and
known etiology. It generally causes respiratory myelopathy, but seventh nerve involvement is
symptoms, with the appearance of hilar lymph- not particularly common. Pulmonary symp-
adenopathy and noncaseating granulomas toms usually manifest as a pleuritis with or
in the lungs, but can affect any organ system. without pleural effusion, but one would not
Acute sarcoidosis can develop suddenly over a see granulomas on radiography.
period of weeks, with both constitutional and Answer E is incorrect. TB is caused by the
respiratory symptoms. The Heerfordt-Walden- acid-fast bacterium Mycobacterium tuberculo-
strm syndrome of acute sarcoidosis includes sis, which produces a primary infection of the
the development of fever, parotid enlargement, lungs. Symptoms include fever, night sweats,
anterior uveitis, and facial nerve palsy, as seen malaise, weakness, and dry cough. Radiogra-
in this patient. Of the neurologic symptoms phy may reveal paratracheal or hilar lymph-
seen in sarcoidosis, seventh nerve involvement adenopathy, as in this patient. However, while
is the most common. it is possible that her nonpulmonary symptoms
Answer A is incorrect. Lyme disease is a multi- may occur with extrapulmonary TB, her puri-
system infection caused by the spirochete Bor- fied protein derivative test is negative, making
relia burgdorferi, carried by the Ixodes scapu- it less likely that she has been exposed to the
laris tick. Within the first few weeks after an bacterium.
High-Yield Principles
Chapter 5: Immunology Answers 119

25. The correct answer is D. This patient is likely normal IgG level is characteristic of Wiskott-
presenting with renal amyloidosis. (Remem- Aldrich syndrome. Wiskott-Aldrich syndrome
ber, amyloid deposits show apple-green bire- is an X-linked disorder that results in a reduced
fringence in polarized light). Clonal plasma IgM response to encapsulated bacteria. The
cells express abnormal amounts of light chain triad of symptoms consists of recurrent pyo-
protein. The organs most affected are the kid- genic infections, eczema, and thrombocytope-
neys and the heart. Symptoms include neurop- nia.
athy, proteinuria, edema, hepatosplenomegaly,
Answer D is incorrect. Normal immunoglobu-
and congestive heart failure.
lin levels and a negative nitroblue tetrazolium
Answer A is incorrect. C2 is a complement dye reduction test are characteristic of chronic
protein; complement is a system of proteins granulomatous disease. Chronic granuloma-
that aid in humoral immunity and inflamma- tous disease results from an NADPH oxidase
tion. It is not involved in amyloidosis patho- deficiency that reduces the ability of phago-
genesis. cytes to kill catalase-positive bacteria. It does

Immunology
not present with low levels of immunoglobu-
Answer B is incorrect. CD8 is a protein found
lins. The definitive test for this disorder is a
on cytotoxic T lymphocytes and is involved in
negative nitroblue tetrazolium dye reduction
immune response. It is not involved in amyloi-
test.
dosis.
Answer E is incorrect. Normal immunoglob-
Answer C is incorrect. The Fab fragment is
ulin levels can be seen in thymic aplasia (Di-
the part of the antibody that binds to the anti-
George syndrome). Thymic aplasia, in which
gen and includes both light and heavy chains.
the thymus and parathyroids fail to develop,
Amyloidosis is associated only with abnormal
results from the failure of the third and fourth
light chain protein.
pharyngeal pouches to develop. Consequently,
Answer E is incorrect. Major histocompatibil- T cells are completely absent. Patients with
ity complex II is a protein complex that is in- thymic aplasia typically present with recur-
volved in presenting antigens to immune cells. rent viral and fungal infections. They may also
It is not involved in amyloid protein deposi- have disorders of the great vessels and heart
tion. and may experience tetany due to hypocalce-
mia.
26. The correct answer is B. Selective immuno-
globulin deficiency is a deficit in a specific 27. The correct answer is D. Type IV hypersen-
class of immunoglobulins. IgA deficiency is sitivity reactions (also known as delayed-type
the most common of these. Because IgA is the hypersensitivity) are mediated by previously
most prominent immunoglobulin found in activated T-helper 1 (Th1) cells. These cells
mucous membranes, patients suffering from a recognize the TB-derived peptide and carbo-
deficiency of it can present with sinus and lung hydrate mixture that is administered during
infections. the tuberculin test. These Th1 cells become
Answer A is incorrect. A very high IgE level activated to secrete interferon- and tumor
and normal levels of all other immunoglobu- necrosis factor-b, which mediate a local in-
lins are characteristic of Job syndrome. Job flammatory response within 24-48 hours after
syndrome is a disorder of the immune system administration of the injection. These Th1 ef-
that involves the failure of helper T cells to fector cells are present only in individuals who
produce interferon-. It presents with multiple have previously been exposed to Mycobacte-
cold (or noninflamed) skin lesions and high rium tuberculosis or those who were vaccinated
IgE levels. with bacille Calmette-Gurin. It is important
to note that other type IV hypersensitivity reac-
Answer C is incorrect. A low IgM level in tions include celiac disease and contact hyper-
conjunction with an elevated IgA level and a sensitivities such as poison ivy.
High-Yield Principles
120 Section I: General Principles Answers

Answer A is incorrect. While mast cells are telangiectasia. Ataxia-telangiectasia is an auto-


involved in the pathogenesis of type I hyper- somal recessive disorder caused by a mutation
sensitivity reactions, the tuberculin test is an on chromosome 11q22-23 that results in a de-
example of a type IV reaction. fect in DNA repair enzymes. It manifests as a
variable combination of progressive neurologic
Answer B is incorrect. While cytotoxic T lym-
impairment, cerebellar ataxia, variable im-
phocytes are involved in the pathogenesis of
munodeficiency (usually IgA deficiency) with
type II hypersensitivity reactions, the tubercu-
susceptibility to sinopulmonary infections, im-
lin test is an example of a type IV reaction.
paired organ maturation, x-ray hypersensitivity,
Answer C is incorrect. Mast cells are not di- ocular and cutaneous telangiectasia, and a pre-
rectly involved in the pathogenesis of type IV disposition to malignancy.
hypersensitivity reactions.
Answer A is incorrect. A noninflamed or
Answer E is incorrect. While a positive tuber- cold abscess is characteristic of Job syndrome
culin test is an example of a type IV hypersen- which results from a failure of interferon-
Immunology

sitivity reaction, it is mediated by T-helper 1 production by helper T cells. The lack of


(Th1) cells, not Th2 cells. Th2 cells are those interferon- leads to the failure of the neutro-
that help the humoral (antibody-mediated) phil response to chemotactic stimuli. Patients
arm of the immune response. with Job syndrome present with eczema,
coarse facies, retained primary teeth, and high
28. The correct answer is A. The patient in this levels of IgE.
scenario has myasthenia gravis. This condition
is characterized by ptosis, limb weakness, and Answer B is incorrect. Cleft palate is a com-
difficulty breathing. The key mediator is an mon feature of thymic aplasia (DiGeorge syn-
autoantibody to the acetylcholine receptor on drome). Thymic aplasia results from failure of
the postsynaptic membrane. All antibody mol- the third and fourth pharyngeal pouches (and
ecules consist of two identical heavy chains thus the thymus and parathyroid glands) to de-
and two identical light chains that are held to- velop. The disease often presents with congeni-
gether by disulfide bonds. tal defects such as cardiac abnormalities, cleft
palate, and abnormal facies. Thymic aplasia
Answer B is incorrect. Hydrogen bonds are can also present with tetany due to hypocalce-
weaker than disulfide bonds and do not con- mia.
nect the antibody chains.
Answer D is incorrect. Granulomas are col-
Answer C is incorrect. Ionic bonds are found lections of cells seen in (among other things)
in chemicals such as sodium chloride but are chronic granulomatous disease. This disease
not responsible for holding antibody chains to- is caused by an inability of neutrophils to kill
gether. bacteria once they have phagocytosed them.
Answer D is incorrect. Triple covalent bonds Answer E is incorrect. Visual hallucinations
are seen between some atoms, such as nitro- are not a symptom of any of the known im-
gen, but are not responsible for holding the mune deficiencies.
chains of antibody molecules together.
Answer E is incorrect. Van der Waals forces 30. The correct answer is A. Microscopic poly-
are weak attraction forces and do not play a angiitis is one of the trio of diseases (with
significant role in holding antibody chains to- Wegener granulomatosis and Churg-Strauss
gether. syndrome) that are referred to as the ANCA
(antineutrophil cytoplasmic antibody)-asso-
29. The correct answer is C. The image shows ciated vasculitides. Over 80% of patients with
spider angiomas, which are common on this disease have ANCA, namely the peri-
the ears and cheeks of patients with ataxia- nuclear pattern of staining (P-ANCA) type.
Inflammation of the pulmonary capillaries,
High-Yield Principles
Chapter 5: Immunology Answers 121

which can lead to hemoptysis, is common in Answer D is incorrect. SLE is associated with
these patients, and 90% of patients have necro- anti-nuclear, anti-dsDNA, anti-Smith antibod-
tizing glomerulonephritis (leading to hematu- ies. None of these are particularly associated
ria). Other common symptoms include intesti- with microscopic polyangiitis.
nal pain/bleeding, muscle pain, and weakness.
Answer E is incorrect. While the clinical pre-
Churg-Strauss syndrome also involves the pul-
sentation is similar, Wegener granulomatosis is
monary vasculature and is associated with eo-
associated with cytoplasmic (not perinuclear)
sinophilia as well as elevated P-ANCA levels.
ANCA, which is not very common in patients
Answer B is incorrect. The CREST variant of with microscopic polyangiitis.
scleroderma is associated with anti-centromere
antibodies, which are not particularly associ-
ated with microscopic polyangiitis.
Answer C is incorrect. Sjgren syndrome is

Immunology
associated with antiribonucleoprotein (anti-
RNP) antibody SS-A (Ro), which is present
in 70%-95% of patients, and SS-B (La), which
is present in 60-90% of patients. Neither anti-
body is associated with microscopic polyangi-
itis.
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Chapter 6

Pathology

123
High-Yield Principles
124 Section I: General Principles Questions

Q u e st i o n s

1. A 19-year-old college student is admitted to the (C) Pseudopalisading tumor cells surrounding
hospital for bacterial meningitis. The patient necrotic regions
initially recovers and responds to treatment. (D) Sharply demarcated areas of tumor cells
However, later in her hospital stay she begins located at the grey-white matter junction
to experience headache and blurred vision. (E) Whorled pattern of concentrically ar-
Her physicians note cognitive decline and a ranged spindle cells with psammoma bod-
gait disturbance that was not evident during ies
her brief recovery phase. CT of the head shows
enlarged ventricles. Which of the following 3. A 43-year-old woman presents to her primary
mechanisms is most likely responsible for the care physician for a regular check-up. A neuro-
patients deterioration? logic examination shows that when the patient
looks to the left, the right eye stops at the mid-
Pathology

(A) Destruction of brain parenchyma


line and the left eye shows monocular horizon-
(B) Excessive cerebrospinal fluid production
tal nystagmus. When the patient looks to the
(C) Fusion of the cranial sutures
right, both eyes seem to move appropriately.
(D) Impaired cerebrospinal fluid resorption
Convergence is normal. What is the most
(E) Obstruction of the cerebral aqueduct
likely cause of this patients findings?
2. A 41-year-old man visits his physician because (A) Lesion of the left medial longitudinal fas-
of increasingly painful headaches. CT of the ciculus
head reveals an abnormality and an MRI of (B) Lesion of the left sixth cranial nerve
the brain with contrast (shown below) is per- (C) Lesion of the right medial longitudinal fas-
formed for further evaluation. If a biopsy of ciculus
this tumor were obtained, what would the pa- (D) Lesion of the right oculomotor nerve
thologist likely see under the microscope? (E) Pupillary light-near dissociation
(F) Relative afferent pupillary defect

4. A 22-year-old man presents to his primary care


physician with complaints of weakness and a
rash. Physical examination shows slight oral
mucosal bleeding and diffuse petechiae. He
has a history of generalized tonic-clonic sei-
zures that are well controlled with medication
but is otherwise healthy. Results of a bone mar-
row aspirate are shown in the image. Which
of the following is the most likely cause of his
symptoms?

Courtesy of Dr. Per-Lennart Westesson, University of Roches-


ter Medical Center.

(A) Densely packed cells with halos of cyto-


plasm surrounding large round nuclei
(B) Perivascular pseudorosettes with tumor
cells surrounding vessels
High-Yield Principles
Chapter 6: Pathology Questions 125

(A) Compared to the general population,


smoking would present an increased risk of
bronchogenic cancer in this patient
(B) Lungs in this patient will have silicotic
nodules
(C) The findings are associated with exposure
to air pollution
(D) The patient does not have an increased
risk of mesothelioma
(E) The patient has a condition associated
with increased tuberculosis susceptibility
(F) The patient will have localized intra-
alveolar fibrosis
Reproduced, with permission, from USMLERx.com.
6. A 7-year-old African-American boy is brought

Pathology
to the pediatricians office by his mother after
(A) Adverse drug reaction he begins crying inconsolably and complain-
(B) Alcoholism ing that his fingers hurt. His mother reports
(C) Idiopathic thrombocytopenic purpura that he had been playing in the sun all day
(D) Pernicious anemia long. A peripheral blood smear is shown in the
(E) Vitamin C deficiency image. Which of the following complications
is associated with this patients disease?
5. A 57-year-old man presents with a cough and
progressively increasing shortness of breath.
The patient has been a plumber for 20 years,
and before that job he worked on ships. High-
resolution CT reveals areas of pleural thicken-
ing with calcified plaques. A specially stained
specimen from a patient with a similar condi-
tion is shown in the image. Which of the fol-
lowing best describes the patients condition?

Courtesy of the Sickle Cell Foundation of Georgia: Jackie


George, Beverly Sinclair.

(A) Myelofibrosis
(B) Cyclical fevers
(C) Eosinophilia
(D) Microangiopathic hemolytic anemia
(E) Acute chest syndrome
Courtesy of Dr. Edwin P. Ewing Jr, Centers for Disease
Control and Prevention.
High-Yield Principles
126 Section I: General Principles Questions

7. A mother takes her previously healthy 7-year-


old son to the doctor because he appears
puffy. Physical examination reveals pitting
edema bilaterally in his lower limbs and swell-
ing of his eyelids. Urinalysis reveals a pH of 5
with 4+ proteinuria; glucose and ketones are
absent. What is most likely the cause of the pa-
tients edema?
(A) Congestive heart failure
(B) A thickening of the glomerular basement
membrane
(C) A loss of the negative charge in the glo-
merular filtration barrier
(D) Inadequate dietary protein Reproduced, with permission, from USMLERx.com.
Pathology

(E) Split glomerular basement membrane sec-


ondary to a mutation in type IV collagen
(A) To block attachment of bacteria and vi-
8. A 26-year-old woman visits her physician with ruses to mucous membranes
complaints of vaginal bleeding after sexual in- (B) To fix complement and serve as an antigen
tercourse. She started menses at age 14 years receptor on the surface of B lymphocytes
and has 32-day cycles. She acknowledges hav- in the primary immune response
ing unprotected sex with multiple partners. (C) To increase interleukin-2 receptor synthe-
Cytologic specimens are taken from the cervix sis by helper T-lymphocyte and B-lympho-
and vagina. On microscopy, cervical cells have cyte proliferation
large nuclei with open chromatin; several cells (D) To mediate a type I hypersensitivity reac-
have mitotic figures. What additional findings tion by causing the release of secretory
would most likely be present in the specimens products from basophils or mast cells
that account for these findings? (E) To opsonize bacteria, neutralize toxins and
viruses, and fix complement in the second-
(A) Double-stranded DNA virus
ary immune response
(B) Gram-negative diplococci
(F) To promote vasodilation and leukocyte ex-
(C) Gram-positive cocci
travasation
(D) Single-stranded RNA
(G) To stimulate growth of helper and cyto-
(E) Squamous cells covered with bacteria
toxic T lymphocytes
9. A 67-year-old man is admitted to the hospital
after fracturing the neck of his right femur. A
pathologic fracture is suspected. Serum pro-
tein electrophoresis shows an abnormal mono-
clonal paraprotein spike. Subsequent bone
marrow biopsy demonstrates an abnormal
proliferation of the cells shown in the image.
Which of the following describes the function
of the secretory product these cells normally
produce?
High-Yield Principles
Chapter 6: Pathology Questions 127

10. Autopsy of a patient shows bilaterally enlarged, 12. A 51-year-old man complains lately of recur-
cystic kidneys and a vascular lesion at the base rent vomiting. He cannot remember when it
of the brain, as seen in the image. Which chro- began, but he says he is concerned because
mosome was most likely mutated in the pa- sometimes he throws up blood. On physi-
tient? cal examination, there is some lower extrem-
ity edema, and some tortuous veins on the
surface of his abdomen. He admits to having
several recent sexual partners, and has never
been tested for sexually transmitted diseases.
He also reports drinking a few drinks a night.
Results of a liver biopsy are shown in the im-
age. Which of the following best describes the
pathologic process occurring in this patients
liver?

Pathology
Reproduced, with permission, from USMLERx.com.

(A) 4
(B) 15
(C) 16
(D) 22
(E) X

11. A 3-year-old developmentally delayed girl pre


sents to the pediatric neurologist for evalua-
Reproduced, with permission, from USMLERx.com.
tion of new onset seizures. The parents are also
concerned because the child frequently exhib-
its inappropriate outbursts of laughter. Physical (A) At this stage in disease, hepatocytes fail to
examination is significant for abnormal facies regenerate
marked by microcephaly, deep-set eyes, and (B) Lipid deposition is taking place
a large mouth with a protruding tongue. The (C) Mallory bodies are commonly seen in this
childs gait is unstable. The most likely diagno- condition
sis is an example of which of the following ge- (D) The architectural changes that are occur-
netic phenomena? ring are irreversible
(A) Anticipation (E) The liver will be enlarged
(B) Heteroplasmy
(C) Imprinting
(D) Locus heterozygosity
(E) Mosaicism
High-Yield Principles
128 Section I: General Principles Questions

13. A 55-year-old recent immigrant from Taiwan 15. A patient with AIDS and a CD4+ cell count
presents to the clinic with a three-month his- <50/mm3 is suffering from an infection that af-
tory of worsening nasal congestion, epistaxis, fects his lungs, eyes, gastrointestinal tract, and
and recurrent ear infections. Physical examina- central nervous system. Results of a biopsy are
tion reveals painless firm lymph node enlarge- shown in the image. With what is the patient
ment in the neck. CT of the head reveals a most likely infected?
large mass situated in the upper nasopharynx.
Biopsy of the lesion shows large epithelioid
cells intermixed with numerous infiltrating
lymphocytes. The infectious agent directly as-
sociated with this patients pathology is best de-
scribed by which category?
(A) DNA virus
(B) Eubacterium
Pathology

(C) Fungus
(D) Mycobacterium
(E) RNA virus

14. A 56-year-old man is admitted to the emer-


gency department with a chief complaint of se-
Courtesy of Dr. Edwin P. Ewing Jr, Centers for Disease Con-
vere abdominal and flank pain. The physician
trol and Prevention.
orders x-ray of the abdomen, as shown in the
image. The patients condition necessarily im-
plies which of the following? (A) Candida albicans
(B) Cryptococcus neoformans
(C) Cytomegalovirus
(D) Herpes simplex virus
(E) Mycobacterium avium
(F) Pneumocystis jiroveci

16. The attending pathologist reviews a hematoxy-


lin-eosin-stained slide from the liver biopsy of
a 50-year-old man suffering from dyspnea on
exertion, lower extremity edema, and orthop-
nea. In addition, the patient has recent onset
diabetes mellitus and testicular atrophy. One
of the patients four brothers also has the same
set of medical problems. The pathologist per-
forms one more study, which confirms the sus-
Reproduced, with permission, from USMLERx.com. pected diagnosis (see image). Which of the fol-
lowing is the most likely diagnosis?
(A) Acidic urine, pH <7.2
(B) Alkaline urine, pH >7.2
(C) Ammonium in the urinary tract
(D) Sodium chloride in the collecting ducts
(E) Uric acid in the renal pelvis
High-Yield Principles
Chapter 6: Pathology Questions 129

(A) APC
(B) BRCA1
(C) MSH2
(D) NF1
(E) p53

18. A 5-year-old boy presents with an unsteady gait


and severe vertigo and nausea. A brain lesion
is seen on CT scan. A biopsy of the lesion is
shown in the image. Where in the brain is the
patients lesion?

Reproduced, with permission, from USMLERx.com.

Pathology
(A) a1-Antitrypsin deficiency
(B) Alcoholic hepatitis
(C) Cystic fibrosis
(D) Hereditary hemochromatosis
(E) Wilson disease

17. A 37-year-old HIV-positive man presents for


evaluation of anogenital lesions. He states that
the lesions have been present for years, but
have recently grown in size and become pru-
ritic and tender. On examination he is circum- Reproduced, with permission, from USMLERx.com.
cised and has multiple hyperkeratotic papules
on his penis shaft, perineum, and anal area.
(A) Cerebellar vermis
He also has a palpable rectal mass with guaiac-
(B) Intermediate section of the cerebellar
positive stool and conjunctival pallor. On fur-
hemisphere
ther questioning, he admits to recent uninten-
(C) Lateral section of the cerebellar hemi-
tional weight loss, constipation, and bloating.
sphere
His CD4+ cell count is 150/mm3 and his he-
(D) Occipital cortex
matocrit is 26%. CT of the abdomen shows a
(E) Postcentral gyrus of the parietal lobe
3 4-cm rectal mass with multiple metastatic
lesions in his liver. What tumor-suppressor
protein is targeted by the virus causing this pa-
tients rectal cancer?
High-Yield Principles
130 Section I: General Principles Questions

19. A 64-year-old retired shipyard worker has been 20. A 12-year-old boy is brought to the doctor for
experiencing shortness of breath, a cough, and progressive fatigue and shortness of breath on
chest pain for five months. In that time he has exertion. He was born full term and has been
lost 14.5 kg (32 lb). He develops progressive as- generally healthy until a few months ago,
cites, and ultimately dies due to a pulmonary when his parents noticed that he became tired
embolus. Autopsy results are shown in the im- after only five minutes of playing with his sib-
age. Exposure to which substance is a risk fac- lings. Physical examination reveals a loud,
tor for this patients disorder? holosystolic murmur and mild cyanosis of his
lips. Examination of his hands reveals club-
bing of the fingers. Which of the following car-
diac defects is most likely to be found on echo-
cardiogram?
(A) Bicuspid aortic valve
(B) Left-to-right shunt
Pathology

(C) Mitral regurgitation


(D) Right-to-left shunt
(E) Valvular vegetations

Reproduced, with permission, from USMLERx.com.

(A) Aflatoxin B
(B) Asbestos
(C) Benzene
(D) Cadmium
(E) Silica
High-Yield Principles
Chapter 6: Pathology Answers 131

An s w e r s

1. The correct answer is D. The arachnoid gran- 2. The correct answer is C. This patient has a le-
ulations are outgrowths of the arachnoid mater sion consistent with glioblastoma multiforme
through the dura mater and into the superior (GBM), which is the most common primary
sagittal sinus. They are responsible for return- brain tumor. The MRI shows an irregular mass
ing fluid from the cerebrospinal fluid (CSF) lesion with avid peripheral contrast enhance-
into general circulation. Following irritation of ment and central hypoenhancement, which is
the meninges secondary to meningitis or sub- due to central necrosis suggestive of high-grade
arachnoid hemorrhage, the arachnoid granu- malignancy. Note the butterfly shape of the
lations may become scarred and fail to resorb lesion due to fact that it narrows as it passes
adequate CSF. This causes CSF to build up through the corpus collosum while crossing
in both the subarachnoid space and the ven- the midlinethis is a classic imaging finding
tricles, producing communicating hydrocepha- in GBM. On histopathology, the lesion con-

Pathology
lus. sists of highly malignant astrocyte tumor cells
that surround areas of necrosis; this is known
Answer A is incorrect. Enlarged ventricles are
as pseudopalisading. GBM has been associated
commonly seen in advanced neurodegenera-
with genetic alterations, including loss of p53
tive diseases such as Alzheimers. As brain mass
function, increased activity of the epidermal
is progressively lost, CSF accumulates to fill
growth factor receptor gene (EGFR), and loss
the void, a phenomenon known as hydroceph-
of heterozygosity on chromosome arm 10q.
alus ex vacuo. Substantial loss of brain paren-
GBM has a poor prognosis, with a mean sur-
chyma is not generally seen in meningitis and
vival of 8-10 months after diagnosis; most pa-
thus is an unlikely mechanism for the develop-
tients die within two years.
ment of hydrocephalus in this setting.
Answer A is incorrect. Densely packed cells
Answer B is incorrect. Overproduction of
with halos of cytoplasm surrounding large
CSF by the choroid plexus is an uncom-
round nuclei are characteristic of oligoden-
mon cause of hydrocephalus. It may occur in
drogliomas, which are slow-growing tumors
the setting of a choroid plexus papilloma but
originating in the cerebral hemispheres. These
would not be a consequence of meningitis.
lesions have a better prognosis than astrocyto-
Answer C is incorrect. Closure of the cranial mas, with a mean patient survival of 5-10 years.
sutures is a normal phenomenon that occurs as
Answer B is incorrect. Perivascular pseudo-
infants grow and is not responsible for the de-
rosettes with tumor cells surrounding vessels
velopment of hydrocephalus. In young infants,
are characteristic of ependymomas, which are
the flexibility of the cranium prior to suture fu-
tumors located in the periventricular space or
sion allows the head to enlarge noticeably in
in the spinal cord that may obstruct the flow of
the setting of hydrocephalus.
CSF.
Answer E is incorrect. Obstruction of the flow
Answer D is incorrect. Sharply demarcated
of CSF within the ventricular system leads to
areas of tumor cells located at the grey-white
noncommunicating hydrocephalus, in which
matter junction are characteristic of secondary
pressure builds up within the ventricles, but
metastatic lesions from a primary tumor else-
not in the subarachnoid space. Such obstruc-
where in the body, most commonly the breast,
tion is commonly the result of brain tumors
lung, thyroid, skin, kidney, and gastrointestinal
(particularly neoplasms of the ependymal cells
(GI) tract.
lining the ventricles), or congenital malforma-
tions. Answer E is incorrect. A whorled pattern of
concentrically arranged spindle cells with
calcified psammoma bodies is characteristic
High-Yield Principles
132 Section I: General Principles Answers

of meningiomas, which are the second most Answer E is incorrect. Pupillary light-near
common primary intracranial neoplasm. Me- dissociation is also known as Argyll Robertson
ningiomas are benign, slow-growing tumors of pupil and is an absent miotic reaction to light
the meninges. with preserved accommodation. This condi-
tion can occur in neurosyphilis, diabetes, and
3. The correct answer is C. The description is systemic lupus erythematosus.
consistent with internuclear ophthalmoplegia,
Answer F is incorrect. A relative afferent
which consists of ipsilateral medial rectus palsy
pupillary defect is also known as a Marcus
on attempted lateral conjugate gaze away from
Gunn pupil. It results from a lesion in the
the lesion with associated monocular hori-
afferent limb of the pupillary light reflex and
zontal nystagmus in the contralateral abduct-
can be seen in the retrobulbar neuritis of mul-
ing eye with preserved convergence. It results
tiple sclerosis. It would not result in medial
from damage to the ipsilateral medial longitu-
rectus palsy on attempted lateral conjugate
dinal fasciculus (MLF), which is the connec-
gaze.
tion between the abducent and oculomotor
Pathology

nuclei, so that the two nerves actions become


4. The correct answer is A. The bone marrow
unlinked. The third nerve and medial rectus
aspirate is hypocellular without any abnormal
muscle function normally in convergence but
cells, suggestive of aplastic anemia. Given the
not during actions that require conjugate eye
clinical history, this patients seizures were
movements. In young patients, it is most com-
likely treated with carbamazepine, which can
monly the result of central nervous system in-
cause aplastic anemia. Other causes of aplas-
fection or multiple sclerosis, whereas in older
tic anemia include viruses (Epstein-Barr virus,
patients it is more commonly the result of vas-
hepatitis C, and parvovirus B19), toxins (ben-
cular disease.
zene and insecticides), and other drugs (can-
Answer A is incorrect. A lesion of the left me- cer chemotherapeutics). Aplastic anemia can
dial longitudinal fasciculus (MLF) would pro- also be idiopathic.
duce an internuclear opthalmoplegia, as in
Answer B is incorrect. Alcoholism has many
this case. However, the findings of a left MLF
metabolic and clinical sequelae, including
lesion would include impaired left (ipsilateral)
decreases in all cell lines due to marrow sup-
eye adduction with rightward gaze as well as
pression. Therefore, this patients clinical pic-
right (contralateral) eye horizontal nystagmus.
ture could be explained by alcoholic cirrhosis.
The clinical description in the vignette is the
However, the hypoplastic bone marrow and
mirror image, consistent with a lesion of the
known antiepileptic drug use make the diagno-
right MLF.
sis of aplastic anemia most likely.
Answer B is incorrect. A pure sixth-nerve
Answer C is incorrect. This patient does have
palsy would have almost the opposite effect of
symptoms of thrombocytopenia, but the bone
this scenario and would cause a lateral rectus
marrow aspirate should appear normal in idio-
palsy as opposed to a medial rectus palsy seen
pathic thrombocytopenic purpura.
here.
Answer D is incorrect. Pernicious anemia,
Answer D is incorrect. Recall that cranial
the leading cause of megaloblastic anemia,
nerve (CN) III, or the oculomotor nerve, in-
does uncommonly occur in this age group.
nervates all the extraocular muscles with the
However, the bone marrow aspirate is not con-
exception of the lateral rectus (innervated by
sistent with pernicious anemia, as this disease
CN VI) and the superior oblique (innervated
does not affect neutrophils, platelets, or any
by CN IV). In a lesion of CN III the affected
myeloid cell line other than erythrocytes.
eye looks down and out while at rest, or ab-
ducted and depressed.
High-Yield Principles
Chapter 6: Pathology Answers 133

Answer E is incorrect. Although vitamin C is explained by a vasoocclusive crisis, a situa-


deficiency can cause gingival bleeding, it does tion in which sickled cells clog the microvas-
not cause anemia or a hypoplastic bone mar- culature and produce painful tissue ischemia.
row. Sickle cell anemia also is characterized by
splenic sequestration (with eventual functional
5. The correct answer is A. The image shows the asplenia and an increased risk for sepsis and
classic barbell ferruginous bodies seen in as- osteomyelitis), cerebrovascular accidents, and
bestosis. These bodies can only be seen when acute chest syndrome. Acute chest syndrome is
the slide is stained with Prussian blue. Asbes- a severe complication of vasoocclusive disease
tosis is most common in plumbers, construc- and presents with chest pain, hypoxemia, and
tion workers, and shipbuilders. Pleural plaques chest infiltrates. Because hypoxemia can insti-
are suggestive of asbestos exposure. Patients gate further sickling and pulmonary vasoocclu-
with asbestosis have an increased risk of bron- sion, acute chest syndrome is an indication for
chogenic carcinoma. This risk is compounded emergent exchange transfusion.
greatly by smoking, making smoking an even

Pathology
Answer A is incorrect. Myelofibrosis (agno-
riskier habit in someone with asbestosis.
genic myeloid metaplasia) is associated with
Answer B is incorrect. Silicotic nodules are teardrop cells and nucleated RBCs on periph-
seen in the lungs of patients with silicosis, eral blood smear. In this disorder, dysplastic
while ferruginous bodies and ivory-white pleu- megakaryocytes produce increased fibroblast
ral plaques are seen in lungs of patients with growth factors, leading to marrow fibrosis and
asbestosis. The ferruginous bodies can be de- marrow failure.
tected on biopsy by Prussian blue staining.
Answer B is incorrect. Cyclical fevers are
Answer C is incorrect. Anthracosis (carbon characteristic of malaria. Intracorpuscular
deposits) is seen in patients exposed to pollu- parasites would be anticipated on peripheral
tion (usually seen in city-dwellers). This would blood smear.
grossly look like black spots on the lung, and is
Answer C is incorrect. Eosinophilia is associ-
not considered to be pathologic.
ated with parasite infection and would not ex-
Answer D is incorrect. The patient has an in- plain the sickled cells seen in the image. In
creased risk of both mesothelioma and bron- addition parasite infections are associated more
chogenic carcinoma. often with iron deficiency anemia and fatigue,
Answer E is incorrect. Silicosis, a disease rather than with acute painful episodes.
caused by exposure to free silica dust, is associ- Answer D is incorrect. Microangiopathic he-
ated with increased tuberculosis susceptibility. molytic anemia is found in both disseminated
Asbestosis is not associated with this increased intravascular coagulation and thrombotic
susceptibility. thrombocytopenic purpura. Schistocytes (frag-
Answer F is incorrect. Lungs with asbesto- mented RBCs) are found on the blood smear.
sis have diffuse pulmonary interstitial fibrosis
7. The correct answer is C. The presentation
caused by inhaled asbestos fibers. The distribu-
described is typical of nephrotic syndrome.
tion is not localized or intra-alveolar.
Minimal change disease is the most common
6. The correct answer is E. This patients blood cause of nephrotic syndrome in children. It is
smear is strongly suggestive of sickle cell ane- characterized by a lack of abnormalities visible
mia, an autosomal recessive disorder caused by by light microscopy, and it usually does not in-
defective hemoglobin S (HbS). Hypoxic con- volve any abnormalities that can be seen using
ditions result in the polymerization and sick- immunofluorescence. Only when examined
ling of HbS, leading to vulnerable RBCs and with electron microscopy does the tissue show
hemolytic anemia. This patients history likely effacement of the foot processes of visceral epi-
thelial cells (podocytes). It is thought that the
High-Yield Principles
134 Section I: General Principles Answers

selective proteinuria that is present in minimal Answer C is incorrect. There are no gram-
change disease is caused by a loss of the fixed positive cocci associated with cervical cancer.
negative charge in the glomerular filtration
Answer D is incorrect. There is no single-
barrier. The disease usually responds to treat-
stranded virus associated with cervical cancer.
ment with steroids.
Answer E is incorrect. Squamous cells cov-
Answer A is incorrect. Edema is most often
ered with bacteria can be found in bacterial
caused by cirrhosis, nephrotic syndrome, or
vaginosis, which causes foul-smelling dis-
congestive heart failure (CHF). CHF in a
charge. There is no known association be-
child is uncommon. If the patient were to have
tween bacterial vaginosis and cervical cancer.
CHF, a different set of symptoms would be
seen, including exertional dyspnea and parox- 9. The correct answer is E. This patient most
ysmal nocturnal dyspnea. likely has multiple myeloma, a hematologic
Answer B is incorrect. Thickening of the glo- cancer in which the primary pathologic pro-
merular basement membrane (GBM) is seen cess is a neoplastic, monoclonal proliferation
Pathology

in patients with membranous glomerulopa- of plasma cells within the bone marrow. Com-
thy, which is a leading cause of nephrotic syn- mon manifestations of the disease include
drome in adults. It has characteristic findings bone pain, lytic bone lesions (which can lead
on light microscopy (thickening of the GBM), to pathologic fractures), renal insufficiency,
and this is in contrast with the lack of light mi- susceptibility to infection, and hypercalce-
croscope changes for minimal change disease. mia. The primary secretory product of the
plasma cells in multiple myeloma is IgG (55%
Answer D is incorrect. Urinalysis shows that
of cases). IgG functions to opsonize bacteria,
the patient is losing protein in the urine, and
neutralize toxins and viruses, and fix comple-
his physical appearance is not that of protein-
ment in the immune response.
calorie malnutrition.
Answer A is incorrect. This choice describes
Answer E is incorrect. The answer choice de-
the function of IgA, which blocks attachment
scribes Alport syndrome, which often causes
of bacteria and viruses to mucous membranes.
a nephritic syndrome with gross hematuria,
Although IgA also is produced by plasma cells,
but less significant protein loss. This child has
IgA-producing multiple myelomas comprise
significant edema, suggesting that a nephrotic
only 25% of all cases of multiple myeloma.
syndrome may be the culprit.
Answer B is incorrect. This choice describes
8. The correct answer is A. The findings on the function of IgM. Although IgM also is
microscopy indicate a malignant transforma- produced by plasma cells, IgM-producing
tion of normal cells. Increased nuclear-to- multiple myelomas are rare. Waldenstrm
cytoplasm ratio, open chromatin, and mitotic macroglobulinemia is an uncommon form of
figures indicate that cells are actively dividing. lymphoma that secretes monoclonal IgM para-
Given the patients history of multiple sexual protein. This condition, however, typically is
partners and postcoital bleeding, these cells not associated with bone lesions.
likely indicate the presence of cervical cancer.
Answer C is incorrect. This answer describes
Cervical cancer is commonly linked to human
the function of tumor necrosis factor-a, a criti-
papillomavirus infection. The virus can be iso-
cal inflammatory cytokine produced by macro-
lated during cytology through various meth-
phages.
ods. It is a double-stranded DNA virus.
Answer D is incorrect. This choice describes
Answer B is incorrect. Gram-negative diplo-
the function of IgE, which mediates type I hy-
cocci are not associated with cervical cancer.
persensitivity reactions. Multiple myelomas
However, they can be found in gonorrhea cer-
producing IgE are rare.
vicitis.
High-Yield Principles
Chapter 6: Pathology Answers 135

Answer F is incorrect. This answer describes mental retardation and speech impairment
the function of histamine, which is stored in are usually present, and 80%-90% of patients
granules in mast cells and basophils. It is re- have epilepsy. Angelman syndrome, along with
leased in response to the cross-linking of IgE Prader-Willi syndrome, is a classic example of
molecules on the surfaces of these cells. imprinting, which occurs when the phenotype
differs depending on whether the mutation is
Answer G is incorrect. This choice describes
of paternal or maternal origin. Deletions in
the function of interleukin-2, a cytokine that is
Prader-Willi syndrome, a phenotypically dis-
important in triggering the secondary immune
tinct disorder, occur exclusively on the pater-
response. It is produced by helper T lympho-
nal chromosome 15, whereas deletions at the
cytes rather than plasma cells.
same site of chromosome 15 on the maternal
10. The correct answer is C. The patient most chromosome result in Angelman syndrome.
likely had adult polycystic kidney disease Answer A is incorrect. Anticipation is the
(APKD). Eighty-five percent of patients with phenomenon in which the severity of a dis-

Pathology
this disease have a mutation in the PKD1 ease worsens in succeeding generations. This
gene, which is located on the short arm of occurs, for example, in triplet repeat diseases
chromosome 16. Patients with APKD suffer such as Huntington disease, wherein the trip-
from renal failure due to multiple, large cysts let repeat tends to lengthen, age of onset de-
in the kidney. These patients can also develop creases, and disease severity increases with
intracranial berry aneurysms (as seen in the successive generations. This does not occur in
image). Angelman syndrome.
Answer A is incorrect. Huntington disease is Answer B is incorrect. Heteroplasmy describes
caused by a nucleotide repeat expansion in the the presence of both normal and mutated mi-
Huntington gene on the short arm of chromo- tochondrial DNA. This phenomenon is re-
some 4. sponsible for the variable expression of mito-
Answer B is incorrect. Marfan syndrome is chondrial inherited diseases.
caused by a mutation in the fibrillin-1 gene on Answer D is incorrect. Locus heterozygosity
the long arm of chromosome 15. describes the phenomenon by which muta-
Answer D is incorrect. Neurofibromatosis type tions at different loci can result in the same
2 is caused by a mutation in the merlin tumor phenotype. An example of this is albinism,
suppressor gene on the long arm of chromo- which can be caused by a number of different
some 22. mutations.

Answer E is incorrect. Many diseases are due Answer E is incorrect. Mosaicism occurs
to mutations of the X chromosome. One ex- when cells in the body have different genetic
ample is fragile X syndrome, which is due to makeup. This sometimes occurs, for example,
a nucleotide repeat expansion in the FMR1 in Turner syndrome. This does not occur in
RNA-binding protein gene on the X chromo- Angelman syndrome.
some.
12. The correct answer is D. The image demon-
11. The correct answer is C. This child most strates micronodular cirrhosis, typically seen
likely has Angelman syndrome. Individuals with regenerative nodules with thick collag-
with this phenotype have a characteristic fa- enous septa. Some proliferation of bile ducts
cies with microcephaly, maxillary hypoplasia, is also seen. This microscopic view of the
deep-set eyes, and a large mouth with tongue liver is most consistent with cirrhosis. In end-
protrusion. Their gait is jerky and puppet- stage disease, it is often difficult to determine
like, and their behavior is marked by frequent the primary etiology, but the most common
paroxysms of inappropriate laughter. Severe cause in the Western World is alcoholic liver
disease (60-70% of cases), followed by viral
High-Yield Principles
136 Section I: General Principles Answers

hepatitis. An important feature of cirrhosis is 13. The correct answer is A. This patient has de-
that the normal architecture is disrupted. This veloped nasopharyngeal carcinoma, a condi-
can lead to impedance of blood and bile flow, tion common in certain parts of the world, in-
causing portal hypertension and/or cholestasis cluding Asia and Africa. Development of this
with jaundice. The early stages of alcoholic tumor is always associated with infection by
liver disease, such as steatosis (build-up of lipid Epstein-Barr virus (EBV), a DNA virus in the
droplets within cells) and alcoholic hepatitis, herpesvirus family. Development of this tumor
are reversible if alcohol use is discontinued. is believed to be related to a synergistic interac-
However, once the process of fibrosis begins, it tion between EBV and a diet high in carcino-
is irreversible. genic nitrosamines (common in foods that has
been smoked or preserved). Common symp-
Answer A is incorrect. In cirrhosis, hepatocyte
toms include nasal congestion, epistaxis, ear
regeneration continues between the fibrous
infections (due to tumor-induced blockage of
septae, forming uniform micronodules.
the eustachian tubes), and headache.
Thus, although the liver ultimately loses its
Pathology

function and normal architecture, regenera- Answer B is incorrect. Many bacteria are ca-
tion of hepatocytes still occurs. pable of infecting the nasopharynx; however,
none are directly associated with malignancy.
Answer B is incorrect. Steatosis is character-
ized by accumulation of lipid droplets within Answer C is incorrect. Nasopharyngeal zygo-
hepatocytes. This is a common characteris- mycosis is a condition that could present with
tic in many disease states such as alcoholic these symptoms in an immunocompromised
and nonalcoholic steatohepatitis, the latter of patient. However, biopsy would show filamen-
which is strongly associated with obesity and tous nonseptate hyphae and a granulomatous
hyperlipidemia. It is important to remember response.
that these disease states are often reversible
Answer D is incorrect. Although a tubercu-
when the offending agent (eg, alcohol use or
loma in the nasopharynx can be confused with
high serum lipid levels) is removed. However,
a nasopharyngeal tumor, biopsy would show
if untreated, these conditions can eventually
caseating granulomas with multinucleated gi-
progress to cirrhosis. Regenerative nodules and
ant cells.
fibrotic bands are not seen in steatosis.
Answer E is incorrect. Although a retrovirus
Answer C is incorrect. Mallory bodies, degen-
such as HIV can create an immunocompro-
erating hepatocytes full of eosinophilic cyto-
mised state favoring the development of a ma-
plasmic inclusions, are common in alcoholic
lignancy, it is not the direct cause of tumor
hepatitis. Alcoholic hepatitis is also character-
formation. Lymphomas can be associated with
ized by neutrophilic infiltrates, ballooning of
the retrovirus human T-cell lymphoma virus;
hepatocytes, and cytokeratin intermediate fila-
however, biopsy would show sheets of malig-
ments. However, the characteristic nodular re-
nant T lymphocytes typical of this lymphoma.
generation with scarring seen in cirrhosis is not
Other RNA viruses are not associated with ma-
a feature of alcoholic hepatitis. If alcohol use
lignancy.
continues over years, alcoholic hepatitis pro-
gresses to cirrhosis. However, Mallory bodies 14. The correct answer is B. The abdominal ra-
are rare in the cirrhotic liver. diograph shows staghorn renal calculus in
Answer E is incorrect. In alcoholic hepatitis, the left kidney. A stone that involves the renal
the fatty and inflamed liver will be larger than medulla and extends into at least two calyces
normal and usually weighs >2 kg. However, as is considered a staghorn calculus. Approxi-
cirrhosis develops over years of continued alco- mately three quarters of all staghorn calculi are
hol use, the liver becomes fibrotic and shrinks. caused by struvite stones. Struvite stones are
It can sometimes weigh as little as 1 kg. made up of a phosphate mineral that requires
an alkaline urine to precipitate.
High-Yield Principles
Chapter 6: Pathology Answers 137

Answer A is incorrect. Acidic urine would hin- Answer D is incorrect. Herpes simplex virus
der formation of staghorn calculi. in HIV-infected individuals can cause recur-
rent orolabial, genital, and perianal lesions. A
Answer C is incorrect. Presence of ammonia
Tzanck smear is positive for multinucleated
(not ammonium) in urine is a requirement for
epithelial giant cells. It does not cause the
formation of staghorn calculi, which allows
large intranuclear inclusion body shown.
for crystallization of magnesium ammonium
phosphate and carbonate apatite. Answer E is incorrect. Mycobacterium avium
causes lung disease in immunocompromised
Answer D is incorrect. Sodium chloride is not
hosts and is subsequently spread via the blood
usually a component of renal calculi and is not
to the liver, spleen, bone marrow, and other
required for their formation.
sites. Histology of mycobacterium is not con-
Answer E is incorrect. Uric acid is a com- sistent with this image. Rather, acid-fast stain-
ponent of some renal calculi but is not radi- ing would show organisms in foamy macro-
opaque and is not part of staghorn calculi. phages, granulomas, giant cells, and cells with

Pathology
eosinophilic necrosis.
15. The correct answer is C. The image shows
the typical large, round, intranuclear inclu- Answer F is incorrect. Pneumocystis jiroveci
sion with perinuclear halo that is seen in cells (formerly carinii) causes pneumonia in immu-
affected by cytomegalovirus (CMV) infec- nocompromised individuals.
tion. These structures are called owls eyes
16. The correct answer is D. Hereditary hemo-
due to their microscopic appearance. In im-
chromatosis is an iron-overload disease caused
munocompromised patients, CMV infection
by mutations in the HFE gene. Patients clas-
can present as retinitis, pneumonitis, inflam-
sically present with the triad of diabetes, cir-
mation along the GI tract, polyradiculopathy,
rhosis, and bronze skin pigmentation. This
transverse myelitis, and focal encephalitis. In
patient has many of the signs of advanced
patients with HIV/AIDS, these sequelae occur
hereditary hemochromatosis: diabetes due
most prominently when the CD4+ cell count
to pancreatic iron deposition, heart failure
is <100/mm3 or when the HIV viral load is
as a result of cardiac iron deposition, cirrho-
>10,000 copies/mm3. CMV can cause further
sis from hepatic iron deposition, and testicu-
immunosuppression, leading to other opportu-
lar atrophy as a result of dysfunction of the
nistic infections such as Pneumocystis and As-
hypothalamic-pituitary system from iron de-
pergillus pneumonia.
position. In addition, one of his siblings is also
Answer A is incorrect. Candida is a fungus affected, indicating the autosomal recessive
that produces a wide spectrum of diseases, nature of the disease. The brown granular pig-
ranging from superficial mucocutaneous dis- ment in hepatocytes seen in the image sug-
ease in immunocompetent hosts to invasive ill- gests hemosiderosis, but an iron stain (Prussian
nesses in immunocompromised hosts. Histol- blue) is also necessary because the brown pig-
ogy reveals round or ovoid yeast cells, hyphae, ment resembles lipofuscin in hematoxylin and
or pseudohyphae. eosin stains.
Answer B is incorrect. Cryptococcus neofor- Answer A is incorrect. a1-Antitrypsin de-
mans causes meningitis and meningoencepha- ficiency is due to mutations in the pro-
litis in patients with AIDS. This fungus is dif- tease inhibitor gene on chromosome 14.
ficult to observe with routine hematoxylin and a1-Antitrypsin is a protein produced in the
eosin stains, so methenamine silver or periodic liver and has a number of functions, the most
acid-Schiff stains are used to identify the char- common being protection of the lungs from
acteristic narrow-based buds and round-to-oval elastase, an enzyme produced by neutrophils.
yeast, surrounded by a polysaccharide capsule. Patients with a deficiency in this protein may
present with respiratory complaints and can
High-Yield Principles
138 Section I: General Principles Answers

develop emphysema. In some patients, cirrho- anorectal cancer, as seen here. Immunodefi-
sis may occur due to accumulation of a1-anti- ciency predisposes to the development of HPV-
trypsin in the liver. Histopathologic examina- induced transformation. The mechanism of
tion would not show brown granular pigment HPV-induced transformation involves the pro-
in hepatocytes. Rather, microscopic examina- duction of a viral protein, E6, which binds to
tion of a liver biopsy would show periodic acid a cellular ubiquitin ligase E6AP. On binding
Schiff-positive, diastase-resistant globules in to E6, E6AP polyubiquitinates the tumor sup-
hepatocytes. pressor p53, leading to dysregulated cell prolif-
eration and, eventually, oncogenesis.
Answer B is incorrect. Intracytoplasmic hya-
line inclusions derived from cytokeratin inter- Answer A is incorrect. APC is a tumor sup-
mediate filaments called Mallory bodies and pressor gene mutated in certain hereditary
microvesicular steatosis are common findings forms of colon cancer. The APC protein
in alcoholic hepatitis. Accumulation of iron is normally degrades the transcription factor
not associated with this condition. b-catenin, which is involved in colonic epithe-
Pathology

lial cell proliferation. In the absence of APC,


Answer C is incorrect. Cystic fibrosis is an
increased levels of b-catenin accumulate,
autosomal recessive disease caused by muta-
eventually leading to oncogenesis.
tions in the CFTR gene on chromosome 7.
This gene encodes for a chloride ion chan- Answer B is incorrect. BRCA1 is a tumor
nel. Patients typically present early in life with suppressor gene commonly mutated in he-
meconium ileus, multiple respiratory tract in- reditary forms of breast and ovarian cancers.
fections, or failure to thrive. Patients typically The BRCA1 protein functions in DNA repair
have a number of upper and lower pulmonary processes, and inherited mutations in BRCA1
manifestations, especially recurrent respiratory interfere with DNA repair, leading to the ac-
infections. Patients also have GI symptoms cumulation of mutations and, eventually, on-
due to insufficient release of pancreatic en- cogenesis.
zymes for digestion. This causes protein and fat
Answer C is incorrect. The MSH2 gene regu-
malabsorption, leading to steatorrhea and fat-
lates a mismatch repair enzyme and is mutated
soluble vitamin deficiencies.
in certain hereditary forms of colon cancer.
Answer E is incorrect. Wilson disease is an In the absence of MSH2, increased levels of
autosomal recessive disease of copper accumu- DNA mutations accumulate, leading to even-
lation in various tissues. It is due to mutations tual cellular transformation.
in the ATP7B gene, which encodes a copper-
Answer D is incorrect. NF1 is a tumor suppres-
transporting ATPase. Patients may have a vari-
sor gene mutated in neurofibromatosis type 1.
ety of hepatic manifestations, ranging from as-
The NF1 protein functions as a GTPase activat-
ymptomatic hepatomegaly to acute fulminant
ing protein for the small G protein Ras. Because
hepatitis. They also have neurologic manifes-
Ras is only active when it is GTP-bound, NF1-
tations such as tremor, dysarthria, or gait ab-
mediated GTP hydrolysis leads to inactivation
normalities. Psychiatric manifestations, such
of Ras. In the absence of NF1, Ras is hyperac-
as mood or personality changes, are also com-
tive, leading to enhanced growth factor signal
mon, and Kayser-Fleischer rings are evident
transduction and, eventually, oncogenesis.
on ophthalmic exam in almost all patients.
This patients liver biopsy does not show any 18. The correct answer is A. The boys brain bi-
changes specific to Wilson disease. opsy demonstrates medulloblastoma. This is a
poorly differentiated neuroectodermal tumor
17. The correct answer is E. This HIV-positive pa-
that occurs predominantly in children and
tient has multiple anogenital warts, or condylo-
exclusively in the cerebellum. The cerebellar
mata acuminata, which are caused by human
vermis is the medial section of the cerebellum
papillomavirus (HPV) types 6 and 11. A feared
and is responsible for proximal muscle coordi-
complication of condylomata acuminata is
High-Yield Principles
Chapter 6: Pathology Answers 139

nation, balance, and vestibulo-ocular reflexes. Answer A is incorrect. Aflatoxin B is produced


As seen in this patient, lesions of the vermis by Aspergillus and is a common contaminant
lead to vertigo, nausea, and difficulties in co- of cereals, spices, and nuts. It has been associ-
ordinating movement of trunk and proximal ated with carcinoma of the liver.
limb muscles. The presence of medulloblas-
Answer C is incorrect. Long-term exposure to
toma commonly leads to obstruction of the
high levels of benzene can lead to leukemia
outflow of CSF and the potential for hydro-
and Hodgkin lymphoma. Benzene is the main
cephalus, a life-threatening condition.
component of light oil, and is found in gaso-
Answer B is incorrect. Medulloblastomas arise line and other fuels.
in the midline of the cerebellum in children.
Answer D is incorrect. Cadmium is a carcino-
The intermediate section of the cerebellar
gen associated with the development of pros-
hemisphere is more lateral than the vermis.
tate cancer. It can be found in batteries and in
Lesions in the intermediate section would
metal coatings.
cause deficits in coordinating movements of

Pathology
the ipsilateral distal extremities, not the vertigo Answer E is incorrect. Exposure to silica may
and proximal limb problems seen in this pa- occur in the manufacturing of several mate-
tient. rials, such as glass, ceramics, and electron-
ics. Silicosis is characterized by bilateral, fine
Answer C is incorrect. Medulloblastomas
nodularity in the upper lung lobes. It is slowly
arise in the midline of the cerebellum in chil-
progressive. Its role as a carcinogen is contro-
dren. Lesions of the lateral hemisphere would
versial.
likely cause deficits in planning movements of
the ipsilateral distal extremities, not the vertigo 20. The correct answer is D. This boy most likely
and proximal limb problems seen in this pa- suffers from Eisenmenger syndrome, which is
tient. demonstrated by the cyanosis and digital club-
Answer D is incorrect. Medulloblastomas bing. In Eisenmenger syndrome a ventricular
arise in the midline of the cerebellum in chil- septal defect (VSD), atrial septal defect (ASD),
dren, not in the occipital cortex. Occipital cor- or patent ductus arteriosus causes a left-to-right
tex lesions could lead to defects in vision, not shunt and thus an acyanotic lesion, which is
the vertigo and proximal limb problems seen why he has been asymptomatic for much of his
in this patient. life. Over time the uncorrected shunt reverses
as the right ventricle hypertrophies in response
Answer E is incorrect. Medulloblastomas arise
to increased pulmonary vascular resistance,
in the midline of the cerebellum in children,
and becomes a right-to-left shunt and thus acy-
not in the parietal cortex. The postcentral gy-
anotic heart disease. The resultant low blood
rus of the parietal lobe is the primary somato-
oxygen levels can lead to the development of
sensory cortex. Lesions of this area would
exercise intolerance, cyanosis, and clubbing of
cause sensory deficits, not the vertigo and prox-
the fingers as seen in this patient.
imal limb problems seen in this patient.
Answer A is incorrect. Patients with bicuspid
19. The correct answer is B. This image demon- aortic valves often have no symptoms, but later
strates an advanced case of mesothelioma, dif- in life the valve can become calcified, leading
fusely involving the pleura and encasing lung to premature aortic stenosis in the fifth and
parenchyma. The clinical history supports this sixth decades. However, bicuspid aortic valve
diagnosis. Asbestos is present in certain build- is an unlikely cause of symptoms such as cya-
ing materials and fire-resistant materials, and nosis and clubbing in a 12-year-old child.
exposure to asbestos is a risk factor for the de-
velopment of mesothelioma.
High-Yield Principles
140 Section I: General Principles Answers

Answer B is incorrect. Before the develop- Answer E is incorrect. A holosystolic murmur


ment of Eisenmenger syndrome, congenital may be heard in the setting of endocarditis,
defects such as VSD, ASD, and patent ductus and valvular vegetations would be seen on
arteriosus produced a left-to-right shunt. How- echocardiogram. However, this would not ex-
ever, this boys symptoms indicate that the di- plain the boys other symptoms.
rection of the shunt has reversed.
Answer C is incorrect. Mitral regurgitation
classically produces a holosystolic murmur that
radiates to the axilla. Although chronic mitral
regurgitation can lead to CHF, it is an unlikely
cause of symptoms such as cyanosis and club-
bing in a 12-year-old child.
Pathology
Chapter 7

Pharmacology

141
High-Yield Principles
142 Section I: General Principles Questions

Q u e st i o n s

1. AIDS is currently managed with highly active tient gastric emptying study shows esophageal
anti-retroviral therapy, combining a series of dysmotility. The best treatment option for this
medications to overwhelm the virus and min- patient is which of the following?
imize its ability to form resistance to any one
(A) Esophageal resection
of the medications. Currently, protease inhibi-
(B) Metoclopramide
tors, nucleoside reverse transcriptase inhibi-
(C) Omeprazole
tors, and non-nucleoside reverse transcriptase
(D) Ondansetron
inhibitors are three types of medications that
(E) Vagotomy
can be used in combination. Which of the fol-
lowing is a non-competitive reverse transcrip- 4. Patients with hyperthyroidism have several op-
tase inhibitor? tions to treat their disease, including subtotal
Pharmacology

(A) Didanosine thyroidectomy and radioactive ablation. When


(B) Lamivudine a patient is unwilling or unable to undergo
(C) Nevirapine these procedures, pharmacological therapy is
(D) Saquinavir often pursued. One particular medication in-
(E) Zidovudine hibits the conversion of iodide to iodine and
inhibits the organification of iodine with tyro-
2. A patient is being treated with b-blockers sine. Which of the following is an additional
for hypertension. Which of the following mechanism of action of this drug?
describes the effects of b-blockers on end-
(A) Permanently reducing thyroid activity
diastolic volume (EDV), blood pressure (BP),
(B) Binding to and blocking the iodide trans-
contractility, heart rate (HR), and ejection
port mechanism of thyroid follicular cells
time?
(C) Binding to intracellular nuclear receptors
of peripheral tissue and activating genes
Choice EDV BP Contractility HR Ejection time (D) Blocking the peripheral conversion of thy-
A no effect or little/no effect little/no effect roxine to triiodothyronine
B (E) Inhibiting the binding of thyroxine to
C thyroid-binding globulin
D
E 5. A 36-year-old man who works at an explo-
sives factory comes to the clinic for an annual
Reproduced, with permission, from USMLERx.com. check-up. He is concerned about long-term
exposure to industrial chemicals. He reports
that although he is in excellent health other-
(A) A wise, he experiences headaches, dizziness, and
(B) B palpitations every Monday. Laboratory studies
(C) C show:
(D) D
(E) E WBC count: 8000/mm3
Hematocrit: 46%
3. A 68-year-old woman with type 2 diabetes mel- Hemoglobin: 15 g/dL
litus and a 30-pound weight loss over the past Platelet count: 310,000/mm3
two months presents to the physician with a Na+: 137 mEq/L
history of nause