I-1. and I-2. The answers are C and C. (Chap. 3) In evaluating the usefulness of a test, it is
imperative to understand the clinical implications of the sensitivity and specificity of that
test. By obtaining information about the prevalence of the disease in the population—the
specificity and sensitivity—one can generate a two-by-two table, as shown below. This table
is used to generate the total number of patients in each group of the population:
The sensitivity of the test is TP/(TP + FN). The specificity is TN/(TN + FP). In this case
the table is filled in as follows:
I-3. The answer is A. (Chap. 3) A capitation system provides physicians with a fixed payment
per patient per year. This has the potential to encourage physicians to take on more
patients but to provide patients with fewer services because the physician is liable for
expenses. A fixed salary system encourages physicians to take on fewer patients. A fee-forservice
system encourages physicians to provide more services. Out-of-pocket services not
covered by insurers are available only to patients with adequate means to receive the service.
I-4. The answer is C. (Chap. 3) A receiver operating characteristic curve plots sensitivity on
the y-axis and (1 – specificity) on the x-axis. Each point on the curve represents a cutoff
point of sensitivity and 1 – specificity. The area under the curve can be used as a quantitative
measure of the information content of a test. Values range from 0.5 (a 45° line) representing
no diagnostic information to 1.0 for a perfect test. See Figure I-4.
I-5. The answer is A. (Chap. 3) Bayes’ theorem is used in an attempt to quantify uncertainty
by employing an equation that combines pretest probability with the testing characteristics
of specificity and sensitivity. The pretest probability quantitatively describes
the clinician’s certainty of a diagnosis after doing a history and physical examination. The
Test Result Present Absent
Positive True-positive False-positive
Negative False-negative True-negative
Total number of patients with disease Total number of patients without disease
Test Result Present Absent
Positive 42 237
Negative 8 713
Total number of patients with disease
Total number of patients without disease
Posttest probability Pretest probability ﾗ test sensitivity
Pretest probability ﾗ test sensitivity +
(1 – disease prevalence) ﾗ test false-positive rate
In this manner, the uncertainty one faces in clinical decision making is quantified. By inserting
numbers into the equation, one can see that a low pretest probability combined
with a poorly sensitive and specific test will yield a low posttest probability. However, the
same test result, when combined with a high pretest probability, will yield a high posttest
probability. There have been criticisms of this theorem. Unfortunately, few tests have
only two outcomes: positive and negative. This theorem does not take into account the
useful information that is gained from nonbinary test results. Further, it is cumbersome
to calculate the posttest probability for each individual circumstance and patient. Perhaps
the most useful lesson from Bayes’ theorem is to take into account pretest probability
when ordering tests or interpreting test results. To be clinically useful, a clinical scenario
with a low pretest probability will require a test with high sensitivity and specificity. Conversely,
a high pretest probability presentation can be confirmed by a test with only average
sensitivity and specificity.
I-6. The answer is D. (Chap. 3) A positive likelihood ratio can only be interpreted in the
context of a pretest probability of disease. Disease prevalence in a certain region contributes
to the patient’s pretest probability. However, other factors such as the patient’s age,
clinical history and risk factors for the disease in question are also important in determining
pretest probability. Armed with an estimated pretest probability and a positive
test with a known likelihood ratio, the clinician can estimate a posttest probability of disease.
Generally, diagnostic tests are most useful in patients with a medium pretest probability
(25–75%) of having a disease. For example, in a patient with a low pretest
probability of disease, a positive test can be misleading in that the patient’s posttest probability
of disease is still low. The same applies for a patient with a high pretest probability
of disease with a negative test: the negative test usually does not rule out disease. It is
therefore incumbent upon the physician to have a rough estimate of the pretest probability
of disease, positive likelihood ratio of the diagnostic test, and negative likelihood ratio
of the diagnostic test prior to ordering the test.
I-7. and. I-8. The answers are B and C. (Chap. 3) The goal of a meta-analysis is to summarize
the treatment benefit conferred by an intervention. Risk reduction is frequently expressed
by relative risk or odds ratios; however, clinicians also find it useful to be familiar with the
absolute risk reduction (ARR). This is the difference in mortality (or another endpoint)
between the treatment and the placebo arms. In this case, the absolute risk reduction is
10% – 2% = 8%. From this number, one can calculate the number needed to treat
(NNT), which is 1/ARR. The NNT is the number of patients who must receive the intervention
to prevent one death (or another outcome assessed in the study). In this case the
NNT is 1/8% = 12.5 patients.
FIGURE I-4 The receiver operating characteristic
(ROC) curves for three diagnostic exercise tests for detection
of CAD: exercise ECG, exercise SPECT, and exercise
echo. Each ROC curve illustrates the trade-off
that occurs between improved test sensitivity (accurate
detection of patients with disease) and improved test
specificity (accurate detection of patients without disease),
as the test value defining when the test turns
from “negative” to “positive” is varied. A 45° line would
indicate a test with no information (sensitivity = specificity
at every test value). The area under each ROC
curve is a measure of the information content of the
test. Moving to a test with a larger ROC area (e.g., from
exercise ECG to exercise echo) improves diagnostic accuracy.
However, these curves are not measured in the
same populations and the effect of referral biases on the
results cannot easily be discerned. (From KE Fleischmann
et al: JAMA 280:913, 1998, with permission.)
False-positive rate (1 – specificity)
True-positive rate (1 – sensitivity)
0.0 0.2 0.4 0.6 0.8 1.0
20 I. INTRODUCTION TO CLINICAL MEDICINE — ANSWERS
I-9. The answer is D. (Chaps. 3 and 219) Based on her age and history, the patient’s pretest
probability of coronary artery disease is extremely low. Even though the SPECT scan is a
test with good performance characteristics, a positive test is only meaningful in a patient
with medium pretest probability of coronary disease. This patient’s posttest probability of
coronary disease is still low to medium. The test should not have been ordered in the first
place and is an example of defensive medicine. Any further testing could expose the patient
to undue invasive testing and further anxiety. Her aspirin should be stopped; she should be
reassured; other causes of chest pain in a healthy young woman should be evaluated.
I-10. The answer is C. (Chap. 6) Alzheimer’s disease (AD) affects women twice as commonly
as men. Women with AD have lower levels of circulating estrogen than agecontrolled
women without disease. Despite this, placebo-controlled trials have shown no
benefit in terms of cognitive decline for estrogen replacement in women with AD.
I-11. The answer is D. (Chap. 54) Men more commonly present with ventricular tachycardia
and women more commonly present with cardiogenic shock after MI. Younger women with
MI are more likely to die than their male counterparts of similar age. This may be partly related
to the observation that physicians are less likely to suspect heart disease in women with
chest pain and are less likely to perform diagnostic and therapeutic procedures in women.
I-12. The answer is D. (Chap. 6) Exercise electrocardiographic testing has both higher false
positives and false negatives in women than in men. Women with myocardial infarctions
less often receive angioplasty, thrombolytics, aspirin, beta blockers, or CABGs than men.
While women have a greater perioperative mortality, lower graft patency rate, and less
angina relief than men after CABG, their 5- and 10-year mortality rates are not different
from those of men.
I-13. The answer is D. (Chap. 6) Aspirin does not provide primary prevention for myocardial
infarction for women with coronary heart disease, but it does provide primary prevention
for ischemic stroke and is therefore a useful drug for women at risk for
atherosclerotic disease. Cholesterol-lowering drugs are as effective in women as in men
for primary and secondary prevention of coronary heart disease. Low HDL and diabetes
mellitus are more important risk factors in women than in men. Overall, women receive
fewer risk modification interventions than men, likely because of the perception that they
are at lower risk of coronary heart disease.
I-14. The answer is C. (Chap. 10) Echinacea constituents have in vitro activity to stimulate
humoral and cellular immune responses. Yet clinical trials have not shown convincing efficacy
for respiratory infections. Ginkgo biloba is being evaluated in a large trial to evaluate
its efficacy in reducing the rate of onset or progression of dementia. However, there is
no current evidence that it improves cognition. Saw palmetto and African plum are
widely purchased by Americans to relieve symptomatic BPH, yet clinical trials of saw palmetto
have not shown efficacy. While St.-John’s-wort showed benefit in small and noncontrolled
trials, high-quality placebo-controlled trials showed no superiority compared
to placebo for patients with major depression of moderate severity. Only glucosamine/
chondroitin sulfate have proven benefit in a large multicenter controlled trial. It is not
known if it slows cartilage degeneration.
I-15. The answer is D. (Chap. 5) Steady-state serum levels are achieved after five elimination
half-lives, when the dosing interval is 50% of the half-life. Therefore, from a pharmacokinetic
standpoint, the patient may not achieve full efficacy of the antihypertensive agent
until 10 days into therapy. Therefore checking for effect at 3 days is premature. Doubling
the dose or increasing the frequency may predispose to toxicity. There is no reason to add
a second agent or switch to another agent until completing a trial of adequate duration
on the current agent.
I-16. The answer is A. (Chap. 5) The patient is developing full-blown cirrhosis and as a result
has impaired hepatic clearance of his morphine. This is due to impaired first-pass
metabolism as a consequence of abnormal liver architecture, depressed cytochrome P450
activity, and perhaps portacaval shunting. Physical and laboratory examinations reveal
evidence of worsening cirrhosis and opiate toxicity. Hepatic encephalopathy and subacute
bacterial peritonitis are considerations in the cirrhotic patient with impaired mental
status. However, the patient has no discernible ascites and no evidence of hepatic
encephalopathy on examination. The focus should be on reducing centrally acting therapies
such as morphine, rather than adding another medicine such as haloperidol.
I-17. The answer is B. (Chap. 20) This patient presents with frostbite of the left foot. The
most common presenting symptom of this disorder is sensory changes that affect pain
and temperature. Physical examination can have a multitude of findings, depending on
the degree of tissue damage. Mild frostbite will show erythema and anesthesia. With
more extensive damage, bullae and vesicles will develop. Hemorrhagic vesicles are due to
injury to the microvasculature. The prognosis is most favorable when the presenting area
is warm and has a normal color. Treatment is with rapid rewarming, which usually is accomplished
with a 37 to 40°C (98.6 to 104°F) water bath. The period of rewarming can be
intensely painful for the patient, and often narcotic analgesia is warranted. If the pain is
intolerable, the temperature of the water bath can be dropped slightly. Compartment
syndrome can develop with rewarming and should be investigated if cyanosis persists after
rewarming. No medications have been shown to improve outcomes, including heparin,
steroids, calcium channel blockers, and hyperbaric oxygen. In the absence of wet
gangrene or another emergent surgical indication, decisions about the need for amputation
or debridement should be deferred until the boundaries of the tissue injury are well
demarcated. After recovery from the initial insult, these patients often have neuronal injury
with abnormal sympathetic tone in the extremity. Other remote complications include
cutaneous carcinomas, nail deformities, and, in children, epiphyseal damage.
I-18. The answer is C. (Chap. 9) Urinary incontinence occurring randomly without associated
Valsalva or other stress is most likely detrusor overactivity. This disorder is the most
common type of incontinence in the elderly, both males and females. In females there is
no need to do further testing in a patient with long-standing incontinence; however, in
males urethral obstruction is often coexistent, and urodynamic testing is indicated to investigate
this possibility. An abrupt onset of symptoms or associated suprapubic pain in
either sex should prompt cystoscopy and urine cytologic testing to evaluate for bladder
stones, tumor, or infection. First-line therapy is behavioral therapy with or without biofeedback.
Frequent timed voiding is often successful. If drugs are imperative, oxybutynin
or tolterodine can be tried with close follow-up to ensure that urinary retention does not
occur. Desmopressin must be used with extreme caution in this population. Indeed, patients
with heart failure, chronic kidney disease, or hyponatremia should not take this
medication. Indwelling catheters are rarely indicated for this disorder; instead, external
collection devices or protective pads or undergarments are favored.
I-19. The answer is B. (Chaps. 5 and 9) Adverse drug reactions in the geriatric population are
common, occurring two to three times more frequently than they do in younger patients.
This is due to several factors. Drug clearance is altered because of decreased renal plasma
flow and glomerular filtration as well as decreased hepatic clearance. Furthermore, the volume
of distribution of many drugs is decreased with a drop in total body water. However, in
older persons there is a relative increase in fat, which will lengthen the half-life of fat-soluble
medications. Serum albumin levels decline in general in the elderly, particularly in the hospitalized
and sick population. As a result, drugs that are primarily protein-bound, such as warfarin
and phenytoin, will have higher free or active levels at similar doses. Care must be taken
in interpreting total serum levels for these drugs because a low total level may be accompanied
by a normal free level and thus be appropriately therapeutic.
I-20. The answer is A. (Chap. 5) In population surveys of noninstitutionalized elderly, up to
10% had at least one adverse drug reaction in the prior year. Adverse drug reactions are
common in the elderly and are related to altered drug sensitivity, impaired renal or hepatic
clearance, impaired homeostatic mechanisms, and drug interactions. Long half-life
benzodiazepines are linked to the increased occurrence of hip fractures in the elderly. The
association may be due to the increased risk of falling (related to sedation) in a population
with a high prevalence of osteoporosis. This association may also be true for other
drugs with sedative properties such as opioids or antipsychotics. Exaggerated responses
to cardiovascular drugs such as ACE inhibitors may occur because of a blunted vasoconstrictor
or chronotropic response to reduced blood pressure. Conversely, elderly patients
often display decreased sensitivity to beta blockers.
I-21. The answer is C. (Chap. 5) Grapefruit juice inhibits CYP3A4 in the liver, particularly at
high doses. This can cause decreased drug elimination via hepatic metabolism and increase
potential drug toxicities. Atorvastatin is metabolized via this pathway. Drugs that may enhance
atorvastatin toxicity via this mechanism include phenytoin, ritonavir, clarithromycin,
and azole antifungals. Aspirin is cleared via renal mechanisms. Prevacid can cause impaired
absorption of other drugs via its effect on gastric pH. Sildenafil is a phosphodiesterase inhibitor
that may enhance the effect of nitrate medications and cause hypotension.
I-22. The answer is A. (Chaps. 18 and 185) Based on the characteristic rash and Koplik’s
spots, this patient has measles. A rare but feared complication of measles is subacute sclerosing
panencephalitis. His examination does not support epiglottitis as he has no drooling
or dysphagia. His rash is not characteristic of acute HIV infection, and he lacks the
pharyngitis and arthralgias commonly seen with this diagnosis. The rash is not consistent
with herpes zoster, and he is quite young to invoke this diagnosis. Splenic rupture occasionally
occurs with infectious mononucleosis, but this patient has no pharyngitis, lymphadenopathy,
or splenomegaly to suggest this diagnosis.
I-23. and. I-24. The answers are D and D. (Chap. 215) This patient has symptoms of an acute
cholinergic crisis as seen in cases of organophosphate poisoning. Organophosphates are
the “classic” nerve agents, and several different compounds may act in this manner, including
sarin, tabun, soman, and cyclosarin. Except for agent VX, all the organophosphates
are liquid at standard room temperature and pressure and are highly volatile, with
the onset of symptoms occurring within minutes to hours after exposure. VX is an oily
liquid with a low vapor pressure; therefore, it does not acutely cause symptoms. However,
it is an environmental hazard because it can persist in the environment for a longer period.
Organophosphates act by inhibiting tissue synaptic acetylcholinesterase. Symptoms
differ between vapor exposure and liquid exposure because the organophosphate acts in
the tissue upon contact. The first organ exposed with vapor exposure is the eyes, causing
rapid and persistent pupillary constriction. After the sarin gas attacks in the Tokyo subway
in 1994 and 1995, survivors frequently complained that their “world went black” as
the first symptom of exposure. This is rapidly followed by rhinorrhea, excessive salivation,
and lacrimation. In the airways, organophosphates cause bronchorrhea and bronchospasm.
It is in the alveoli that organophosphates gain the greatest extent of entry into
the blood. As organophosphates circulate, other symptoms appear, including nausea,
vomiting, diarrhea, and muscle fasciculations. Death occurs with central nervous system
penetration causing central apnea and status epilepticus. The effects on the heart rate and
blood pressure are unpredictable.
Treatment requires a multifocal approach. Initially, decontamination of clothing and
wounds is important for both the patient and the caregiver. Clothing should be removed
before contact with the health care provider. In Tokyo, 10% of emergency personnel developed
miosis related to contact with patients’ clothing. Three classes of medication are
important in treating organophosphate poisoning: anticholinergics, oximes, and anticonvulsant
agents. Initially, atropine at doses of 2 to 6 mg should be given intravenously
or intramuscularly to reverse the effects of organophosphates at muscarinic receptors; it
has no effect on nicotinic receptors. Thus, atropine rapidly treats life-threatening respiratory
depression but does not affect neuromuscular or sympathetic effects. This should
be followed by the administration of an oxime, which is a nucleophile compound that
reactivates the cholinesterase whose active site has been bound to a nerve agent. Depending
on the nerve agent used, oxime may not be helpful because it is unable to bind
to “aged” complexes that have undergone degradation of a side chain of the nerve agent,
making it negatively charged. Soman undergoes aging within 2 min, thus rendering
oxime therapy useless. The currently approved oxime in the United States is 2-pralidoxime.
Finally, the only anticonvulsant class of drugs that is effective in seizures caused
by organophosphate poisoning is benzodiazepines. The dose required is frequently
higher than that used for epileptic seizures, requiring the equivalent of 40 mg of diazepam
given in frequent doses. All other classes of anticonvulsant medications, including
phenytoin, barbiturates, carbamazepine, and valproic acid, will not improve seizures related
to organophosphate poisoning.
I-25. The answer is E. (Chap. 215) Cyanide is an asphyxiant that causes death by inhibiting
cellular respiration. It is a colorless liquid or gas that has a typical smell of almonds. The
onset of symptoms after cyanide exposure is rapid and usually begins with eye irritation.
The skin is flushed. The patient rapidly develops confusion, tachypnea, and tachycardia.
With severe poisoning, death results from acute respiratory distress syndrome (ARDS)
and hypoxemia with lactic acidosis. The antidote for cyanide poisoning is a combination
of sodium nitrite and sodium thiosulfate.
I-26. The answer is A. (Chap. 215) Sulfur mustard was the first weaponized chemical and
was first used in World War I, accounting for 70% of the estimated 1.3 million chemical
casualties in that war. It remains a significant terrorist threat today because of simplicity
of manufacture and effectiveness. Sulfur mustard constitutes both a vapor and a liquid
chemical threat. It acts as a DNA-alkylating agent and affects rapidly dividing cells. The
effects of sulfur mustard are delayed 2 h to2 days, depending on the severity of exposure.
The organs most commonly affected are the skin, eyes, and airways. Late bone marrow
suppression also occurs 7 to 21 days after exposure. Erythema resembling a sunburn is
the mildest form of injury. This progresses to large flaccid bullae containing sterile serous
fluid. Large portions of body-surface area may be affected, similar to the situation in
burn victims. The primary airway lesion is necrosis of the mucosa. Clinically, this causes
pseudomembrane formation and, in the most severe cases, airway obstruction. Laryngospasm
may also occur. The effects on the eyes include conjunctivitis, blepharospasm,
pain, and corneal damage. Death results from airway obstruction, pneumonia, secondary
skin infections, or sepsis with neutropenia. There is no antidote to mustard gas or liquid
exposure. Treatment is supportive, ensuring adequate analgesia and hydration. Application
of topical glucocorticoids before denudation of skin may be useful. Small blisters
should be left intact, but large bullae should be unroofed. The fluid is sterile and does not
contain mustard derivatives. Silver sulfadiazine or other topical antibiotics should be
used to prevent secondary skin infections. Conjunctival irritation should be treated with
topical solutions, including antibiotics. Petroleum jelly should be applied to the eyelids to
prevent them from sticking together. Intubation may be necessary for protection against
airway obstruction. Repeated bronchoscopy may also be needed to remove pseudomembranes.
Finally, careful follow-up for the development of marrow suppression is needed.
I-27. The answer is C. (Chaps. 18 and 167) This patient likely has Rocky Mountain spotted
fever. The headache and thrombocytopenia after a recent camping trip in a rickettsial endemic
region are typical findings. As this is usually a serologic diagnosis requiring significant
laboratory processing time, and can be fatal, empirical therapy with doxycycline is
warranted. The lack of a rash does not preclude this diagnosis because the characteristic
macular rash spreading from the wrists and ankles centripetally appears 2–5 days after
the first fever. Atovaquone is used for babesiosis, a disease that is defined by hemolysis
and is not prevalent in the Ozarks. The patient has no evidence of bacterial meningitis to
warrant empirical coverage. While fever and myalgias are typical of influenza, it is most
common in winter and does not typically cause thrombocytopenia.
I-28. The answer is C. (Chaps. 18 and 129) This case is likely toxic shock syndrome, given
the clinical appearance of septic shock with no positive blood cultures. The characteristic
diffuse rash, as well as the lack of a primary infected site, make staphylococcus the more
likely inciting agent. Streptococcal toxic shock usually has a prominent primary site of in
fection, but the diffuse rash is usually much more subtle than in this case. Staphylococcal
toxic shock can be associated with immunosuppression, surgical wounds, or retained
tampons. Mere Staphylococcus aureus colonization (with an appropriate toxigenic strain)
can incite toxic shock. Centers for Disease Control and Prevention guidelines state that
measles, Rocky Mountain spotted fever, and leptospirosis need to be ruled out serologically
to confirm the diagnosis. However, this patient is at very low risk for these diagnoses
based on vaccination and travel history. JRA would become a consideration only if the fevers
were more prolonged and there was documented evidence of organomegaly and enlarged
I-29. The answer is C. (Chap. 214) Using the characteristics listed in the question, the CDC
developed classifications of biologic agents that are based on their potential to be used as
bioweapons. Six types of agents have been designated as category A: Bacillus anthracis,
botulinum toxin, Yersinia pestis, smallpox, tularemia, and the many viruses that cause viral
hemorrhagic fever. Those viruses include Lassa virus, Rift Valley fever virus, Ebola virus,
and yellow fever virus.
I-30. The answer is E. (Chaps. 18 and 149) Vibrio vulnificus is a marine-borne gram-negative
rod that causes overwhelming sepsis in the immunocompromised host, particularly
cirrhotic patients. Modes of infection are direct wound inoculation or ingestion via raw
seafood. Presentation is rapid with the classic skin findings described in this case, which
approximate purpura fulminans as the illness progresses. Mortality is >50%, even with
appropriate and early antibiotics.
I-31. The answer is C. (Chap. 17) Hyperthermia occurs when exogenous heat exposure or an
endogenous heat-producing process, such as neuroleptic malignant syndrome or malignant
hyperthermia, leads to high internal temperatures despite a normal hypothalamic
temperature set point. Fever occurs when a pyrogen such as a microbial toxin, microbe
particle, or cytokine resets the hypothalamus to a higher temperature. A particular temperature
cutoff point does not define hyperthermia. Rigidity and autonomic dysregulation
are characteristic of malignant hyperthermia, a subset of hyperthermia. Fever, not
hyperthermia, responds to antipyretics.
I-32. The answer is D. (Chap. 17) This patient has malignant hyperthermia, for which dantrolene
and external cooling are appropriate interventions. Malignant hyperthermia occurs
in individuals with a genetic predisposition that causes elevated skeletal muscle
intracellular calcium concentration after exposure to some inhaled anesthetics or succinylcholine.
Cardiovascular instability is common within minutes. Although malignant
hyperthermia is rare, these drugs are used commonly, and without prompt recognition
the condition may be fatal. There is no role for antipyretics as the thalamic set point for
temperature is likely not altered in the setting of hyperthermia.
I-33. The answer is E. (Chap. 17) The elderly and the very young are at highest risk of nonexertional
heat stroke. Environmental stress (heat wave) is the most common precipitating
factor, particularly in the bedridden or for those living in poorly ventilated or nonair-
conditioned conditions. Medications such as antiparkinson treatment, diuretics, or
anticholinergic therapy increase the risk of heat stroke.
I-34. The answer is A. (Chap. 20) Initial focus should be aggressive rewarming. Further attempts
at defibrillation are unlikely to work until core temperature is normalized.
Pharmacologic strategies are also ineffective in the setting of hypothermia, though the
possibility of toxicity based on accumulation of drug does exist once successful rewarming
is achieved. If initial active rewarming techniques are ineffective, cardiopulmonary
bypass, warmed hemodialysis, peritoneal lavage with warmed fluid, or pleural
lavage with warmed fluid should be considered on an emergent basis. A pacemaker will
not be effective for ventricular fibrillation and may provoke arrhythmias due to ventricular
I-35. The answer is B. (Chap. 72) Albumin has a half-life of 2 to 3 weeks and is a sensitive
but nonspecic measure of protein-calorie malnutrition. Other situations in which albumin
is low include sepsis, surgery, overhydration, and increased plasma volume, including
congestive heart failure, renal failure, and chronic liver disease. Among the
other markers of nutritional state, transferrin has a half-life of 1 week. Prealbumin and
retinol-binding protein complex have the same half-life of 2 days. Fibronectin has the
shortest half-life: 1 day.
I-36. The answer is C. (Chap. 20) This patient has severe frostbite vesiculations implying
deep tissue injury, including the microvasculature. Medical therapy with intravenous or
topical vasodilators is not effective in this setting. Decisions regarding surgical debridement
and amputation are best made in the chronic stage of management rather than
acutely in the absence of infection. Initially, rewarming and aggressive analgesia with opiates
are the mainstay of therapy.
I-37. The answer is D. (Chap. 4) It is important to contrast the relative risk reduction of an
intervention versus the absolute risk reduction. The ARR is 0.88% – 0.59% = 0.29%
(note: rates are per 1000 persons). The relative risk reduction in this case is ~30%. It
might be predicted, therefore, that this intervention might result in a 30% decrease in colon
cancer mortality if widely implemented in a target population. However, the ARR is
much smaller; 1 divided by the absolute risk reduction (1/ARR) equals the number
needed to treat to prevent one colon cancer death. In this case, that number is ~330.
Therefore, while the impact on a population level might be large, it takes a large number
of patients to prevent one event with the intervention (FOBT).
I-38. The answer is B. (Chap. 4) Predicted increases in life expectancy are average numbers
that apply to populations, not individuals. Because we often do not understand the true nature
of risk of disease, screening and lifestyle interventions usually benefit a small proportion
of the total population. For screening tests, false positives may also increase the risk of
diagnostic tests. While Pap smears increase life expectancy overall by only 2–3 months, for
the individual at risk of cervical cancer, Pap smear screening may add many years to life.
The average life expectancy increases resulting from mammography (1 month), PSA (2
weeks), or exercise (1–2 years) are less than from quitting smoking (3–5 years).
I-39. The answer is B. (Chaps. 4 and 235) Current guidelines from the National Cholesterol
Education Project Adult Treatment Panel III recommend screening in all adults >20 years
old. The testing should include fasting total cholesterol, triglycerides, low-density lipoprotein
cholesterol, and high-density lipoprotein cholesterol. The screening should be repeated
every 5 years. All patients with Type 1 diabetes should have lipids followed closely
to decrease cardiovascular risk by combining the results of lipid screening with other risk
factors to determine risk category and intensity of recommended treatment.
I-40. The answer is C. (Chap. 386) Generalized anxiety disorder is common, with a lifetime
prevalence of approximately 5% and with the onset of symptoms often occurring
before age 20. These patients frequently report having feelings of anxiety and social
phobia that date back to childhood. Clinically, these patients report persistent, excessive,
and unrealistic worries that prevent normal functioning. In addition, there is often
the complaint of feeling “on edge” with nervousness, arousal, and insomnia.
However, unlike panic disorder, palpitations, tachycardia, and shortness of breath are
rare. Pathophysiologically, there is likely to be impaired function of the GABA receptor
with decreased binding of benzodiazepines at that receptor. Therapy should include a
combination of drugs and psychotherapy. Drugs that may be used include benzodiazepines,
buspirone, and anticonvulsants with GABAergic properties, such as gabapentin,
tiagabine, and divalproex.
I-41. The answer is D. (Chap. 10; Wilt et al.) Because plant products are in widespread use in
the well-accepted therapeutic armamentarium of Western medicine (e.g., digoxin, taxol,
penicillin), it should not be surprising that several “herbal remedies” have been demon
strated in prospective clinical trials to be beneficial. For example, Saint John’s wort is
more effective than placebo for mild to moderate depression; the mechanism is not
known, although the metabolism of several neurotransmitters is inhibited by this substance.
Kava products have antianxiolytic activity. Extracts of the fruit of the saw palmetto,
Serona repens, have been shown to decrease nocturia and improve peak urinary
flow compared with placebo in males with benign prostatic hypertrophy. Saw palmetto
extracts affect the metabolism of androgens, including the inhibition of dihydrotestosterone
binding to androgen receptors.
I-42. The answer is D. (Chap. 76) The most important feature of patients with anorexia nervosa
is refusal to maintain even a low-normal body weight. The full syndrome of anorexia
nervosa occurs in about 1 in 200 individuals. These patients are always markedly
underweight, hardly ever menstruate, and often engage in binge eating. The mortality
rate is 5% per decade. The etiology of this serious eating disorder is unknown but probably
involves a combination of psychological, biologic, and cultural risk factors. This illness
often begins in an obsessive or perfectionist patient who starts a diet. As weight loss
progresses, the patient has increasing fears of gaining weight and engages in stricter dieting
practices. This disorder essentially occurs only in cultures in which thinness is valued,
suggesting a strong cultural influence. Bulimia nervosa, in which patients continue to
maintain a normal body weight but typically engage in overeating with binges followed
by compensatory purging or purging behavior, has a higher than expected prevalence in
patients with childhood or parental obesity. It is unclear whether anorexia nervosa is hereditary
I-43. The answer is C. (Chap. 71) Certain medications, including isoniazid used for tuberculosis,
L-dopa used for Parkinson’s disease, and penicillamine used for scleroderma,
promote vitamin B6 (pyridoxine) deficiency by reacting with a carbonyl group on 5-
pyridoxal phosphate, which is a cofactor for a host of enzymes involved in amino acid
metabolism. Foods that contain vitamin B6 include legumes, nuts, wheat bran, and meat.
Vitamin B6 deficiency produces seborrheic dermatitis, glossitis, stomatitis, and cheliosis
(also seen in other vitamin B deficiencies). A microcytic, hypochromic anemia may result
from the fact that the first enzyme in heme synthesis (aminolevulinic synthetase) requires
pyridoxal phosphate as a cofactor. However, vitamin B6 is also necessary for the
conversion of homocysteine to cystathionine. Consequently, a deficiency of this vitamin
could produce an increased risk of cardiovascular disease caused by the resultant hyperhomocystinemia.
I-44. The answer is C. (Chap. 9) Hypertension and diabetes are the most important chronic
diseases whose prevalence increases with age. In those >65 years old, the prevalence of
hypertension is estimated at 60–85%. These numbers will likely increase in the near future
as the population ages and obesity is more prevalent. Recent data suggest that the
frequency of uncontrolled hypertension is increasing in older adults in the United States.
The presence of uncontrolled hypertension accelerates functional and cognitive decline
in older adults. These data also have important implications on the frequency of cardiovascular
disease and stroke in older adults.
I-45. The answer is B. (Chap. 4) The prevalence of diabetes in older adults is ~18–21%. This
rate will likely increase with increasing obesity in older adults. Diabetes has been linked
with physical decline, while hypertension has been linked with cognitive decline. However,
both disorders are commonly present in the elderly. Diabetes and stroke are most
consistently associated with a diminished capacity for functional recovery in the elderly.
I-46. The answer is A. (Chap. 9) Functional status, as defined by a patient’s ability to provide
for his or her own daily needs, is the most important indicator for prognosis. A decline in
functional status should prompt a search for medical illness, dementia, change in social
support, or depression. Screening for functional status should include assessment of activities
of daily living, gait and balance, cognition, vision, hearing, and dental and nutritional
I-47. The answer is A. (Chaps. 9 and 26) Delirium can cause prolonged hospitalization and
may be life threatening. It is often underdiagnosed. The Confusion Assessment Method
(CAM) is highly sensitive and specific for identifying delirium. One common misconception
is that all delirious patients are agitated. In fact, delirium is often associated with a
decreased level of consciousness, and patients can appear withdrawn or aloof, rather than
agitated, combative, or anxious. Another crucial diagnostic criterion is that the patient’s
mental state represents a clear, acute deviation from their baseline status.
I-48. The answer is E. (Chap. 9) Fall rates increase with age and have substantial effect on
mortality and morbidity. Some 3–5% of falls result in fracture, and falls are an independent
risk factor for nursing home placement. All older adults should have at least annual
fall risk assessment and be asked about falls during clinic visits. Fall prevention necessitates
a multidisciplinary approach including management of medical conditions associated
with falls, limitation of psychotropic medicines (especially benzodiazepines),
frequent visual examinations, interventions such as tai-chi geared towards stabilizing
gait, and close examination of circumstances associated with past falls.
I-49. The answer is B. (Chap. 9) Physical examination of all immobilized or bed-bound patients
must include careful examination of common sites for pressure sores. The heels, lateral
malleoli, sacrum, ischia, and greater trochanters account for 80% of pressure sores.
Shear forces and moisture are predisposing factors. In older adults and nursing home residents,
the development of a pressure sore increases mortality fourfold. Infectious complications
include osteomyelitis and sepsis. A fairly innocuous-appearing lesion can progress
to a deep, easily infected, and very difficult-to-manage stage 4 decubitus ulcer in a very
short period of time without aggressive wound care and off-loading by nursing staff.
I-50. The answer is E. (Chap. 9) This patient has stress incontinence. Stress incontinence,
due to dysfunction of the urethral sphincter, is common in women and uncommon in
men. It most often occurs with activities that increase abdominal pressure. The most
common risks are previous childbearing, gynecologic surgery, and menopause. Kegel exercises
may be useful, but surgery is considered the most effective intervention. Oxybutynin
and bladder training exercises are sometimes effective for urge incontinence, which is
more common in men. α-Adrenergic blockers and 5-α-reductase inhibitors are used for
prostate hypertrophy in men. Close monitoring for hyperglycemia and diabetes is useful
in elderly patients with incontinence, but this patient does not describe polyuria and her
past vaginal deliveries and pelvic surgery put her at risk for stress incontinence.
I-51. The answer is B. (Chap. 23) The patient has Brown-Séquard syndrome, likely because
of a new multiple sclerosis plaque. The lack of cranial nerve involvement and other cortical
deficits, in the presence of upper extremity and lower extremity deficits, suggests a
high cord lesion. These often lead to differing ipsilateral and contralateral sensory deficits,
as in this patient. The combination of left side motor deficit and right side sensory
deficit makes the cortical lesion unlikely. Brainstem lesions will also not account for the
localization and bilaterality. A cervical cord root lesion would not be bilateral.
I-52. The answer is A. (Chaps. 23 and 292) The patient’s weight loss predisposes him to superior
mesenteric artery (SMA) syndrome. Due to loss of the omental fat pad, the SMA
compresses the duodenum in this condition, leading to obstruction. Laparoscopy is less
likely to be of diagnostic benefit (i.e., for adhesions) as the patient has never had abdominal
surgery. An upper GI series may be useful for evaluation of an obstructing mass,
though SMA syndrome is more likely in this clinical context. While patients with advanced
HIV are at risk of a variety of infectious causes of diarrhea, they are unlikely to
present with acute small-bowel obstruction. Serum CEA levels may be elevated in colon
cancer but would not be helpful in explaining the cause of acute small-bowel obstruction.
I-53. The answer is C. (Chap. 23) Amyloidosis predisposes to autonomic neuropathy, which
in turn causes both orthostasis and gastroparesis. Gastrointestinal amyloidosis is another
possibility in this patient, though his early satiety and bloating are typical for gastropare
sis. Treatment can include pro-motility agents, such as metoclopramide as well as dietary
changes that this patient has already instituted on his own. Small-bowel obstruction
would not be relieved by smaller frequent meals. Gastric cancers may present with early
satiety and vomiting as well as weight loss. Diverticulosis and irritable bowel syndrome
present with lower gastrointestinal symptoms.
I-54. The answer is D. (Chap. 39) This patient has developed tardive dyskinesia that may be
irreversible. Prochlorperazine is an antidopaminergic agent that suppresses emesis by
acting centrally at the dopamine D2 receptors. This class of agents is most effective for the
treatment of medication-, toxin-, and metabolic-induced emesis. However, these agents
freely cross the blood-brain barrier and can cause anxiety, galactorrhea, sexual dysfunction,
and dystonic reactions. Tardive dyskinesia is the most serious of these neurologic
toxicities. Erythromycin is a prokinetic that may worsen nausea and vomiting. Ondansetron
acts at the 5-HT3 receptor and has no antidopaminergic activity. Scopolamine is an
anticholinergic that may cause delirium, stupor, and other neurologic side effects, but
not tardive dyskinesia. Glucocorticoids also do not cause tardive dyskinesia.
I-55. The answer is D. (Chap. 34) Chronic cough is defined as a cough present for >8 weeks.
Mycoplasma infection can cause a cough acutely or a postinfectious cough that persists
for as long as 8 weeks. Asthma, postnasal drip, and reflux disease are the three most common
causes of chronic cough in a nonsmoker not taking angiotensin-converting enzyme
(ACE) inhibitors. All ACE inhibitors, including lisinopril, can cause chronic cough, possibly
due to altered bradykinin metabolism. Patients with ACE inhibitor cough may be
switched to an angiotensin receptor blocker, which does not cause cough.
I-56. The answer is B. (Chaps. 34 and 252) The putrid smell and polymicrobial gram stain
suggest a polymicrobial lung abscess consisting of normal oral flora, including anaerobes
and Streptococcus viridans. The anaerobes contribute to the putrid smell of the sputum.
The patient’s protracted mild clinical course is typical for this process, and his alcoholism
is a clear risk factor as well. The superior segment of the right lower lobe is the most common
site of aspiration and lung abscess, followed by the posterior segment of the right
upper lobe and the superior segment of the left lower lobe. Tricuspid valve endocarditis
may cause lung abscess due to staphylococcal (S. aureus) bacteremia. The patient is
clearly at risk for pulmonary tuberculosis (TB) given his imprisonment; however, the
sputum would not likely be putrid and purulent with this microscopic appearance. The
cavitary lesions of TB are typically in the upper lobes. Wegener’s granulomatosis may
cause cavitary masses, but they are usually multiple and would not have putrid sputum.
Squamous cell lung cancer may also cavitate by outgrowing its blood supply and may be
secondarily infected, although usually not with this degree of anaerobic characteristics.
I-57. The answer is D. (Chap. 34) Hemoptysis in these conditions originates from the bronchial
circulation that is supplied by the aorta or intercostal arteries, not the pulmonary
artery. Because of the high pressures, bleeding may be sudden and massive. Embolization
of bronchial arteries feeding the suspected area may stop the bleeding. Cough suppressants
may help decrease the irritating effects on the submucosa of coughing. Direct bronchoscopic
cautery may be beneficial for friable tumors. Selective intubation of the right
main bronchus may be supportive by protecting the non-bleeding right lung. Occlusion
of the right lung bronchus by coagulating blood could lead to respiratory failure. The patient
should be placed with his non-bleeding lung up, not down, as the goal is to prevent
blood from entering the non-bleeding lung.
I-58. The answer is B. (Chaps. e9 and 277) A collapsing variant of focal segmental glomerulosclerosis
is typically diagnostic of HIV nephropathy, which presents with proteinuria and
subacute loss of renal function. Diabetes typically causes thickening of glomerular basement
membrane, mesangial sclerosis, and arteriosclerosis. Multiple myeloma causes proteinuria
via deposition of light chains in the glomeruli and tubules and the development of renal
amyloidosis. Microscopy shows amyloid proteins with Congo red staining. SLE causes membranous
and proliferative nephritis due to immune complex deposition. Wegener’s granulomatosis
and microscopic polyangiitis cause pauci-immune necrotizing glomerulonephritis.
I-59. The answer is A. (Chaps. 35 and 244) This patient has central cyanosis, which is due to
arterial desaturation. In central cyanosis, skin and mucus membranes are affected. Peripheral
cyanosis is the result of peripheral hypoperfusion of various causes either due to
hypotension, as with heart failure (e.g., myocardial infarction, myocarditis) or sepsis, or
due to peripheral vasoconstriction, as with cold exposure or Raynaud’s phenomenon. In
these cases, the extremities are most affected, with the mucus membranes usually spared.
This patient has Eisenmenger’s physiology with right-to-left shunting of deoxygenated
blood. Other causes of central cyanosis include severe lung disease, pulmonary arteriovenous
malformations, alveolar hypoventilation, or hemoglobin abnormalities.
I-60. The answer is C. (Chap. 35) Cirrhotic patients are at risk of developing pulmonary arteriovenous
fistulas. These, as well as portopulmonary shunts, cause platypnea and orthodeoxia
(dyspnea and desaturation with sitting up). The fistulas, which are preferentially
at the base of the lungs, increase the right-to-left shunting (and therefore hypoxemia)
when upright. In the supine position, the apex of the lung is better perfused and the hypoxemia
improves. The oxygen desaturation in the upright position causes the platypnea.
Congenital pulmonary arteriovenous malformations may also cause platypnea and orthodeoxia.
Ventricular septal defects will not cause hypoxemia until they develop right-toleft
I-61. The answer is D. (Chap. 36) The patient’s positional edema that is worse in hot
weather strongly suggests idiopathic edema. Idiopathic edema occurs mostly in women
and is characterized by episodes of edema that may include abdominal distention. It is
typically diurnal, with worsening after being upright for prolonged periods or in hot
weather. Cyclical edema occurs with menstruation and is related to estrogen stimulation
of fluid retention. Congestive heart failure, nephrotic syndrome, and cirrhosis are ruled
out by history and by physical and laboratory examinations. Initially, therapy should include
patient education regarding the need to lie flat for a few hours each day, as well as
compression stockings put on in the mornings. Idiopathic edema may be related to abnormal
activation of the renin-angiotensin system, and angiotensin-converting enzyme
inhibitors may play a role if conservative interventions are not effective. Diuretics may be
beneficial initially but may lose effectiveness if used continuously.
I-62. The answer is D. (Chap. 37) Palpitations are a common complaint among patients
who report fluttering, pounding, or thumping sensation in the chest. Palpitations may
arise from cardiac, psychiatric, miscellaneous (thyrotoxicosis, drugs, ethanol, caffeine,
cocaine), or unknown causes. While most arrhythmias do not cause palpitations, patients
with palpitations and known heart disease or risk factors are at risk of atrial or ventricular
arrhythmias. Overall, patients complaining of palpitations >15 min are more likely to
have psychiatric causes. Most patients with palpitations do not have serious arrhythmias.
History, physical examination, Holter monitoring, and electrocardiography may be used
to evaluate for arrhythmias.
I-63. The answer is D. (Chap. 7) Blood pressure >140/90 mmHg during the second trimester
is markedly abnormal. During the second trimester, blood pressure should fall due to
a decrease in systemic vascular resistance. Elevated blood pressure is associated with an
increase in perinatal morbidity and mortality. Delaying diagnosis may be harmful. Blood
pressure should be performed in the sitting position because in the lateral recumbent position
the decrease in preload may cause a reduced blood pressure. The diagnosis of hypertension
requires measurement of two elevated blood pressures at least 6 hours apart.
Hypertension may be caused by preeclampsia, chronic hypertension, gestational hypertension,
or renal hypertension. If hypertension is diagnosed, a safe antihypertensive
should be initiated and a referral to a high-risk obstetrician should be considered.
I-64. The answer is D. (Chap. 7) This patient has severe eclampsia, and delivery should be
performed as rapidly as possible. Mild eclampsia is the presence of new-onset hypertension
and proteinuria in a pregnant woman after 20 weeks’ gestation. Severe eclampsia is
eclampsia complicated by central nervous system symptoms (including seizure), marked
hypertension, severe proteinuria, renal failure, pulmonary edema, thrombocytopenia, or
disseminated intravascular coagulation. Delivery in a mother with severe eclampsia before
37 weeks’ gestation decreases maternal morbidity but increases fetal risks of complications
of prematurity. Aggressive management of blood pressure, usually with labetalol,
decreases maternal risk of stroke. Angiotensin-converting enzyme inhibitors and angiotensin-
receptor blockers should not be used due to the potential of adverse effects on fetal
development. Eclamptic seizures should be controlled with magnesium sulfate; it has
been shown to be superior to phenytoin.
I-65. The answer is D. (Chap. 7) Mitral stenosis is associated with flash pulmonary edema,
atrial arrhythmias, and risk of maternal death. The risk is likely related to the increase in
cardiac output and circulating blood volume during pregnancy. Sudden death due to arrhythmia
or pulmonary hypertension may occur. During delivery, patients with mitral
stenosis should be managed with careful heart rate control. Balloon valvuloplasty may
be performed during pregnancy. The decrease in systemic vascular resistance during
pregnancy makes mitral, tricuspid, and aortic regurgitation generally well tolerated because
heart failure is not likely. If aortic stenosis is severe, balloon valvuloplasty may be
I-66. The answer is C. (Chap. 7) Pregnancy causes a hypercoagulable state, and DVT occurs
in about 1 in 2000 pregnancies. DVT occurs more commonly in the left leg than
the right leg during pregnancy due to compression of the left iliac vein. Approximately
25% of pregnant women with DVT have a factor V Leiden mutation, which also predisposes
to preeclampsia. Prothrombin G20210A mutation (homozygotes and heterozygotes),
and methylenetetrahydrofolate reductase C677 mutation (homozygotes) are
also risk factors for DVT during pregnancy. Coumadin is strictly contraindicated during
the first and second trimesters due to risk of fetal abnormality. Low-molecularweight
heparin is appropriate therapy but may be switched to heparin infusion at delivery,
if an epidural is likely. Ambulation, rather than bedrest, should be encouraged
as with all DVTs. There is no proven role for local thrombolytics or an inferior vena
cava filter in pregnancy. The latter would be considered only in scenarios where anticoagulation
is not possible.
I-67. The answer is E. (Chap. 7) Pregnancy complicated by diabetes is associated with
greater maternal and perinatal morbidity and mortality rates. Women with gestational
diabetes are at increased risk of preeclampsia, delivering infants large for gestational age,
and birth lacerations. Their infants are at risk of hypoglycemia and birth injury. Appropriate
therapy can reduce these risks. Not performing diabetes screening during pregnancy
should be considered only in low-risk patients (age <25,>65 years. Axial stiffness, stooped posture, shuffling gait, and pillrolling
tremor are distinctive. Other progressive neurologic disorders such as those listed
above may present with Parkinsonian features. The atypical Parkinsonian syndromes can
be difficult to differentiate from Parkinson’s disease. However, the presence of a pillrolling
tremor is specific for Parkinson’s disease.
I-72. The answer is A. (Chap. 24) The gait of cerebellar dysfunction most closely resembles a
drunken gait with very poor balance, frequent lurching, and high risk of fall. However,
unlike patients with inner ear dysfunction, these symptoms are usually not associated
with subjective dizziness, vertigo, and nausea. Frontal gait disorder or gait apraxia is
common in the elderly and has a variety of causes. Typical features include a wide base of
support, short strides, shuffling, and difficulty with starts and turns. The most common
cause of frontal gait is subcortical small-vessel cerebrovascular disease. Patients with Parkinsonian
syndromes have a shuffling gait, with difficulty initiating and turning en bloc.
Sensory ataxia may be caused by tabes dorsalis or vitamin B12 neuropathy. Patients have a
narrow base and look down; their gait is regular with path deviation. They have no difficulty
initiating gait but have postural instability and falls.
I-73. The answer is E. (Chap. 24) The inability to walk in a stable fashion without direct visual
observation of the feet suggests a deficit in proprioception due to large-fiber neuropathy.
The narrow-based gait with no difficulty initiating gait and normal strength is
consistent with sensory ataxia. Classically this was caused by tabes dorsalis, although
vitamin B12 deficiency is a treatable disease that may present with this form of neuropathy
and gait disorder. This suspicion is even greater in the context of a macrocytic
anemia, a finding that is consistent with vitamin B12 deficiency. Further signs of impaired
proprioception, such as decreased ability to sense joint position, are even more
suggestive of the diagnosis. Cerebellar ataxia will have a wide-based gait with a lurching
stride. Cerebrovascular disease may present with a frontal gait disorder that is characterized
by a wide-based, slow, shuffling gait. Parkinson’s disease also causes a shuffling
gait with difficulty initiating and turning en bloc. Amyotrophic lateral sclerosis does
not cause a sensory or proprioceptive neuropathy but will alter gait due to muscle
I-74. The answer is E. (Chap. 25) Abnormalities of the tests listed with intact primary sensation
in an alert cooperative patient identify lesions in the parietal cortex or the thalamocortical
projection to the parietal lobe. Though two-point discrimination is a common
screening technique for cortical sensory deficits, each of the above techniques is a quick
and helpful alternative to evaluate for a cortical sensory deficit. Two-point discrimination
is best tested with a set of calipers that simultaneously touch the skin. Normally, one can
distinguish 3-mm separation of points on the pads of the fingers. Touch localization is
performed by having the patient close his or her eyes and identify the site of the examiner
touching the patient lightly (with finger or cotton swab).
I-75. The answer is B. (Chap. 29) This patient has a Marcus Gunn pupil, or afferent pupil
defect. As the response is only abnormal when light is shone in her left eye, this implies
an afferent defect in that eye mediated by retinal or optic nerve damage. The right and
left efferent systems are intact, based on normal pupillary constriction bilaterally with
light exposure to the right eye. A corneal defect in the left eye may impair vision but
would not block light transmission to the left retina and optic disc: pupillary responses
would therefore remain intact. Common causes of a Marcus Gunn pupil include retrobulbar
optic neuritis and other optic nerve diseases.
I-76. The answer is E. (Chap. 29) This patient has a bitemporal hemianopia implying a lesion
at the optic chiasm. Crossed fibers are more damaged than uncrossed lesions by compression.
Therefore mass lesions at the chiasm may cause bilateral temporal visual field defects.
Sellar lesions such as pituitary adenoma, meningioma, craniopharyngioma, and aneurysm
can lead to this bitemporal hemianopia, which may be subtle to the patient and the examiner.
Optic nerve lesions such as ischemic optic neuropathy, retinal vascular occlusion, advanced
glaucoma, or optic neuritis will cause a horizontal scotoma. Post-chiasmic lesions,
cortical lesions, or geniculate body lesions will cause homonymous hemianopia.
I-77. The answer is A. (Chap. 29) A red and painful eye is often caused by a corneal abrasion.
History is very useful to determine the pretest probability of this type of lesion, because
it will be increased in the context of contact lens use, recent eye trauma, or
particulate exposure. Cobalt-blue examination with fluorescein is then used to confirm
the presence of corneal abrasion. It is particularly important as it occasionally reveals a
dendritic pattern consistent with Herpes simplex virus keratitis, a diagnosis that necessi
tates a very different type of treatment. Lid eversion is useful if there is suspicion that the
foreign body is still present. Corneal abrasion should be treated with topical antibiotic
ointment and patching. Cycloplegia may reduce pain by relaxing the ciliary body.
I-78. The answer is B. (Chap. 29) Conjunctivitis is the most common cause of a red, irritated
eye. Pain is minimal and visual acuity is only minimally impacted. It is usually due
to adenovirus infection. Bacterial infection causes a mucopurulent discharge. Conjunctivitis
invariably presents with ocular discharge, whereas episcleritis does not. Episcleritis,
inflammation of the episclera, a thin layer between the sclera and the conjunctiva, is often
more localized than conjunctivitis, but this cannot always be used to discriminate the
two. Scleritis, a deeper, more intense inflammatory condition than episcleritis, is associated
commonly with various connective tissue disorders and should always be considered
in patients with these conditions.
I-79. The answer is B. (Chap. 29) Herpes simplex virus (HSV) keratitis is a major cause of
blindness in the developed world. Several clues to the diagnosis of HSV keratitis may be
present on examination, including periocular vesicles on the skin and a dendritic pattern
of cornea ulceration on fluorescein examination (which is pathognomonic). However,
these findings are not always present. Viral culture and corneal examination by an experienced
ophthalmologist should always be performed in cases where the diagnosis is unclear.
Angle-closure glaucoma is rare but can be easily ruled out by an ophthalmologist
with a measure of ocular pressure and slit-lamp examination. Uveitis is notable for “cells
and flare” and occasionally hypopyon in the iris and perilimbic sparing. Endophthalmitis
involves the entire globe and evokes pain with ocular movement. Internationally, keratitis
due to trachoma is a common cause of blindness, but it is uncommon in the developed
I-80. The answer is E. (Chap. 29) Uveitis involving the anterior portion of the eye is referred
to as iritis or iridocyclitis. It is diagnosed by slit-lamp examination. The differential diagnosis
for anterior uveitis includes sarcoidosis, ankylosing spondylitis, juvenile rheumatoid
arthritis, inflammatory bowel disease, reactive arthritis, and Behçet’s disease. It may
also be associated with Lyme disease, syphilis, and other infections. Often no cause is
found. Posterior uveitis involves the vitreous, retina, or choroid. It may also accompany
autoimmune diseases, Behçet’s disease, sarcoid, and inflammatory bowel disease. A wide
variety of infections may cause posterior uveitis. Toxoplasmosis specifically causes a posterior
uveitis rather than an anterior uveitis. The extent of screening for diseases associated
with anterior uveitis should depend on a risk assessment for each disorder based on
the history and physical examination.
I-81. The answer is B. (Chap. 29) Optic neuritis is a common inflammatory lesion of the
optic nerve. In a large clinical study, the mean age of patients was 32 years and 75% of the
patients were female. Pain is common with eye movement. Vision loss usually recovers
somewhat even without treatment. Steroids hasten vision gain but do not alter the final
visual acuity. Multiple sclerosis (MS) is a primary concern for all newly diagnosed cases
of optic neuritis. The 10-year cumulative likelihood of developing multiple sclerosis after
an episode of optic neuritis is almost 40%. Patients with a first episode of optic neuritis
should receive a brain MRI to evaluate for MS. It may show characteristic lesions of the
disease prior to the development of CNS symptoms and is a helpful tool for monitoring
progression of disease of this condition while on therapy.
I-82. The answer is A. (Chap. 29) Sudden blindness in a patient with fever and high risk of
endovascular infection is endocarditis until proven otherwise. Even primary bacteremia
in the absence of cardiac vegetation can seed the eye, often leading to endogenous endophthalmitis
or central retinal artery occlusion. Another consideration in this patient
would be septic thrombophlebitis with septic emboli to the eye. Stroke, vasculitis, syphilis,
and hematologic malignancy are possible causes of acute blindness, but are less likely
given the acute presentation with fever
I-83. The answer is B. (Chap. 216) Beta radiation consists of small negatively charged electrons.
These particles can only travel short distances in tissue and lead primarily to burns
similar to thermal injury. Plastic layers and clothing can prohibit penetration of most
beta particles. Beta radiation is frequently released in radiation accidents, and radioactive
iodine is the best-recognized member of this group. Alpha radiation consists of heavy
positively charged particles consisting of two protons and two neutrons. Because of the
large size, alpha particles cannot penetrate tissue. However, if alpha particles are internalized,
they will cause damage to cells within the immediate proximity. The most damaging
particles emitted during a nuclear explosion are gamma rays, x-rays, and neutrons.
Gamma rays and x-rays are both photons and have similar ability to penetrate through
matter. They are the principal type of radiation to cause total body exposure. Neutrons
are heavy, but uncharged, and possess a range of energy. These neutrons can ionize DNA
directly or through generation of free radicals.
I-84. The answer is D. (Chap. 216) Much of the initial damage related to a “dirty” bomb is
related to the power of the blast rather than the radiation. Following a terrorist attack, it
is important to identify all individuals who might have been exposed to radiation. The
initial treatment of these individuals should be to stabilize and treat the most severely injured.
Those with severe injuries should have contaminated clothing removed prior to
transportation to the emergency room, but further care should not be withheld for additional
decontamination as the risk of exposure to health care workers is low. Individuals
with minor injuries who can be safely decontaminated without increasing the risk of
medical complications should be transported to a centralized area for decontamination.
A further consideration regarding treatment following radiation exposure is the total
dose of radiation that an individual was exposed to. At a dose <2>50%. Potential treatments of radiation exposure include
use of colony-stimulating factors and supportive transfusions. Stem cell transfusion and
bone marrow transplantation can be considered in the case of severe pancytopenia that
does not recover. However, this is controversial, given the lack of experience with the procedure
for this indication. Following the Chernobyl nuclear reactor accident, none of the
bone marrow transplants were successful.
I-85. The answer is E. (Chap. 216) This patient has been exposed to radioactive polonium-
210, a strong emitter of alpha radiation, which can be used as a calibration source or neutron
source in nuclear reactors. The patient is presenting with acute radiation sickness after
an unknown ingestion amount. However, his symptoms began early after ingestion,
and there is also severe bone marrow suppression, suggesting that the dose was >2 Gy.
Polonium accumulates in the spleen and kidneys. In addition to supportive care with
transfusions and colony-stimulating factors, chelation with dimercaprol should be attempted
as polonium has a radiologic half-life of 138.4 days and a biologic half-life of 60
days. A bone marrow transplant could be considered if his bone marrow fails to recover.
The presumed ingestion occurred >36 h previously, and a gastric lavage is unlikely to be
helpful. Potassium iodide is useful in radioactive iodine poisoning or overdose.
I-86. The answer is C. (Chap. 215) Mustard gas (sulfur mustard) is a vesicant agent that has
been used as a chemical agent of warfare and terrorism since World War I. In World War I,
sulfur mustard was responsible for 70% of the 1.3 million individuals killed by chemical
warfare, but overall, it had a mortality rate of only 1.9%. Sulfur mustard is composed of
both vapor and liquid components that can cause damage to epithelial surfaces. However,
the effects of mustard gas exposure are delayed several hours after exposure. An initial clue
to which agent the individuals were exposed was the smell of horseradish or burned garlic,
which is characteristic of mustard gas. The earliest effects of mustard exposure involve the
nose, sinuses, and pharynx. Common symptoms include burning in the nares , epistaxis ,
sinus pain, and pharyngeal pain. Damage to the upper airway may cause laryngitis and
nonproductive cough. Lower airway involvement results in nonproductive cough and
dyspnea, but pulmonary hemorrhage is rare. Pseudomembranes may form and cause airway
obstruction. The eyes are the most sensitive organ to mustard vapor injury with a
shorter latency to symptoms than the skin. Ocular symptoms include irritation, conjunctivitis,
photophobia, blepharospasm, pain, and corneal damage. Erythema of the skin begins
2 h to 2 days after exposure and is greatest at warm, moist locations such as the axillae,
neck, antecubital fossae, perineum, and genitalia. Small vesicles may develop, which coalesce
to form bullae. The bullae are usually large and flaccid and filled with a clear to strawcolored
fluid. Death from mustard gas exposure is usually due to sepsis and respiratory
failure, although high-dose exposure can lead to bone marrow failure 7–21 days after the
initial exposure. Phosgene oxime is also a vesicant agent that may present with similar
symptoms, but it can be differentiated from mustard gas by its pungent pepperish odor.
Further, phosgene presents with immediate symptoms and pain. Chlorine is a gas that
causes inhalant damage to the lungs with noncardiogenic pulmonary edema as the primary
presentation. Cyanide is an asphyxiant with rapid onset of symptoms, including
death. Soman is a nerve agent that would present with cholinergic symptoms of miosis,
salivation, muscle fasciculations, and copious secretions. The symptoms have a rapid onset,
with respiratory depression and death within minutes of exposure.
I-87. The answer is F. (Chap. 215) These individuals have been exposed to organophosphorus
nerve agents (soman, sarin, tabun, cyclosarin, and VX) that act by inhibition of tissue
synaptic acetylcholinesterase. The symptoms of nerve agents are those of a cholinergic crisis.
Symptoms manifest in the order in which organ systems are exposed. When nerve
agents are released as a vapor, the first organ that is usually affected is the eyes with miosis
and a feeling that the world is “going black,” as was reported during the Tokyo subway terrorist
attack in which sarin was released. Exposure of the nasopharynx to organophosphates
causes rhinorrhea, excessive salivation, and drooling. Bronchorrhea and cough
frequently occur. After inhalation of the toxin, it is rapidly absorbed into the blood across
the alveolar-capillary membrane. The gastrointestinal tract is usually rapidly affected once
the agents are in the bloodstream, with resultant diarrhea, cramping, nausea, and vomiting.
When death occurs due to nerve agents, it is usually because of the central nervous
system (CNS) effects of these agents. Acetylcholine and its receptor are widely distributed
in the brain, and exposure to large amounts of organophosphate agents leads to rapid unconsciousness,
seizures, and central apnea. Nerve agents have a short half-life in circulation,
and thus, if intervention is made rapidly, improvement in symptoms should likewise
be rapid, without subsequent recurrence of symptoms. The initial treatment for nerve
agents is administration of atropine, which is widely available worldwide. Atropine acts
quickly at muscarinic acetylcholine receptors to alleviate the central apnea but does not reverse
the neuromuscular effects. In addition to anticholinergic therapy with atropine, use
of oximes is also recommended after nerve gas exposure. Oximes such as 2-pralidoxime
(2-PAM) reactivate the cholinesterase to restore normal enzyme function. In individuals
with severe CNS toxicity and seizures, benzodiazepines, such as diazepam, are the treatment
of choice. Typical anticonvulsant drugs, such as phenytoin, carbamazepine, phenobarbital,
and valproic acid are ineffective in treating the seizures caused by nerve agents.
I-88. The answer is B. (Chap. 358) This child has the classic clinical findings of phenylketonuria,
an autosomal recessive disorder of amino acid metabolism in which phenylalanine
cannot be converted to tyrosine. It is the most common inherited disorder of amino acid
metabolism. Untreated or unrecognized cases will usually have a normal birth but will
rapidly begin to show signs of this illness, which include microcephaly, mental retardation,
and seizures. The “mousy” odor is due to phenylacetate accumulation in skin, hair,
and urine. The toxicity of phenylalanine is due to its inhibition of transport of other
amino acids necessary for normal protein, myelin, and neurotransmitter synthesis.
Screening for phenylalanine in the blood should occur prior to 3 weeks of age (usually
this is done at birth) to prevent symptoms. Treatment consists of lifelong dietary phenylalanine
restriction and tyrosine supplementation. If detected at birth, affected children
do not develop the aforementioned complications. Women with phenylketonuria who
become pregnant must maintain strict control before and during pregnancy to avoid
congenital defects, microcephaly, growth retardation, and mental retardation in the baby.
I-89. The answer is A. (Chap. 358) Alkaptonuria is a rare disorder of homogentisic acid oxidase
deficiency which leads to urinary excretion and tissue accumulation of oxidized homogentisic
acid. Patients may present in their thirties or forties with arthritis and darkly
colored urine, as well as tissue pigmentation (ochronosis) from homogentisic acid. The arthritis
is typically in the large joints such as hips, knees, shoulders, and low back. The graybrown
pigmentation is characteristic and can involve the sclera and the ear. The diagnosis
should be suspected in a patient whose urine darkens to blackness. Hawkinsinuria is a related
disorder of amino acid metabolism, in which a 4-hydroxyphenylpyruvate dioxygenase
enzyme defect leads to failure to thrive in infancy. Unlike most amino acid disorders, it is
autosomal dominant. Tryptophanuria results in mental retardation, skin photosensitivity,
and ataxia; however, the enzyme defect leading to this phenotype has not been identified.
Hyperprolinemia type I is caused by a proline oxidase defect and is typically benign. Homocystinuria
is caused by a cystathionine β-synthase defect and leads to mental retardation.
I-90. and. I-91. The answers are C and D. (Chap. 356) Myophosphorylase deficiency (type V
glycogen storage disease), also known as McArdle disease, is the most common adult glycogen
storage disease. The enzyme deficiency limits ATP production via glycogenolysis. It
is characterized by exercise intolerance, muscle cramping, myoglobinuria, and elevated
CKs (at rest and increased with exercise). Symptoms usually develop in adulthood as a
result of either brief intense activity or sustained exertion. Rhabdomyolysis after intense
activity may cause myoglobinuria and subsequent renal failure and is the major clinical
risk about which patients should be warned. Heart disease does not occur. The most
common childhood disorder glycogen storage disease is glucose-6-phosphatase deficiency
(type I), also known as von Gierke’s disease, which presents at age 3–4 months
with growth retardation and hepatosplenomegaly. Lactate dehydrogenase deficiency and
pyruvate kinase deficiency present similarly to McArdle disease but are very rare.
I-92. The answer is C. (Chap. 356; J Shen et al.) Type III glycogen storage disease, a deficiency
in debranching enzyme, causes abnormalities in glycogen degradation. Clinical
manifestations include hepatomegaly, hypoglycemia, short stature, variable skeletal myopathy,
and cardiomyopathy. Dementia does not occur. When liver and muscle are involved,
the disease is termed type IIIa; however, in 15% of patients, liver disease
predominates and these patients are characterized as having type IIIb disease. Fasting ketosis
will occur if glucose/protein intake is not maintained. In most patients, hepatomegaly
improves with age; however, chronic liver disease and cirrhosis may occur in
adulthood, requiring liver transplantation. Hepatocellular carcinoma has also been reported.
Treatment consists of dietary management with frequent high-carbohydrate
meals and possible nocturnal drip feeding to avoid hypoglycemia. Linkage analysis markers
can be used for screening carriers and prenatal diagnosis.
I-93. The answer is C. (Chap. 64) Presymptomatic testing applies to diseases where a specific
genetic alteration is associated with a near 100% likelihood of developing the disease, such
as Huntington’s disease. In contrast, predisposition testing predicts a risk for disease that is
<100%.>42 years of age have a 33% chance of a trisomic conception. Despite this well-described
association, little is known about the mechanism that drives it.
I-95. The answer is E. (Chap. 63) Human cells contain 46 chromosomes: 22 pairs of autosomal
chromosomes and one pair of sex chromosomes, XX in females and XY in males.
Deviation in the number or structure of these chromosomes is common and is estimated
to occur in 10–25% of all pregnancies. They are the most common cause of fetal loss. In
pregnancies surviving to term, they are the leading known cause of birth defects and
I-96. The answer is C. (Chap. 343) This group of genetic conditions often presents with disorders
of sexual differentiation. Genetically, Klinefelter syndrome results from a meiotic
nondysjunction of sex chromosomes during gametogenesis, producing a 47,XXY individual.
Phenotypically, these individuals are male but have eunuchoid features, small testes,
decreased virilization, and gynecomastia. The other disorders listed in the question
may result in sexual ambiguity, more commonly in males. In mixed gonadal dysgenesis,
there is mosaicism resulting from the genotype 46,XY/45,X. Depending on the proportion
of cells with the 46,XY genotype, the phenotype can be either male or female. Testicular
dysgenesis results from the absence of müllerian inhibiting substance during
embryonic development and may be caused by multiple genetic mutations and may be
associated with the absence of müllerian-inhibiting substance and reduced testosterone
production. Feminization may also occur through androgen insensitivity and mutations
in the androgen receptor. Virilization of females with resultant ambiguous sexual differentiation
most commonly occurs in patients with congenital adrenal hyperplasia (CAH).
The most common cause of CAH is 21-hydroxylase deficiency, which results in ambiguous
female genitalia, hypotension, and salt wasting.
I-97. The answer is E. (Chap. 343) Turner syndrome, or gonadal dysgenesis, is a common
chromosomal disorder that affects 1 in 2500 female births. The most common genetic
defect is the 45,XO karyotype, which causes half of all phenotypic cases of this syndrome.
Age at diagnosis is variable, based on the clinical manifestations. Most cases are diagnosed
perinatally on the basis of reduced fetal growth or lymphedema at birth with nuchal
folds, a low posterior hairline, or left-sided cardiac defects. Some girls may not be
diagnosed in childhood and come to attention much later in life because of delayed
growth and lack of sexual maturation. Limited pubertal development occurs in up to
30% of girls with Turner syndrome, with approximately 2% reaching menarche. Owing
to the frequency of congenital heart and genitourinary defects, a thorough workup
should be done after the diagnosis, including an echocardiogram and renal imaging.
Long-term management includes growth hormone replacement during childhood and
estrogen replacement to maintain bone mineralization and feminization.
I-98. The answer is B. (Chap. 357) This patient presents with the classic findings of an inherited
disorder of connective tissue, particularly Marfan syndrome. The presentation is
not consistent with the bony deformities or blue sclera seen in patients with osteogenesis
imperfecta, and he is tall with long extremities, which makes chondroplasia very unlikely.
However, his hypermobility and lens disorders suggest Marfan syndrome or, less commonly,
Ehlers-Danlos syndrome. Given the high risk of aortic root disease in Marfan syndrome,
echocardiography is indicated in this patient. The other screening tests are not
specific to Marfan syndrome and are not appropriate in a 30-year-old male.
I-99. The answer is C. (Chap. 62) Neoplastic disorders may arise from mutations in DNA that
affect oncogenes, tumor suppressor genes, apoptotic genes, and DNA repair genes. Several
genetic disorders involving DNA repair enzymes underscore the importance of these mutations.
Patients with xeroderma pigmentosum have defects in DNA damage recognition and
in nucleotide excision and repair. These patients often have skin cancers as a result of the
mutagenic effects of ultraviolet light. Ataxia-telangiectasia is characterized by large telangiectatic
lesions on the face, cerebellar ataxia, immunologic defects, and hypersensitivity to
ionizing radiation. Mutation in the ATM gene that causes AT gives rise to defects in meiosis
and increasing damage from ionizing radiation. Fanconi’s anemia is caused by mutations in
multiple complementation groups that are characterized by various congenital anomalies
and a marked predisposition to aplastic anemia and acute myeloid leukemia. HNPCC is
caused by mutations in one of several mismatch repair genes that result in microsatellite instability
and a high incidence of colon, ovarian, and uterine cancers. Fragile X syndrome is
caused by unstable trinucleotide repeats that destabilize DNA. It is characterized by Xlinked
inheritance and typical large ears, macroorchidism, and mental retardation.
I-100. The answer is C. (Chap. 62) Mendelian inheritance patterns do not apply to mitochondrial
genetics. Mitochondrial DNA (mtDNA) consists of small encoding transfer and ribosomal
RNAs and various proteins that are involved in oxidative phosphorylation and
adenosine triphosphate (ATP) generation. mtDNA exists as a circular chromosome within
cells. The mitochondrial genome does not recombine. The genetic material that is introduced
into the egg by the sperm does not contain mitochondrial DNA, therefore, inheritance
is maternal. All the children of an affected mother will inherit the disorder. An
affected father will not transmit the disorder. The clinical manifestations of the various disorders
in mitochondrial genetics are characterized by alterations in oxidative phosphorylation
that lead to reductions in the ATP supply and apoptosis. Areas of high dependence on
oxidative phosphorylation include skeletal and cardiac muscle and the brain. During replication,
the number of mitochondria can drift among various cells and tissues, resulting in
heterogeneity, or heteroplasmy. This results in further variation in the clinical phenotype.
Acquired mutations in the mitochondrial genome are thought to play a significant role in
age-related degenerative disorders such as Alzheimer’s disease and Parkinson’s disease.
I-101. The answer is B. (Chap. 62) Genetic imprinting is gene inactivation that results in
preferential expression of an allele depending on its parental origin. It has an important
role in a number of diseases, including malignancies. Abnormal expression in the paternally
derived copy of the insulin-like growth factor II (IGF-II) gene results in the cancer
predisposing Beckwith-Wiedemann syndrome. Uniparental disomy is the inheritance of
dual copies of either maternal or paternal chromosomes. This may result in similar phenotypes,
as in the case of imprinting. The Prader-Willi and Angelman’s syndromes may
result from uniparental disomy involving inheritance of defective maternal or paternal
chromosomes, respectively. Similarly, hydatidiform moles may contain normal numbers
of diplid chromosomes, all of which are of paternal origin. The opposite occurs in ovarian
teratomas. Lyonization is epigenetic inactivation of one of the two X chromosomes in
every cell of the female. Somatic mosaicism is the presence of two or more genetically distinct
cell lines in the tissue of an individual. The term anticipation is often used to refer to
diseases caused by trinucleotide repeats that are often characterized by worsening of clinical
phenotypes in successive generations. These diseases, such as Huntington’s disease
and fragile X syndrome, are characterized by expansion of these repeats in subsequent
generations of individuals, resulting in earlier and often more severe clinical phenotypes.
I-102. The answer is D. (Chap. 357) Connective tissue is composed of macromolecules (collagen,
elastin, fibrillin, proteoglycans, etc.) that are assembled into an insoluble extracellular
matrix. Disorders of any of these macromolecules may result in a disorder of
connective tissue. Osteogenesis imperfecta is caused by mutations in type I procollagen.
Over 400 mutations have been found in patients with OI. Clinically, it is characterized by
decreased bone mass, brittle bones, blue sclerae, dental abnormalities, joint laxity, and
progressive hearing loss. The phenotype may range from severe disease with in utero death
to milder forms with lesser severity and survival into adulthood. Ehlers-Danlos syndrome
is a heterogenous set of disorders characterized by joint laxity, hyperelasticity of the skin,
and other defects in collagen synthesis. A variety of defects have been identified in different
types of collagen as well as enzymes that facilitate collagen cross-linking. Marfan syndrome
is characterized by a triad of features: long, thin extremities (with arachnodactyly
and loose joints), reduced vision as a result of ectopia lentis, and aortic aneurysms. Defects
in the fibrillin gene are responsible for this syndrome. Alport syndrome is caused by mutations in type IV collagen, resulting in the most common phenotype of X-linked inheritance,
hematuria, sensorineural deafness, and lenticonus. McArdle’s disease is a defect in
glycogenolysis that results from myophosphorylase deficiency.
I-103. The answer is D. (Chap. 355) Lysosomes are subcellular organelles that contain specific
hydrolyases that allow the processing and degradation of proteins, nucleic acids, carbohydrates,
and lipids. Lysosomal storage diseases result from mutations in various genes for
these hydrolyases. Clinical symptoms result from the accumulation of the undegraded macromolecule.
Tay-Sachs disease is caused by a deficiency of hexosaminidase A. Buildup of
GM2 gangliosides results in a phenotype that is characterized by a fatal progressive neurodegenerative
disease. In the infantile form, these patients have macrocephaly, loss of motor
skills, an increased startle reaction, and a macular cherry red spot. The juvenile-onset form
presents with ataxia and progressive dementia that result in death by age 15. The adult-onset
form is characterized by clumsiness in childhood, progressive motor weakness in adolescence,
and neurocognitive decline. Death occurs in early adulthood. Survival to the third or
fourth decade is rare. Splenomegaly is uncommon. The disease is seen most commonly in
Ashkenazi Jews, with a carrier frequency of about 1 in 30. Inheritance is autosomal recessive.
I-104. The answer is D. (Chap. 355) Gaucher disease is an autosomal recessive lysosomal storage
disorder caused by decreased activity of acid β-glucosidase. Nearly 200 mutations have been
described. Type 1 Gaucher disease can present from childhood to young adulthood. The average
age at diagnosis is 20 years in white people. Clinical features result from an accumulation
of lipid-laden macrophages, termed Gaucher cells, throughout the body. Hepatosplenomegaly
is present in virtually all symptomatic patients. Bone marrow involvement is common,
with subsequent infarction, ischemia, and necrosis. Anemia and thrombocytopenias may occur.
Bone pain is common. Although the liver and spleen may become massive, severe liver
dysfunction is very rare. The disease is most common in Ashkenazi Jewish populations. The
diagnosis is made by measuring enzyme activity. Enzyme therapy is currently the treatment of
choice in significantly affected patients. Other therapies include symptomatic management of
the blood cytopenias and joint replacement surgery for bone injury. Type 2 Gaucher disease is
a rare, severe central nervous system (CNS) disease that leads to death in infancy. Type 3 disease
is nearly identical to type 1 disease except that the course is more rapidly progressive.
I-105. The answer is A. (Chap. 62) The information provided in the pedigree is adequate to
determine the mode of a single-gene inheritance pattern. The example provided is typical
of patients with hemophilia A or Duchenne’s muscular dystrophy. Other examples exist.
X-linked recessive inheritance is marked by the fact that the incidence of the trait is much
higher in males than in females. The genetic trait is passed from an affected male through
all his daughters to, on average, half their sons. The trait is never transmitted directly from
father to son. The trait may be transmitted through a series of carrier females; if that occurs,
the affected males are related to each other through the female, as in this case.
I-106. The answer is A. (Chap. 62) Many common diseases are known to “run in families” yet
are not inherited in a simple Mendelian fashion. It is likely that the expression of these disorders
depends on a family of genes that can impart a certain degree of risk and then be modified
by subsequent environmental factors. The risk of the development of disease in a relative
of an affected person varies with the degree of relationship; first-degree relatives (parents,
siblings, and offspring) have the highest risk, which in itself varies with the specific disease.
Many of these multifactorial genetic diseases are inherited in a greater frequency in persons
with certain HLA (major histocompatibility system) types. For example, there is a tenfold increased
risk of celiac sprue (gluten-sensitive enteropathy) in persons who have HLA-B8. This
genotype also imparts an increased risk for chronic active hepatitis, myasthenia gravis, and
Addison’s disease. The incidence of diabetes mellitus is much higher in those expressing
HLA-D3 and HLA-D4. Spondyloarthropathies, psoriatic arthritis (HLA-B27), hyperthyroidism
(HLA-DR3), and multiple sclerosis (HLA-DR2) are other examples of diseases with
histocompatibility predispositions. By contrast, Wilson’s disease and cystic fibrosis are inherited
in an autosomal recessive fashion, and adult polycystic kidney disease and neurofibromatosis
are among the disorders inherited in an autosomal dominant manner.
I-107. The answer is C. (Chap. 19) Fever of unknown origin (FUO) is defined as the presence
of fevers to >38.3°C (101.0°F) on several occasions occurring for >3 weeks without a defined
cause after appropriate investigation into potential causes have failed to yield a diagnosis.
Initial laboratory investigation into an FUO should include a complete blood count
with differential, peripheral blood smear, ESR, C-reactive protein, electrolytes, creatinine,
calcium, liver function tests, urinalysis, and muscle enzymes. In addition, specific testing
for a variety of infections should be performed, including VDRL for syphilis, HIV, CMV,
EBV, PPD testing, and blood, sputum, and urine cultures if appropriate. Finally, the
workup should include evaluation for inflammatory disorders. These tests include antinuclear
antibodies, rheumatoid factor, ferritin, iron, and transferrin. In several large studies,
infectious etiologies are the most commonly identified source of FUO. In the earlier studies,
infectious etiologies accounted for 32–36% of all FUO. In more recent studies, up to 30% of
individuals will not have an identified cause of FUO, and infectious etiologies continue to
comprise 25% of all FUO. The most common infection causing FUO is extrapulmonary tuberculosis.
Viral and fungal etiologies are also common. In addition, intraabdominal, retroperitoneal,
renal, and paraspinal abscesses should be considered. In earlier studies,
neoplasm was the second most common cause of FUO. However, given the improvements
in imaging and diagnostic techniques, neoplasm accounts for fewer cases of FUO than previously
described. Presently the second most common cause of FUO is noninfectious inflammatory
disorders. In the elderly, giant cell arteritis can present as an FUO, as can many
other inflammatory disease such as polymyositis, Behçet’s disease, and adult Still’s disease.
Drug fever and hereditary periodic fever syndromes are grouped in the “miscellaneous” category
and are among the least common causes of prolonged fever of uncertain origin.
I-108. The answer is C. (Chap. 58; R Crapo et al.) Chronic hypoxia, seen in people acclimated
to high altitudes, causes a shift in the oxygen dissociation curve to the right (decreased
affinity) causing more oxygen to be released in tissues deprived of oxygen.
This is achieved by increased red blood cell production of 2,3-diphosphoglycerate
(2,3-DPG). Four factors decrease the affinity of hemoglobin for oxygen: high temperature,
increased partial pressure of carbon dioxide (the Bohr effect), increased levels of
2,3-DPG, increase in acidity. The opposite changes in these four factors increase hemoglobin
affinity for oxygen and impair delivery of oxygen to peripheral tissues. Healthy
men acclimated to altitude (1400 m) have an average pH/PaCO2 of 7.43/34 mmHg and
healthy women 7.44/33 mmHg. Hemoglobin concentration will increase due to the
stimulatory effect of hypoxia on erythropoietin production.
I-109. The answer is E. (Chap. e3) Minority patients have poorer health outcomes from many
preventable and treatable conditions such as cardiovascular disease, asthma, diabetes,
cancer, and others. The causes of these differences are multifactorial and include social
determinants (education, socioeconomic status, environment) and access to care (which
often leads to more serious illness before seeking care). However, there are also clearly described
racial differences in quality of care once patients enter the health care system.
These differences have been found in cardiovascular, oncologic, renal, diabetic, and palliative
care. Eliminating these differences will require systematic changes in health system
factors, provider level factors, and patient level factors.
I-110. The answer is B. (Chap. e6) To be able to differentiate among the disorders that cause
memory loss, it should be determined whether the patient has nondeclarative or declarative
memory loss. A simple way to think of the differences between nondeclarative and
declarative memory is to consider the difference between “knowing how” (nondeclarative)
and “knowing who or what” (declarative). Nondeclarative memory loss refers to loss
of skills, habits, or learned behaviors that can be expressed without an awareness of what
was learned. Procedural memory is a type of nondeclarative memory and may involve
motor, perceptual, or cognitive processes. Examples of nondeclarative procedural memory
include remembering how to tie one’s shoes (motor), responding to the tea kettle
whistling on the stove (perceptual), or increasing ability to complete a puzzle (cognitive).
Nondeclarative memory involves several brain areas, including the amygdala, basal ganglia, cerebellum, and sensory cortex. Declarative memory refers to the conscious memory
for facts and events and is divided into two categories: semantic memory and episodic
memory. Semantic memory refers to general knowledge about the world without specifically
recalling how or when the information was learned. An example of semantic memory
is the recollection that a wristwatch is an instrument for keeping time. Vocabulary
and the knowledge of associations between verbal concepts comprise a large portion of
semantic memory. Episodic memory allows one to recall specific personal experiences.
Examples of episodic memory include ability to recall the birthday of a spouse, to recognize
a photo from one’s wedding, or recall the events at one’s high school graduation. The
areas of the brain involved in declarative memory include the hippocampus, entorhinal
cortex, mamillary bodies, and thalamus.
I-111. The answer is F. (Chap. 60) This patient’s lymphadenopathy is benign. Inguinal nodes
<2>5% of the total
body weight over a 6- to 12-month period should prompt an evaluation. In the elderly,
weight loss is an independent predictor of morbidity and mortality. Studies in the elderly
have found mortality rates of 10–15%/year in patients with significant unintentional
weight loss. It is important to confirm the weight loss and the duration of time over which
it occurred. The causes of weight loss are protean and usually become apparent after a
careful evaluation and directed testing. A thorough review of systems should be performed
including constitutional, respiratory, gastrointestinal, and psychiatric. Travel history and
risk factors for HIV are also important. Medications and supplements should be reviewed.
The physical examination must include an examination of the skin, oropharynx, thyroid
gland, lymphatic system, abdomen, rectum, prostate, neurologic system, and pelvis. A reasonable
laboratory approach would include an initial phase of testing including the tests
outlined in this scenario. In the absence of signs or symptoms, close follow-up rather than
undirected testing is appropriate. Total-body scanning with PET or CT has not been
shown to be effective as screening tests without a clinical indication.
I-120. The answer is A. (Chaps. 56 and 311) Drugs can trigger inflammatory mediators (histamine,
leukotrienes, etc.) directly; i.e., the pharmacoimmune concept. These “anaphylactoid”
responses are not IgE-mediated. NSAIDS, aspirin, and radiocontrast media are
frequent causes of pharmacologically mediated anaphylactoid reactions. Given that this is
an investigational drug, it is improbable that patients in this study have taken this drug
before. T cell clones have been obtained after pharmacologically mediated anaphylactoid
reactions, with a majority being CD4+. A constitutively IgE receptor would not manifest
solely after drug exposure.
I-121. The answer is D. (Chap. 214) Anthrax is caused by the gram-positive spore-forming
rod Bacillus anthrax. Anthrax spores may be the prototypical disease of bioterrorism. Although
not spread person to person, inhalational anthrax has a high mortality, a low infective
dose (five spores), and may be spread widely with aerosols after bioengineering. It
is well-documented that anthrax spores were produced and stored as potential bioweapons.
In 2001, the United States was exposed to anthrax spores delivered as a powder in
letters. Of 11 patients with inhalation anthrax, 5 died. All 11 patients with cutaneous anthrax
survived. Because anthrax spores can remain dormant in the respiratory tract for 6
weeks, the incubation period can be quite long and post-exposure antibiotics are recommended
for 60 days. Trials of a recombinant vaccine are underway.
I-122. The answer is D. (Chap. 214) The three major clinical forms of anthrax are gastrointestinal
(GI), cutaneous, and inhalational. GI anthrax results from eating contaminated
meat and is an unlikely bioweapon. Cutaneous anthrax results from contact with
the spores and results in a black eschar lesion. Cutaneous anthrax had a 20% mortality
before antibiotics became available. Inhalational anthrax typically presents with the most
deadly form and is the most likely bioweapon. The spores are phagocytosed by alveolar
macrophages and transported to the mediastinum. Subsequent germination, toxin elaboration,
and hematogenous spread cause septic shock. A characteristic radiographic finding
is mediastinal widening and pleural effusion. Prompt initiation of antibiotics is
essential as mortality is likely 100% without specific treatment. Inhalational anthrax is
not known to be contagious. Provided that there is no concern for release of another
highly infectious agent such as smallpox, only routine precautions are warranted.
I-123. The answer is F. (Chap. 214) Smallpox has been proposed as a potential bioweapon. It
is essential that clinicians be able to recognize this infection clinically and distinguish it
from the common infection with varicella. Infection with smallpox occurs principally
with close contact, although saliva droplets or aerosols may also spread disease. Approximately
12–14 days after exposure, the patient develops high fever, malaise, nausea, vomiting,
headache, and a maculopapular rash that begins on the face and extremities and
spreads (centripetally) to the trunk with lesions at the same stage of development at any
given location. This is in contrast to the rash of varicella (chickenpox), which begins on
the face and trunk and spreads (centrifugally) to the extremities with lesions at all stages of
development at any given location. Smallpox is associated with a 10–30% mortality. Vaccination
with vaccinia (cowpox) is effective, even if given during the incubation period.
I-124. The answer is C. (Chap. 214) Tularemia, caused by the small nonmotile gram-negative
coccobacillus Francisella tularensis, has been proposed as a potential bioweapon (CDC
category A) because of its high degree of environmental infectiousness, potential for
aerolization, and ability to cause severe pneumonia. It is not as lethal as anthrax or plague
(Yersinia pestis). Infection with F. tularensis is most common in rural areas where small
mammals serve as a reservoir. Human infections may occur from tick or mosquito bites
or from contact with infected animals while hunting. The isolation of this pathogen in
two patients without obvious exposure risk factors should prompt concern that a terrorist
has intentionally aerosolized F. tularensis as an agent of bioterror. It is highly infectious,
with as few as 10 organisms causing infection, and outbreaks have been reported in
microbiology laboratory workers streaking Petri dishes. However, it is not infectious person-
to-person. Streptomycin, doxycycline, gentamicin, chloramphenicol, and ciprofloxacin
are likely effective agents; however, given the possibility of genetically altered
organisms, broad-spectrum antibiotics are indicated pending sensitivity testing. In outbreaks,
tularemia pneumonia has a mortality of 30–60% in untreated patients and <2%
with appropriate therapy.
I-125. The answer is C. (Chap. 389) The most common physical effects of smoking marijuana
are conjunctival infection and tachycardia; however, tolerance for the tachycardia
develops quickly among habitual users. Smoking marijuana can precipitate angina in
those with a history of coronary artery disease, and such patients should be advised to
abstain from smoking marijuana or using cannabis compounds. This effect may be more
pronounced with smoking marijuana than cigarettes. Because chronic use of marijuana
typically involves deep inhalation and prolonged retention of marijuana smoke, chronic
smokers may develop chronic bronchial irritation and impaired single-breath carbon
monoxide diffusion capacity (DLCO). Decreased sperm count, impaired sperm motility,
and morphologic abnormalities of spermatozoa have been reported. Prospective studies
demonstrated a correlation between impaired fetal growth and development with heavy
marijuana use during pregnancy.
I-126. The answer is B. (Chap. 389) Although LSD abuse has been a well-known public health
hazard, the use of LSD may be increasing in some communities in the Unites States among
adolescents and young adults. LSD causes a variety of bizarre perceptual changes that can
last for up to 18 h. Panic episodes due to LSD use (“bad trip”) are the most frequent medical
emergency associated with LSD. These episodes may last up to 24 h and are best treated
in a specialized psychiatric setting. Marijuana intoxication causes a feeling of euphoria and
is associated with some impairment in cognition similar to alcohol intoxication. Heroin intoxication
usually produces a feeling of euphoria and intoxication; panic attacks during usage
are uncommon. Methamphetamine intoxication produces feelings of euphoria and
decreases the fatigue associated with difficult life situations. Psychosis is possible with the
ingestion of most illicit substances, depending on the user and the environmental setting;
however, the classic panic attack associated with the “bad trip” of LSD is distinct in the predominance
of paranoia and fear of imminent doom.
I-127. The answer is E. (Chap. e35) “Body packing” is a common practice among members of
the illicit drug trade for transport of illicit drugs across international borders. Human
“mules” swallow sealed packages of illicit drugs in special bags to conceal the drug from
drug enforcement officials. Because these bags may rupture while in the gastrointestinal
tract, all persons who are unconscious at airports, or who develop symptoms after returning
from a country where drug trafficking is common, should be evaluated for this
particular contingency. Initial examination is a cursory orifice examination, but abdominal
imaging and bowel lavage are necessary in many cases. Confirmed cases need to be
followed closely as further absorption of the drug is possible. Blood cultures and echocardiogram
are only necessary if infective endocarditis is suspected. However, this patient
has no fevers or indication of active drug abuse. CSF analysis would be necessary only if
no obvious cause of the patient’s mental status change were available. As her respiratory
rate is now elevated rather than low, her mental status is normal, and her oxygen saturations
are high, there is little reason to expect CO2 retention or hypoxemia. A blood gas
can likely be avoided unless her clinical status changes.
I-128. The answer is D. (Chap. e35) Sympathetic toxidromes share many features including
increased pulse, blood pressure, neuromuscular activity, tremulousness, delirium, and
agitation. In many cases, these syndromes can be subclassified according to other features
or relative strengths of the above symptoms. Sympathomimetics like cocaine and amphetamines
cause extreme elevations in vital signs and organ damage due to peripheral
vasoconstriction, usually in the absence of hallucinations. Benzodiazepine and alcohol
withdrawal syndromes present similarly but hallucinations, and often seizures, are common
in these conditions. Hot, dry, flushed skin, urinary retention, and absent bowel
sounds characterize anticholinergic syndromes associated with antihistamines, antipsychotics,
antiparkinsonian agents, muscle relaxants, and cyclic antidepressants. Nystagmus
is a unique feature of ketamine and phencyclidine overdose.
I-129. The answer is E. (Chap. e35) Opiate overdose falls broadly into a toxidrome characterized
by physiologic depression and sedation. If a history is obtained suggesting a toxic ingestion
or injection, then the diagnosis is straightforward. However, this history is often
absent and it can be a challenge initially to differentiate opiate toxicity from other central
nervous system (CNS) and physiologic depressants. Therefore, naloxone should always
be given as a diagnostic and therapeutic trial under circumstances of unexplained altered
mental status, especially in the presence of coma or seizures. An immediate clinical improvement
characterizes opiate overdose. In opiate overdose, abnormal vital signs occur
exclusively as a result of central respiratory depression and the accompanying hypoxemia.
Low blood pressure in an alert patient should prompt a search for an alternative explanation
for the hypotension. An anion gap metabolic acidosis with normal lactate is seen in
syndromes such as methanol or ethylene glycol ingestion: mental status change usually
precedes vital sign changes, and vital signs are often discordant as a result of physiologic
adjustments to the severity of the acidosis. Mydriasis is a result of stimulant use. Miosis is
associated with CNS depression. Sweating and drooling are manifestations of cholinergic
agents such as muscarinic and micotinic agonists.
I-130. The answer is A. (Chap. e35) Lithium interferes with cell membrane ion transport,
leading to nephrogenic diabetes insipidus and falsely elevated chloride. This can cause
the appearance of low anion gap metabolic acidosis. Sequelae include nausea, vomiting,
ataxia, encephalopathy, coma, seizures, arrhythmia, hyperthermia, permanent movement
disorder, and/or encephalopathy. Severe cases are treated with bowel irrigation, endoscopic
removal of long-acting formulations, hydration, and sometimes hemodialysis.
Care should be taken because toxicity occurs at lower levels in chronic toxicity compared
to acute toxicity. Salicylate toxicity leads to a normal osmolal gap as well as an elevated
anion gap metabolic acidosis, respiratory alkalosis, and sometimes normal anion gap
metabolic acidosis. Methanol toxicity is associated with blindness and is characterized by
an increased anion gap metabolic acidosis, with normal lactate and ketones, and a high
osmolal gap. Propylene glycol toxicity causes an increased anion gap metabolic acidosis
with elevated lactate and a high osmolal gap. The only electrolyte abnormalities associated
with opiate overdose are compensatory to a primary respiratory acidosis.
I-131. The answer is B. (Chap. e35) The clinical ramifications of this question are critical.
Drug effects begin earlier, peak later, and last longer in the context of overdose, compared
to commonly referenced values. Therefore, if a patient has a known ingestion of a toxic
dose of a dangerous substance and symptoms have not yet begun, then aggressive gut decontamination
should ensue, because symptoms are apt to ensue rapidly. The late peak
and longer duration of action are important as well. A common error in practice is for
patients to be released or watched less carefully after reversal of toxicity associated with
an opiate agonist or benzodiazepine. However, the duration of activity of the offending
toxic agent often exceeds the half-life of the antagonists, naloxone or flumazenil, requiring
the administration of subsequent doses several hours later to prevent further central
nervous system or physiologic depression.
I-132. The answer is E (Chap. e35) Management of the toxin-induced seizure includes addressing
the underlying cause of the seizure, antiepileptic therapy, reversal of the toxin effect,
and supportive management. In this patient, lithium toxicity has led to diabetes
insipidus and encephalopathy. The patient was unlikely to take in free water due to his incapacitated
state, and as a result developed hypernatremia. The hypernatremia and lithium
toxicity are contributing to his seizure and should be addressed with careful free
water replacement and bowel irrigation, plus hemodialysis. As he is not protecting his
airway, supportive management will need to include endotracheal intubation. Antiseizure
prophylaxis with first-line agent, a benzodiazepine, has failed, and therefore he
should be treated with a barbiturate as well as a benzodiazepine. Benzodiazepines should
be continued as they work by a different mechanism than barbiturates in preventing seizures.
Phenytoin is contraindicated for the use of toxic seizures due to worse outcomes
documented in clinical trials for this indication.
I-133. The answer is E. (Chap. e35) Gastric decontamination is controversial because there
are few data to support or refute its use more than an hour after ingestion. It remains a
very common practice in most hospitals. Syrup of ipecac is no longer endorsed for inhospital
use and is controversial even for home use, though its safety profile is well documented,
and therefore it likely poses little harm for ingestions when the history is clear
and the indication strong. Activated charcoal is generally the decontamination method of
choice as it is the least aversive and least invasive option available. It is effective in decreasing
systemic absorption if given within an hour of poison ingestion. It may be effective
even later after ingestion for drugs with significant anticholinergic effect (e.g.,
tricyclic antidepressants). Considerations are poor visibility of the gastrointestinal tract
on endoscopy following charcoal ingestion, and perhaps decreased absorption of oral
drugs. Gastric lavage is the most invasive option and is effective, but it is occasionally associated
with tracheal intubation and bowel-wall perforation. It is also the least comfortable
option for the patient. Moreover, aspiration risk is highest in those undergoing
gastric lavage. All three of the most common options for decontamination carry at least a
1% risk of an aspiration event, which warrants special consideration in the patient with
mental status change.
I-134. The answer is C. (Chap. 60) To keep body weight stable, energy intake must match energy
output. Energy output has two main determinants: resting energy expenditure and
physical activity. Other, less clinically important determinants include energy expenditure
to digest food and thermogenesis from shivering. Resting energy expenditure can be
calculated and is 900 + 10w (where w = weight) in males and 700 + 7w in females. This
calculation is then modified for physical activity level. The main determinant of resting
energy expenditure is lean body mass.