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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 ganI.
glia, 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>

1-112 The answer is E. (Chap. 60) Hard, matted, nontender lymph nodes are worrisome for
tumor and should always prompt a workup, including excisional biopsy, if possible, and
examination for a primary source depending on the location of the nodes. Supraclavicular
lymphadenopathy should always be considered abnormal, particularly when documented
on the left side. A thorough investigation for cancer, particularly with a primary gastrointestinal
source, is necessary. Splenomegaly associated with diffuse adenopathy can be
associated with tumor, particularly lymphoma, but is most often associated with systemic
infections, such as mononucleosis, cytomegalovirus, or HIV, that often cause diffuse lymphadenopathy.
Generalized lymphadenopathy and splenomegaly may be found in autoimmune
diseases such as systemic lupus erythematosus or mixed connective tissue
disease. Tender adenopathy of the cervical anterior chain is nearly always associated with
infection of the head and neck, most commonly a viral upper respiratory infection.

I-113. The answer is C. (Chap. 60) Portal hypertension causes splenomegaly via passive congestion
of the spleen. It generally causes only mild enlargement of the spleen as expanded
varices provide some decompression for elevated portal pressures. Myelofibrosis necessitates
extramedullary hematopoiesis in the spleen, liver, and even other sites such as the
peritoneum, leading to massive splenomegaly due to myeloid hyperproduction. Autoimmune
hemolytic anemia requires the spleen to dispose of massive amounts of damaged
red blood cells, leading to reticuloendothelial hyperplasia and frequently an extremely
large spleen. Chronic myelogenous leukemia and other leukemias/lymphomas can lead
to massive splenomegaly due to infiltration with an abnormal clone of cells. If a patient
with cirrhosis or right-heart failure has massive splenomegaly, a cause other than passive
congestion should be considered.

I-114. The answer is A. (Chap. 60) The presence of Howell-Jolly bodies (nuclear remnants),
Heinz bodies (denatured hemoglobin), basophilic stippling, and nucleated red blood
cells in the peripheral blood implies that the spleen is not properly clearing senescent or
damaged red blood cells from the circulation. This usually occurs because of surgical
splenectomy but is also possible when there is diffuse infiltration of the spleen with malignant
cells. Hemolytic anemia can have various peripheral smear findings depending
on the etiology of the hemolysis. Spherocytes and bite cells are an example of damaged
red cells that might appear due to autoimmune hemolytic anemia and oxidative damage,
respectively. DIC is characterized by schistocytes and thrombocytopenia on smear, with
42 I. INTRODUCTION TO CLINICAL MEDICINE — ANSWERS
elevated INR and activated partial thromboplastin time as well. However, in these conditions,
damaged red cells are still cleared effectively by the spleen. Transformation to acute
leukemia does not lead to splenic damage.

I-115. The answer is A. (Chap. 60) Splenectomy leads to an increased risk of overwhelming
postsplenectomy sepsis, an infection that carries an extremely high mortality rate. The most
commonly implicated organisms are encapsulated. Streptococcus pneumoniae, Haemophilus
influenzae and sometime gram-negative enteric organisms are most frequently isolated.
There is no known increased risk for any viral infections. Vaccination for S. pneumoniae, H.
influenzae, and Neisseria meningitidis is indicated for any patient who may undergo splenectomy.
The vaccines should be given at least 2 weeks before surgery. The highest risk of sepsis
occurs in patients under 20 because the spleen is responsible for first-pass immunity and
younger patients are more likely to have primary exposure to implicated organisms. The risk
is highest during the first 3 years after splenectomy and persists at a lower rate until death.

I-116. The answer is A. (Chap. 49) Erectile dysfunction increases with age but is not considered
a normal part of the aging process. This patient has evidence of atherosclerosis, which is the
most common organic cause of erectile dysfunction in males. Medications account for 25%
of cases of erectile dysfunction: diuretics, beta blockers and other antihypertensives being
common culprits. Psychogenic erectile dysfunction can cause or be caused by organic erectile
dysfunction. We are given no indication that this patient is experiencing a relationship conflict
or that he has developed performance anxiety. This patient is not clinically hypogonadal.
I-117. The answer is D. (Chap. 49) This patient has vasculogenic erectile dysfunction. Sildenafil,
tadalafil, and vardenafil are the only approved and effective agents for erectile dysfunction
due to psychogenic, diabetic, or vasculogenic causes or resulting from postradical
prostatectomy and spinal cord injury. As such, they should be considered as first-line therapy.
If the patient were to fail to respond to oral agents, intraurethral vasoactive substances
are a reasonable next choice. Implantation of a penile prosthesis would be of consideration
if intraurethral or intracavernosal injections failed. Sex therapy will not address the organic
dysfunction that this patient has, as evidenced by the lack of nocturnal erections.

I-118. The answer is C. (Chap. 49) Female sexual dysfunction (FSD) includes disorders of desire, arousal, pain, and muted orgasm. The risk factors for FSD are similar to those in
men including cardiovascular disease, endocrine diseases, neurologic disorders, and
smoking. The female sexual response requires the presence of estrogens and possibly androgens.
While the neurotransmission for clitoral corporal engorgement are the same as
for men and include nitric oxide, the use of PDE-5 inhibitors for FSD has not been
proven efficacious and should be discouraged until proof is available that they are effective.
PDE-5 inhibitors have not been shown to be of more or less benefit in pre- or postmenopausal
women. For FSD, behavioral and nonpharmacologic therapies including
lifestyle modification, medication adjustment, and use of lubricants should be a first step.

I-119. The answer is B. (Chap. 41) Patients with unintentional weight loss of >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%>

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.