Clerkship Qstream Flashcards

Question

A 17-year-old Airman who is scheduled to be deployed to Iraq presents to your office because of shortness of breath and wheezing on exertion, particularly during basketball season. He does not notice any shortness of breath with routine activity. There is no family history of asthma. On physical examination, he is in no respiratory distress. His lungs are clear, with no wheezing during either tidal breathing or forced expiration. His cardiac examination is normal. Baseline spirometry is normal. What is the BEST next diagnostic step? Allergy testing Exercise testing with postexercise spirometry Overnight oximetry Reassurance

Answer 1

The most likely diagnosis is exercise-induced asthma, and exercise testing with postexercise spirometry is the most appropriate diagnostic test. Exercise testing for exercise-induced asthma should attempt to mimic the activity that induces the shortness of breath. In addition to establishing the diagnosis of exercise-induced asthma, exercise testing can reveal exercise-induced laryngeal dysfunction that sometimes mimics exercise-induced asthma. All patients with significant disease should also be instructed to use prophylactic treatment 5 to 10 minutes before exercise, usually two puffs of a medium-acting inhaled beta2-agonist (albuterol). A better term for this condition is “exercise-induced bronchospasm,” because not all persons with the condition have asthma. The estimated prevalence of exercise-induced bronchospasm ranges from 7% to more than 20% in the general population. Exercise-induced bronchospasm probably results from changes in airway physiology triggered by the large volume of relatively cool, dry air inhaled during vigorous activity. Bronchodilation is the more common first event during exercise and lasts for 1 to 3 minutes after exercise. In patients with exercise-induced bronchospasm, the initial bronchodilation is followed by bronchoconstriction, which begins within 3 minutes, generally peaks within 10 to 15 minutes, and resolves by 60 minutes. Acute bronchoconstriction was previously followed by late-phase bronchoconstriction in some patients; however, the risk and severity of late-phase bronchoconstriction due to exercise-induced bronchospasm is decreased when compared with allergen-induced asthma. Other answers: Although some patients with exercise-induced asthma may also have an allergic component, there is no clear correlation between the development of exercise-induced asthma and allergies. Patients with exercise-induced asthma may have equivocal results on methacholine challenge testing, making it a less helpful test than postexercise spirometry. Overnight oximetry would provide no information regarding the onset of bronchospasm during exercise.

Answer 2

Answer: Direct IL-1 and TNF-alpha stimulation of the bone marrow post-mitotic reserve pool. IL-1 and TNF-a are cytokines with largely overlapping biologic properties that play a major role in mediating acute inflammation. One effect is to act directly on the bone marrow post-mitotic reserve pool resulting in a rise in the number of immature neutrophils (bands) in addition to rapid release of mature neutrophils. Other answers: LPS (lipopolysaccharide) is found in the membranes of Gram negative bacteria. PGE2 plays a role in induction of fever and stimulation of vasodilation and increase vascular permeability. It has no role in causing a left-shift. C-reactive protein (CRP) is an acute phase reactant released by the liver in response to IL-6 production. CRP binds to phosphocholine on certain bacterial polysaccharide capsules and on dead and dying cells. Once bound to a cell or bacterial surface, CRP activates the complement system and functions as an opsonin to enhance clearance of dead cells and bacteria by macrophages. G-CSF stimulates bone marrow synthesis of mature neutrophils. Robbins PBOD 8ed. p75.

Answer 3

The radial nerve has a specific sensory distribution that is consistent and that covers the dorsoradial aspect of the hand. These sensory fibers are transmitted via the superficial branch of the radial nerve (the deep branch transmits primarily motor impulses), with little if any “cross-over” from the other nerves distal to the wrist.

Answer 4

Incidence is number of new cases divided by population at risk of disease. There were 6 new cases during the follow-up period. Although the entire population consists of 10,000 personnel, 42 were initially positive and thus could not become a new case, so the population at risk is 10,000 – 42 = 9,958. Incidence is 6/9,958 over the 5 year period.

Answer 5

The correct answer is a polysaccharide capsule. The disease described is most likely meningococcal meningitis. A primary virulence factor of Neisseria meningitidis is its anti-phagocytic polysaccharide capsule. Protection against common types of N. meningitidis is provided through vaccination of young people with a polyvalent vaccine that consists of several of these capsular antigens. Other answers: The M protein is a helical protein component of the cell wall of Group A streptococci that has an antiphagocytic property as well. Several organisms produce IgA proteases that have activity against that class of secretory immunoglobulins, however IgA is a poor activator of complement and opsonizes very weakly. While N. meningitidis expresses lipooligosaccharide (LOS), this is not a mechanism by which the bacteria resists complement-mediated phagocytosis. Rather, LOS contributes to clinical disease by binding to toll-like receptor 4 on innate immune cells, resulting in the release of massive amounts of pro-inflammatory cytokines.

Answer 6

Answer: 1/8 versus 1/200 If the child is affected by autosomal recessive disease he must be a homozygote. Therefore, his parents are obligate heterozygotes. Either the deceased husband's mother or father is also a heterozygote, because their son must have inherited the mutant gene from one of them. Then the chance that the deceased husband's brother is a carrier is 1/2 (he can inherit either a normal or a mutant allele from the heterozygous parent). If the mother and the deceased husband's brother are heterozygotes the chance of the fetus inheriting both mutant alleles is 1/4 so the total risk is 1/2 X 1/4 = 1/8. The mother is an obligate heterozygote. The disease allele frequency in this population is √q = √ 1/10000 = 1/100. Normal allele frequency is 1–1/100 ~ 1. Carrier (heterozygote) frequency is 2pq = 2 x 1 x 1/100 = 1/50. This is the risk of a random person being a carrier. If the mother and a random Finnish male are both carriers for autosomal recessive disease the chance of their child being affected is 1/4. Total risk for the fetus is 1/4 x 1/50 = 1/200.

Answer 7

The correct answer is bromocriptine. The patient’s symptoms, breast enlargement with lactation and loss of vision, are compatible with hyperprolactinemia resulting from an anterior pituitary prolactin-secreting adenoma. A blood test for serum prolactin should be performed to confirm your diagnosis. A long-acting dopamine agonist, like bromocriptine, will inhibit prolactin secretion and cause the adenoma to shrink. None of the other drugs [testosterone, pegvisomant (a GH antagonist), or sermorelin (GHRH1-29)] would affect prolactin levels or the adenoma. The patient may eventually want to have the adenoma surgically removed, but it would be appropriate to shrink the adenoma before proceeding with the surgery.

Answer 8

The correct answer is Listeria monocytogenes. Although all of these agents may be found in unpasteurized milk, Listeria monocytogenes is capable of actually replicating at refrigerator temperatures and hence is often linked to refrigerated meats and dairy products. Generally speaking, healthy people develop only mild self-limiting flu-like or gastrointestinal symptoms from foods contaminated with Listeria, but individuals that lack good cell mediated immunity are at risk from this facultatively intracellular pathogen. Unlike the other agents listed, Listeria has the capacity to cross the placenta in pregnant patients and cause stillbirth or meningitis in the newborn. Meningitis is also seen in AIDS patients or the elderly infected with listeria. Brucella causes a recurrent febrile syndrome, E. coli causes hemorrhagic colitis and hemolytic uremic syndrome, and M. bovis is associated with miliary TB, especially where unpasteurized milk is a major food source.

Answer 9

The correct answer is codeine. Explanation: In order to be an effective analgesic, codeine must be converted to morphine by CYP2D6. In patients deficient in CYP2D6, codeine is ineffective as an analgesic. Incorrect answers: Morphine and fentanyl are full mu opiate agonists that need no modification for activity. Loperamide lacks any analgesic property because it is rapidly pumped out of the CNS by the MDR transporter. Loperamide is an opiate that is used as an anti-diarrheal agent.

Answer 10

Answer: Activation of macrophages and lymphocytes, production of TGF-b and PDGF, and decrease in metalloproteinase activity. Explanation: Chronic inflammation as observed in chronic diverticulitis results in tissue fibrosis. Activated macrophages and lymphocytes release a variety of mediators, including PDGF and TGF-β, which play a role in promoting fibroblast proliferation and collage synthesis as well as inhibiting metalloproteinase synthesis (with resultant decreased collagen degradation). Other answers: Activation of mast cells, secretion of histamine, and increased vascular permeability are observed in type 1 hypersensitivity reactions. Secretion of IFN-γ by Th1 cells, macrophage activation, and focal collections of epithelioid cells are involved in granulomatous inflammation. Secretion of IL-5 by Th2 cells, recruitment of eosinophils, and release of major basic protein are observed in allergic reactions and in response to helminth infections. Robbins PBOD 8ed. pp 107-108

Answer 11

Ans: Place the patient on a ventilator and adjust the settings to achieve adequate arterial PO2 and PCO2. The patient is suffering from an inability to provide sufficient exchange of CO2 and oxygen. Administering increased oxygen signals to the respiratory centers to slow down the ventilatory rate. However, because of her COPD, she needs to breathe more rapidly to exchange CO2. Increasing CO2 does not stimulate increased breathing because the patient has been at elevated CO2 levels for so long that her receptors have accommodated to the increased CO2. Therefore, mechanical intervention is required to get her balance of ventilation rate and volume to the point that her PaCO2 will be reduce to acceptable levels.

Answer 12

The correct answer Capsule. Explanation: Capsular polysaccharides are the basis for a number of vaccines including Stretococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis. To develop an anamnestic immune response, these polysaccharides are often conjugated to proteins to stimulate a T-cell response. Protection against colonization with pili is a potential strategy but thus far there are no such vaccines available. The toxic nature of lipopolysaccharide rules it out as a potential immunogen, although it is easy to envision that anti-LPS antibody would be useful in blocking shock associated with Gram-negative infections. Antibodies against drug resistance pumps have not been used as a vaccine strategy.

Answer 13

Ans: Central chemoreceptor adaptation. Hypoxemia is the cause of the observed symptoms. Lowered levels of oxygen will cause the peripheral chemoreceptors to increase the rate of breathing in an attempt get more oxygen into the system. This will cause a decrease in PaCO2 which will cause the central chemoreceptors to slow the breathing rate, again decreasing PaO2 . Breathing rate must increase to maintain adequate PaO2. This back and forth feedback continues until the central chemoreceptor adapt to lower PaCO2 levels at the higher respiratory rates. One would expect that red cell production will be stimulated but the differentiation of erythrocytes will take about a week before the increased numbers will show up in the bloodstream.

Answer 14

Correct answer: Trinucleotide repeat. Explanation: These findings are typical of fragile X syndrome, a condition in which there are 250-4000 tandem repeats of the trinucleotide sequence CGG. In normal individuals there are between 10-50 CGG repeats but in families with this disorder the number of repeats tends to increase with succeeding generations (“genetic anticipation”). The gene is on chromosome X at q27.3. Other diseases with unstable trinucleotide repeats of C_G include Myotonic Dystrophy – CTG, Huntington Disease – CAG, and Kennedy's Disease – CAG. In Fragile X Syndrome, the number of CGG repeats affects the phenotype with 6-60 repeats (normal allele) producing a normal phenotype, 60-200 repeats (premutation allele) also producing a normal phenotype but one who is an obligate carrier, and >200 repeats (full mutation allele) leading to various expression of the Fragile X phenotype. Robbins PBOD 8ed. pp 169-171

Answer 15

Correct answer: Periductal and perivascular lymphocytes and germinal centers. Explanation: This is a case of Sjogren’s syndrome, an autoimmune exocrinopathy. In this condition CD4+ T cells reacting to exocrine gland self-antigens are believed to stimulate ductal epithelial cell hyperplasia, with resulting duct obstruction and acinar cell atrophy and fibrosis. This leads to reduced production of exocrine gland secretions, accounting for many of the signs and symptoms of this disease, including dry eyes and dry mouth. Most of the lymphocytes infiltrating the salivary gland are CD4+ T-cells, and 10% are B cells. Other answers: Eosinophils are typically seen in allergic conditions and infections with nematodes. Some autoimmune diseases exhibit granulomatous inflammation (e.g. Wegener granulomatosis, temporal arteritis, etc.), but not Sjogren’s syndrome. Although acinar epithelial cells are injured in Sjogren’s syndrome, they do not undergo metaplasia. Robbins PBOD 8ed. pp 221-223.

Answer 16

The correct answer Fluconazole. Explanation: The patient has candidemia (Candida infection of the blood). The only two antifungal agents listed are amphotericin B and fluconazole. Clinical studies in immunocompetent patients have demonstrated that fluconazole and amphotericin B are equally effective at treating bloodstream infections with Candida albicans. Of the two agents, amphotericin B has a substantially worse side effect profile, with significant risk of renal toxicity. Having ascertained by the germ-tube test that the yeast is most likely Candida albicans (which, in addition to the rare Candida dublinensis is the only Candida species which is germ tube positive), fluconazole would be a more appropriate choice of drug than amphotericin B in this situation. An echinocandin would also be a reasonable choice. Ampicillin/sulbactam and ceftazidime target bacterial cell wall synthesis and therefore would not be useful against this yeast infection. If the yeast was germ tube negative, one would be concerned that the patient could possibly be infected with a Candida species that is resistant to fluconazole, such as Candida glabrata or Candida krusei. Thus, in the setting of a germ-tube negative yeast, one would not start with fluconazole. Rather, one would use an echinocandin or amphotericin B. Additionally, because of the widespread use of azoles in the prophylaxis of cancer patients that become neutropenic, patients with neutropenia who develop a Candidemia are frequently started on an echinocandin or amphotericin for initial coverage.

Answer 17

Answer: pseudogout The presentation is suggestive of either a septic joint or crystal-induced synovitis, with severe pain of rapid onset and low-grade fever. This presentation is not really compatible with a fracture (no history of trauma). The appropriate diagnostic test was the joint fluid aspiration, which demonstrated crystals. Uric acid crystals are needle-shaped on polarized microscopy and are negatively birefringent. Calcium pyrophosphate crystals, in contrast, are blue-yellow birefringent. Because the aspiration revealed positively birefringent crystals, the correct answer is pseudogout.

Answer 18

The correct answer is Neisseria gonorrhoeae Although all these agents are pathogenic in the reproductive tract, the one associated with hematogenous spread, joint infection, and disseminated gonorrheal infection (DGI) is Neisseria gonorrhoeae. In fact, the leading cause of septic arthritis in people of reproductive age is Neisseria gonorrhoeae. It may be difficult to confirm the diagnosis by culturing synovial fluid or the skin lesions that accompany such an infection. Culture of the urethra, cervix, rectum or pharynx is often positive and would confirm the diagnosis. Chlamydia trachomatis, serovars D-K, cause urethritis, cervicitis, pelvic inflammatory disease, and neonatal pneumonia and conjunctivitis. Chlamydia trachomatis, serovars L1, L2, L2a and L3 cause lymphogranuloma venereum (LGV), which can cause a painless genital ulceration, inguinal lymphadentis/lymphangitis, and proctitis. Haemophilus ducreyi causes painful genital ulcerations.

Answer 19

Explanation: The zona pellucida is a glycoprotein shell that surrounds the ovum, acts as receptors for sperm and induces the acrosome reaction. At the end of the fourth day the zona pellucida disappears and the conceptus implants into the uterine lining at ~day 6. The conceptus would not be able to implant if it was still surrounded by the zona pellucida. Incorrect answers: The allantois forms after implantation. Cilia on the endometrial epithelium do not disappear. The sperm acrosome disappears during the process of fertilization, an event that occurs ~6 days before implantation.

Answer 20

ANSWER: Culture the tissue in heart-brain infusion broth at 32⁰C . Explanation: The lymphadenopathy with the necrotizing granulomas is typical of cat scratch disease (CSD), typically seen in children, but also in adults, who have been in contact with cats, usually kittens. The diagnosis is usually made by positive serology in combination with certain clinical criteria*. To identify the organism, however, the organism typically needs to be grown in culture. The organism causing CSD (Bartonella henselae) is a fastidious bacillus that grows best in heart-brain infusion broth at 32⁰C - 35⁰C. The typical culture medium (blood agar) used to culture most bacterial and fungal organisms has a low yield for identifying Bartonella henselae. Stains such as H& E, trichrome, gram and Wright will not stain the organism. Silver stains such as Warthin-Starry will show clusters of the bacilli in area of necrosis within the necrotizing granulomas. PCR identification of B. henselae is also useful, but not that sensitive (thus negative PCR does not rule out the diagnosis). It is important to recognize that special stains and culture approaches are needed when considering the diagnosis of CSD, so that the appropriate tests can be ordered on biopsy samples. * Clinical criteria supportive of a diagnosis of cat scratch disease include: - -> cat or flea contact of any kind - -> negative serology for other causes of adenopathy OR + Bartonella PCR OR + liver and spleen lesions on CT OR sterile pus from lymph node aspiration - -> biopsy with granulomatous inflammation OR a positive Warthin-Starry silver stain

Answer 21

The correct answer is carbidopa. Emesis and orthostatic hypotension result from the peripheral actions of dopamine. Carbidopa inhibits the decarboxylation of l-dopa to dopamine, but since carbidopa does not enter the brain, it prevents the conversion of l-dopa to dopamine only in peripheral tissue. None of the other drugs listed would prevent the peripheral side effects associated with l-dopa administration. Benztropine is an anticholinergic agent that can be used as a 2nd line agent for Parkinson’s disease to reduce tremor. However, it would not reverse the peripheral effects of l-dopa administration. Pramiprexole is a dopamine agonist that is sometimes used in early treatment of Parkinson’s disease. Like levodopa, its side effects include nausea, vomiting, and orthostatic hypotension. Rasagiline is an irreversible monoamine oxidase inhibitor that can be used in early Parkinson’s or as an additional agent in late Parkinson’s disease. It would not reverse the peripheral effects of l-dopa administration.

Answer 22

The correct answer is Vitamin A. Explanation: Vitamin A is needed for epithelial maturation. Absence of vitamin A leads to squamous metaplasia of the lacrimal ducts leading to dry eyes and corneal softening (keratomalacia). Other symptoms of vitamin A deficiency include night blindness, corneal ulceration, pruritis, and growth retardation. Other answers: B12 and folic acid deficiencies are associated with megaloblastic anemia. Additionally, B12 deficiency can cause decreased vibratory sensation. Vitamin C deficiency leads to scurvy, which is characterized by vascular fragility and bone changes. Some other notable vitamin deficiencies include Vitamin D deficiency (which causes rickets), Vitamin K deficiency (which causes hemorrhagic diathesis), and Niacin deficiency (which causes pellagra -- diarrhea, dementia and dermatitis). Robbins PBOD 8ed pp 430-431

Answer 23

The correct answer An extended spectrum beta-lactamase. Explanation: It is not unusual, especially in the hospital setting, to encounter members of the family Enterobacteriaceae that have acquired the genes to encode an extended spectrum beta-lactamase (ESBL). This enzyme is capable of inactivating numerous beta-lactam antibiotics of the penicillin and Cephalosporin families. In addition Enterobacter cloacae, other Enterobacteriaceae that often express ESBLs include Escherichia coli, Klebsiella pneumonia, Klebsiella oxytoca, Salmonella species, Proteus mirabilis. Pseudomonas aeruginosa, which is not a member of the Enterobacteriaceae family, is another common nosocomial gram negative organism that can also express an ESBL.

Answer 24

The correct answer is Lead toxicity. Lead toxicity is associated with CNS injury leading to intellectual and psychologic impairment in children. Lead interferes with enzymes important in heme synthesis, including aminolevulinic dehydratase, aminolevulinic acid synthetase, and ferrochelatasae. Consequently, lead intoxication can result in decreased iron incorporation into heme, causing a microcytic anemia and increased levels of zinc protoporphyrin in the blood. Basophilic stippling is often seen in anemia due to lead poisoning. This phenotype is believed to be due to lead inhibition of a pyrimidine 5’ nucleotidase, which results in increased degradation of ribosomal RNA. Other features of lead toxicity include abdominal colic, growth retardation, neuropathy and nephrotoxicity. Lead lines may be observed in the gums on physical examination. These typically appear as a blue line along the gums, with a blue/black coloring of the gum tissue adjacent to teeth. Deposition of lead in the bones of children can often be observed as a transverse hyperdense line in the metaphysis of long bones. Other answers: Cadmium toxicity is associated with obstructive lung disease and renal tubular injury. Arsenic toxicity is associated with gastrointestinal, cardiovascular, and CNS dysfunction. Transverse white lines in the nails (Mees lines) are seen with arsenic exposure. There is also an increase in skin and lung cancer from chronic exposure. Mercury toxicity is associated with diarrhea, visual field defects and nephrotoxicity. Robbins PBOD 8ed pp406-407

Answer 25

ANSWER: Presence of N-MYC amplification. Explanation: The patient has a neuroblastoma, a tumor that arises from primitive sympathetic ganglion cells. These tumors can arise anywhere within the sympathetic nervous system, including the adrenal glands, abdomen, and thoracic cavity. About 2/3 of neuroblastomas originate in the abdomen (and 2/3 of those are from an adrenal gland). Neuroblastoma cells typically have defective catecholamine synthesis, and thus release increased amounts of catecholamine intermediates such as HVA, VMA, and dopamine. There are many types of neuroblastomas, and they can cause a wide variety of clinical diseases (from benign, mature tumors, to aggressive and metastatic ones). Neuroblastomas can metastasize by both lymphatic and hematogenous routes. Tumors can spread to the skin, where they typically appear as firm, non-tender, bluish nodules. The infant in the clinical stem most likely has a neuroblastoma with involvement of the left adrenal gland, the liver, the skin and the bone marrow (but not cortical bone). N-MYC (or MYCN) is an oncogene that is an important prognostic feature of neuroblastomas. Presence of the N-MYC oncogene portends a poor prognosis, while absence of N-MYC amplification is associated with a more favorable prognosis. Of note, the child in this question stem most likely had a 4S tumor. While metastatic neuroblastomas typically have a very poor prognosis, children under 1 year of age who have metastatic neuroblastoma without spread to cortical bone typically do quite well with frequent spontaneous regression of the tumors. In these special 4S cases, when the skin lesions regress a biopsy will show only mature ganglion cells. The liver and bone marrow involvement will also disappear. Other answers: Malformations of the kidney are not associated with neuroblastoma. Blastemal cells are a component of nephroblastoma (Wilms tumor). AFP staining of hepatocytes is associated with hepatoblastoma. Robbins PBOD 8ed. pp 475-479

Answer 26

The correct answer is Heat labile toxin. By the description of the agent we know that it is a Gram-negative organism that ferments lactose. That distinguishes E. coli (which is lactose fermenting) from non-lactose fermenters such as Vibrio (which makes cholera toxin) and Campylobacter (which produces cytolethal distending toxin). Heat labile toxin and Shiga toxin are both associated with E. coli, which is lactose fermenting. However Shiga toxin is associated with bloody diarrhea and the Hemolytic Uremic Syndrome. The description in this case is of a secretory diarrhea which is the classic ETEC, or traveler’s diarrhea picture associated with heat labile toxin, an analogue of Cholera toxin.

Answer 27

ANSWER: Surfactant deficiency. Explanation: Prematurity (birth weight under 2500 gms) is frequently complicated by respiratory distress (also called hyaline membrane disease) if the infant is less than 35-36 weeks gestation. Prior to that gestational age the lung has not developed a sufficient number of Type 2 alveolar cells to produce an adequate amount of surfactant to prevent the infant’s lungs from collapsing when exhaling. In fact, any event that may lead to the destruction of Type 2 alveolar lining cells (e.g. anoxia during delivery, congenital infection) can lead to surfactant deficiency even in term infants. Surfactant is a mixture of lipids (about 90%, mostly phosphatidylcholine), proteins, and glycoproteins. Surfactant decreases the surface tension within alveoli, which decreases the pressure required to expand them. Decreased surfactant production increases alveolar collapse. In alveolar cells, surfactant is stored within specialized granules called lamellar bodies. As fetal lungs mature, the ratio of lecithin to sphingomyelin (both glyoproteins in surfactant) increases. Tests on amniotic fluid can be helpful in predicting degree of pulmonary immaturity before birth. These include measuring the lecithin-sphingomyelin ratio, fluorescence polarization, and lamellar body counts. The recent development of synthetic surfactant has allowed treatment of pulmonary immaturity immediately after birth. Other answers: Congenital pulmonary airway malformation, also known as congenital cystic adenomatoid malformation, is the most common primary congenital abnormality of the lung. CPAMs occur as focal growths in the developing lung that can have cystic and adenomatous components. Large lesions can inhibit development and growth of normal alveolar tissue in the lung by compression. In contrast to surfactant deficiency, these do not typically improve as a baby gets older. Thus, symptomatic CPAMS at birth are frequently treated by surgical resection. Congenital lobar emphysema is a rare congenital abnormality of the lungs that presents with hyperinflation and air trapping. Chest x-ray shows distention of one lung and compression of the contralateral one. As with CPAMs, congenital lobar emphysema does not typically resolve on its own. Asymptomatic cases can be followed. Treatment for symptomatic congenital lobar emphysema usually involves surgical resection of the affected lobe. Tetralogy of Fallot (TOF) includes RV outflow tract obstruction, ventricular septal defect, overriding aorta to the right (such that the origin of the aorta overrides the VSD), and RV hypertrophy. Infants presenting with respiratory distress due to TOF would not be expected to improve substantially without surgical correction. Robbins PBOD 8ed. pp Robbins 456-458

Answer 28

The correct answer is Coagulative necrosis and neutrophilic infiltrate. Explanation: The patient is presenting with classic symptoms and EKG findings of a myocardial infarction. Histopathological changes seen during a myocardial infarction are as follows. Wavy fibers are seen at the border of infarcts in the first 4 hours. Edema and hemorrhage is maximal in the first 12 hours. Neutrophilic infiltrate and coagulative necrosis are maximal in days 1-3. Phagocytosis and macrophages are seen most in days 3-7. Later findings include development of granulation tissue (days 7-10), and collagen formation(weeks 2-8). Robbins PBOD 8ed. pp page 550, table 12-5.

Answer 29

The correct answer is Myocarditis. Explanation: Myocarditis can be seen after viral illnesses and is a cause of sudden cardiac death. Myocarditis (inflammation of the muscular tissue of the heart) has both infectious and non-infectious causes. The most common cause is viral infection, especially enteroviruses including Coxsackie B. Other viral infectious causes include adenovirus, HIV, parvovirus B19, herpes virus 6, and hepatitis C. While myocarditis often presents with heart failure, it can also be a cause of sudden death, most likely due to ventricular tachycardia or ventricular fibrillation). Other answers: Cardiac myxoma is a primary cardiac tumor. These often cause symptoms such as dyspnea and orthopnea by obstructing flow of blood, but are not a common cause of sudden cardiac death. Atrial septal defect is a congenital cardiac defect which is generally well tolerated and often not recognized until the patient is in their 30s. Papillary fibroeleastoma is a benign neoplasm usually found as an incidental finding at autopsy. Robbins PBOD 8ed. p 558.

Answer 30

The correct answer Assaying the boy's serum for an elevated titer of streptolysin O antibodies. Explanation: Glomerulonephritis is a post-suppurative complication of streptococcal pharyngitis. As such, the bacteria responsible for the infection are likely to have been cleared by the time of clinical presentation with glomerulonephritis. However, antibody to the bacterial enzyme streptolysin O will remain elevated, and thus provides a useful tool for diagnosis of this syndrome. Other answers: Capsular antigens are not useful for diagnosis of Group A streptococci, which produce a hyaluronic acid capsule that is not highly immunogenic. The other options listed focus on Shiga toxin-producing E. coli, which would have been more likely had the patient presented with prior or ongoing blood diarrhea rather than a pharyngitis. Infections with Shiga-toxin producing E. coli typically occur after consumption of contaminated food or water can result in bloody diarrhea. A dangerous sequela that may occur following infection with Shiga toxin-producing E. coli is the hemolytic uremic syndrome (HUS). Symptoms of HUS include kidney failure, thrombocytopenia, and hemolytic anemia.

Answer 31

The correct answer is Partial chromosomal deletion. Explanation: The patient most likely has chronic lymphocytic leukemia, a chronic lymphoproliferative disorder (neoplasm) of mature B cells. CLL is the most common leukemia in the U.S. It is more common in men than women, but is not X-linked. It typically occurs in older individuals, with the median age at diagnosis being around 70. Patients can present with fevers, sweats, weight loss, and fatigue. Physical signs include lymphadenopathy and splenomegaly. Invovlement of skin (and other organs) can also occur. Blood counts demonstrate an absolute lymphocytosis, and frequently the disease is diagnosed in asymptomatic patients after detection of lymphocytosis on a routine blood count. In some cases it can present with an unexpected infection such as streptococcal pneumonia. Flow cytometry of CLL cells demonstrates expression of B-cell antigens such as CD19 (or CD20), CD5 (a T-cell antigen that is also present on B1 B cells), and low levels of surface immunoglobulin. Cells in CLL are also typically TdT negative (TdT is terminal deoxynucleotidyl transferase, a DNA polymerase typically expressed in immature pre-T and pre-B cells). In this case, the lymph node enlargement is consistent with the high WBC count and the finding of CD5+ lymphocytes. In ~20% of cases there is a mild hemolytic anemia which would cause a reticulocytosis in early stages of the disease. While the lymphocytes are mature and may produce immunoglobulin they do not produce free light chains as in multiple myeloma. A partial deletion of chromosome 13 (13q14 = deletion of region 14 on the long "q" arm of chromosome 13) occurs in over half of CLL cases and is a positive prognostic indicator (mechanism unknown). Unless immunosuppressed, the patient is unusually old for Burktt’s lymphoma and associated t(8;14). Robbins PBOD 8ed. pp 603-605

Answer 32

The correct answer is D, tamsulosin. Explanation: One way to increase urine flow in a male with benign prostatic hyperplasia is to administer a drug that will relax smooth muscle lining his urethra. Blockade of a1 adrenergic receptors on urethral smooth muscle will prevent norepinephrine from causing constriction of the urethra. Both prazosin and tamsulosin block a1 receptors and both would relieve the symptoms of benign prostatic hyperplasia. However, tamsulosin is selective for a 1A receptors while prazosin blocks both a 1A and a1B receptors. Since urethral smooth muscle expresses only a 1A receptors and vascular smooth muscle expresses both a1A and a 1B receptors, tamsulosin can effectively relax urethral smooth muscle without preventing vasoconstriction since a1B receptors remain unblocked. On the other hand, prazosin would block both a1A and a 1B receptors on the vasculature and may result in an unsafe drop in blood pressure.

Answer 33

Answer: Squamous cell carcinoma. The patient’s age and heavy smoking history are important clues. His clinical history is also significant for chronic bronchitis, which also is consistent with his smoking history. The features that favor a diagnosis of squamous cell carcinoma are his prior smoking history, recent significant weight loss and the presence of a radiographic lung shadow. His history of constipation, weakness and an elevated serum calcium level are all consistent with a hypercalcemia paraneoplastic syndrome, also a feature of squamous cell carcinoma. None of the other possibilities have a relationship to cigarette smoking although they may coincidentally occur in smokers. Silicotic nodules tend to be multiple and bilateral. Bronchiectasis typically is associated with production of copious, foul-smelling sputum. Tuberculosis can be associated with significant weight loss. However, it frequently also presents with fevers and/or night sweats, and hypercalcemia is not a typical feature of tuberculosis. Robbins PBOD 8ed. pp 721-729

Answer 34

Answer: primary hyperparathyroidism Hypercalcemia should normally cause suppression of PTH; therefore this patient has hyperparathyroidism. While frequently asymptomatic, hyperparathyroidism can cause a range of symptoms in patients. The high PTH levels lead to development of kidney stones, bone disease, proximal renal tubular acidosis, and hyperuricemia with associated gout. High PTH levels also cause electrolyte abnormalities such as low phosphate and magnesium levels. High calcium levels from any cause can cause disease in multiple organ systems, including the kidneys (kidney stones, nephrogenic diabetes insipidus causing increased thirst and polyuria and polydipsia, distal RTA, and renal insufficiency), the gastrointestinal system (nausea, vomiting, anorexia, pancreatitis, constipation due to decreased bowel motility), the musculoskeletal system (osteopenia, bone pain, muscle aches and weakness), the neurologic system (confusion, decreased concentration), and the cardiovascular system (decreased QT interval, hypertension, and bradycardia). Other answers: Hypercalcemia of malignancy is mediated through a PTH-related protein that mimics PTH effects on receptors, but is not measured by the PTH immunoassay. Sarcoidosis and other granulomatous diseases cause hypercalcemia through increased conversion of 25 hydroxyvitamin D to 1,25 dihydroxyvitamin D. All of these conditions should present with low PTH levels.

Answer 35

Answer: Interstitial fibrosis associated with ferruginous bodies. The patient’s occupational history is consistent with prior heavy asbestos exposure that has been well described in insulators and Navy personnel working aboard ships during WW II. The clinical picture is highly suggestive of asbestosis, as reflected by weakness and a non-productive cough in association with bibasilar inspiratory rales. Asbestosis classically is associated with bilateral irregular opacities in the lower lung zones, findings that are characterized by interstitial pulmonary fibrosis associated with dumbbell-shaped, beaded, brown asbestos (ferruginous) bodies. Persons occupationally exposed to asbestos also may have bilateral parietal or diaphragmatic pleural plaques that frequently calcify. These asbestos-related pleural plaques/calcifications occur independently from asbestosis but both types of asbestos-related lesions may coexist in the same patient. Other answers: None of the other diagnostic possibilities have any relationship to asbestos exposure. Exposure to silica typically occurs in miners, sandblasters (individuals working in quarries), and artists (especially those working with ceramics). Silicosis is characterized by birefringent silica particles within concentric fibrous nodules, mainly in the upper lobes. This is distinct from the lower lobe location of asbestosis. Caseous necrosis is the hallmark of tuberculous granulomas and alveolar hyaline membranes are pathognomonic of adult respiratory distress syndrome. Robbins PBOD 8ed. pp 696-701

Answer 36

Answer: Leukoplakia. Leukoplakia refers to firm, white, warty plaques in the oral cavity, generally of long duration, which cannot be scraped off. They are typically seen in cigarette, pipe or cigar smokers. They must be regarded as premalignant lesions although only about 5-25% actually are premalignant. They occur most commonly in males between 40 and 70 years of age. Other answers: Oral thrush, which can be seen in young infants, individuals with AIDS or other severe immunodeficiencies, and individuals on systemic or inhaled corticosteroids, is caused by the yeast Candida albicans and is characterized by painful, creamy white, slightly raised lesions on the tongue, inner cheeks, roof of the mouth, gums, tonsils, or back of the throat. Lesions of oral thrush typically bleed slightly when scraped. Oral squamous cell carcinoma manifests either as firm, exophytic or ulcerative growths on the tongue, inner surface of the cheeks or soft palate. Pleomorphic adenoma is a generally benign, slow-growing tumor of the major salivary glands and usually is characterized by painless, progressive enlargement of the parotid gland. It is not seen on the dorsal surface of the tongue. Robbins PBOD 8ed. pp 743-745

Answer 37

Answer: Cercarial dermatitis Cercariae are the infectious stage of parasites of the genus Schistosoma, the causative agent of schistosomiasis. The species of schistosome prevalent in Brazil is Schistosoma mansoni. In this case, the village upstream has inhabitants who are infected and who are passing eggs in their stools. The eggs can be washed into the stream by rainfall. Once in water, the eggs hatch and the small ciliated miracidium stage seeks out the appropriate species of snail which serves as the intermediate host. It is from this snail host that the cercariae emerge, then swim tadpole-like in the water seeking a human host. A cercaria has enzymes in its anterior end that allow it to penetrate intact human skin, enter the capillary bed, and eventually end up in the liver where maturation to an adult worm takes place. The process of penetration of skin can invoke a local inflammatory response in the human host, causing a punctate, pruritic rash that is referred to as cercarial dermatitis. A similar skin rash can occur in humans exposed to water infected with various types of bird schistosomes, including bodies of water such as the Chesapeake Bay and the Great Lakes. This dermatitis is referred to as swimmer’s itch. These non-human schistosomes cannot complete their life cycle, so persons who have swimmer’s itch in the U.S. are not in danger of developing the disease schistosomiasis. Other answers: The itch referred to as ‘sarcoptic’ refers to the arthropod that causes it, the scabies mite Sarcoptes scabei. This is transmitted primarily by direct contact with an infested person and their fomites (clothing, bedding, etc.). Contact dermatitis is typically due to a delayed hypersensitivity response to an irritant (such as a detergent or chemical solvent) or allergen (such as poison ivy or adhesives or certain metals such as nickel) and requires that the inciting (noninfectious) agent be in direct contact with the skin. Pustular dermatitis would not have the same chronology of water exposure and the lesions (pustules) are distinctly different in appearance from the punctate, nonpustular lesions seen in cercarial dermatitis.

Answer 38

The correct answer is Serum cobalamin. ‘Digestive problems’ raise the possibility of chronic gastritis or intestinal malabsorption associated with folate or cobalamin (B12) deficiencies. Microscopic examination of the blood smear for evidence of oval macrocytosis, enlarged polylobulated neutrophils, or giant bands forms would be useful but not sufficient to distinguish between folate and cobalamin deficiencies. The latter is most critical to exclude since treatment with folate alone can mask disease progression toward neuropathy (which occurs with vitamin B12 deficiency). The lack of evidence for blood loss, the failure of iron supplements to correct the anemia, and the low WBC count also raise the possibilities of bone marrow dysfunction due to chronic disease or a sideroblastic anemia associated with aging. Exclusion of these conditions might require bone marrow biopsy if the serum tests were not informative. Other answers: Provided healthy kidney function, serum EPO can be expected to increase in many types of anemia. It can be useful in distinguishing between aplastic anemia (increase) and anemia of chronic renal disease (decrease). Gastrin levels are often elevated in pernicious anemia. However, high gastrin levels are not specific for pernicious anemia or B12 deficiency, and would not be obtained as a first line test for determining whether a pt is B12 deficient. Additionally, autoantibody damage to gastrin producing glands can occur in pernicious anemia, decreasing gastrin levels. Autoantibodies in pernicious anemia may cross-react with the thyroid gland epithelium and lead to a compensatory increase of TSH, but TSH levels alone would not illuminate the underlying cause. Robbins PBOD 8ed. pp 656-658

Answer 39

Answer: Pleomorphic adenoma. The parotid gland is the favored site of pleomorphic adenomas but is also the exclusive location of Warthin tumor. However, the patient’s age favors pleomorphic adenoma since the highest incidence of Warthin tumor is in the 5th-7th decades of life. Warthin’s tumor also is closely linked to smoking. Mumps occurs in much younger patients, is acute in onset and is associated with painful enlargement of the parotid gland. Nasopharyngeal carcinoma presents with neck swelling and/or nasal obstruction but does not involve the parotid region. This tumor is rare in Caucasians and is especially common in Chinese nationals. Robbins PBOD 8ed. pp 757-759

Answer 40

Answer: Pyridoxine The clinical vignette is characteristic of Parkinson disease. The conversion of L-dopa to dopamine is a decarboxylation reaction that normally takes place in the brain as well as in peripheral tissues. Amino acid decarboxylases require pyridoxal phosphate (PLP) derived from the vitamin pyridoxine (vitamin B6)*. Carbidopa is an analog of L-dopa that acts as a dopa decarboxylase (DDC) inhibitor. Because it does not pass the blood-brain barrier, carbidopa acts peripherally, but does not block dopamine formation in the brain. The peripheral action of carbidopa prevents adverse systemic effects of dopamine and helps to maintain high levels of dopa sufficient for entry into brain tissue via aromatic amino acid transporters (minimizing the pharmacological first pass effect). Consumption of high levels of vitamin B6 has the potential to promote systemic decarboxylation of L-dopa by increasing activity of residual decarboxylase, counteractive to the effect of the DDC inhibitor. Biotin is incorrect because biotin is used for carboxylation reactions, not decarboxylations. Thiamine is involved in decarboxylations, but with alpha-keto acids (like pyruvate and alpha-ketoglutarate) not amino acids. Vitamin B12 is used for only two reactions in humans; methyl transfer reactions (methionine synthase) and a radical rearrangement that converts methylmalonyl-CoA to succinyl-CoA (methylmalonyl-CoA mustase) involved in odd-chain fatty acid and branched-chain amino acid catabolism. *Decarboxylation reactions are also involved in converting other amino acids to a number of other neurotransmitters (e.g., histamine, GABA, serotonin). PLP is also used for other types of reactions performed on amino acids such as racemization, transamination and beta/gamma eliminations. Major metabolic pathways that require PLP include: amino acid metabolism, heme biosynthesis, neurotransmitter biosynthesis and the formation of sphingolipids. Vitamin B6 is therefore essential for normal function of the nervous system and hematopoiesis.

Answer 41

The correct answer is T-cell lymphoma. The child has Celiac disease, an immune mediated disease due to hypersensitivity to gluten-containing products in genetically predisposed individuals. Most individuals who develop celiac disease carry the Class II HLA allelles, HLA-DQ2 or HLA-DQ8. Clinically they present with anemia, chronic diarrhea and fatigue. Many patients are asymptomatic. The morphology of celiac disease is villous atrophy, crypt hyperplasia and intraepithelial lymphocytosis composed of CD8+ lymphocytes. T cell lymphoma and digestive tract cancers appear to occur with greater frequency in patients with Celiac disease than in the general population. Dermatitis herpetiformis (a skin condition characterized by papules and vesicles on the extremities and trunk), Type 1 diabetes, and IgA deficiency are non-malignant diseases associated with Celiac disease. Other answers: Hemochromatosis is a multisystem disease due to mutation in the HFE gene leading to iron overload that leads to cirrhosis, heart failure and secondary diabetes. Aspergillosis is seen in immunodeficient individuals leading to blood vessel obstruction and infarction. Hepatitis B is an enveloped DNA virus that causes acute and chronic hepatitis. While chronic infection with hepatitis B virus is associated with some extrahepatic diseases, celiac disease is not one of them. Extrahepatic manifestations of hepatitis B are typically due to circulating immune complexes and include serum sickness, polyarteritis nodosa, membranous nephropathy, and membranoproliferative. Robbins PBOD 8ed pp 795-796

Answer 42

The correct answer is gabapentin. Lamotrigine, phenytoin, valproate, and carbamazepine all share inhibition of Na+ channels as a mechanism of action. Gabapentin, in contrast, does not inhibit Na+ channels. While the mechanism of action of gabapentin is not yet fully understood, it appears that interaction with voltage sensitive calcium channels is important for its function. Gabapentin is: 1) approved for adjunct therapy in patients with complex partial seizures; 2) does not significantly overlap mechanisms of action with lamotrigine; and 3) of all the listed anti-seizure drugs, has the lowest propensity for drug interactions because it is excreted unchanged in the urine.

Answer 43

The correct answer is The patient is at increased risk for a pulmonary embolism. The patient most likely had a pancreatic carcinoma. Total removal of the pancreas is the treatment for pancreatic carcinoma and a needle biopsy or frozen section during surgery would have confirmed the diagnosis. Attachment to a vein suggest vascular invasion. Hypercoagulability is a recognized risk in these cases. Other answers: Pancreatitis due to bile reflux can be associated with excessive ethanol intake, but in this case it presumably occurred as a consequence of secretory stasis due to a slowly growing carcinoma impinging upon the intraglandular portion of the duct of Wirsung or the duct of Santorini. While chronic pancreatitis associated with alcohol can lead to pseudocyst formation there is no evidence of a relation to carcinogenesis. Islets of Langerhans are concentrated in the pancreatic tail. Except in far advanced cases function is not usually compromised either in pancreatitis. Cystic fibrosis is frequently associated with exocrine pancreas insufficiency (and thus could account for the patient’s malabsorptive syndrome) and often with impairment of islet cell function as well (causing diabetes). However, CF does not lead to mass lesions within the pancreas. In this case, the patient’s high HgbA1c is likely due to type II diabetes unrelated to the pancreatic cancer. Robbins PBOD 8ed. pp 900-903

Answer 44

Correct answer: oxidized LDL A stroke is often the consequence of cerebral atherosclerosis. LDL is the major vehicle for the delivery of cholesterol to the tissues, including the arterial walls. When LDL levels are increased or when other factors including hypertension, smoking, and diabetes are present, there is a higher degree of LDL oxidation. Scavenger receptors (SR-A1 and SR-A2) expressed in macrophages nonspecifically take up oxidized LDL into the arterial wall. This initiates the formation of atheromas or plaques that can restrict blood flow, and eventually leads to the production of emboli or a rupture in the arterial wall. Of note, in contrast to LDL, HDL is thought to act as a protective factor against atherosclerosis. HDL is involved in VLDL and chylomicron maturation, and in reverse cholesterol transport. The latter process involves the transport of cholesterol from cholesterol‑rich cells back to the liver. Incorrect answers: Lipoprotein lipase (LPL) is an enzyme expressed on endothelial cells in heart, muscle, and adipose tissue. LPL is a triglyceride hydrolase that requires ApoCII as a cofactor. Deficiencies in LPL lead to elevated levels of triglycerides in the blood. Individuals with LPL deficiency generally have lower levels of LDL cholesterol. Chylomicrons are formed in intestinal epithelial cells and deliver dietary fats to the liver. Triglycerides are the most abundant component of chylomicrons. Chylomicrons are the most elevated lipoprotein when LPL or ApoCII is defective. VLDL particles are synthesized in the liver and transport triglycerides to extrahepatic tissues. Although elevated levels of VLDL increase the risk for premature atherosclerosis, the risk is far greater when LDL levels are high.

Answer 45

The correct choice is Crescents. The immunofluorescence image shows a linear pattern consistent with anti-GBM disease. Most patients with anti-GBM disease (Goodpasture disease, if pulmonary involvement is present) develop crescents (crescentic glomerulonephritis). Mesangial, subendothelial and subepithelial deposits are not features of anti-GBM disease. Arteriolosclerosis is seen in hypertension. Robbins PBOD 8ed pp 913, 920-921

Answer 46

Answer: occluding (tight) junctions Explanation: Paracellular transport is the movement of substances through an epithelial layer by moving between cells; in this case between the lateral sides of epithelial cells. Epithelial cells are joined together by junctional complexes. Occluding (tight) junctions are the most apical junctions and allow epithelial cells to function as a barrier. The amount of material that is transported along the paracellular pathway is dependent on the permeability of the occluding junctions. Incorrect answers: Desmosomes (macula adherens) are localized spotlike, anchoring junctions between cells. They do not provide a continuous structure around the cell so are not able to function as a barrier. Gap junctions allow direct passage of molecules from the cytoplasm of one cell to the cytoplasm of the adjacent cell. Centrosomes are located within the cell and are the microtubule-organizing center of the cell. (Note: this is different from basal bodies, which are located near the plasma membrane under the apical surface of epithelial cells and are the microtubule organizing centers of cilia.)

Answer 47

The correct answer is – “activates constitutive androstane receptors (CAR) resulting in an increase in the expression of CYP2C9 protein, increasing the elimination of iburofen" Explanation: Since ibuprofen is metabolized to a significant extent by CYP2C9, a marked increased in the amount of this enzyme is likely to increase the clearance of ibuprofen from the blood by increasing its metabolism. Phenobarbital is a known inducer of the expression of this enzyme in the liver, acting by binding to the CAR receptor. The CAR-phenobarbital complex forms part of the transcriptional protein complex that increases the rate of transcription of the CYP2C9 mRNA for this protein, and thus the amount of active protein generated. The other answers are incorrect statements.

Answer 48

Answer: compression of the left side of the spinal cord Upper motor neuron signs in the left lower limb (including exaggerated reflexes and plantar extension reflex) suggest a lesion to the lateral corticospinal tract on the left side of the spinal cord or the primary motor cortex on the medial aspect of the frontal lobe on the right. The sensory deficits pinpoint the lesion to the spinal cord. Specifically, loss of vibration and position sense on one side and pain on the opposite side is a hallmark of spinal hemisection. In this case, the posterior columns and anterolateral spinothalamic tracts were damaged on the left side near L1. Since the posterior column system does not cross until the lower medulla, vibration and joint position sense were lost on the left. Since the anterolateral spinothalamic tract fibers are already crossed in the cord, pain sensation was lost on the side opposite the lesion (right side).

Answer 49

Correct answer: Familial Mediterranean Fever. Explanation: Familial Mediterranean Fever (FMF) is due to mutations in the MEFV gene and is associated with spontaneous attacks of fever and pain due to serosal inflammation. The most common pain syndrome is abdominal pain due to sudden peritonitis. Pleuritis and synovitis are other common clinical manifestations. Attacks typically last for a few days and then resolve. While the pathophysiology underlying FMF is not completely understood, it is clear that inflammation plays a key role. During attacks, there is an abnormally high production of IL-1 leading to the autoinflammatory syndrome. Over time, patients with FMF can develop secondary (AA) amyloidosis. AA amyloid is produced in the setting of chronic inflammation, due to increased hepatic synthesis of the acute phase protein serum amyloid A. The AA amyloid can then deposit in the kidneys, spleen, liver, and intestines. Renal amyloidosis in FMF often progresses to nephritic syndrome and then, over a period of many years, to end-stage renal disease. Intestinal amyloidosis in FMF can result in malabsorption. Other answers: Patients with multiple myeloma and production of a monoclonal antibody (M spike) may have AL amyloid resulting from free light chains (i.e. Bence-Jones protein). Amyloid in medullary thyroid carcinoma is composed of calcitonin and is localized to the tumor. Familial amyloidotic neuropathy leads to deposition of ATTR amyloid composed of transthyretin. Of note, Alzheimer disease (not listed as an option) demonstrates Aβ amyloid, especially in the brain, derived from the APP protein.

Answer 50

In a fasted state, blood glucose levels are maintained by liver glycogenolysis and gluconeogenesis. After about 24 hours of fasting, glycogen supplies are exhausted so gluconeogenesis is the only pathway that can maintain blood glucose. Ethanol is metabolized in the liver to acetate via two dehydrogenase reactions that convert NAD+ to NADH. The effect is to greatly elevate the NADH/NAD+ ratio in the liver, thereby affecting all pathways that use this pair of cofactors. One of the pathways is gluconeogenesis, which requires pyruvate and/or oxaloacetate as starting materials. When the ratio of NADH/NAD+ is high, pyruvate is reduced to lactate and oxaloacetate is reduced to malate, making the starting materials unavailable for gluconeogenesis. Therefore, one of the mechanisms by which ethanol causes hypoglycemia is inhibition of gluconeogenesis in the liver. Additionally, there is recent data that ethanol may also cause hypoglycemia by increasing insulin release from the pancreas. Incorrect answers: Inhibition of glycogen breakdown in the liver is incorrect because Ann’s 2-day fast depleted her of liver glycogen. Also, ethanol does not affect glycogen breakdown, which is why most people don’t faint when they drink moderately. Inhibition of insulin release would result in increased glucose levels. Also, there is recent data suggesting ethanol actually increases insulin release. One cannot rule out activation of glycogen synthesis on first principles; ethanol could have some regulatory effect on the pathways of glycogen synthesis, but this potential mechanism has not been demonstrated.

Answer 51

Ans B. right, increasing the off-loading of O2 at peripheral tissues The acidosis causes the shift of the curve to the right. Oxygen delivery to peripheral tissues is increased because the decreased affinity of hemoglobin for oxygen at the lower pH permits off-loading of oxygen at higher PaO2. Interestingly, oxygen binding to hemoglobin in the lung is only minimally changed because the partial pressure of oxygen in the lung is often still high enough to saturate hemoglobin (i.e. conditions are at the upper plateau of the curve). A graph illustrating the oxygen hemogloblin dissociation curve from the Guyton and Hall physiology textbook is below. Note that in addition to low pH, high temperature and high levels of DPG (2,3-Disphosphoglycerate, an organophosphate made in red blood cells) also drive the curve to the right.

Answer 52

The correct answer is Complex atypical hyperplasia. ``` The correct order of progression from benign endometrial change to malignant disease is as follows: Proliferative endometrium to Simple hyperplasia to Complex hyperplasia to Complex atypical hyperplasia to Endometrial carcinoma ``` Complex atypical hyperplasia is considered a pre-neoplastic condition. Robbins PBOD 8ed. pp 1030-1034

Answer 53

This is the egg of the causative agent of urogenital schistosomiasis, Schistosoma hematobium. All schistosomes have a snail intermediate host, and infect humans via skin penetration by the larval stage known as cercariae. Wading in irrigation canals is a typical way in which this disease is transmitted in Egypt, where S. hematobium is endemic. High rates of transitional cell carcinoma of the bladder in Egypt have been epidemiologically linked to infection with this organism. Other answers: Watercress is a leafy plant that is associated with the transmission of the liver fluke Fasciola hepatica. Drunken crab is a dish served in Southeast Asia and China, consisting of a species of freshwater crab pickled in rice wine. This crab serves as the secondary intermediate host for the lung fluke, Paragonimus westermani. The larvae (metacercariae) encysted in the crab are able to survive the pickling process. Steak tartare is prepared with raw beef and can serve as a vehicle for infection with any number of pathogens (think bacteria!); among the parasitic agents acquired by consumption of raw beef is the beef tapeworm Taenia saginatta.

Answer 54

The correct answer is Entamoeba histolytica. Explanation: Although all of these agents can cause diarrhea, the problem with amebiasis is that infection my lead to liver abscess formation due to dissemination of the organism from the GI tract. The hepatomegaly, pain, fever and chills lead us to consider a liver abscess.

Answer 55

Correct Answer: Intravenous injection of adenosine. This is the first choice for termination of PSVT. Incorrect answers It is unlikely that Valsalva maneuver will work since the patient has already tried many times. Intravenous injection of verapamil is as effective as intravenous injection of adenosine in terminating PSVT. However, whether the patient has accessory pathways (eg, WPW syndrome) is not absolutely clear. Verapamil can inhibit AV conduction and enhance conduction through accessory pathways, leading to ventricular tachycardia or fibrillation. Digoxin is also often effective in terminating PSVT. However, it has a similar problem as described for verapamil.

Answer 56

Correct answer: Self reported attention and memory problems since exposure to toxic chemicals during this mission. Explanation: A change cognitive abilities following potential injury to the brain is an important reason for referral to a neuropsychologist. Most symptoms listed in the other answers are consistent with posttraumatic stress or re-adjustment issues and may be more appropriate for referral to a psychologist/behavioral health professional. However, when cognitive impairment, identified brain pathology, or deteriorating mental status is present, a referral for neuropsychological assessment is most appropriate to help with diagnosis, monitoring and treatment planning.

Answer 57

The correct answer is Her2/neu amplification. The histological description indicates infiltrating ductal carcinoma. Among the 4 choices Her2/neu amplification would portend the worst prognosis. The other features would indicate a better prognosis. Generally, the following features indicate a poor prognosis: distant metastases, lymph nodes metastases, tumors greater than 2 cm in diameter, presence of inflammatory carcinoma, high grade histology, Her2/neu amplification, and ER receptor negativity. Robbins PBOD 8ed. pp 1066-1093

Answer 58

Correct answer: The developing follicles enlarge and become more sensitive to LH and FSH through up-regulation of gonadotropin receptors. Explanation: LH and FSH receptors are upregulated to increase the sensitivity of the follicle. At the same time the developing follicles enlarge in size, enhancing their ability for steroid biosynthesis. Other answers: The positive feedback actions of estrogen are only manifest for a brief period at the time of ovulation. The half life of LH and FSH are not regulated during the course of the cycle. There is no regulation of the hypothalamic set point during the cycle, thus negative feedback by estrogen and progesterone is incorrect.

Answer 59

The correct answer is d: This is an autoimmune disorder caused by a type 2 hypersensitivity reaction. Explanation. The clinical features suggest hyperthyroidism due to Graves’ disease. Graves’ disease is an autoimmune disorder resulting from a type 2 hypersensitivity reaction (Robbins, table 6-4). Specifically, autoantibodies in Graves’ disease bind and activate the TSH rececptor. These autoantibodies tend to be of the IgG1 subclass and oligoclonal in nature. Hypersensitivity reactions are divided into four types: type 1 (immediate, IgE mediated), type 2 (delayed, antibody mediated), type 3 (delayed, immune complex deposition with complement activation), and type 4 (delayed, T-cell mediated). As Graves’ disease is due to IgG autoantibodies, it can be thought of as a type 2 reaction. Other answers: A diffuse increase of thyroid radioactive iodine uptake, not a multinodular increase, is typical of Graves disease (Robbins, page 1115). Decreased thyroid radioactive iodine uptake is a characteristic of thyroiditis (Robbins, page 1113). TSH is the single most useful screening test for hyperthyroidism since levels are decreased even at the earliest stages of disease (Robbins, page 1109).

Answer 60

In a case-control study, participants are identified based on their disease or outcome status, and information about their prior exposure is collected retrospectively. Here, the disease or outcome is stroke. Cases (stroke patients) and controls (healthy neighbors of stroke patients) were interviewed about their level of exposure in the past (stressful life experiences in the past year). A case series only evaluates patients with disease and does not include a comparison group. Cross-sectional studies measure exposure and disease at the same time, so would be unable to distinguish between stress as a risk factor for stroke and stress as a consequence of stroke. Cohort studies identify participants on the basis of exposure and follow them forward in time; a cohort study of stress and stroke might identify participants with high and low stress and follow them forward to determine the incidence of stress in each group.

Answer 61

The answer is Culture of an aspirate or punch biopsy from the edge of the lesion. Explanation: The duration of this infection, the geographic history of the patient, and the failure of antibiotics to eradicate the ulcer suggest the infection is attributable to Leishmania species. These parasites enter the body as flagellated promastigotes through the bite of the sandfly. The promastigotes are rapidly taken up by macrophages where they change into the amastigote replicative stage. These non-flagellated amastigotes remain intracellular except when their growth results in cell lysis and spread to neighboring cells. The diagnosis is typically made by culture for Leishmania parasites using NNN (Novy, MacNeal, Nicolle) media or liquid Schneider’s media. Sample for culture is typically obtained by injecting and then aspirating sterile saline solution from multiple areas of the lesion, or by obtaining a punch biopsy near the edge of the lesion. Histology is also typically performed, and may reveal amastigote forms in macrophages. At WRNMMC, we also perform PCR on aspirates and biopsies for speciation. While Leishmania ulcerations often become superinfected with bacteria (as appears may have occurred in this case), the bacteria are not the underlying cause of the lesion.

Answer 62

Answer: chi square test The research question involves comparing two proportions, and chi square tests are used to compare proportions among two or more groups. T tests and analysis of variance are used to compare means, not proportions -- t tests compare two means and analysis of variance can be used to compare more than two means. Pearson correlation describes the extent to which subjects with high values for one variable have high values for a second variable.

Answer 63

Correct answer: lead time bias Explanation: All of these are biases inherent in evaluating screening programs, but lead time bias is what is described above. If a new screening test is used on a population and it is able to identify cases of disease at a point earlier in the course of disease, but the available treatment is ineffective in delaying death, lead time bias may be present in interpretation of the results. Lead time bias is a bias that occurs when a test identifies a disease state earlier than current practice, but does not alter actual survival time. For example: Consider a person is diagnosed at age70 with a specific cancer and dies from that cancer at age 75. Now assume a screening test could have found the cancer at age 65, but the treatment was ineffective and the person still would have died at age 75. The person’s survival from diagnosis without screening was 5 years. The person’s survival from diagnosis with screening was 10 years. Thus, if you just looked at survival from diagnosis, it appears that screening doubled survival time. However, the person derived no mortality benefit from screening as they died at the exact same age. Consequently, if you implement a screening test, you have to take into account how much earlier in the course of disease the test identified disease in considering the benefits of screening. If there is no effective treatment, you may actually cause harm in that the person may just live with the knowledge they are going to suffer and die prematurely. Length bias occurs when a better prognosis for cases detected directly by the screening procedure than for cases diagnosed between screening exams is used as evidence that the screening program is effective (i.e. screening detects less aggressive cases with better prognosis). Overdiagnosis bias occurs when screening identifies cases that would not have clinically surfaced in a patient’s lifetime because of lack of progressive potential or death from another cause. Examples include breast and prostate cancer in older patients, who will normally die with the disease, not from it. Selection bias occurs when comparison groups differ in ways other than the main factors under study, but which influence the outcome. One example of this is the fact that healthy volunteers are more likely to engage in screening procedures than controls, making the screening test seem more effective than it truly is.

Answer 64

ANSWER: Cytomegalovirus. The cell in this image is infected with cytomegalovirus (CMV). The histologic features of a large cell with a large, eccentric nucleus containing a smooth, dark-purple, intranuclear inclusion with smaller, cytoplasmic inclusions is pathognomonic of CMV. One of the TORCH group of infections (Toxoplasmosis, Other, Rubella, CMV, Herpes) seen in newborns, CMV is acquired in utero through an infection of the mother that is transferred to the developing infant through the placenta. When infection occurs in the first trimester, the effects may be severe, including CNS necrosis and calcification, microophthalmia, deafness, hepatomegaly, and pneumonia, among others. With second or third trimester infections, the sequelae are much milder and may include only shedding of the virus, detectable in the urine. Other answers: Herpes virus infection may rarely be acquired in utero and usually infects the infant as he or she is passing through the infected birth canal of the mother. However, the herpes virus inclusions are intranuclear only. RSV and EB virus are seen in older infants and children but rarely as a congenital infection. Robbins PBOD 8ed. pp 353-355

Answer 65

The correct answer is Fecalith. The patient has acute appendicitis diagnosed based on transmural inflammation of the appendix. Fecalith, a hard mass of fecal material, can cause appendicitis by obstructing the appendix. Obstruction of the appendix can lead to distension of the appendix by mucus, resulting in distension of the appendix and increased transmural and intraluminal pressures within the appendix. These processes can lead to thrombosis and occlusion of the small vessels of the appendix, resulting in ischemia and ultimately necrosis of the appendix. Other causes of appendicitis include lymphoid hyperplasia, tumors, calculia, and infections. However, it is important to note that most patients operated on for appendicitis do not have a fecalith or other obvious cause of appendix obstruction found at surgery. Ectopic pregnancy, pelvic inflammatory disease, and ruptured ovarian cyst all may present with abdominal pain but do not cause acute appendicitis although they may lead to serosal inflammation of the appendix. Robbins PBOD 8ed pp 826-827

Answer 66

Correct answer: Release of growth factors such as PDGF. Explanation: Release of growth factors, such as PDGF (platelet-derived growth factor), from macrophages, platelets and vascular wall cells is important for smooth muscle cell recruitment. Smooth muscle cells are recruited into atherosclerosis, they do not atrophy. Neutrophils are not a major part of atherosclerosis, whereas monocytes and T-lymphocytes are. Turbulence is important for atherosclerotic plaque formation, laminar flow is protective. Endothelial cell dysfunction with increased endothelial cell permeability is important for atherosclerosis. Robbins PBOD 8ed. pp 496-503

Answer 67

Graves’ disease is a hyperthyroid disease which is often associated with goiter, proptosis, and, in rare cases, an infiltrative skin condition known as pretibial myxedema. The disease is due to autoantibodies which activate the TSH receptor. Additionally, the proptosis in Graves’ disease is likely due to the action of autoantibodies, possibly targeting fibroblasts in the eye muscles and causing inflammation within the orbit. While Hashimoto’s thyroiditis typically leads to hypothyroidism (and thus high TSH levels), early in the course of disease it can cause hyperthyroidism with decreased TSH levels. However, neither Hashimoto’s thyroiditis nor thyroid carcinoma typically causes proptosis. TSH is increased in TSH secreting adenoma.

Answer 68

The correct answer is lidocaine. Explanation: Lidocaine is the only amide-type (non-ester) local anesthetic in the list of choices. Furthermore, benzocaine is primarily used topically in the clinic and not injected.

Answer 69

The correct answer is parvovirus B19. The typical course of infection with parvovirus B19 is a febrile illness that is followed by a rash that is pronounced on the face (slapped cheek) AFTER the resolution of the febrile stage. The development of polyarthritis separates parvovirus B19 infection (fifth disease) from sixth disease associated with HHV6 for which the rash is more predominant on the torso and not as much so on the face. The rash of varicella-zoster virus is typically vesicular and classically occurs on the trunk and head, and then extends to the limbs. The rash of measles is classically a generalized (all over the body) macular/papular rash.

Answer 70

Correct answer is Point mutations of the c-KIT receptor tyrosine kinase would be an expected genetic change. The clinical findings are consistent with systemic mastocytosis. Urticaria pigmentosa is a limited cutaneous form of this disease that affects mainly children. About 10% of individuals with mastocytosis have the systemic form of the disease with cells infiltrating multiple organs. Systemic mastocytosis can occur with or without skin involvement. Systemic mastocytosis occurs primarily in adults. Many of the signs and symptoms of systemic mastocytosis are caused by the release of histamine and heparin. Epinephrine may be used to treat severe cases manifesting as anaphylaxis. Point mutations of the c-KIT receptor tyrosine kinase increase c-KIT signaling and drive mast cell growth and survival. The cells responsible for this condition are mast cells, not lymphocytes. Mast cells are primarily tissue-residing cells with intracytoplasmic granules and multilobed nuclei. Metachromatic stains (toluidine blue, Giemsa) may help visualize the granules . (Robbins, page 1185-1186).

Answer 71

The best choice is C reduce cyclosporine A dosage and administer mycophenolate mofetil (MMF). The key to this question is avoiding nephrotoxicity by reducing the dose of the calcineurin inhibitor. MMF is an antimetabolite extensively used in solid organ transplant patients experiencing calcineurin inhibitor-induced nephrotoxicity. It effectively prevents acute graft rejection in combination with low-dose cyclosporine A. Tacrolimus is another calcineurin inhibitor associated with nephrotoxicity, so this is not an acceptable alternative to preserve renal function. Discontinuing immunosuppressive treatment of any kind will likely lead to acute allograft rejection, whereas maintaining the current dose of cyclosporine A will precipitate a further decline in renal function.

Answer 72

The correct answer is Osteomyelitis due to Staphylococcus aureus. Explanation: Two pyogenic cocci, Staphylococcus aureus and Streptococcus pneumoniae (not a choice here) predominate in bone and joint infections of children. These bacteria generally reach the site of infection by the hematogenous route from infections elsewhere in the body. In this age group disseminated gonorrheal infection is rare. Ostemyelitis attributable to S. epidermidis is uncommon but occurs in conjunction with post-operative infections in joint replacement. Reiter’s syndrome, also referred to as reactive arthritis, is a sequela to infection with certain gastrointestinal and urogenital pathogens such as Shigella, Neisseria and Chlamydia. It typically is not common in young children nor is it accompanied by a high fever and bone tenderness.

Answer 73

Correct answer: ventral midbrain The deficits are consistent with damage to the corticospinal and corticobulbar tracts as well as cranial nerve III. Cranial nerve III, the oculomotor nerve, controls most of the eye’s movements and is responsible for elevating the eyelid (by innervating the levator palpebrae superioris) and for constricting the pupil (by innervating sphincter papillae). Thus, a lesion to CNIII causes the eye to rotated in a “down and out” position and the pupil to be dilated. The descending cortical fibers are located in the crus cerebri on the ventral aspect of the midbrain, and CN III fibers pass through the crus cerebri to exit the brainstem en route to the orbit. This patient most likely had a CVA involving the penetrating paramedian branches of the posterior cerebral artery that supply the right ventral midbrain.

Answer 74

The correct answer is Sarcomas develop in 0.7-0.9% of affected individuals, usually osteosarcomas or fibrosarcomas. This patient has Paget disease of the bone. Sarcomas develop in 0.7-0.9% of affected individuals, usually osteosarcomas or fibrosarcomas. An initial osteolytic phase typically ends in a quiescent osteosclerotic phase. The net effect is a gain in bone mass. 15-40% of individuals with Paget disease have a family history suggestive of autosomal dominant inheritance. Some familial and sporadic cases have SQSTM1 gene mutations that through RANK signaling increased osteoclastic activity. A mosaic pattern of cancellous bone, produced by prominent cement lines, is the histologic hallmark of this disease. Robbins pages 1216-17

Answer 75

Answer: deaminates to thymidine Cytosine spontaneously deaminates to form uracil; uracil is not normally found in DNA and since it base-pairs with adenine, if it is not removed and replaced with cytosine, a C∙G →T∙A transition mutation will result after a round of DNA replication. Because of this, uracil is routinely removed from DNA via a uracil N-glycosylase (a base excision repair enzyme). In contrast to cytosine deamination, 5meC deaminates to thymidine. Since thymidine is a normal component of DNA, it is not recognized by the base excision repair enzymes, resulting in an uncorrected C∙G →T∙A mutation.

Answer 76

The correct answer is This disease principally affects the joints, producing a non-suppurative, proliferative and inflammatory synovitis. The patient has rheumatoid arthritis, which causes a non-suppurative, proliferative and inflammatory synovitis. MCP and PIP joints, as in the question stem, are frequently involved. The pathogenesis of rheumatoid arthritis involves autoimmune activation of CD4+ helper T-cells, which in conjunction with cytokines and local inflammatory mediators, destroy joints. 80% of affected patients have autoantibodies to the Fc portion of autologous IgG. This type of antibody is called rheumatoid factor. The isotype of rheumatoid factor is usually IgM (not IgG as mentioned in one of the incorrect answers). The presence of rheumatoid factor and anti-CCP antibodies together, in conjunction with appropriate clinical findings, are fairly sensitive and specific for rheumatoid arthritis. A positive rheumatoid factor alone is not very sensitive, as it can be elevated in a number of autoimmune and other inflammatory conditions. Anti-TNF may prevent or slow joint damage, but does not cure the disease. Robbins pages 1237-40.

Answer 77

Correct answer: increase the sensitivity of exercising muscle to insulin. Explanation: Exercise increases the number and activity of glucose transporters working on the membrane of muscle cells. Incorrect answers The utilization of glucose by the CNS does not vary under physiologic conditions The hypothalamic-pituitary-adrenal axis is activated in response to the “stress” of exercise. Exercising muscle, not adipose, is the tissue that responds to exercise with increased insulin sensitivity. Adipose tissue mobilizes its energy stores (free fatty acids and glycerol) in response to the counter regulatory hormones.

Answer 78

The answer is Choriocarcinoma. A history of undescended testicle is a risk factor for germ cell tumor development. Germ cell tumors include seminoma, embryonal carcinoma, choriocarcinoma, yolk sac tumor, and teratoma. About 30% of germ cell tumors are mixed, meaning they have cells from 2 or more germ cell tumor types. Choriocarcinoma is frequently found in combination with other germ cell tumors. Choriocarcinoma is typically more aggressive than the other germ cell tumors due to its tendency to metastasize via the vascular system to liver, lung, brain, and bone. Thus, when present in a mixed germ cell tumor, presence of choriocarcinoma generally drives what medical therapy is given. Chemotherapy is used to treat metastatic choriocarcinoma and radiation therapy is generally used for localized disease. Embryonal carcinoma, Seminoma, and Yolk sac tumor are germ cell tumors that are less aggressive clinically than choriocarcinoma. Leydig tumor is designated as a sex cord-gonadal stromal tumor, not a germ cell tumor. Robbins PBOD 8ed. pp 987-993

Answer 79

The correct answer is hydrochlorothiazide. Explanation: Thiazide diuretics, like hydrochlorothiazide, are the only diuretics that decrease the amount of Ca2+ in urine. Ms. Stone was probably originally on a loop diuretic, like furosemide, that increases Ca2+ secretion and caused the formation of Ca2+-containing kidney stones.

Answer 80

The correct answer is Single-stranded, segmented, enveloped negative-sense RNA virus. Explanation: Influenza virus infection predisposes people to secondary bacterial infections by agents such as Staphylococcus aureus and Steptococcus pneumoniae. The case does not allow us to discriminate between those bacterial infections. However, the history suggests that the patient’s problems started with influenza, a single stranded, segmented virus with negative sense RNA.

Answer 81

Correct answer is Symmetrical distal sensory loss in a “stocking-glove” distribution. The patient has diabetic neuropathy, a complication seen in over 50% of diabetics. It is a symmetrical process that distally involves both motor and sensory functions. It is typically a bilateral process. Diffuse enlargement of peripheral nerves is not observed in diabetic neuropathy – it is typically encountered in hypertrophic (hereditary) forms of neuropathies such as Dejerine-Sotas disease. Deep tendon reflexes are decreased in diabetic neuropathy as it is a peripheral neuropathy. Increased DTRs are indicative of upper motor neuron lesions.

Answer 82

Answer: unstable angina/acute coronary syndrome This patient is presenting to the Emergency Room with classic angina pectoris. His history reveals high risk features including male, age, sedentary lifestyle, and smoking history. His presentation and examination demonstrate findings common in uncontrolled essential hypertension, a strong risk factor for atherosclerotic coronary artery disease. The acute presentation here excludes stable angina. Although a pulmonary embolism may present with chest pain, this is classic angina without pleuritic findings, and no observed DVT or historical precipitating factors (such as a long flight or car ride, recent surgery) or clinical risk factors (no known malignancy and no known inherited clotting disorders). It is possible for pericarditis to present rather quickly. However, his chest pain is not characteristic of pericarditis, given its dull quality. Also, there is no palliation of the pain with leaning forward or sitting upright.

Answer 83

Correct answer: an increased risk for the presence of a visceral cancer. This is an example of a case of dermatomyositis. 20-25% of adult patients with this diagnosis also harbor a visceral cancer. Other answers: Mutations within the DMD gene are the underlying cause of the most common forms of childhood-onset muscular dystrophy. Trinucleotide repeat expansion of a region on the 19q chromosome is the underlying cause of myotonic dystrophy. Although myopathy is the most common complication of statin therapy (1.5% of users), it does not have the associated features (heliotrope rash, pulmonary fibrosis) present in dermatomyositis that were described in the question stem.

Answer 84

Correct answer: Establish a regular exercise regimen, seek a supportive social environment, and quit smoking. Explanation: Engaging in regular exercise, seeking social support, and smoking cessation are all behavioral recommendations that physicians in clinical practice are encouraged to suggest to their patients for the improvement of cardiovascular health. Other answers: Omega-3 fatty acids may improve cardiovascular health and, therefore, increased (not decreased) consumption is often encouraged in patients with atherosclerotic heart disease. While weight maintenance is central to cardiovascular health, there are no empirically supported practice guidelines that patients should adhere a diet of a specific caloric amount. While stress management contributes to cardiovascular health, elimination of stress is not a feasible recommendation. Second, regular exercise is encouraged, but 6 days per week for 30-60 minutes exceeds the minimum recommended frequency and duration necessary for improvement of cardiovascular health.

Answer 85

Correct answer: Rupture of a berry (sacular) aneurysm. The question stem describes a classic presentation of a ruptured berry aneurysm. Robbins 8ed. pp 1297-8. Incorrect answers: Headache may appear in meningitis but it is not apoplectic (abrupt) in onset and is associated with the accumulation of polymorphonuclear cells (pus) in the subarachnoid space (CSF), not blood. Multiple sclerosis is not associated with headache or blood in the subarachnoid space. Arterial occlusion leads to ischemic stroke and not subarachnoid hemorrhage.

Answer 86

Correct answer: pericardiocentesis Explanation: The anatomical location of the stab wound and the presence of Beck’s triad (muffled heart sounds, distended neck veins, and low arterial blood pressure) make cardiac tampanode the most likely diagnosis. In the presence of bleeding from a stab wound to the heart, the tough, fibrous pericardium is unyielding and the pressure around the heart gradually increases as blood leaks from the affected cardiac chamber (usually the right ventricle, due to its anterior, substernal position). This increasing pressure eventually prevents the heart from filling normally and cardiac output falls (hence the drop in blood pressure and cardiac output). The pressure backs up, causing the large veins to dilate (distention of the neck veins), and the increasing layer of blood in the pericardium muffles the heart sounds. This can rapidly cause acute cardiac arrest and death. The most effective immediate treatment is pericardiocentesis (needle drainage of the pericardium). It is done by careful insertion of a large-bore needle into the pericardial sac and removing the accumulated blood. A catheter can be left in the pericardium to allow continued drainage and to prevent re-accumulation of blood on the way to the OR, where the cardiac wound can be repaired. A tension pneumothorax can cause decreased blood pressure and would be treated by insertion of a right-sided chest tube. However, lung sounds on the affected side are usually diminished. Other possible signs of tension pneumothorax that are not present in the case include shift of the trachea and of the point of maximal impulse to the unaffected side, and hyper-resonant percussion on the affected side.

Answer 87

Correct answer: nephrogenic diabetes insipidus. The patient has nephrogenic diabetes insipidus. The renal-ADH mechanism is defective and cannot respond to endogenous or exogenous ADH Incorrect answers: The ADH system is functional in individuals with compulsive water drinking. While affecting salt and water balance, the absence of renin does not inhibit the functions of the ADH system While affecting salt and water balance, a defective thirst mechanism does not inhibit the functions of the ADH system

Answer 88

The correct answer is His brain demonstrates plaque-like accumulation of beta-amyloid protein and intraneuronal accumulation of the protein tau. Alzheimer’s disease is the most common cause of dementia in this age group. Histology demonstrates plaque-like accumulation of beta-amyloid protein and intraneuronal accumulation of the protein tau. Incorrect answers: Prion-related disorders which are caused by PRNP gene mutations are extremely rare conditions and produce much more rapid neurologic deterioration. Loss of upper and lower neurons is indicative of amyotrophic lateral sclerosis, which is characterized by progressive weakness rather than dementia. The hereditary disorder with loss of medium spiny neurons in the caudate nucleus is Huntington’s disease. It is characterized by prominent choreiform movements and has an onset at a much younger age. Robbins PBOD 8ed. pp 1313-1317

Answer 89

Correct answer: thymoma. The patient’s clinical history and chest radiographic appearances are suggestive of neoplastic involvement of the mediastinum with either pressure effects or infiltration of adjacent mediastinal structures such as mainstem bronchi, esophagus and superior vena cava. The distension of the venous return in the head, neck and arms is indicative of the superior vena cava syndrome. Of the possibilities listed, thymoma and lung adenocarcinoma would be most likely to produce these clinical features, although the other two conditions may rarely do so. The histologic appearances of lymphocytes (thymocytes) admixed with epithelial cells having bland round, vesicular nuclei resembling normal thymic cortical epithelial cells are classic for thymoma. The patient’s weakness toward the end of the day is consistent with systemic myasthenia gravis, a well-known disease association with thymoma. Other answers: Nodular sclerosing Hodgkin disease typically involves the mediastinal lymph nodes of young adults and is characterized histologically by dense bands of collagen separating a mixed pleomorphic infiltrate composed of lymphocytes, eosinophils, histiocytes and lacunar variant Reed Sternberg cells with giant multilobed nuclei. Absence of gland formation by the tumor cells excludes a diagnosis of lung adenocarcinoma, and myasthenia gravis is not one of the paraneoplastic syndromes associated with lung adenocarcinoma. Acute lymphoblastic leukemia is primarily a disease of children and young adults in which the leukemic infiltrates comprise a monotonous, monomorphic population of leukemic blast cells. Robbins PBOD 8ed. pp 636-637

Answer 90

The presence of uric acid crystals in urine ("sand" in the diaper) indicates extremely high levels of uric acid are being excreted. The motor disability and hypotonia evident from the clinical picture taken together with the lab findings suggest Lesch-Nyhan disorder -- the condition in which the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT) is lacking entirely. The bizarre self-injurious behavior associated with this disorder manifests later on in childhood. Without functional salvage activity, purine bases are destined to be degraded to uric acid. The resulting decreased nucleotide pools together with increased PRPP levels lead to loss of feedback inhibition and dysregulation of the de novo synthesis pathway. This causes even higher levels of purines to be produced, which can go nowhere else but to form uric acid. Xanthine oxidase produces uric acid (converts the bases hypoxanthine to xanthine, and xanthine to uric acid), so a deficiency of that enzyme would not lead to increased uric acid. PRPP synthetase and the phosphoribosyl amidotransferase enzyme (aka PRA synthase) are involved in de novo synthesis of purines, so a deficiency is likewise unlikely to cause uric acid overproduction.

Answer 91

Dynein is a motor protein that is associated with microtubules and is found in cilia. The other proteins listed are not found in cilia. Individuals with primary ciliary dyskinesia often have genetic mutations in genes encoding dynein. Patients with primary ciliary dyskinesia often have poor mucociliary clearance, and thus are susceptible to recurrent respiratory infections. Males with this disease often present with infertility because of immotile sperm. Kartagener’s syndrome is the combination of recurrent respiratory infection due to primary ciliary dsykinesia and situs inversus (left to right reversal of organs).

Answer 92

Answer: increased plasma lactate/pyruvate ratio The pyruvate dehydrogenase complex (PDC) is located in the mitochondrial matrix and functions to convert pyruvate to acetyl-CoA for subsequent entry into the TCA cycle in aerobic metabolism. Deficiency of PDC results in increased production of lactic acid in order to maintain flux through glycolysis for ATP production. Absolute levels of lactate increase, as does the lactate/pyruvate ratio. Defects in this enzyme (or for that matter, any other enzyme required for energy production) would not be predicted to cause increased levels of ATP or an increase in the ATP/ADP ratio. Cellular oxygen consumption would be expected to decrease or remain largely unaffected because part of the acetyl-CoA, that amount coming from carbohydrates via glycolysis, is no longer available as fuel for oxidation and consumption of oxygen. The brain has limited ability to utilize fatty acids for oxidation, and relies heavily on glucose and ketone bodies for energy. A defect in PDC reduces the amount of energy available from aerobic oxidation of carbohydrates and the brain is then forced to rely more heavily on ketone bodies for energy. Indeed, ketogenic diets have been found to be highly beneficial to control neurologic symptoms in patients with PDC deficiency. However, such diets appear to be less effective in cases where defects exist in other OXPHOS enzymes, such as those directly involved in the electron transport chain, because at later stages the ability to derive energy is impaired for all fuel sources.

Answer 93

The defect described is anencephaly, which is due to failure of the rostral (anterior) portion of the neural tube to close. Neural tube closure normally occurs near the end of the fourth week of development. Other answers: Following formation of the neural tube, a region of the upper medulla & pons opens dorsally to form the forth ventricle. A defect in this process would affect the development of the brainstem and cerebellum, but not the higher regions of the brain. Agenesis of the corpus callosum results in complete or partial absence of the corpus callosum. This is a very rare congenital abnormality with multiple causes that is not typically a lethal birth defect. Neural crest cells detach from the neural tube as it closes and migrate away to form much of the peripheral nervous system and a number of non-neural structures (eg facial skeleton & pigment cells). Defects in this process can result in cleft lip, albinism, and underdevelopment of sensory and autonomic neurons in the PNS, but do not affect development of the CNS.

Answer 94

This patient most likely has Medium Chain Acyl CoA Dehydrogenase Deficiency (MCADD). This is a dysfunction of fatty acid metabolism. Fatty acid oxidation by mitochondria is important for energy production, especially during times of fasting. Failure to use fatty acids efficiently as an energy source during the fasting state forces cells to rely more heavily than usual on glucose metabolism, which probably contributes to hypoglycemia. Thus, individuals with fatty acid metabolism disorders often present fatigues and with a change in mentation during times of fasting or low carbohydrate intake. MCADD is a relatively common inborn error, and accounts for all the findings in the case. The accumulation of octanoic acid and 4-decenoic acid is consistent with a block in the beta-oxidation of medium chain fatty acids. Accumulated carboxylic acids are often excreted as their carnitine derivatives, so these derivatives are expected in MCADD. Fatty acids that cannot be oxidized by the mitochondria are treated as toxic materials and are metabolized by the omega oxidation pathway of the SER to dicarboxylic acids, so these metabolites are also expected to appear in the blood and urine. The omega pathway involves mixed function oxidation of the terminal methyl carbon of the fatty acyl chain.

Answer 95

The correct answer is complex partial - valproate. Explanation: The impaired consciousness with postictal abnormalities is indicative of a complex partial seizure. Valproate can be used as initial treatment for complex partial seizure. Felbamate is used only for refractory seizures due to the high risk of severe adverse effects and ethosuximde is not indicated for complex partial seizures.

Answer 96

Answer: SIADH The elder gentleman described in this vignette has pneumonia, but appears euvolemic, based on "tilt negative" BP and pulse and jugular venous pressure of 6 cm of water. The pulmonary crackles are most likely secondary to the pneumonic process. He has true hypo-osmolar hyponatremia, because the measured serum osmolality of 238 mOsm/L is close to the calculated serum osmolality of 236 mOsm/L. Relative to his very low serum osmolality, his urine osmolality is inappropriately high, at 250 mOsm/L (should be able to get it down to at least 100 mOsm/L). Additionally, his high urinary sodium level of 44 mEq/L suggests either euvolemia or diuretic therapy. Thus, the syndrome of euvolemic hypoosmolar hyponatremia fits here. The most likely diagnosis is the syndrome of inappropriate antidiuresis (SIAD). As a purist, you would need to check to make sure his adrenal and thyroid function are normal, as adrenal insufficiency and hypothyroidism can look like this. Be leery of this diagnosis among diuretic users, as well! The clinical setting is a clue, because SIAD is prominently associated with intracranial disease (including dementia) and pulmonary disease (including pneumonia).

Answer 97

Correct answer: progesterone. Progesterone, a steroid hormone, is lipid soluble and readily diffuses through the cell membrane into target cells where it acts in the nucleus, via nuclear receptors, to regulate gene expression. The rest of the choices are water soluble hormones that are excluded by the cell plasma membrane and therefore act on cell surface receptors.

Answer 98

Answer: the ability of Ras to hydrolyze GTP to GDP Ras is a monomeric G-protein that commonly stimulates MAP kinase signaling cascades often leading to unregulated cell division and tumor growth. When Ras is bound to GDP, it is inactive and cannot transduce signal. When it is bound to GTP, its protein conformation changes and it can bind to Raf to stimulate the signaling cascade. Ras is a "molecular clock" in that is has an intrinsic enzymatic activity that hydrolyzes GTP to GDP, thus terminating the signal. In many cancers, there are mutations that disrupt this enzymatic activity and thus the MAP kinase signaling cascade is unregulated and always on. These mutations do not disrupt any of the other functions listed.

Answer 99

Answer: killing of bacteria living in macrophage phagolysosomes Explanation: Failure to express class II MHC molecules will prevent the thymic development of CD4+ T cells, a primary function of which is to provide T cell help for the killing of phagocytosed bacteria by macrophages. Incorrect answers: Cytotoxic lymphocytes are derived from CD8+ T cells, which do not require class II MHC for their development. While the failure to express class II MHC results in a loss of T cell help for the killing of phagocytosed bacteria, the ability of macrophages to phagocytose antigens is not affected. While the failure to express class II MHC results in a loss of T cell help, B cells can produce IgM in the absence of T cell help.

Answer 100

Correct answer: lack of NADPH production due to an inborn error of glucose 6-phosphate dehydrogenase Glucose 6-phosphate dehydrogenase deficiency is a common inborn error in the African/African American male population. One of the products of the glucose 6-phosphate dehydrogenase reaction is NADPH, which is necessary to provide the reducing equivalents to reduce oxidized glutathione to reduced glutathione. Reduced glutathione is necessary to eliminate reactive oxygen species (ROS) that are formed in several reactions. High levels of ROS are generated by the metabolism of several drugs, notably antimalarials, but also some antibiotics. Normal individuals have a large excess of the enzyme glucose 6-phosphate dehydrogenase to cope with oxidative emergencies, but individuals with the deficiency are living on the edge, with an activity level about 10% of normal. Their deficiency manifests in situations of unusually high ROS production. Incorrect answers: One cannot rule out an unusual reaction in which a drug destroys thiamine. However, thiamine depletion would cause many more symptoms than red-cell hemolysis, notably neurological symptoms, as seen in some alcoholics suffering from thiamine deficiency. “ATP depletion due to rapid destruction of NAD+ by the sulfa drug” is incorrect because the pentose pathway does not produce ATP. The answer “Glutathione depletion due to inhibition of glutathione synthetase” cannot be ruled out from first principles, but the clinical presentation is classic for G6PDH’ase deficiency, so this is the most likely cause of the hemolysis (i.e., pick “horses” over “zebras.”)

Answer 101

Correct answer: bipolar disorder This patient is demonstrating classic symptoms of bipolar disorder. The syndrome is typified by periods of mania or hypomania and depression. This patient is currently in a manic episode, evidenced by a week of no sleep and extreme focus. Oftentimes the patients feel they are performing very well and do not appreciate the diagnosis until the depressive symptoms return. Mania is not a feature of major depressive disorder. Although he states he has strong religious affiliations, he does not have hallucinations common with schizophrenia. While hyperthyroidism can be associated with decreased sleep, it is more commonly associated with tremor, palpitations and heat intolerance.

Answer 102

The correct answer is exacerbation of chronic Stronglyoides stercoralis infection following steroid therapy. Of the agents listed S. stercoralis helminths are known to persist for long periods of time within human hosts due to autoinfection (the intermittent penetration of L1 larvae through the intestinal wall that restarts the infection cycle). These larvae enter the circulation, become trapped in the lungs, migrate up the trachea, and are swallowed to initiate new intestinal infections. With reduced immunity attributable to steroid therapy, the autoinfection cycle proceeds unchecked. Bacterial sepsis results from the concomitant release of bowel flora during penetration of large numbers of strongyloides larvae through the intestinal walls.

Answer 103

Correct answer: methotrexate. Explanation: The best treatment for rheumatoid arthritis is a drug that does more than relieve symptoms. Ibuprofen is often used to relieve symptoms, but is not a disease modifying anti-rheumatic drug (DMARD). Etanercept and infliximab are DMARDs, but they are “biologics” which specifically inhibit TNF-alpha action. It is known that treatment with these biologic drugs will frequently lead to reactivation of latent TB, if present. Therefore neither of these drugs should be used in a patient with latent TB. Therefore the best answer is methotrexate, a DMARD that does not have this side effect.

Answer 104

Correct answer: hydrophobic interactions The side chain of Glu is charged whereas that of Val is uncharged and nonpolar. Therefore the change from Glu to Val favors hydrophobic interactions (choice “d”). Since H-bonding requires two polar moieties, Val cannot facilitate such an interaction, ruling out hydrogen bonding. Similarly, Val, having a neutral side chain, cannot take part in ionic interaction, ruling out ionic interactions. Disulfide bond formation is not a correct answer because the disulfide bond is a specific covalent linkage between two adjacent cysteine side-chains.

Answer 105

Answer: anisocoria Damage to the superior cervical ganglion disrupts sympathetic outflow to the head region, causing Horner’s syndrome (ptosis – drooping of the eyelid, miosis – constricted pupil, and anhidrosis – decreased sweating). The pupil on the ipsilateral side would be smaller than the other pupil due to loss of sympathetic input to the dilator puppillae. Since anisocoria means unequal pupils, anisocoria is the correct answer. The light reflex would be unaffected because it is mediated by CNIII. Salivation (CN IX & VII) and lacrimation (CN VII) also would not be affected. Sweating on the face would be reduced , not increased, by the lesion.

Answer 106

The correct answer is, “maximal heart rate is achieved at lower workloads than normal.” Explanation: Patients with mitral stenosis have a low stroke volume at rest. They compensate for this by having an increased heart rate. This adjustment at resting levels leaves less reserve to compensate for increased demand during exercise. Consequently, heart rate will reach maximum at lower workloads in subjects with mitral stenosis relative to individuals without mitral stenosis. Incorrect answers “Maximal arterial-venous oxygen difference is higher than normal.” Maximal a-v O2 difference is limited by how much O2 can be extracted from blood. Arterial O2 content cannot be increased. So the drop in venous O2 content limits the amount extracted. In a normal person maximum extraction is reached at about 75% oxygen saturation. The body has difficulty extracting more than that. Although mitral stenosis subjects may compensate for the low stroke volume at rest by having an increased a-v O2 difference, the maximum difference that can be achieved with an increasing workload is similar to normal subjects but achieved at a lower workload than normal. “Exercise capacity is as high as a trained athlete.” Trained athletes can achieve a higher maximal cardiac output than normal primarily due to a lower resting heart rate. In a mitral stenosis subject, resting heart rate is even higher than normal in order to counterbalance the inability to increase stroke volume as a way of maintaining cardiac output in a normal range. Consequently, maximal heart rate will then be achieved at a lower workload in these subjects and therefore cardiac output will also be maximal at a lower workload. Since the patient’s cardiac output is compromised, exercise capacity will be limited. “Resting heart rate is lower than normal.” Since stroke volume is lower than normal, a lower heart rate would further lower cardiac output. The patient probably has a heart rate above normal.

Answer 107

Answer: lysosomal hydrolases The sphingolipidoses are a subset of the lysosomal storage diseases; in each case a hydrolytic enzyme required for degradation of one or more of the sphingolipids is defective. Consequently the substrate(s) of the defective lysosomal hydrolase accumulate and cause severe damage, especially when excessive storage occurs in the nervous system. The other enzymes are involved in lipid synthesis, not degradation, and are not located in the lysosome.

Answer 108

Correct answer: intestine to increase the absorption of calcium. Explanation: The intestine is an important site for 1,25-(OH)2vitamineD3, bioactive vitamine D. Incorrect answers. PTH, but not 1,25-(OH)2vitamin D3, bioactive vitamin D, causes the kidney to increase the reabsorption of calcium. The parathyroid senses calcium and responds to hypocalcemia, not 1,25-(OH)2vitamin D3 The calcitonin secreting cells within the thyroid senses calcium and respond to hypercalcemia, not 1,25-(OH)2vitamin D3, bioactive vitamin D

Answer 109

Correct answer: The patient is experiencing fatigue for a number of reasons. These include iron deficiency anemia and deficiencies in vitamins such as thiamine, riboflavin, and niacin. It is less likely, but possible, that she also has subclinical deficiencies of pantothenate or biotin. Phosphoenolpyruvate carboxykinase; Fructose -1,6- bis phosphatase; and Glucose 6-phosphatase are enzymes of the gluconeogenic pathway in liver, an essential pathway to maintain blood glucose in a fasted state. They are activated and/or induced by counter-regulatory hormones, especially glucagon. Incorrect answers: Glucokinase; Phosphofructokinase-1; Pyruvate kinase: These enzymes are active in the well-fed state, and activated by insulin. They take glucose out of the blood. Glucokinase traps glucose in the cell as glucose 6-phosphate. The other two enzymes are part of the glycolytic pathway, which opposes gluconeogenesis. Glycolysis is switched off when the gluconeogenic pathway is active. Phosphodiesterase; Protein phosphatase-2; Glycogen synthase: These enzymes iare activated by insulin, and reverse the effects of glucagon on the cAMP signaling cascade. They are active in the well fed state, not the fasted state. Acetyl CoA carboxylase; Pyruvate dehydrogenase; Citrate lyase: These enzymes are also activated by insulin. Pyruvate dehydrogenase is activated when glucose is being used for energy or for fatty acid biosynthesis. Acetyl CoA carboxylase and citrate lyase are part of the pathways for synthesis of fatty acids from glucose, relevant only in the well-fed state.

Answer 110

Explanation: Oligodendroglia are the only cells in the CNS that synthesize myelin. Incorrect answers: Astrocytes provide physical and metabolic support for neurons of the central nervous system. Microglia are phagocytic cells found in the central nervous system. Schwann cells synthesize myelin in the peripheral nervous system.

Answer 111

Correct answer: superficial inguinal lymph nodes Explanation: The dentate line (also called the pectinate line or mucocutaneous line) demarcates the limit of the anal valves and can be visualized within the anal canal. It is an important landmark and indicates the junction of the superior (visceral) part of the anal canal (from the embryonic hindgut) and the inferior (somatic) part (from the embryonic proctodeum). Above and below this line, the arterial supply, innervation, and venous and lymphatic drainage differ dramatically. Inferior to the dentate line (towards the perineum), the lymphatics (like most of the rest of the perineum) characteristically drain into the superficial inguinal lymph nodes and one must adopt palpation of the inguinal lymph nodes as a routine examination for any lesion in this area. If the nodes are found to be positive histologically for metastases, it will have an important bearing on the accurate staging of the lesion. This may then impact on treatment decisions.

Answer 112

Correct answer: maintained constant due to local mechanisms. Explanation: Autoregulation of blood flow is local mechanism, the ability of a tissue to maintain constant blood flow in the face of a change in perfusion pressure. Blood pressure and thereby perfusion pressure is down to about 75 mmHg. The normally healthy brain can maintain blood flow to a perfusion pressure of about 50 mmHg. Incorrect answers: “decreased due to reflex vasoconstriction” Blood flow is maintained. The brain’s vasculature is relatively insensitive to the influence of nerves. “maintained constant due to reflex cerebrovascular constriction” Vasoconstriction would cause an increase in vascular resistance and decrease flow. “maintained constant due to baroreceptor mediated cerebrovascular dilation” The brain’s vasculatureis relatively insensitive to the influence of nerves. Autoregulation is a function of the tissue itself. Nerves do not participate in local autoregulation.

Answer 113

Correct answer: transport through the portal venous system Explanation: Of the choices, the most likely route is a blood-borne metastasis through the portal system: i.e., from the superior rectal vein into the inferior mesenteric vein, and thence directly to the liver. Incorrect answers: The tributaries of the vena caval system correspond to the paired visceral and parietal branches of the abdominal aorta and do not classically drain the distal colon. Rather, the unpaired viscera (like the rectosigmoid colon) are drained by tributaries of the portal venous system, which ends in the liver. The superficial inguinal nodes characteristically drain the skin and its adnexae from the part of the perineum that is inferior to the pectinate line of the anal canal. Thus, superficial inguinal nodal metastases are sometimes seen with transitional cell carcinomas of the anus – but not usually with adenocarcinomas of the rectosigmoid. Regarding the left peritoneal gutter: Although the descending colon is retroperitoneal and is covered anteriorly by the peritoneum of the left peritoneal gutter, the sigmoid colon is intraperitoneal and distal to this region. Although a direct extension of a rectosigmoid carcinoma could conceivably reach the left peritoneal gutter, this is usually a late finding and a blood-borne metastasis via the portal system is much more likely.

Answer 114

Answer: Hydrolysis of triglyceride to diglycerides and fatty acid in adipose tissue Uncontrolled Type I diabetics have high levels of fatty acids in their blood owing to lack of control of the first step in fat mobilization, hydrolysis of triglycerides to diglycerides and fatty acids in adipose tissue. The enzyme that catalyzes this step is aptly named hormone-sensitive-lipase. It is activated by counter-regulatory hormones such as glucagon and epinephrine, via the cAMP signalling cascade. Insulin reverses the effects of these hormones., slowing down or blocking fat mobilization. Ordinarily, even in a fasted state, the rate of the lipase reaction is controlled by a balance of opposing effects of insulin and counter-regulatory hormones. In the absence of insulin, the large flux of fatty acids into the blood and into the liver causes over production of ketones by simple mass action, i.e., by providing a large amount of substrate for the relevant pathways. Insulin inhibits one other step in the list shown above – transport of fatty acids across the liver mitochondrial matrix (via the carnitine transport system). However, even in a normal individual, with basal insulin, the transport system is operating at maximal velocity in the fasted state.

Answer 115

Correct answer: Transcapillary flux of interstitial fluid due to low capillary pressure. Explanation: Low capillary pressure will enhance the movement of cell free fluid from the interstitium into the blood (Starling’s law of capillary exchange), reducing the concentration of red blood cells. Capillary pressure is reduced through two major mechanisms. First, when blood pressure is lowered capillary pressure is also. Secondly, reflex sympathetic vasoconstriction causes an increase in the pressure drop from artery to capillary and, decreasing capillary pressure even more. Incorrect answers: Whole blood administration would tend to maintain hematocrit because whole blood contains blood cells in a normal concentration. A person bleeds whole (unconcentrated and undiluted) blood from a wound. A significant bleed would not be associated with hemoconcentration. Turbulence has no effect on red blood cell loss but would favor bleeding of whole blood. Venoconstriction would occur as a reflex response to hemorrhage. However, as this would mobilize whole blood from the splanchnic circulation into other areas of the body, it would serve to maintain hematocrit and cardiac output.

Answer 116

Correct answer: posterior dislocation of the hip Explanation: Anatomically, this scenario is classic for a posterior dislocation of the hip joint. It can be associated with axial loading of the femur when the passenger is thrown forward, slamming the bent knee into the dashboard. Clinically, the head of the femur is forced posteriorly and superiorly, and sometimes it also fractures the posterior rim of the acetabulum as it is driven back. The lower extremity is characteristically anatomically shortened and the thigh is internally (medially) rotated since the hip adductors and medial hamstrings are now quite tight. This tightening also brings the knee into flexion and it cannot be straightened by the patient. On the other hand, with an anterior hip dislocation, there is no anatomic shortening of the extremity, the thigh is externally (laterally) rotated, and the anteriorly displaced femoral head can usually be palpated under the skin just inferior to the middle of the inguinal ligament - sometimes with the femoral artery “draped” over it and easily palpable. Sciatic nerve palsy is not associated with this posture, but is rather characterized by flaccid weakness of the knee flexors (hamstrings) and calf musculature and hypesthesia (poor sensation) of the sensory territories innervated by the tibial and common fibular (peroneal) nerves (characteristically including parts of the sole of the foot).

Answer 117

Answer: Chronic obstructive lung disease Compliance is change in volume / change of pressure. COPD is a condition with floppy lungs. the volume expands with little effort, but the lack of elasticity makes it difficult to expel the air. In contrast, fibrosis is “stiff lung” and compliance is decreased. Removal of a lung should not change the characteristics of the remaining lung if it is otherwise healthy.

Answer 118

Explanation: IgG crosses the placenta from mother to fetus and is stable in the circulation for several months after birth. If the mother previously had chickenpox (or the vaccine), some of her IgG would be specific for VZV, neutralizing the virus in the infant. Incorrect answers CD8+ T cells cannot cross the placenta from mother to fetus; the infant would not have VZV-specific memory CD8+ T cells at the time of infection. IgM cannot cross the placenta from mother to fetus, and the infant would have VZV-specific IgM-secreting B cells at the time of infection. Neutrophils do not play a major role in anti-viral immunity

Answer 119

Correct answer: extension of the wrist and digits Explanation: The above type of fracture is most closely associated with radial nerve injury. In its course through the arm, the radial nerve is closely applied to the middle third of the humerus within the radial (spiral) groove of the humerus. Certain fractures in this area, especially if the fragments are displaced and depending on the force of the injury, can injure the radial nerve, causing a weakness or paralysis of the muscles that are innervated by the radial nerve. These include the wrist and digital extensor units, and such injuries can result in inability to raise (extend) the wrist and digits of the hand. The other responses are associated with injuries to the median and ulnar nerves.

Answer 120

Correct Answer: Cohort study. Explanation: A cohort study starts with exposed and unexposed groups and assesses outcomes at a later time. The rate or proportion of the outcome in the exposed group is compared to the rate or proportion of outcome in the unexposed group to assess risk associated with the exposure. The exposures in a cohort study are not assigned by the investigator, but occur based on environmental, lifestyle, genetic, or other factors. Other answers: Clinical Trial: the investigator assigns the exposure in a clinical trial and then follows to assess the rate of outcomes in the different exposure groups. Ecologic Study: an ecologic study uses population exposure data and population outcome data. Thus, you don’t necessarily know if the persons with the outcome were the same persons who were exposed. These studies are generally less expensive since they use existing data and you may use the results to generate or support a hypothesis, which in turn may justify more rigorous studies. Cross-sectional study: also known as a prevalence study, this design looks at the current “burden of disease” in a population and may be useful for health services planning or hypothesis generation. The outcome and exposure status of each individual in a population of interest is assessed at the same time, thus you often are not certain whether the exposure occurred before the outcome.

Answer 121

Answer: high sodium intake is associated with a more than 3-fold increase in odds of pre-HBP/HBP The odds ratio of 3.5 indicates that the odds of pre-HBP/HBP among children with high sodium intake is 3.5 times higher than the odds of pre-HBP/HBP among children with low sodium intake. The 95% confidence interval does not include 1.0, indicating that the odds ratio is significantly different from 1.0 at the 5% significance level (P

Answer 122

Correct answer: Rituximab. Explanation. Rituximab is far less toxic than cyclophosphamide (an alkylating agent) and irinotecan (a “natural product” inhibitor of DNA topoisomerase I.) Rituximab is a chimeric (mouse/human) anti-CD20 monoclonal antibody that promotes complement mediated lysis of malignant B-cells in CD20-positive non-Hodgkin’s B cell lymphoma, and CLL. Cetuximab is directed against the EGF receptor and not CD-20.

Answer 123

Answer: NADPH oxidase Explanation: Failure to reduce NBT indicates a defect in the neutrophil oxidative burst, especially in phagocyte NADPH oxidase enzyme which catalyzes the reaction between NADPH and oxygen to form superoxide. Individuals with defects in oxidative burst have a decreased ability to kill phagocytosed organisms. This defect underlies the disease chronic granulomatous disease (CGD). CGD occurs in about 1 per 200,000 births in the U.S. Patients with CGD develop recurrent pneumonia, superficial skin infections, abscesses of the skin and organs such as the liver, bacteremia, and osteomyelitis. Common infectious agents include Staphylocci, Burkholderia, Serratia, Nocardia, and Asperigllus. All of these are usually controlled in part by oxidative burst inside macrophages after the organisms have been phagocytosed. Incorrect answers Cytochrome oxidase is an oxidizing enzyme containing iron and a porphyrin. It is found in mitochondria and is important in cell respiration as an agent of electron transfer from certain cytochrome molecules to oxygen molecules In the presence of H2O2 produced by eosinophils, and either chloride or bromide ions, eosinophil peroxidase provides a potent mechanism by which eosinophils kill multicellular parasites. Granzyme B is one of the serine proteases located in the granules of cytotoxic lymphocytes and NK cells

Answer 124

Correct answer: The norepinephrine and serotonin transporters but not the dopamine transporter. Explanation: Duloxetine is an SNRI – a specific serotonin and norepinephrine reuptake inhibitor. In general the SSRIs and the SNRIs do not affect the dopamine transporter. None of the other answers provide the correct specificity of inhibition of the transporters.

Answer 125

Post nasal drip syndrome is the most common cause of chronic cough followed by asthma and GERD. In the absence of symptoms or signs suggesting the latter two diagnoses and with the nasal mucosal findings and cobblestoning the most likely diagnosis is post-nasal drip syndrome. There are no cardiac findings to support a diagnosis of CHF. Additionally, if mitral stenosis were the cause of this patient’s chronic cough one would expect to hear a murmur on cardiac exam and potentially observe an abnormal cardiac silhouette on chest x ray.

Answer 126

Correct answer: in the postmenopausal state. The postmenopausal state is the condition that exists after ovarian follicles have been depleted and the production of estrogen and progesterone is essentially reduced to zero. Accordingly, the pituitary is relieved of steroid hormone negative feedback and the secretion of LH and FSH is therefore unrestrained. Incorrect answers At the time of puberty levels of LH, FSH, estrogen and progesterone are all rising to normal adult levels At ovulation levels of estrogen, LH and FSH are all elevated, marking the follicular growth that has occurred during the follicular phase and the ovulatory surge of the gonadotropins. In a newborn all activities of the hypothalamic-pituitary-gonadal axis are profoundly suppressed.

Answer 127

Correct answer: fexofenadine. The anti-histamines, diphenydramine and meclizine, are first generation anti-histamines and therefore cross the blood brain barrier and cross react with a number of different receptors, causing drowsiness and loss of alertness and reaction time. Meclizine is used to treat motion sickness and not allergic rhinitis. For a truck driver you need to be particularly aware of the detrimental side effects of first generation anti-histamines like diphenhydramine, and prescribe a second generation anti-histamine, which do not cause drowsiness. The only one provided here is fexofenadine. Verapamil is a calcium channel blocker. It is not used to treat allergic rhinitis.

Answer 128

Answer: Ductus arteriosus The ductus arteriosus is a vessel that connects the pulmonary artery to the aorta in utero. Since pulmonary vascular resistance is very high in the non-respiring fetal lung, pulmonary artery pressure is high pushing blood into the aorta. This shunts poorly oxygenated blood toward the placenta. During pregnancy, prostaglandins help keep the ductus arteriosus open. At birth, the ductus typically closes within 15-20 hours. The process of closure is complex, and is likely due to a number of mechanisms including decreased prostaglandin levels (due to removal of the placenta, a main source of prostaglandins during pregnancy) and vasoconstriction initiated by increase in blood oxygen levels. A patent ductus arteriosus is detrimental after birth. After birth, the intake of oxygen into the lungs by breathing results in vasodilation of the pulmonary vascular bed, substantially decreasing pulmonary vascular resistance. This decreased pulmonary vascular resistance relative to systemic resistance results in a reversal of flow through a patent ductus (from right to left shunting, to left to right shunting). Thus, after birth blood is shunted through a patent ductus arteriosus from the systemic circulation to the pulmonary circulation. The increased flow of blood through the pulmonary artery increases pulmonary artery pressure and puts additional stress on the right heart. This causes enlargement of the heart. These stresses can be reduced by closure of the ductus. A prostaglandin inhibitor can help close a patent ductus arteriousus. Incorrect answers Blood is also shunted from right to left via the foremen ovale. However, closure of the foremen is not believed to be chemically controlled. The FO closes due to the reversal of pressures in the atrium closing it like a flap or valve. The Crista Dividens is part of the foramen ovale and is not sensitive to chemicals. The ductus venosus carries blood from the placenta to the right heart, bypassing the liver. It atrophies when the placenta is removed and no longer carries blood.

Answer 129

Answer: elevated serum EPO The hemogram points toward a post-viral pancytopenia associated with the onset of either a transient or life-threatening aplastic anemia. Provided retained normal renal function, a homeostatic increase in serum EPO would be anticipated. Changes in the serum bilirubin would suggest accelerated RBC destruction but targeted RBC destruction is not typically accompanied by a decreased WBC or an elevation in the platelet count. An elevated platelet count with a decreased neutrophil count would be paradoxical since they share common bone marrow precursors. Elevated reticulocyte count would be observed in cases of RBC loss (bleeding) or destruction. Robbins PBOD 8ed. pp 662-665

Answer 130

The correct answer is HLA genotype. Explanation: Patients of East Asian descent that harbor the HLA-B*1502 allele are at risk for carbamazepine-induced Steven-Johnsons Syndrome, a life-threatening skin condition associated with a Type IV hypersensitivity reaction. Although carbamazepine use is associated with a small risk of causing proteinuria, proteinuria is not a contraindication for using carbamazepine and is not related to a drug-induced hypersensitivity reaction.

Answer 131

Answer: call the CDC to begin process of obtaining IV artesunate while patient is admitted to the ICU and started on IV quinidine. This is a medical emergency. A non-immune patient with hyperparasitemic infection with Plasmodium falciparum has a high risk of death due to complicated malaria. This blood smear shows ~ 50 RBCs, of which 7 are parasitized cells, so she has a parasitemia of approximately 14%. Of course, additional laboratory studies should be obtained to determine whether she has evidence of organ dysfunction (hepatic, renal, pulmonary), metabolic acidosis, or coagulopathy. She should also have serial neurological assessments of her level of consciousness. Nonetheless, with only this blood smear in hand, you know this patient warrants immediate admission to the ICU and prompt initiation of intravenous antimalarial chemotherapy. Intravenous quinidine remains the only FDA-approved therapy for severe malaria in the US but intravenous artesunate is available under an emergency IND (investigational new drug) program that is run by the CDC in collaboration with the Walter Reed Army Institute of Research. Frequently, hospital formularies no longer carry intravenous quinidine since it is no longer used by cardiologists as an antiarrhythmic drug. Quinidine can be a complicated medication to manage because of consequential QT interval prolongation. If the patient had received a quinolone-based oral treatment enroute to care, that would have to be taken into account while choosing the initial quinidine dosing. Quinidine only acts on the 3rd ring trophozoite stage of the parasite. Artesunate and related medications, however, are active against all blood stages of the parasite. While awaiting the arrival of IV artesunate, if no quinidine is available, oral artemether-based combination therapy should be initiated. (The number to call at CDC is always provided in the Sanford Guide to Antimicrobial Therapy; it is also found at http://www.cdc.gov/malaria/diagnosis_treatment/artesunate.html.) Other answers: Despite the lack of a given history of vomiting in this patient’s presentation, high parasitemia meeting critera for severe malaria should be treated with parenteral therapy. Doxycycline alone can be used for chemoprophylaxis, but it is a relatively slow acting drug that should never be used alone for treatment, regardless of plasmodium species or level of parasitemia. Doxycycline + oral quinine is an acceptable regimen for uncomplicated malaria with low parasitemia, but in a non-immune patient with falciparum malaria it should be used cautiously and NOT as an outpatient. Now that artemether + lumefantrine (Co-Artem®, Sanofi) is an approved product in the USA, this would be a better choice of oral regimen if the patient had no evidence of complicated malaria or high parasitemia

Answer 132

Correct answer: cyclophosphamide Explanation: Cyclophosphamide and lomustine are the only alkylating agents listed. The requirement for activation by cytochrome p450 only applies to cyclophosphamide. This is a frequent Step 1 question. Incorrect answers: Cetuximab is an antibody directed against the EGF receptor. Irinotecan is a “natural product” inhibitor of DNA topoisomerase I.

Answer 133

Correct answer: compression neuropathy of the left fibular (peroneal) nerve Explanation: This scenario is characteristic of a fibular (aka peroneal) nerve injury secondary to compression neuropathy. In this case, the cause is arguably inadequate padding during the time that the patient was positioned with her left side down, while undergoing a contralateral surgical procedure. The weight of her opposite lower extremity, the surgical drapes, and possibly instruments are then transmitted to the left side and its pressure points: the left greater trochanter of the femur; the left knee and fibular nerve; and the left lateral malleolus. The fibular nerve, which is motor to the anterior and lateral compartments of the leg (the “leg” is anatomically defined as that part of the lower extremity from the knee to the ankle), innervates the main ankle and toe extensors (tibialis anterior, extensor digitorum longus, and extensor hallucis longus). Without this function, it becomes impossible for the patient to effectively extend the ankle during ambulation and the patient continually stumbles because the foot and toes cannot clear the walking surface. Fast walking or running become impossible. When a patient is unconscious, the common fibular nerve is vulnerable to compression because it is situated relatively superficially between the skin and the neck of the fibula. As such, it can be easily compressed between the bone and any hard surface. This injury characteristically occurs when the patient is unconscious (as during a surgical procedure) or inebriated. Unfortunately, some of these neuropathies can be permanent. It is incumbent on the surgeon himself/herself to routinely check all pressure points when the patient is asleep and positioned on the operating table, and before commencing any procedure. This is a responsibility that should not be delegated, and must be done on every case in order to personally confirm that vulnerable areas are well protected with adequate padding. As such, it should also be logged in the operation report that this is done postoperatively.

Answer 134

Answer: epithelium of the intestinal villi. Of the choices provided, the cells of the epithelium of the intestinal villi are the only ones that reproduce with a high turnover rate. Consequently, these cells are most affected by the chemotherapy. The other cell types divide slower and are not significantly affected.

Answer 135

Answer: germinal centers Explanation: Germinal centers are the location of B cells and antibody production within lymph nodes. Staphylococci and streptococci are extracellular pathogens, which are typically cleared in part by antibody responses. Incorrect answers Since the DTH responses are normal, there is no evidence of a T- cell defect Since the phagocytic function in the child is normal, and macrophages are a major phagocytic cell, it is unlikely macrophages would be absent from the lymph nodes. The paracortex is the area within the secondary lymphoid organs where T cells reside. Since the DTH responses are normal, there is no evidence of a T- cell defect.

Answer 136

Correct answer: within the cardinal (transverse cervical) ligaments Explanation: The cardinal (transverse cervical) ligaments are a portion of the uterosacral support system and help to support the uterus and uterine cervix. The uterine arteries run within the peritoneal broad ligament and the ureters are close to these vessels. The ureters pass on each side of the cervix area and are caudal to the uterine arteries (a relationship referred to as “water runs under the bridge”). Because of this proximity to the uterine arteries, the ureters are vulnerable to injury during a hysterectomy since these arteries must be clamped and ligated during this procedure. An injury to the ureter, especially if not immediately repaired, can be devastating to ureteric and renal function.

Answer 137

Correct Answer: N5- methyl FH4 --> FH4 Explanation: See Fig 40.9 of Marks (3rd Edition) for the “methyl cycle.” Vitamin B12 is necessary to recycle FH4. When B12 is deficient, all the folate in the cell winds up as methyl FH4, the so called “methyl trap.” In this situation, other forms of folate are depleted, one of which is N5, N10 –methylene FH4 , needed to produce dTMP from dUMP (Fig 40.5). Without dTMP, DNA cannot be formed. The clinical consequence is megaloblastic anemia, caused by the inability of hematopoietic cells to divide.

Answer 138

Explanation: Microglia are phagocytic cells found in the central nervous system. Incorrect answers: Astrocytes provide physical and metabolic support for neurons of the central nervous system. Ependymal cells line the fluid-filled cavities of the central nervous system and place a role in fluid transport within the brain. Neurons are the functional units of the nervous system.

Answer 139

Answer: S cells release secretin. S cells release secretin which stimulates the secretion of bicarbonate by the pancreas. This neutralizes acidic chyme entering the duodenum. Incorrect answers: Histamine would increase acid secretion in the stomach by the parietal cells. Peptidases are released in the inactive form, but this is irrelevant to the acid problem. “The duodenum has a stratified epithelial mucous membrane” is an incorrect statement. The duodenum has a simple columnar epithelium.

Answer 140

Answer: cluster headache This headache is most consistent with a type of neurovascular headache called cluster headache. Cluster headaches occur most often in young men, have a characteristic periodicity (they cluster together in time, then go away for a period of time, then return), and cause lacrimation, nasal stuffiness, and sometimes conjunctival inflammation. Migraines tend not to come and go in this manner, are more throbbing, and are more likely to be associated with nausea and vomiting. Sinusitis is usually bilateral and may have associated fever and purulent discharge. Tension headaches are usually described as bandlike, without lacrimation or nasal congestion.

Answer 141

The correct answer is: Increased in response to raised myocardial metabolic activity. An increase in heart rate and/or an increase in systolic blood pressure will augment the work of the heart and myocardial metabolic demand. Since the coronary circulation has limited ability to extract more O2 from each milliliter of blood, coronary blood flow must increase to satisfy the greater demand. Incorrect answers: “Unchanged due to coronoary homeostatic mechanisms” is incorrect. Myocardial O2 demand is increased by the greater metabolic activity associated with the increase in heart rate and blood pressure. Since the O2 content is already low in venous blood returning from the myocardium, this increased O2 demand must be met by increased supply or ischemia will occur. Coronary blood flow must increase. “Decreased due to altitude-induced coronary vasoconstrictor reflexes” is incorrect. This is the opposite of what occurs. Increased O2 demand requires increased supply, which occurs through dilation of coronary arteries. “acute myocardial hypoxia” is not occurring. This is documented by her nearly-complete hemoglobin O2 saturation (98%) at summit. Systemic arterial saturations of 95-100% are normal at rest and during strenuous exertion. Even in the absence of systemic arterial hypoxia, one might argue that transient local micro-hypoxia stimulates the increase in blood flow. However, the extent of hypoxia must be very small: myocardium supplied by normal coronary arteries and perfused with normal levels of fully saturated hemoglobin never exhibits hypoxic dysfunction, even at maximal exertion.

Answer 142

Answer: pore-forming proteins and proteases Explanation: Pore-forming proteins such as perforins are secreted by the cytolytic T cell and create pores in the membranes of target cells. Proteases such as granzymes are secreted by cytolytic T cells and enter target cells via the perforin-induced pores, causing target cell death. Incorrect answers Cytolytic T cells do not secrete antibodies or complement. Cytolytic T cells do not secrete complement or acute phase proteins. Fas ligand, which induces apoptotic cell death when it binds to its receptor, is expressed on the surface of cytolytic T cells but is not secreted.

Answer 143

Answer: vasovagal syncope Everything in this case favors vasovagal syncope, aka "the common faint.” There is a clear-cut strong emotional provocation, followed by premonitory (warning) symptoms of an impending faint: the transient feelings of warmth, nausea, and lightheadedness with associated dimming of vision proceeding to "blackout.” Other answers: Prompt recovery after hitting the deck makes seizure unlikely. The fact that the event was not associated with significant exertion mitigates against aortic or pulmonic outflow tract obstruction, as does the normal physical exam. Patients with syncope due to an arrhythmia often experience no prodrome prior to losing consciousness. The normal ECG also decreases the likelihood that arrhythmia was the underlying cause.

Answer 144

Correct answer: CT Angiography. In this hypothetical scenario, the CT angiography is more sensitive than the V/Q scan (90% vs 70%). In other words, it has a lower false negative rate (10% vs 30%), which means a negative result is better at ruling out a pulmonary embolism. Specificity is more important for ruling in disease, so the V/Q scan in this case would be better. Because the sensitivities are different, they are not equal at ruling out disease (CT angiography is better). Remember the mnemonic “SPin SNout”: specific tests are better for ruling in, while sensitive tests are better for ruling out.

Answer 145

The correct answer is survives in the environment within free-living amebas. Explanation: This case describes legionnaire’s disease. Legionella pneumophila is a facultative intracellular organism that colonizes the alveolar macrophages in a manner similar to its lifestyle in the environment where it parasitizes and survives within amebas. Clues to this being Legionella pneumophila are the age, occupation and lifestyle of the patient. Unlike other types of pneumonias, this disease is often accompanied by gastrointestinal symptoms. Diagnostic tests are difficult and time consuming, but fortunately there is a urine antigen detection kit that recognizes the Legionella LPS. The other pneumonia-causing organisms alluded to in the other answers are Chlamydia psittaci (which has a zoonotic reservoir in parrots and domesticated fowl), Mycobacterium tuberculosis (which is acid-fast and grows very slowly on Lowenstein-Jensen agar) and Klebsiella pneumonia (which is lactose positive and produces a mucoid capsule).

Answer 146

Answer: epilepsy Thin, white, flat tissue fragments are most consistent with proglottid segments of a tapeworm. Infections with intestinal tapeworms rarely cause systemic symptoms. Rather, individuals sometimes just report seeing proglottid segments in their stool or may report the sensation of proglottid segments moving through the anus. Infection with the pork tapeworm, Taenia solium, increases the risk of epilepsy because ingestion of eggs leads to neurocysticercosis (infection with larval cysts in the brain). Remember – the adult tapeworm stage is acquired by ingestion of infective larvae in undercooked pork. The larvae cannot mature in humans and so die in tissue, sometimes being enveloped in cysts, becoming calcified, or both. Patients with high exposures to this parasite sometimes have abnormalities on plain radiography of their muscle girdles, shoulders, back and thighs. Even strict vegetarians can acquire neurocysticercosis by ingesting eggs in food that has been contaminated with human fecal matter. Patients with active adult tapeworms, such as the patient in this vignette, are at increased risk for neurocysticercosis because they are at increased risk of swallowing eggs passed in their own stool. T. saginata is the beef tapeworm. Distinguishing between these two tapeworms requires a close inspection of the worm. The beef tapeworm is not associated with cysticercosis. Other answers: Of parasitic infections, iron deficiency anemia is most commonly associated with hookworm infections. Roundworm infections such as hookworms do not typically present as pieces of tissue passed in the stool. While most tapeworms do not cause anemia, Diphylobothrum latum can but typically does so by inducing vitamin B12 deficiency, not iron deficiency. Also, D. latum is much less prevalent than T. solium worldwide in humans and is not endemic in Africa. Liver abscesses are typically caused by bacteria or amoebae. The larval form of the dog tapeworm Echinococcus multilocularis, which is acquired by ingesting eggs from the feces of dogs infected with the adult parasite, typically causes cystic lesions in the liver but can be present in other organs or body compartments. This tapeworm is very small, and the adult worms do not infect humans. Bladder cancer has been associated with Schistosoma haemotobium, a fluke infection which resides primarily in the veins draining the bladder.

Answer 147

Correct answer: Increased conflict with other physicians and nurses, lower work productivity, impairments in memory, and increased risk for medical errors. Explanation: Increased conflict with colleagues, lower work productivity, and impaired memory have all been observed in sleep-deprived individuals. Further, as compared to the other response options, all three of these behaviors would be most likely to contribute to impaired occupational performance. Other answers: Hypervigilance is not associated with sleep deprivation; in contrast, sleep deprivation impairs vigilance. Hyperarousal and decreased appetite are not associated with sleep deprivation. While weight changes and eating behavior changes are observed in individuals who are not getting sufficient sleep, decreased appetite is not as strongly associated with sleep deprivation. While increased caffeine use may be observed to compensate for drowsiness, this behavior would not cause as strong a reason for concern relating to occupational performance as the behaviors in the correct response. Additionally, while social isolation may indicate a mood disturbance precipitated by sleep deprivation, it is not directly associated with sleep deprivation and would not be as strong a contributor to occupational impairment.

Answer 148

The correct answer is ramelteon. Explanation: Ramelteon is a melatonin agonist with short acting hypnotic properties that can be used for sleep onset insomnia. Of the mentioned medications, use of ramelteon has the highest risk of increased serum prolactin and decreased serum testosterone levels. Dantrolene and modafinil are a muscle relaxant and stimulant, respectively. Phenobarbitol is not generally prescribed to treat insomnia.

Answer 149

Answer: normal axis: follow patient for developing hypertension. Mean QRS axis is between 0º and 30º and is normal. Normal is about -30º to +100º. The characteristics of this ECG may occur for several normal reasons. Normal blood pressure is 120/80. This patient is prehypertensive by definition (systolic BP between120-139 or diastolic between 80-89 mmHg). BP can possibly be reduced with exercise and diet. Incorrect answers: “Severe left axis deviation and probable left ventricular hypertrophy: admit this patient for cardiac catheterization.” Left shift of the QRS would be accompanied by a mean axis of the QRS 120º. Lead I would be negative. “Mild left axis deviation: recommend that patient take a β-blocker.” The patient does not have left axis deviation and even if he did, that would not be an indication for drug therapy since left axis deviation can occur for many reasons unrelated to hypertension. While drug therapy for hypertension might include a beta blocker, this patient has not met the criteria for having hypertension. BP can possibly be reduced with exercise and a diet with higher content of fruits and vegetables, and it is always appropriate to recommend these measures to anyone with borderline high blood pressure.

Answer 150

Correct answer: indirect inguinal hernia Explanation: An inguinal hernia is a protrusion of parietal peritoneum and viscera (such as omentum or small intestine) through a normal or abnormal opening from the cavity in which they belong. Inguinal hernias account for 75% of abdominal hernias and about 2/3 to 3/4 of these are of the indirect type. Inguinal hernias can be classified anatomically by their relationship to the inferior epigastric artery. Those that proceed lateral to the inferior epigastric artery and course within the processus vaginalis on into the inguinal canal are classified as indirect inguinal hernias. Those that are medial to the inferior epigastric artery and course through or around the inguinal canal are classified as direct inguinal hernias. The classification of the hernia may directly impact the method that is selected for the anatomical repair of the hernia.

Answer 151

Correct answer: methotrexate – inhibition of dihydrofolate reductase Explanation: To answer this question correctly you must know the mechanism of action of each of these commonly used cancer chemotherapeutic drugs. Knowing these mechanisms allows you to use them correctly and in appropriate combinations while avoiding predictable drug-drug interactions. The inhibition of dihydrofolate reductase by folate analogues is a recurring theme in many areas of pharmacology and is something that appears over and over on Step 1 exams. Incorrect answers: The mechanism of action of 5-fluorouracil is irreversible inhibition of thymidylate synthesis (TS) after conversion of 5-FU to 5-FdUMP. Remember that TS is the enzyme that transfer the methyl group to 5-dUMP to create 5-dTMP, and essential precursor for DNA synthesis. Doxorubicin is an intercalating agent that results in DNA damage, and an inhibitor of topoisomerase. It does not inhibit thymidylate synthetase. Etoposide is an inhibitor of DNA topoisomerase II (the ATP-dependent topoisomerase), not topoisomerase I. This may seem like minutiae, but the distinction between the type I and type II topoisomerases is what makes it possible to use irinotecan AND etoposide in the same therapeutic protocol. Note: Other commonly used cancer chemotherapy drugs are paclitaxel and vinca alkaloids. Paclitaxel freezes microtubules in the polymerized state. Vinca alkaloids like vincristine inhibit polymerization. This is why the two should never be used together.

Answer 152

Correct answer: sympathetic vasoconstriction and cardiac excitation. Explanation: Baroreceptors sense the acute drop in blood pressure created by hemorrhage. The reflex output is designed to raise blood pressure towards normal (120/80 mmHg). The reflex response will be to excite the sympathetic nervous system and inhibit the parasympathetic. The net result will be 1) an increase in heart rate via sympathetic stimulation and reduction in parasympathetic input to the SA and AV nodes, 2) an increase in contractility due primarily to increased sympathetic activity to the myocardium and a modest effect of reducing parasympathetic activity, and 3) vasoconstriction due almost entirely to sympathetic activation of vascular nerves. Incorrect answers “parasympathetic vasoconstriction and cardiac excitation” There is minimal innervation of the blood vessels by the parasympathetic nerves. Parasympathetics also have no influence on basal vascular tone. So, removal of parasympathetic activity will not cause vasoconstriction. Reduction in parasympathetic activity will increase heart rate and mildly increase contractility but not to the degree that sympathetic stimulation does. “sympathetic vasodilation and cardiac excitation” Vasodilation would tend to lower blood pressure. Withdrawal of sympathetic activity would cause vasodilation and cardiac depression, both of which would reduce blood pressure and make the situation worse. “abdominal compression” Abdominal compression may cause pain which could cause a transient increase in heart rate. Abdominal compression could transiently increase venous return and thus cardiac output. Neither of these could sustain an increase in blood pressure or heart rate. Blood is dried so any transients would have subsided. The activation of the sympathetic and deactivation of the parasympathetic nervous system mediated by the arterial baroreceptors would be strong and sustained and the most likely and efficient means to maintain blood pressure.

Answer 153

Correct answer is C. 75% Explanation: There are at least two different ways to solve this problem. The first is with likelihood ratios, starting with the pre-test probability of 50%, as follows: a) Pretest Odds = p/(1-p) = 0.5/0.5 = 1 b) Likelihood Ratio positive= Sn/(1-sp) = 0.9/0.3 = 3 c) Posttest Odds = pretest odds x LR+ = 1 x 3 = 3 d) Posttest Probability = odds/(1 + odds) = 3/(1+3) = ¾ = 75% Secondly, complete a 2x2 table using the provided sensitivity and specificity. Then calculate the PPV = 75%.

Answer 154

The correct answer is: reduce her dosage and monitor closely. Dabigatran is a direct thrombin inhibitor. It does not require tests for monitoring its anticoagulant effect. Unlike heparin and warfarin, there is no specific therapy available to reverse the anticoagulant effect of dabigatran. Without a reliable test to gauge the efficiency of new oral anticoagulants like dabigatran, excessive bleeding can indicate an overdose. Because there is no approved antidote and severe bleeding is not apparent, reducing her dosage is the best course of action in this scenario.

Answer 155

Correct answer: gap junctions Explanation: Gap junctions allow direct passage of molecules and ions to travel between cells and thus enable ionic continuity between adjacent cells. Incorrect answers: Desmosomes are spot welds that anchor cells together. Hemidesmosomes are spot welds that anchor cells to the basement membrane. Occluding (tight) junctions allow epithelial cells to function as a barrier.

Answer 156

Correct answer: Appearing physically exhausted and stating that she feels hopeless about her future as a surgeon. Explanation: All of the answers contain signs and behaviors of professional burnout that are included in Freudenberger & Richelson’s (1980) Burnout Cycle. However, overt physical exhaustion and endorsing hopelessness both occur toward the end of the cycle where individuals may experience physical and mental collapse indicative of full blown “Burnout Syndrome,” which requires medical intervention. All three of the alternate responses tend to present early in the Burnout Cycle. While they are maladaptive over time and may progress to the more severe syndrome without early intervention, they are not severe enough to warrant medical attention.

Answer 157

Correct answer: A healthy diet, exercise regimen, and behavior modification should be continued indefinitely even after an individual reaches his/her goal weight. Explanation: The correct answer describes a healthy approach to weight loss because it reflects the long-term, lifestyle modifications that are required to maintain a healthy weight after an initial period of weight loss. Other answers Weight loss requires an increase (not decrease) in energy expenditure. 20% reduction in body weight is too ambitious of a weight loss goal for a 6-month period. A goal of 10% every 6 months is more reasonable and supported by the scientific literature. Adherence to weight loss regimens tends to decrease over time, leading to increased difficulty of continued weight loss.

Answer 158

The correct answer is Smallpox virus. Of the vaccines listed above, all are subunit or inactive virus-based vaccines except for the smallpox vaccine, which uses live vaccinia (cowpox) virus. In his immunocompromised state of impaired cell-mediated immunity, this patient is at risk of developing an infection with live virus from the vaccine if exposed. In addition to smallpox vaccination, vaccines that use live attenuated viruses should also generally be avoided in patients with substantially compromised cell-mediated immunity. These include MMR (measles/mumps/rubella), Varicella vaccine, Herpes zoster vaccine, and Yellow fever vaccine.

Answer 159

The correct answer is Insulin resistance by peripheral tissues and inadequate insulin secretion are probably the 2 main metabolic defects of this patient. The clinical findings are consistent with type 2 diabetes mellitus. The main metabolic defects that characterize type 2 diabetes are insulin resistance by peripheral tissues and inadequate insulin secretion (Robbins, page 1132). Incorrect answers: Amyloid deposition within islets is characteristic of type 2 diabetes mellitus, insulitis as described in the question stem of type 1 (Robbins, page 1139). Unlike type 1 diabetes mellitus, type 2 diabetes patients are often older (>40 years old) and obese (Robbins, page 1143). Diabetic ketoacidosis is a serious complication of type 1 diabetes mellitus; it may also occur in type 2 diabetes, but is not as common, or as severe (Robbins, page 1143).

Answer 160

The correct answer is Acyclovir. The development of encephalitis or central nervous system symptoms in an elderly person, particularly with lesions in the temporal lobe, is suggestive of herpes simplex type 1 infection that has reactivated and spread from the trigeminal nerve. HSV replication is inhibited by acyclovir, which becomes phosphorylated by the viral thymidine kinase and is then converted to a triphosphate nucleotide analogue by cellular kinases. The high affinity of this acyclo-GTP nucleotide analogue for the viral DNA polymerase allows it to be readily incorporated during DNA synthesis, but with no 3’ moiety, viral DNA replication terminates in infected cells. Azidothymidine is a nucleoside analog reverse-transcriptase inhibitor predominantly used in combination with other antiretroviral agents for treatment of HIV. Oseltamivir is a neuraminidase inhibitor used in the treatment of influenza virus infection. Ribavirin is a nucleoside antimetabolite with modest activity against a number of viruses, including hepatitis C, influenza, respiratory syncytial virus, and some hemorrhagic fever viruses.

Answer 161

CORRECT ANSWER: Salter Harris (SH) type 1 fracture is the correct answer for this question. SH type 1 fractures affect only the physis without extension to the metaphysis or epiphysis. These may demonstrate widening of the physis or a normal physis with soft tissue swelling that may become more apparent over time as the fracture heals or in comparison to the opposite asymptomatic hand. OTHER ANSWERS: A SH type 2 fracture would involve the physis as well as the metaphysis. A SH type 3 fracture would involve the physis and epiphysis but spare the metaphysis. A SH type 4 fracture would involve the physis as well as the metaphysis and epiphysis. Of note, a SH type 5 fracture (not listed) would also affect only the physis but is typically a crush injury leading to narrowing or decrease of the height of the physis on radiography.

Answer 162

Correct answer: this disease is caused by IgG antibodies against desmogleins. The clinical and morphologic findings are consistent with pemphigus vulgaris. Pemphigus is a rare autoimmune disease that typically presents with blisters of the skin and/or mucous membranes. The three main types of pemphigus are pemphigus vulgaris, pemphigus foliaceus, and paraneoplastic pemphigus. The most prevalent one is pemphigus vulgaris, accounting for 80% of cases. The common histologic determinant of all forms of pemphigus is acantholysis, which is disruption of intercellular connections between epithelial cells. Pemphigus is caused by IgG antibodies to demosmogleins, adhesions molecules that hold epithelial cells together. By disrupting the connections between eplithelial cells, the autoantibodies in pemphigus vulgaris cause superficial (or suprabasal…aka above the basement membrane) intraepidermal bullae with acantholysis. Immunofluorescence of skin biopsy would show antibodies binding to the outlines of individual epithelial cells. Because they are superficial, the bullae in pemphigus are fragile and frequently rupture. This makes patients with pemphigus at high risk for skin infections and scarring. Bullous pemphigoid differs from pemphigus in several respects. Patients with bullous pemphigoid have autoantibodies against BPAG ( a component of hemidesmosomes in the basement membrane of the epidermis). Consequently, bullae are subepidermal and tend to be intact. Immunofluorescence would reveal a linear pattern of antibodies at the base of the epidermis. Because individuals with bullous pemphigoid have less rupture of their bullae than those with pemphigus vulgaris, bullous pemphigoid tends to be less clinically severe than pemphigus vulgaris. Finally, patients with bullous pemphigoid tend not to have oral lesions.

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